Conditions: HIV Infections
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 86
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate whether the combination of BMS-955176 with atazanavir (ATV) \[with or without ritonavir (RTV)\] and dolutegravir (DTG) is efficacious, safe, and well-tolerated in HIV-1 infected treatment experienced adults.

Detailed description:

Arms:
arm 1: BMS-955176 at 120 mg tablet per day + Atazanavir boosted with ritonavir (ATV/r) 300/100 mg tablets per day + DTG 50 mg tablet per day, orally arm 2: TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally arm 3: BMS-955176 at 120 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally arm 4: BMS-955176 at 180 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally arm 5: TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally

Interventions: intervention 1: BMS-955176 intervention 2: Atazanavir (ATV) intervention 3: Ritonavir (RTV) intervention 4: Dolutegravir (DTG) intervention 5: Tenofovir (TDF)
Intervention descriptions: intervention 1: HIV Maturation Inhibitor intervention 2: Atazanavir intervention 3: Ritonavir intervention 4: Dolutegravir intervention 5: Tenofovir

Protocol document:
Prot_000.pdf: 
Page:
1
Protocol Number:
AI468048
IND Number:
118,936
Ex-US
Non-IND
EUDRACT Number
N/A
Date:
28-Jan-2015
Clinical Protocol AI468048
A Phase 2b Randomized, Active-Controlled, Staged, Open-Label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without 
Ritonavir) in Treatment-Experienced HIV-1 Infected Adults
Study Director/Central Medical Monitor
 DO, MPH
5 Research Parkway
Office 201D
Wallingford, CT  06492 USA
Telephone (office): 
Fax: 
24-hr Emergency Telephone Number
USA:
International: 
Bristol-Myers Squibb Research and Development
Virology Clinical Research and Development
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
5 Research Parkway
Wallingford, CT 06492
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (eg, amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 
1.0
Approved
1.0
v
930087072
PPD
PPD
PPD
PPD
PPD


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
2
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved. References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Original 
Protocol
28-Jan-2015
Not applicable
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
SYNOPSIS
Clinical Protocol AI468048
Protocol Title: A Phase 2b Randomized, Active-Controlled, Staged, Open-label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without Ritonavir) in 
Treatment-Experienced HIV-1 Infected Adults
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): Subjects in each arm and per stage will begin QD dosing (in the morning, with a meal) with 
BMS-955176 in combination with atazanavir (ATV) [with or without ritonavir (RTV)] and dolutegravir (DTG), or 
tenofovir (TDF) in combination with atazanavir boosted with ritonavir (ATV/r) and DTG, for a duration of 
96 weeks.
Stage 1:

Arm 1: BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Study Phase: 2b
Research Hypothesis: This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with 
or without RTV) and DTG is efficacious, safe, and well-tolerated in HIV-1 infected treatment-experienced adults.
Objectives:
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg and a TDF 300 mg-containing arm, each when given in 
combination with ATV/r 300/100 and DTG 50 mg by determining the proportion of treatment-experienced 
subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when given in 
combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the antiviral efficacy of TDF 300 mg 
when given in combination with and ATV/r 300/100 mg and DTG 50 mg by determining the proportion of 
treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms (TDF + ATV/r + DTG), 
by determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms, by determining the 
proportion of treatment-experienced subjects with plasma HIV-1 RNA < 200 c/mL at Weeks 24, 48, 96
Date: 28-Jan-2015
4
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess the emergence of HIV drug resistance in samples selected for drug resistance testing (according to 
criteria outlined in Protocol Section 5.4.1)

To assess efficacy of BMS-955176 Arms, and the TDF-containing Arms, by using the mean changes from 
baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by measuring frequency 
of SAEs and AEs leading to discontinuation

To assess disease progression as measured by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV (with or without 
ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
Study Design: This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced subjects total will be randomized into the study. In Stage 1, approximately 80 subjects 
will be randomized 1:1 (approximately 40 per arm) to either of the treatment arms containing BMS-955176 or TDF 
in combination with boosted atazanavir (ATV/r) and DTG. In Stage 2, approximately 120 subjects will be 
randomized 1:1:1 (approximately 40 per arm) to either of the two BMS-955176 treatment arms containing 
unboosted ATV and DTG, or to the TDF-containing Arm containing ATV/r and DTG. The randomization in both 
Stages will be stratified by HIV-1 Clade (AE versus Other). The number of subjects with HIV-1 Clade AE will be 
capped at a maximum of approximately 3 per arm.
Stage 1:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
A Continuation Dose of BMS-955176 will be selected: A dose of BMS-955176 will be selected based on the totality 
of Week 24 data from Stage 1 and available data from study AI468-038 (BMS-955176 in ARV treatment-naive 
HIV-1 infected subjects) with which subjects in Stage 1, Arm 1 may transition to for the remainder of the study. The 
transition may occur on or after Week 48.
The totality of the data from the Week 24 analysis for AI468-038 and Stage 1, including safety, efficacy and 
resistance, will be examined in conjunction with PK/PD modeling to determine if Stage 2 of the study will be 
initiated and confirm the two doses of BMS-955176 for study in Stage 2.
After the Stage 2 Week 24 endpoint, a Continuation Dose of BMS-955176 will be selected based on the totality of 
data from Stages 1 and 2, and study AI468-038 with which subjects in Stage 2, Arms 3 and 4 will transition to for 
the remainder of the study. The switch in Stage 2 may occur sooner, between Week 24 and Week 48, or it may be 
after Week 48.
The assigned backbone for each arm, ATV and DTG, or ATV/r and DTG, will remain unaltered throughout the 
study.
All subjects in both stages are expected to receive study treatment for 96 weeks.
Date: 28-Jan-2015
5
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Population:
Key Inclusion Criteria:

Men and non-pregnant women, at least 18 years of age (or minimum age as determined by local regulatory or as 
legal requirements dictate)

Antiretroviral treatment-experienced, defined as having documented evidence of having failed 1 or 2 regimens 
that include 2 or 3 classes of ARV (with or without documented resistance)

Confirmed Plasma HIV-1 RNA 400 copies/mL

CD4+ T-cell count > 50 cells/mm3

Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, FC < 2.2; DTG; TDF)
Date: 28-Jan-2015
6
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Key Exclusion Criteria:

Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens

Resistance or partial resistance to any study drug

Three or more of the following PI mutations, historical or documented: M36I/V, M46I/L/T, G48M/V, 
I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M

Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S

Any major TDF mutation, historical or documented: K65R or T69ins

Three or more of the following non-accessory thymidine analogue mutations (TAMs): M41L, D67N, K70R, 
L210W, T215Y/F, K219Q/E

Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI resistance), historical or 
documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, Y143C/H/R, E157Q

Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV Ab and HCV RNA)

ALT or AST > 3 × ULN

Alkaline Phosphatase > 5 × ULN

Bilirubin 1.5 × ULN

History of decompensated cirrhosis or active decompensated cirrhosis

Hemoglobin < 8.0 g/dL

Platelets < 50,000 cells/mm3
Date: 28-Jan-2015
7
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for AI468048
Medication 
Potency 
IMP/Non-IMP 
BMS-955176 
60 mg or 120 mga
IMP
Tenofovir (TDF)
300 mg
Non-IMP
Atazanavir (ATV)
200 mg and 300 mg
IMP
Ritonavir (RTV)
100 mg
Non-IMP
Dolutegravir (DTG)
50 mg
IMP and Non-IMP, based on 
country approval status
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Study Assessments: Efficacy assessments will include plasma HIV-1 RNA measurements. Safety Assessments will 
include blood chemistry and hematology, ECGs, Physical Exams and Vital Signs, and assessment of non-serious 
AEs, SAEs and AEs leading to discontinuation.
Statistical Considerations:
Sample Size:
This is an estimation study, without statistical testing, and hence there are no power considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere around 80%. With this 
response rate, and 40 subjects per arm, an exact 95% confidence interval would run from roughly 64% to 91%.
Endpoints:
Primary Endpoint(s) for Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24. This will be assessed with the FDA snapshot algorithm. This uses the last on-treatment plasma HIV-1 
RNA measurement, within an FDA-specified visit window, to determine response
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 RNA < 200 c/mL 
at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with positive response defined as HIV-1 
RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be assessed using the 
most recent version of the IAS-USA list of HIV-1 drug resistance mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the percentage of CD4+ 
T-cells will be assessed using on-treatment laboratory results, and pre-specified visit windows
Date: 28-Jan-2015
8
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly from the case report 
forms (CRFs). The summary will count the number of subjects that have at least one event.

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from the CRFs. The 
summary will count the number of subjects that have at least one event.

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, collected at Week 2 
from a subset of subjects.
Analyses:
The first two interim analyses are scheduled to support the decision on initiating the second stage of this study. This 
decision will be based on the totality of the data, including:  safety, efficacy and resistance data from this study; 
relevant data from other studies in the development program; and PK/PD modeling.
The first interim analysis will be conducted after approximately 50% of the randomized subjects have completed 24 
weeks of therapy in Stage 1. This analysis will use the BMS equivalent of SDTM (Study Data Tabulation Model) 
data (“level 1” data) to facilitate the development of models for: population pharmacokinetics; exposure-response 
relationships; and viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of therapy in Stage 1.  
This will be a complete analysis of the available efficacy, safety and resistance data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well as the recruiting 
time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If Stage 2 is initiated, and recruiting 
follows projected timelines, then it is anticipated that analyses will be conducted when:

The last subject in Arms 3, 4 and 5 completes the Week 24 visit

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4 and 5 completes the Week 96 visit
Date: 28-Jan-2015
9
1.0
Approved
1.0
v
930087072


TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Study Rationale ................................................................................................. 
1.1.1 Rationale to support study design ............................................................ 
1.1.2 Rationale to support the dose selection ................................................... 
1.1.3 Rationale to support any drug combinations ........................................... 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objective .................................................................................... 
1.3.2 Secondary Objectives ............................................................................... 
1.3.3 Exploratory Objectives ............................................................................ 
1.4 Product Development Background ................................................................... 
1.4.1 Background Information BMS-955176 .................................................... 
1.4.1.1 Mechanism of Action....................................................................... 
1.4.1.2 Nonclinical studies .......................................................................... 
1.4.1.3 Clinical studies................................................................................ 
1.4.2 Background Information on TDF ............................................................ 
1.4.3 Background Information on DTG ............................................................ 
1.4.4 Background Information on ATV ............................................................. 
1.4.5 Background Information on RTV ............................................................. 
1.4.6 Drug-Drug Interactions ........................................................................... 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.1.1 Screening.................................................................................................. 
3.1.2 Day 1/Baseline Visit ................................................................................. 
3.1.2.1 Day 1/Baseline Visit for Arms 1 and 2 - Stage 1 ............................ 
3.1.2.2 Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2 ........................ 
3.1.3 Week 2 Intensive PK Visit ........................................................................ 
3.1.4 Visits Week 4 - 96 ..................................................................................... 
3.1.5 Selection of the Continuation Dose of BMS-955176 ............................... 
3.1.5.1 Selection of the Continuation Dose, and the Switch for Stage 1 .... 
3.1.5.2 Selection of the Continuation Dose, and the Switch for Stage 2 .... 
3.1.6 End of the study ........................................................................................ 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
1
3
4
10
14
14
14
16
19
21
21
21
21
22
22
22
22
23
28
31
31
31
31
31
32
35
35
35
35
37
37
37
38
38
38
38
39
39
39
40
40
42
42
42
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Date: 28-Jan-2015
10
1.0
Approved
1.0
v
930087072


3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Other Restrictions and Precautions ......................................................... 
3.5 Discontinuation of Subjects following any Treatment with Study Drug .......... 
3.6 Post Study Drug Study Follow up .................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Instructions for Dose Administration ...................................................... 
4.5.1.1 General Instructions ....................................................................... 
4.5.1.2 Specific Dosing Instructions for Initial Treatment Arm Assignment
...............................................................................................................
4.5.2 Dose Modifications .................................................................................. 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Vital Signs and Physical Examinations ................................................... 
5.3.2 Adverse Events ......................................................................................... 
5.3.3 Concomitant Medication Assessment ...................................................... 
5.3.4 Electrocardiograms ................................................................................. 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.1.1 Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing .................................................................................. 
5.4.1.2 Protocol Defined Virologic Failure ................................................ 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.4.2.1 CD4+ and CD8+ T-Cells ............................................................... 
5.4.2.2 Drug Resistance Testing ................................................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.5.1 Intensive Pharmacokinetic Assessment .................................................... 
5.5.2 Sparse Pharmacokinetic Assessments ...................................................... 
5.6 Biomarker Assessments .................................................................................... 
5.7 Outcomes Research Assessments ..................................................................... 
44
45
46
46
46
46
47
47
47
48
50
50
50
50
51
51
51
51
52
52
52
52
53
54
54
60
60
61
61
61
61
61
61
61
62
63
63
63
63
63
63
65
65
66
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Date: 28-Jan-2015
11
1.0
Approved
1.0
v
930087072


5.8 Other Assessments ............................................................................................ 
5.9 Results of Central Assessments ........................................................................ 
6 ADVERSE EVENTS ................................................................................................. 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) ..................................................... 
6.7 Other Safety Considerations ............................................................................. 
6.7.1 Toxicity Management ............................................................................... 
6.7.1.1 Management of Elevations in Liver Transaminases ....................... 
6.7.1.2 Management of Renal Toxicity ....................................................... 
6.7.1.3 Management of Hyperbilirubinemia ............................................... 
6.7.1.4 Gastrointestinal Toxicity Evaluation and Management Plan ......... 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s)Stage 1 and Stage 2 ................................................. 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Primary Efficacy Analyses .............................................................. 
8.4.2.2 Secondary Efficacy Analyses .......................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.4.1 Sparse Pharmacokinetic Analyses .................................................. 
8.4.4.2 PK/PD and PK/VK Analyses .......................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Other Analyses (including Virologic Futility) ......................................... 
8.5 Interim Analyses ............................................................................................... 
9 STUDY MANAGEMENT ........................................................................................ 
9.1 Compliance ....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
66
66
67
68
69
69
70
70
70
71
71
71
71
71
72
72
72
74
74
74
75
75
75
75
76
76
76
77
77
77
78
78
78
78
78
79
79
79
79
79
80
80
81
81
81
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Date: 28-Jan-2015
12
1.0
Approved
1.0
v
930087072


9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10 GLOSSARY OF TERMS ........................................................................................ 
11 LIST OF ABBREVIATIONS .................................................................................. 
12 REFERENCES ........................................................................................................ 
APPENDIX 1 LISTINGS OF PROHIBITED AND PRECAUTIONARY 
THERAPIES ........................................................................................................... 
APPENDIX 2 AIDS-DEFINING DIAGNOSES.......................................................... 
APPENDIX 3 DAIDS TOXICITY GRADES .............................................................. 
APPENDIX 4 COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE .................................................................................... 
81
82
82
84
85
92
96
98
104
125
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Date: 28-Jan-2015
13
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
1
INTRODUCTION AND STUDY RATIONALE
1.1
Study Rationale
Despite advances in prevention and care, HIV/AIDS remains a significant epidemic in both the 
US and worldwide. AIDS remains the 6th leading cause of death, internationally. Globally, 
approximately 35 million people were living with HIV infection in 2013.1 A number of these 
patients include those who are treatment-experienced. Note: the use of the term 
“treatment-experienced” herein refers to subjects who have failed at least one or two 
antiretroviral (ARV) regimens and who may be harboring drug resistant virus (current or 
archived) to at least one drug class.
In contrast to current HIV treatment guidelines for treatment-naïve patients, the recommended 
composition of combination
antiretroviral therapy (cART) is far less uniform for 
treatment-experienced subjects.2,3 The level of detail in the DHHS and EACS guidelines leads to 
a lack of uniformity in treatment for patients in later lines of therapy. Moreover, drug related 
toxicities (both short and longer term) in treatment-experienced subjects necessitate vigilance 
and continued monitoring. Thus, there is a need for new and efficacious agents with novel 
mechanisms of action (MOA) and favorable safety/tolerability profiles. Given the aging HIV-1 
infected population and overall fewer number of ARV options for treatment-experienced 
patients, there is a need for a more simplified regimen that may have a better long-term safety 
profile such as that of a nucleoside- and booster-sparing cART regimen. As discussed below, this 
study 
evaluates 
the 
merits 
of 
a 
nucleoside-sparing 
cART 
regimen 
and 
a 
nucleoside/booster-sparing cART regimen in Stage 1 and 2, respectively.
Given the aforementioned challenges with existing treatment in ARV treatment-experienced 
adults, the two primary objectives of this two stage, Phase 2b study are to: 1) To study the 
efficacy of one dose (120 mg) of BMS-955176 (a novel HIV-1 maturation inhibitor) when given 
in combination with atazanavir boosted with ritonavir (ATV/r) 300/100 mg and dolutegravir 
(DTG) 50 mg in Stage 1, and 2) to study the efficacy of two doses (120 and 180 mg) of 
BMS-955176 when given in combination with unboosted ATV 400 mg and dolutegravir (DTG) 
50 mg in Stage 2.
Ultimately this Phase 2b clinical trial will provide supportive data in the context of a therapeutic 
dose of BMS-955176 and the clinical safety/efficacy/resistance of the proposed component(s) of 
a single tablet regimen (STR, that is also a nucleoside/ritonavir sparing ARV strategy) for 
Phase 3 trial development in HIV-1 infected treatment-experienced subjects. Specifically, two 
arms in Stage 2 will contain the individual ARV components of a potential STR: BMS-955176, 
ATV, and DTG.
1.1.1
Rationale to support study design
This Phase 2b open-label clinical trial design is in general agreement with published Food and 
Drug 
Administration 
(FDA)
guidance.4
Initially,
in 
Stage 
1, 
approximately 
80 treatment-experienced HIV-1 infected subjects will be randomized 1:1 (approximately 40 per 
treatment group) to one experimental arm (Arm 1) and a TDF-containing arm (Arm 2) 
Date: 28-Jan-2015
14
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
(see Figure 3.1.6-1) to accomplish this study’s Stage 1 primary study objective: to study the 
efficacy of one dose (120 mg) of BMS-955176 when given in combination with ATV/r 
(300/100 mg) and DTG (50 mg). At the Week 24 primary endpoint, Bristol-Myers Squibb 
(BMS) will conduct an analysis of efficacy, safety, and resistance. The Week 24 analysis of 
Arms 1 and 2 together with the Week 24 analysis of all arms in the AI468038 study will be used 
to select a continuation dose for BMS-955176 in Arm 1 of study AI468048, determine if Stage 2 
of study AI468048 will be initiated, and confirm the two doses of BMS-955176 for study in 
Stage 2 of study AI468048. Note, AI468038 is a concurrent Phase 2b study in HIV-1 infected 
treatment naive adults; the primary objective is to evaluate three doses of BMS-955176 (60, 120, 
and 180 mg) and EFV when given in combination with TDF/FTC by determining the proportion 
of subjects with HIV-1 RNA < 40 c/mL at Week 24.
To mitigate the clinical concerns of a potential subtherapeutic regimen and the subsequent 
development of virologic failure/resistance, the clinical trial design will contain a second stage. 
Specifically in Stage 2, approximately 120 additional treatment-experienced HIV-1 infected 
subjects will begin randomization 1:1:1 (approximately 40 per treatment group) to Arms 3, 4,
and 5 based upon the results of two concurrent analyses:

Results of the Week 24 analysis in Stage 1 (Arms 1 and 2), including an analysis for 
virologic futility (see Section 8.4.7)

Results of the Week 24 analysis of Arms 1-4 in AI468038 (treatment-naïve HIV-1 infected 
adults)
Thus, Stage 2 (Arms 3, 4, and 5) will not enroll if the clinical pretest probability of a 
subtherapeutic regimen (in Arms 3 and 4) is high based upon the results of the Week 24 analyses 
from either AI468038 or AI468048 (Stage 1: Arms 1 and 2). Note, subjects in Arm 5 (Stage 2) 
will receive the same ARV regimen as subjects in Arm 2 (Stage 1); Arm 5 in Stage 2 exists to 
maintain similar baseline demographic and clinical characteristics among subjects who are 
randomized to the three Arms in Stage 2. This staged design allows Stage 2 (Arms 3, 4, and 5) to
begin recruitment in a clinically de-risked fashion and accomplish this study’s Stage 2 primary 
study objective: to study the efficacy of two doses (120 mg and 180 mg) of BMS-955176 when 
given in combination with unboosted ATV 400 mg and DTG 50 mg. Ultimately, the totality of 
data from the Week 24 primary endpoint of Stage 2 (Arms 3, 4, and 5), Stage 1 (Arms 1 and 2), 
and all arms in the AI468038 study will be used to select a continuation dose for BMS-955176 in 
Arms 3 and 4 of study AI468048. Across all five arms of this study, subjects will receive 
treatment with three fully-active ARVs (see Section 1.1.3, Rationale to support any drug 
combinations). Ultimately, subjects in experimental Arms 1, 3, and 4 will be given a 
continuation dose of BMS-955176 which has acceptable efficacy, safety, and tolerability
(see Figure 3.1.6-1) for subsequent development in HIV-1 treatment-experienced adults. 
In a recent clinical trial approximately 95% of randomized subjects were noted to be infected 
with HIV-1 clades B, C, and AE.5 Based on in-vitro studies, BMS-955176 is expected to be 
active against a variety of clades albeit with EC50s approximately 2-3 fold less toward HIV-1 
clade AE compared to clade B (see Section 1.4.1). Since the Phase 2a study AI468002 did not 
Date: 28-Jan-2015
15
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
include any subjects infected with HIV-1 clade AE (see Section 1.4.1.3), this multinational 
Phase 2b trial will stratify randomization to ensure each treatment arm has approximately the 
same number of HIV-1 clade AE infected subjects in their respective Stages and cap the number 
of HIV-1 clade AE subjects to a maximum of approximately 3 per treatment arm. The study 
duration is expected to be 96 weeks in length to assess durability of response and longer term 
safety and tolerability.
1.1.2
Rationale to support the dose selection
Phase 1 and Phase 2a clinical trials (AI4680016 and AI4680027) investigating BMS-955176 
utilized a spray-dried dispersion (SDD) suspension. However, this Phase 2b study will utilize a 
micronized crystalline (MC) tablet.
In the concomitant dose-finding Phase 2b study in HIV-1 infected treatment naive adults for 
BMS-955176 (AI468038), doses of BMS-955176 of 60 mg, 120 mg, and 180 mg MC tablet are 
proposed for assessment. These doses are based upon modeling and simulation and formulation 
considerations. A population pharmacokinetic model was developed using single dose 
(10 mg - 120 mg SDD) and multiple dose (10 mg to 80 mg SDD) data in healthy subjects 
(AI468001) as well as multiple dose data in HIV-1 clade B-infected subjects (5 mg to 120 mg
SDD for 10 days, AI468002). An exposure-response analysis was conducted using data from 
Part A of the Phase 2a clinical trial where HIV-1 clade B infected subjects received 
BMS-955176 monotherapy (Dose range: 5 - 120 mg) for 10 days. The exposure-response 
relationship was assessed via an Emax model using observed BMS-955176 steady state Cmin. The 
primary endpoint was predicted maximum viral load decline from baseline.
Steady state BMS-955176 Cmin values in HIV-infected subjects administered MC tablet with 
food were projected according to the following data and assumptions:

Exposures in HIV-infected subjects are 35% less than normal healthy volunteers based on 
observations from AI468001 and AI468002 study

Single dose data projected to multiple dose using accumulation index from AI468001 study

BMS-955176 exposures from the MC tablet formulation with food were projected based on 
studies AI468001 and AI468034. The impact of food on the 60 mg MC tablet dose was 
assumed to be that observed for the 40 mg MC suspension formulation in AI468001. 
Exposures to BMS-955176 120 mg MC tablet with food were determined from observed data 
in Study AI468034, where BMS-955176 C24 increased approximately 70% when 120 mg 
MC tablet was given with a high fat meal, relative to fasted conditions. Finally, exposures to 
BMS-955176 180 mg MC tablet with food were assumed to be 1.5-times that of 120 mg MC 
tablet with food
Figure 1.1.2-1 depicts the simulated maximum viral load decline in HIV-infected subjects 
administered BMS-955176 MC tablet under fed conditions.
Date: 28-Jan-2015
16
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 1.1.2-1:
Simulated Maximum Viral Load Decline from Baseline Under Fed 
Conditions1
1 Solid lines are 10th and 90th percentiles and the median of simulated data, shaded area is the 90% confidence 
interval of simulated data, vertical solid lines are the 25th to 75th percentile of the simulated steady state 
BMS-955176 Cmin for the 60 mg MC tablet dose, vertical dotted lines are the 25th to 75th percentile of the 
simulated steady state BMS-955176 Cmin for the 120 mg MC tablet dose, and vertical dashed and dotted lines 
are the 25th to 75th percentile of the simulated steady state BMS-955176 Cmin for the 180 mg MC tablet dose.
While baseline EC90 was not a covariate included in the model due to the lack of significance; 
this covariate, among others, was considered marginally significant and it is possible this 
covariate will become important with additional data.
Although data from AI468002 Part C (in HIV-1 clade C infected subjects) were not included in 
the exposure-response assessment described above, BMS-955176 doses 40 mg SDD once daily 
demonstrated median maximal reductions in HIV-1 RNA > 1 log10 in both clade B and clade C 
HIV-1-infected subjects (see Section 1.4.1.3); thus, doses of BMS-955176 60 mg, 120 mg, and 
180 mg are expected to yield a similar response in HIV-1 infected subjects of either clade.
Because the lowest dose assessed in AI468038 (BMS-955176 60 mg) has the potential for a 
suboptimal antiviral response and possible development of resistance, BMS-955176 120 mg in 
combination with ATV/r and DTG will be assessed in Stage 1 of this study. Based on previous 
data that demonstrated exposures to BMS-955176 increase approximately 50% when given in 
combination with RTV, exposures to BMS-955176 120 mg given in combination with ATV/r are 
expected to result in exposures similar to BMS-955176 180 mg given without RTV. Finally, 
BMS-955176 180 mg will not be used in Stage 1 because exposures (when administered with 
RTV) are expected to exceed those previously studied in clinical trials.
Date: 28-Jan-2015
17
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.1.2-1 depicts the projected exposure multiples of BMS-955176 60 mg, 120 mg, and 
180 mg MC tablet with food at the NOAEL for pre-clinical findings of interest.
Table 1.1.2-1:
Exposure Multiples of BMS-955176 at NOAELa
Species/ Study 
NOAEL
Multiples
Dose 
(mg/kg/d)
Exposure
PK 
Parameter
60 mg
120 mg
180 mg
Rat/6-month (stomach 
histologic changes) 
No NOAEL
AUC
---
---
---
Dog/9-month (stomach 
histologic changes) 
1
AUC:
64.9 gh/mL
AUC 
3
2
1
Dog/1-month (heart rate)
20
Cmax:
17.8 g/mL 
Cmax
19
10
5
Dog/ Cardiovascular 
telemetry (heart rate) 
2
Cp:
1.93 g/mL 
Cmax
2
1
0.5
Mouse/EFD 
45
AUC:
197 gh/mL 
AUC
10
6
3
a Exposure multiple = animal value ÷ human value. Projected human Cmax values are 0.94, 1.79, and 3.61 g/mL and steady 
state AUC values are 19.3, 35.8, and 69.2 g•h/mL at 60, 120, and 180 mg in HIV-1 subjects receiving BMS-955176 MC 
tablets with high fat meal, respectively. High fat meal provides the highest exposure relative to other meal types or fasted 
state.
With regard to heart rate and the NOAEL of 1.93 g/mL observed in the cardiovascular 
telemetry study in dogs (N=2), it is noted that the projected exposure multiple is 1 at a dose of 
120 mg MC tablet in HIV-infected subjects. However, to date, there have been no clinically 
meaningful changes in heart rate observed in subjects treated with BMS-955176 up to 28 days
(in Part B of the Phase 2a study). With regard to stomach histologic changes, no NOAEL could 
be established based on the 6-month rat study and the projected exposure multiples from the 
9-month dog study are relatively low (eg, 2-fold at the 120 mg MC tablet dose). Despite these 
preclinical findings, a dose of BMS-955176 120mg MC tablet will provide exposures in this 
study which are expected to be generally safe and well tolerated based on existing clinical data 
(see Section 1.4.1).
Data from Study AI468034 demonstrated that BMS-955176 120 mg MC tablet AUC increased 
53% when given with a high fat meal, relative to fasted conditions. Furthermore, preliminary 
data from Study AI468049 demonstrated that a light meal, a standard meal, and a high fat meal 
increased BMS-955176 180 mg MC tablet AUC 1.8-, 2.1-, and 2.5-fold, respectively, relative to 
fasted conditions. Taken together, these data suggest that exposures to BMS-955176 MC tablet 
at doses up to 180 mg increase in a linear fashion when given with food and that similar 
exposures are observed regardless of meal type.
Date: 28-Jan-2015
18
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In total, BMS-955176 120 mg is expected to be safe, well-tolerated, and efficacious in Stage 1 
and will inform the selection of a Stage 1 continuation dose and aspects of Stage 2 (as described 
in detail within Section 1.1.1).
If Stage 2 initiates enrollment, the doses of BMS-955176 will be based upon the Week 24 
analyses of both Stage 1 and Study AI468038. As described in this protocol, the doses in Stage 2 
may be BMS-955176 120 mg and 180 mg in Arms 3 and 4, respectively. However, a thorough 
evaluation of safety, tolerability, efficacy, and resistance will ultimately be combined with 
exposure-response and viral kinetic modeling and simulation to inform the doses of 
BMS-955176 to be given with DTG and ATV (in Arms 3 and 4 of Stage 2).
1.1.3
Rationale to support any drug combinations
This study co-administers BMS-955176, with unboosted ATV 400 mg QD or ATV/r 300/100 mg
QD, and DTG 50 mg. The drug combinations within this clinical trial design will provide 
supportive data in the context of a therapeutic dose of BMS-955176 and the clinical 
safety/efficacy/resistance of the proposed components (Stage 2, Arms 3 and 4) of a single tablet 
regimen (STR) for Phase 3 trial development. Ultimately, BMS will seek approval of 
BMS-955176 for use in treatment-experienced HIV-1 infected adults (including either a STR; 
FDC; and/or monoentity). 
The rationale for using a backbone of ATV and DTG in this treatment-experienced patient 
population is based upon established safety, efficacy, and tolerability of the individual 
components. DTG alone provides a 2.46 log10 c/mL reduction in HIV-1 RNA when administered 
as monotherapy for 10 days.8 Furthermore, DTG has been recently approved and is generally 
safe.9,10,11,12,13 Lastly, ATV/r is often used in treatment-experienced adults’ second-line therapies 
or beyond (for example, in individuals who may have failed an non-nucleoside reverse 
transcriptase inhibitor (NNRTI) and/or integrase inhibitor (INI) based regimen).2,4
This Phase 2b design allows treatment-experienced adults in the experimental Arms to be 
exposed to three fully active ARVs (from three classes). Subjects will benefit from each ARV 
(except RTV) independently providing a > 1 log10
c/mL decrease in HIV-1 RNA
(see Section 1.4.1.3 for details on Phase 2a results [AI468002]). BMS expects the combination of 
two agents (unboosted ATV and DTG) with one investigational agent (BMS-955176) to provide 
a generally improved safety/tolerability profile relative to the respective arm containing ATV/r 
(Arms 3 and 4 relative to Arm 1, respectively) or TDF (Arms 3 and 4 relative to Arm 5, 
respectively).
There is a potential risk of a subtherapeutic regimen to treatment-experienced subjects enrolled 
in Arms 3 and 4 since unboosted ATV is only approved for use in treatment-naïve HIV infected 
adults (within the US) and the therapeutic dose of BMS-955176 has not been established.
Unboosted ATV (400 mg) in treatment-naïve adults results in a 1.41 log10 c/mL reduction in 
HIV-1 RNA after two weeks of monotherapy.14 Despite the monotherapy based reduction in 
HIV-1 RNA, pharmacokinetic data of unboosted ATV in prospective clinical trials,15
cross-sectional,16 and retrospective analyses17 generally supports the finding of DHHS defined 
subtherapeutic ATV levels (< 150 ng/mL) in patients.18
Date: 28-Jan-2015
19
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Despite lower pharmacokinetic (PK) exposure, ATV/r has demonstrated non-inferiority to 
unboosted ATV (TLVOR: 75% vs 70% VR-OC: 87% vs 76%, respectively), similar declines in 
HIV-1 RNA (approx -3.1 log10 c/mL), and increase in CD4 cell counts within treatment-naïve 
adults. However, the unboosted ATV arm had an increased number of subjects with emerging 
ATV and lamivudine (3TC) resistance. In particular, the difference in nucleoside/nucleotide 
reverse transcriptase inhibitor (NRTI) resistance was markedly greater in the unboosted ATV 
compared to RTV boosted ATV arm.19 Of note, in this clinical trial (AI468048) NRTIs are not 
used in the experimental Arms 1, 3, and 4. Similar single arm, prospective studies have 
replicated the viral efficacy and immunologic response using unboosted ATV in treatment-naïve 
HIV infected adults.20
Insights from limited data regarding the use of unboosted ATV in treatment-experienced adults 
have demonstrated a viral decay ranging from -1.4 to -2.7 log10 c/mL over 24 weeks of therapy 
in combination with NRTIs (such as TDF, 3TC, and didanosine).21 Also, observational data 
(mean: 24 months of follow-up) has shown similar percentages of subjects with their last HIV 
RNA being undetectable (80% vs 83%) after receiving unboosted and RTV boosted ATV, 
respectively.22
Taking the key findings from studies of ATV in both treatment-naïve and treatment-experienced 
HIV infected adults, Arms 3 and 4 containing unboosted ATV may have the potential for 
increased resistance (relative to Arm 1 containing RTV boosted ATV) and the development of 
virologic failure. However, several other factors must be taken into consideration. First, these 
Arms will use three potent (> 1 log10
c/mL) ARVs in combination. Moreover, 
treatment-experienced subjects who have failed one or two prior regimens are likely to be either 
naïve to ATV treatment (prior NNRTI- and/or INI-class failure) or will need to be fully 
susceptible to approved ARVs (including unboosted ATV, see Section 3.3.2). Second, both the 
combination of ATV and DTG with BMS-955176 independently have demonstrated additivity to 
synergy in-vitro23 (see Section 1.4.1.3 for clinical data on the combination of ATV and 
BMS-955176). Third, unboosted ATV increases the geometric mean ratio of Ctrough for DTG by 
a factor of 2.8.24 Fourth, in normal healthy volunteers, multiple dose administration of 
BMS-955176 40 mg (SDD suspension formulation) with ATV 400 mg for 14 days resulted in an 
approximate 25% increase in the AUC(TAU) of BMS-955176 administration alone25 and 
preliminary PK data from the Phase 2a (AI468002) demonstrated that BMS-955176 AUC(TAU) 
increased approximately 37% and 52% when ATV was combined with BMS-955176 40 and 
80 mg (SDD suspension formulation), respectively, relative to administration of BMS-955176 
alone. It is clinically unclear whether higher exposures of DTG and BMS-955176 would lead to 
a decreased incidence of unboosted ATV resistance in the context of Arms 3 and 4 
(BMS-955176 120 and 180 mg + ATV + DTG). Combined with these factors, BMS proposes to 
mitigate the potential risk of increased resistance by 1) studying two doses of BMS-955176 
(120 and 180 mg) in combination with unboosted ATV and DTG, and 2) using a two stage 
clinical trial design with Stage 2 (Arms 3, 4, and 5) enrolling after the Week 24 analysis of 
Stage 1 (Arms 1 and 2) and AI468038 are completed, and 3) only enrolling subjects who are 
susceptible to study medication (including unboosted ATV) (see Section 1.1.1, Rationale to 
Date: 28-Jan-2015
20
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
support study design). This risk mitigation is employed to increase the probability of establishing 
clinical efficacy (number of responders at the Week 24) in treatment-experienced HIV-1 infected 
adults.
BMS expects BMS-955176 120 and 180 mg given with unboosted atazanavir to be generally 
safe and well-tolerated. Subjects in Arms 3 and 4 treated with unboosted ATV would potentially 
benefit from a more favorable lipid profile, fewer gastrointestinal (GI) side effects, and 
decreased indirect hyperbilirubinemia. In total, the potential clinical risks for subjects 
randomized to Arms 3 and 4 in Stage 2 do not outweigh the potential benefits of a Nucleoside-
and Booster-sparing cART regimen that may offer both efficacy and long-term safety (including 
but not limited to improved bone mineral density, improved renal function, and improved lipid 
profile). Please see Section 1.5 for further details on the overall risk/benefit assessment.
1.2
Research Hypothesis 
This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with or 
without RTV)
and DTG
is efficacious, safe, and well-tolerated
in HIV-1 infected 
treatment-experienced adults.
1.3
Objectives(s)
1.3.1
Primary Objective
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg, and a TDF 300 mg-containing arm,
each when given in combination with ATV/r 300/100 mg and DTG 50 mg by determining 
the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when 
given in combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the 
antiviral efficacy of TDF 300 mg when given in combination with ATV/r 300/100 mg and 
DTG 50 mg by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
1.3.2
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms (TDF + 
ATV/r + DTG), by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms, by 
determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA 
< 200 c/mL at Weeks 24, 48, 96

To assess the emergence of HIV drug resistance in samples selected for drug resistance 
testing (according to criteria outlined in Section 5.4.1)
Date: 28-Jan-2015
21
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess efficacy of BMS-955176 Arms, and the TDF-containing Arms, by using the mean 
changes from baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ 
T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by 
measuring frequency of SAEs and AEs leading to discontinuation

To assess disease progression as measured by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV 
(with or without ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
1.3.3
Exploratory Objectives

To determine the effect of BMS-955176 Arms, and the TDF-containing Arms, on renal 
clinical parameters and biomarkers through Weeks 48 and 96

To determine the effect of BMS-955176 Arms, and the TDF-containing Arms, on bone 
biomarkers through Weeks 12 and 24

To assess the impact of baseline (pre-therapy) Gag polymorphisms on the efficacy of 
BMS-955176 Arms by determining the proportion of treatment-experienced subjects with 
plasma HIV-1 RNA < 40 c/mL, HIV-1 RNA < 200 c/mL, and the changes from baseline in 
log10 HIV-1 RNA at Weeks 24, 48 and 96, by baseline polymorphisms

To characterize the steady-state plasma PK of DTG when co-administered with BMS-955176 
and ATV (with or without RTV) in treatment-experienced subjects. The effect of 
BMS-955176 on DTG PK in the presence of ATV (without RTV) may be assessed relative to 
historical data

To compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV

To characterize the PK of ATV when co-administered with DTG and BMS-955176, with or 
without RTV

To explore PK/PD and PK/viral kinetic (VK) relationships between BMS-955176, ATV, 
and/or DTG exposure and both efficacy and safety endpoints

To assess the impact of the study therapies on health-related quality of life measures
1.4
Product Development Background
1.4.1
Background Information BMS-955176
1.4.1.1
Mechanism of Action
BMS-955176 is an HIV-1 maturation inhibitor (MI), a novel class of anti-HIV-1 drugs that 
prevents the maturation of HIV-1 virions by binding near a key structural element within the Gag 
polyprotein that is required for virion maturation and assembly. Maturation inhibitors block the 
last protease cleavage event between Gag protein segments designated as capsid (CA) protein 
p24 (p24) and spacer peptide 1 (SP1), resulting in the release of immature noninfectious virus 
particles. BMS-955176 has excellent potency and broad spectrum activity, and mechanism of 
Date: 28-Jan-2015
22
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
action studies indicate that BMS-955176 is a true MI, with a mechanism of action distinct from 
current antiretroviral agents.26 Development of BMS-955176 could potentially lead to novel 
HIV-1 treatment regimens in treatment-experienced HIV-1 patients.
1.4.1.2
Nonclinical studies
Nonclinical Pharmacology and Microbiology
BMS-955176 specifically inhibits HIV-1 protease cleavage at the CA(p24)/SP1 junction within 
the Gag protein in both HIV-1-infected cells and purified HIV-1 Gag virus-like particles (VLPs). 
Radiolabeled BMS-955176 specifically binds to purified HIV-1 Gag VLPs, and its binding is 
dose-dependently inhibited by related MIs and is reversible. BMS-955176 does not directly 
inhibit HIV-1 protease nor bind to a small HIV-1 protease peptide substrate. These results 
indicate that BMS-955176 inhibits late in the HIV-1 life cycle by specific binding to immature 
capsid structures at or near the CA(p24)/SP1 junction, thereby inhibiting cleavage at that 
particular site. In cell culture, the range of values for the concentration producing 50% effect 
(EC50) of BMS-955176 against 7 common laboratory strains of HIV-1 was 1.6 to 10.5 nM 
(mean = 6.0 3.5 nM). Using a reverse transcriptase readout, a phenotyping analysis of 
93 subtype B viruses whose genotypes are representative of 96% of the diversity (found in the 
Los Alamos National Laboratory [LANL] database) in Gag sequences indicates that the mean 
EC50 of this cohort was 2.7 1.9 nM, with a median value of 2.2 nM and a range between 0.6 to 
12 nM. A similar analysis of 23 isolates of subtype C viruses found a mean EC50 of 
6.1 3.1 nM, a median value of 5.6 nM, and a range from 2.5 to 16 nM. When evaluated against 
clinical isolates in peripheral blood mononuclear cells (PBMCs), BMS-955176 exhibited a mean 
EC50 of 24 24 nM against a cohort (N = 22) of subtype B viruses. Activity was also observed 
against viruses from subtypes A, C, D, F, and G, with average EC50 values for 96% of tested 
isolates (N = 41) between 5.9 and 87 nM. Clinical isolates from the CRF01_AE subtype were 
approximately 2- to 3-fold less susceptible to BMS-955176 (average EC50 77 nM, N = 7) 
viruses. BMS-955176 was active against 1 of 3 human immunodeficiency virus type-2 (HIV-2)
isolates (EC50 = 15 nM). BMS-955176 retains complete activity against reverse transcriptase 
(RT), protease, and integrase inhibitor-resistant viruses, with EC50 values similar to wild-type 
(wt) viruses, while the potency of currently approved nucleotide/nucleoside reverse transcriptase 
inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors 
(PIs), and integrase inhibitors (INIs) was undiminished when tested against viruses with reduced 
susceptibility to BMS-955176. BMS-955176 maintained activity against a panel of PI-resistant 
isolates from PI-treated subjects harboring a variety of major and minor PI-resistance
determinants in both protease and Gag.27,28 Protein binding to 100% human serum (HS) was 
86%, and in the presence of 40% HS supplemented with additional human serum albumin 
(HuSA) to match physiologic concentrations, BMS-955176 exhibited an approximately 4-fold 
reduction of antiviral activity. Selection for resistance to BMS-955176 in cell culture identified
changes that map to amino acids adjacent to the CA(p24)/SP1 cleavage site. These include an 
amino acid substitution of A364V or a combination of V362I with secondary changes (V370A, 
A374P or I376V). In vitro, virus with the A364V change exhibited a drastic loss of susceptibility 
to BMS-955176 (>100-fold), while the V362I plus secondary change-containing viruses were 
Date: 28-Jan-2015
23
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
generally less sensitive to BMS-955176 (median EC50 25 nM, range 7.1 to 167 nM). In 2-drug 
combination studies with representative drugs from NRTI, NNRTI, PI, and INI classes, all 
combinations produced additive to synergistic effects, suggesting that BMS-955176 should be 
amenable for use in combination with any of these agents.
Bevirimat (BVM), a first-generation MI, demonstrated proof of concept and dose-dependent 
anti-HIV-1 potency in both Phase 1 and Phase 2 clinical studies. Patients infected with HIV-1 
sensitive to BVM demonstrated an approximate 1.2 log10 decline in HIV-1 RNA. However, 
approximately 50% of patients harboring naturally occurring polymorphisms located close to the 
CA(p24)/SP1 cleavage site showed a significantly reduced response to BVM treatment. In 
addition, BVM exhibited a large reduction in antiretroviral activity in the presence of human 
serum. BMS-955176 was developed to address the key flaws of BVM by providing improved 
coverage of BVM-resistant polymorphic variants and improved potency in serum. BMS-955176 
has been shown to be active against viruses with resistance from all marketed ARVs, and to 
possess a low serum effect. Development of BMS-955176 could potentially lead to novel HIV-1 
treatment regimens in treatment-experienced HIV-1 patients.
Nonclinical Pharmacokinetics
The absolute oral bioavailability of BMS-955176 was low (3.89% to 26.8%) in all preclinical 
species (mice, rats, dogs, and monkeys). In the dog, though there was a positive food effect and 
no pH dependent absorption, upon repeat dosing a less than dose-proportional increase in 
exposure was observed. BMS-955176 distributed preferentially into the duodenum, liver, and 
lymph nodes with little penetration into the brain. Protein binding was 86.1% in human serum 
and 78% to 94% in animal sera
In human in vitro systems, the metabolism of BMS-955176 was primarily mediated via 
cytochrome P450 (CYP)3A4. In vivo in rats, dogs, and monkeys, BMS-955176 was the 
predominant drug-related component in plasma following a single oral dose of BMS-955176. 
BMS-955176 was eliminated principally via metabolism followed by excretion in bile with little 
renal excretion. 
In vitro, BMS-955176 was an inhibitor of CYP2C8 (concentration at which 50% inhibition 
observed [IC50] = 28.5 M), CYP3A4 (IC50 = 32 M), and uridine diphosphate 
glucuronosyltransferase (UGT)1A1 (IC50 = 20 M) enzymes. No P-gp inhibition or 
time-dependent inhibition of CYPs was observed. BMS-955176 was not an inducer of CYP1A2, 
CYP2B6, or CYP3A4. The steady state Cmax of BMS-955176 180 mg tablet in HIV-infected 
patients with food is projected to be approximately 5.2 M. Thus, the potential exists for 
BMS-955176 to inhibit CYP2C8, CYP3A4, and/or UGT1A1 in vivo and increase exposures to 
co-administered drugs that are metabolized by these enzymes. Furthermore the potential exists 
for drug-drug interactions (DDI) if BMS-955176 is co-administered either with an inhibitor or 
inducer of CYP3A4 or P-gp.
BMS-955176 was a substrate of mouse P-glycoprotein (P-gp) based on higher bioavailability in 
P-gp knock-out mice when BMS-955176 was co-administered with elacridar, a potent inhibitor
Date: 28-Jan-2015
24
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
of P-gp and breast cancer resistance protein (BCRP). BMS-955176 could not be reliably assessed 
as a substrate for human P-gp due to nonspecific binding and low solubility. In vitro, 
BMS-955176 inhibited organic anion transporting polypeptide (OATP)1B1 and OATP1B3 
(IC50 5.3 and 4 M, respectively), but was not an inhibitor of P gp, sodium taurocholate 
cotransporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multiple 
drug-resistance protein (MRP)2, and bile salt export pump (BSEP). These findings suggest a 
potential for DDI between BMS-955176 (as the perpetrator) and substrates of OATP1B1 and 
OATP1B3, but not with those of P-gp, NTCP, OAT1, OAT3, MRP2, and BSEP. Furthermore, 
the potential exists for drug-drug interactions (DDI) if BMS-955176 is co-administered either 
with an inhibitor or inducer of CYP3A4 or P-gp. Preliminary data indicate that BMS-955176 
does not inhibit OCT2, a transporter that is inhibited by dolutegravir (DTG), a drug with which 
BMS-955176 is planned to be co-administered.
Nonclinical Toxicology
The toxicity profile of BMS-955176 was evaluated in single- and repeat-dose toxicity, 
genotoxicity, phototoxicity, safety pharmacology, sensitization, reproductive toxicity and 
embryo-fetal development studies. The scope of the toxicologic evaluation for BMS-955176
supports its proposed clinical use for HIV-1 infection. Unless otherwise mentioned, all animal 
studies were dosed by the oral route with an aqueous methylcellulose suspension of a 
BMS-955176 spray-dried dispersion (SDD). 
BMS-955176 was not phototoxic, mutagenic, or clastogenic in vitro and was not genotoxic in a 
rat micronucleus assay at 300 mg/kg/day (AUC 279 g·h/mL). BMS-955176 was not a skin 
sensitizer in the local lymph node assay in the mouse. BMS-955176 had a low potential (IC50 or 
EC50 > 5 M [> 3.45 µg/mL]) for in vitro off-target interactions on a broad range of enzymes, 
transporters, and receptors, including cardiac ion channels. 
In safety pharmacology evaluations in rats, there were no respiratory findings and no direct 
central nervous system (CNS) findings. Decreases in motor activity, arousal, and rearing were 
considered secondary to general toxicity (ie, body weight decreases).
Cardiovascular safety pharmacology evaluations were conducted in rabbits, rats, and dogs. In the 
definitive oral single-dose cardiovascular safety study in conscious telemeterized dogs, blood 
pressure and electrocardiogram were was unaffected at 20 mg/kg; however, increases in heart 
rate (mean 33% to 57% of pretest vehicle) were observed at 8 and 20 mg/kg. The increase in 
heart rate at these doses was primarily due to increases in 2 dogs at each dose that had higher 
plasma concentrations (12.83 g/mL) relative to the dogs without effects on heart rate 
(6.81 g/mL). The no-observed-effect level (NOEL) for cardiovascular effects in dogs was 
2 mg/kg (plasma concentration of 1.93 µg/mL). Importantly, there was no change in heart rate at 
20 mg/kg/day at higher plasma concentrations (Cmax 17.8 µg/mL) in the 1-month study in 
dogs (below). 
Taken together, BMS-955176 has low potential for respiratory, CNS, and cardiovascular effects 
and no cardiovascular effects have been observed in humans to date.
Date: 28-Jan-2015
25
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Two-week, 1-month, and 6-month studies were conducted in rats. As the 2-week study was of 
limited scope, only the 1-month and 6-month studies are presented in this summary. 
BMS-955176 was administered for 1 month at doses of 30, 100, or 300 mg/kg/day. While there
was no mortality at 100 mg/kg/day, the high dose of 300 mg/kg/day was associated with 
pronounced signs of clinical toxicity and early euthanasia of all the rats at that dose level on 
Days 8 to 9. The dose of 30 mg/kg/day was tolerated. The intermediate dose of 100 mg/kg/day 
(AUC 357 g·h/mL) resulted in dose-limiting toxicity including persistent reduction in food 
consumption and body weights. A number of minor hematology (including red cell parameter 
changes with no consistent effect on the erythron) and serum chemistry changes (including 
increased alkaline phosphatase and alanine aminotransferase) without correlating histologic liver 
findings) occurred at 30 and 100 mg/kg/day; these changes were considered not adverse due to 
small magnitude, occurrence only in 1 sex, and lack of microscopic correlates, and most were 
secondary to decreases in food consumption and body weight. Dose-related gastrointestinal 
toxicity was primarily characterized by morphologic changes in the stomach at 100 mg/kg/day 
and the stomach and small and large intestines at 300 mg/kg/day. At the end of the 2-week 
postdose recovery period, there was complete recovery of all BMS-955176-related findings at 
30 mg/kg/day. At 100 mg/kg/day, all findings recovered with the exception of increased red cell 
distribution width in females, minimally higher (1.94×) ALT activity in 1 male without any 
histologic correlates, and decreased mean prostate gland (with seminal vesicles) weights. The 
low dose of 30 mg/kg/day (AUC 113.5 g·h/mL) was considered the no-observed-adverse-effect 
level (NOAEL) because the body weight and food consumption changes were minimal and 
transient and there were no BMS-955176-related morphologic changes.
In a 6-month oral toxicity study in rats with 1-month recovery period, BMS-955176 was 
administered at doses of 10, 25, or 50 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month rat study and occurred at all doses (10 mg/kg/day; 
AUC 71 gh/mL). Findings included decreased body weight, food consumption, and in the 
stomach, minimal to marked atrophy involving both parietal and chief cells, minimal to mild 
single-cell necrosis and minimal regeneration in the glandular mucosa, which were partially 
reversible at the end of the 1-month recovery period. A NOAEL was not established in this 
study.
Five-day, 1-month, and 9-month repeat-dose studies were conducted in dogs. As the 5-day 
toxicokinetics and tolerability studies were of limited scope, only the 1-month and 9-month
studies are presented here. In the 1-month study, BMS-955176 was administered at doses of 2, 8, 
or 20 mg/kg/day. Increased incidences of sporadic vomiting and liquid, yellow, and/or mucoid 
feces occurred at all doses, but had no apparent effect on the overall health of these animals. 
At 20 mg/kg/day, additional findings included occasional decreases in food consumption in a 
few animals, loss of body weight (up to 8%) in 2 females, a minimal increase in serum ALT 
activity (2.10× pretest) in 1 female with no microscopic correlates, and minimal single-cell 
necrosis of stomach glandular epithelium. All BMS-955176-related changes were fully 
reversible by the end of the 2-week recovery period. The dose of 8 mg/kg/day was considered a 
NOAEL (AUC 219.5 g·h/mL) since the sporadic clinical observations had no adverse effects 
Date: 28-Jan-2015
26
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
on the general health of the animals and there were no BMS-955176-related morphologic 
changes. 
In a 9-month oral toxicity study in dogs with 1-month recovery period, BMS-955176 was 
administered at 0 (vehicle), 1, 3, or 10 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month dog
study
and
occurred at doses 3 mg/kg/day 
(AUC 135 gh/mL). Findings included salivation (only males at 10 mg/kg/day), fur thinness 
(males), thin appearance, and abnormal feces (yellow, liquid, pale and/or mucoid) that occurred 
sporadically throughout the study; increases in mean food consumption; minimal to marked chief 
cell depletion in the glandular stomach. Additional findings at 10 mg/kg/day included thin 
appearance that correlated with decreases in body weight in food consumption; occasional 
vomitus in males; in the stomach, minimal to moderate mucous cell hyperplasia (often associated 
with glandular dilatation) correlating with increased thickness macroscopically (males only) and 
minimal to marked parietal cell depletion and single-cell necrosis of glandular epithelial cells; 
and increases in serum gastrin values (1.31 to 4.56× highest control value) for several dogs that
may have reflected the reductions in gastric parietal cells. The NOAEL was 1 mg/kg/day 
(AUC 64.9 gh/mL).
The embryo-fetal development (EFD) studies were conducted in 3 species (rabbits, rats, and 
mice) instead of the standard 2 species due to poor maternal tolerability and inability to achieve 
adequate systemic exposures in rabbits.
In a definitive EFD study in pregnant mice, BMS-955176 was administered at doses of 15, 45, or 
150 mg/kg/day from gestation day (GD) 6 through 15. BMS-955176 was a selective 
developmental toxicant in mice. Dose of 100 mg/kg/day was associated with an increase in 
embryo-fetal lethality (cumulative postimplantation losses of 11.5%, relative to 3.9% in control 
litters, attributed to increased incidences of dead fetuses, early resorptions and late resorptions). 
Cleft palate and exencephaly were observed in a few fetuses; additionally, marginal reductions in 
fetal body weight (5% relative to control values) were observed. There was no maternal toxicity 
at any dose tested. The developmental NOAEL was 45 mg/kg/day (AUC 213 g·h/mL).
In a definitive EFD study in pregnant rats, BMS-955176 was administered at doses of 10, 30, or 
100 mg/kg/day from GD 6 through 15. BMS-955176 was not a selective developmental toxicant. 
Developmental toxicity (reduced fetal body weights, increases in fetal alterations, and reduced 
fetal ossification) occurred only at 100 mg/kg/day; whereas, maternal toxicity (clinical 
observations, reduced body weights, and reduced food consumption) was observed at 
30 mg/kg/day. The developmental NOAEL was 30 mg/kg/day (AUC 114 gh/mL). 
In an EFD study in pregnant rabbits, BMS-955176 was administered at a dose of 80 mg/kg/day 
from GD 7 through 19. BMS-955176 was not a developmental toxicant in rabbits at 
80 mg/kg/day (AUC 3.26 gh/mL), at which reductions in maternal food consumption and 
weight gain were observed.
In the fertility and early embryonic development study in rats, BMS-955176 was evaluated at 
doses of 10, 30, or 100/60 mg/kg/day in males and females. BMS-955176 did not affect 
Date: 28-Jan-2015
27
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
reproduction or early embryonic development at doses 100 mg/kg/day that produced overt 
toxicity. The reproductive NOAEL was 100/60 mg/kg/day (AUC 210 g•h/mL) in male rats and
100 mg/kg/day (AUC 458 g•h/mL) in female rats.
Overall, results from the nonclinical toxicology studies demonstrate that BMS-955176 has a low 
potential for cardiovascular effects, is toxic to the gastrointestinal tract, and is a selective 
developmental toxicant. Clinical monitoring of vital signs (heart rate, systolic and diastolic blood 
pressure) and for gastrointestinal adverse events (AEs) (eg, nausea, vomiting, diarrhea, or fecal 
changes), along with screening for potential renal tubular injury, have not indicated any potential 
for these AEs in Phase 1 or proof of concept (POC) studies in humans. Clinical protocols will 
ensure that appropriate contraceptive measures will be followed to minimize the risk of 
pregnancy while enrolling women of child-bearing potential (WOCBP) males subjects who are 
sexually active with (see Section 3.3.1 Inclusion Criteria).
1.4.1.3
Clinical studies
Phase 1
The safety, tolerability, and PK of BMS-955176 were evaluated in a randomized, double-blind, 
placebo-controlled, sequential single ascending dose (SAD, 10-120 mg) and multiple ascending 
dose (MAD, 10-80 mg QD for 14-28 days) study in healthy subjects (AI468001). No SAEs, 
deaths, or discontinuations related to study drug occurred. No clinically meaningful trends were 
observed in vital signs, physical exam findings, laboratory values, or ECGs. Following 
single-dose and multiple-dose administration of BMS-955176, a slightly less than 
dose-proportional increase in Cmax and AUC(INF) was observed over the dose ranges studied. 
Steady state was reached in approximately 7 days following multiple-dose once daily 
administration of BMS-955176. The half life (T-HALF) of BMS-955176 is approximately 
35 hours. 
Study AI468034 assessed the relative bioavailability and dose proportionality of BMS-955176 
MC tablet - the formulation that will be used in the current study. Relative to 80 mg SDD 
suspension, the bioavailability of BMS-955176 120 mg MC tablet was approximately 23% 
lower. Furthermore, consistent with the low solubility of BMS-955176, considerable overlap in 
exposures was observed between 60 mg, 120 mg and 180 mg MC tablet, when given under 
fasted conditions. The impact of food on exposures to BMS-955176 120 mg MC tablet was
assessed in Study AI468034 as well; a high fat meal increased BMS-955176 AUC approximately 
50% with negligible impact on BMS-955176 Cmax.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose. Preliminary safety 
Date: 28-Jan-2015
28
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
results from AI468049 indicate that GI adverse events (eg, nausea, vomiting, loose stools) only 
occurred in the fed arms (where the BMS-955176 exposures were higher) relative to the fasted 
arms.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose.
Phase 2a
A randomized, double-blind, placebo-controlled proof of concept study in HIV subjects has 
completed enrollment and is undergoing analysis (AI468002). The three parts of this study were: 
1) Part A evaluated doses of 5, 10, 20, 40, 80, and 120 mg of BMS-955176 (SDD suspension) 
given for 10 days in HIV-1 clade B infected subjects, 2) Part B compared the antiviral activity of 
BMS-955176 (SDD suspension) administered with ATV (with or without RTV) against standard 
of care (TDF + FTC + ATV/r) for 28 days in HIV-1 clade B infected subjects, and 3) Part C 
evaluated BMS-955176 40 and 120 mg (SDD suspension) given for 10 days in HIV-1 clade C 
infected subjects. See Table 1.4.1.3-1 for baseline demographics. 
Preliminary results from the Phase 2a study (AI468002) in HIV-1 (clade B and C only) infected 
adults showed that at effective doses, a maximum median reduction in HIV-1 RNA ranging from 
1.3 to 1.7 log10 was observed. In the Phase 2b study BMS-955176 doses estimated to provide 
similar exposure to effective doses in the Phase 2a study will be used. Moreover, when 
BMS-955176 was combined with ATV RTV, these combinations resulted in maximum median 
declines in HIV-1 RNA ranging from 1.9 to 2.2 log10 (see Table 1.4.1.3-2). These results are 
generally similar to the antiviral effect demonstrated by other classes of ARVs in short-term
monotherapy trials, and thus BMS-955176 should contribute substantially with other ARVs to 
form an effective cART regimen. Lastly, preliminary safety data show acceptable safety and 
tolerability across all Phase 2a arms. Most AEs were Grade 1-2 and were most frequently due to 
an indirect hyperbilirubinemia; the levels seen with BMS-955176 and ATV/r were similar to 
those seen with ATV/r combined with TDF/FTC. The arms containing BMS-955176 and 
unboosted ATV had bilirubin levels that were approximately half of those observed in the arms
containing ATV/r. Last, arms containing BMS-955176 alone did not show elevated bilirubin
levels. Many of these events occurred in subjects who were randomized to an arm containing 
BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to headache and an 
increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia occurred in subjects also 
receiving ATV.
Date: 28-Jan-2015
29
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.4.1.3-1:
Phase 2a Baseline Demographics and Characteristics of Subjects 
(Preliminary Results)
Treatment Arm
Subjects
(n)
Median 
age
Male
White
Median 
HIV RNA 
(log10 c/ml)
Median 
CD4 
(cells/mm3)
Part A (Clade B, 10 days monotherapy)
BMS-955176 5 mg
8
43.5
8 (100)
6 (75.0)
4.09
437
BMS-955176 10 mg
8
39
7 (87.5)
7 (87.5)
4.02
539
BMS-955176 20 mg
8
33
8 (100)
8 (100)
3.59
512
BMS-955176 40 mg
8
38
8 (100)
8 (100)
4.03
536
BMS-955176 80 mg
8
31.5
8 (100)
8 (100)
3.82
504
BMS-955176 120 mg
8
37.5
8 (100)
8 (100)
3.84
498
Placebo
12
36
12 (100)
12 (100)
3.98
458
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
8
32.5
8 (100)
6 (75)
4.04
581
BMS-955176 40 mg + ATV 300 mg + 
RTV 100 mg
8
34
8 (100)
8 (100)
4.45
480
BMS-955176 80 mg + ATV 400 mg
8
31.5
8 (100)
7 (87.5)
4.15
549
Truvada® + ATV 300 mg + RTV 100 mg
4
32.5
4 (100)
4 (100)
4.12
427.5
Part C (Clade C, 10 days monotherapy)
BMS-955176 40 mg
7
35
4 (57.1)
2 (28.6)
4.53
554
Placebo
2
38.5
2 (100)
0 (0)
3.78
304
Table 1.4.1.3-2:
Maximum Decline Log10 HIV-1 RNA (Preliminary Results)
Treatment
Mean
S.D.
Median
Max
Min
Part A (Clade B, 10 days monotherapy)
BMS-955176 5 mg
-0.49
0.217
-0.498
-0.78
-0.22
BMS-955176 10 mg
-1.05
0.351
-0.976
-1.76
-0.64
BMS-955176 20 mg
-1.17
0.645
-1.115
-2.12
-0.13
BMS-955176 40 mg
-1.55
0.352
-1.701
-1.88
-0.93
BMS-955176 80 mg
-1.52
0.257
-1.555
-1.82
-1.04
BMS-955176 120 mg
-1.53
0.478
-1.654
-2.07
-0.83
Placebo
-0.48
0.581
-0.381
-1.46
0.56
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
-1.89
0.273
-1.858
-2.37
-1.49
BMS-955176 40 mg + ATV 300 mg + RTV 100 mg
-2.22
0.676
-2.202
-3.52
-1.24
BMS-955176 80 mg + ATV 400 mg
-2.3
0.307
-2.228
-2.68
-1.87
Truvada® + ATV 300 mg + RTV 100 mg
-2.41
0.495
-2.39
-3.04
-1.83
Part C (Clade C, 10 days monotherapy)
BMS-955176 40 mg
-1.5
0.439
-1.285
-2.03
-1.04
Placebo
0.12
0.141
0.12
0.02
0.22
The pharmacokinetics of BMS-955176 were assessed in HIV-1 infected subjects in AI468002. 
Overall, exposures to BMS-955176 are approximately 30% to 35% lower in HIV-1-infected 
subjects compared to healthy subjects administered the same doses and formulation of 
BMS-955176. Furthermore, exposures to BMS-955176 increased in a generally linear fashion up 
Date: 28-Jan-2015
30
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
to 40 mg, with a less than dose proportional increase in exposures between 40 mg and 80 mg, 
and considerable overlap in exposures between 80 mg and 120 mg.
1.4.2
Background Information on TDF
Tenofovir disoproxil fumarate (TDF) is an analog of the nucleotide adenosine 
5’-monophosphate. TDF inhibits HIV-1 reverse transcriptase and is indicated in combination 
with other ARVs for the treatment of HIV-1 infection. The most common adverse reactions 
include rash, diarrhea, headache, pain, depression, asthenia, and nausea. Clinicians are warned 
about new onset or worsening renal impairment, decreases in bone density, and immune 
reconstitution syndrome. For more information
concerning TDF, please refer to the 
TDF/Viread® SmPC or TDF/Viread® USPI.29
1.4.3
Background Information on DTG
Dolutegravir (DTG) is a HIV-1 integrase strand transfer inhibitor indicated in combination with 
other ARVs for the treatment of HIV-1 infection. The most common adverse reactions of 
moderate to severe intensity include insomnia, fatigue, and headache. Clinicians are warned 
about immune reconstitution syndrome. For more information concerning DTG, please refer to 
the DTG/Tivicay SmPC or the DTG/Tivicay USPI.30
1.4.4
Background Information on ATV 
Atazanavir is a protease inhibitor indicated for use in combination with other ARVs for the 
treatment of HIV-1 infection. The most common adverse reactions include nausea, 
jaundice/scleral icterus, rash, headache, abdominal pain, vomiting, insomnia, peripheral 
neurologic symptoms, dizziness, myalgia, diarrhea, depression, and fever. Clinicians are warned 
about hyperbilirubinemia, nephrolithiasis, and cholelithiasis. For more information concerning 
ATV please refer to the ATV/Reyataz® SmPC or ATV/Reyataz® USPI.31
1.4.5
Background Information on RTV
Ritonavir is a protease inhibitor indicated in combination with other ARVs for the treatment of 
HIV-1 infection. The most frequently reported adverse drug reactions with RTV alone or in 
combination with other ARVs include diarrhea, nausea, vomiting, abdominal pain, paresthesia, 
rash, and fatigue/asthenia. Clinicians are warned about total cholesterol and triglyceride 
elevations. For more information concerning RTV please refer to the RTV/Norvir® SmPC or 
RTV/Norvir® USPI.32
1.4.6
Drug-Drug Interactions
In AI468001, coadministration of BMS-955176 as a single dose following two doses of 100 mg 
RTV resulted in an approximate 48% increase in BMS-955176 AUC(INF), consistent with 
inhibition of CYP3A4 and/or P-gp. Multiple-dose administration of BMS-955176 with daily 
400 mg ATV and a standard meal for 14 days resulted in a modest (~25%) increase in the 
BMS-955176 AUC(TAU).
Date: 28-Jan-2015
31
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study AI468005 assessed the two-way interaction between BMS-955176 40 mg (administered as 
an SDD suspension) and TDF at steady state in healthy subjects. Relative to administration of 
each drug alone, neither BMS-955176 nor TDF exposures were meaningfully impacted upon 
coadministration.
Study AI468041 assessed the impact of BMS-955176 80 mg (administered as an SDD 
suspension) on the pharmacokinetics of the components of a combined oral contraceptive 
containing ethinyl estradiol (EE) and norgestimate (NGM). Exposures to both EE and 
norelgestromin (NGMN), the active metabolite of NGM were reduced in the presence of 
BMS-955176. Furthermore, one subject had a serum progesterone level > 300 ng/dL while 
BMS-955176 and the oral contraceptive were concomitantly administered, indicative of 
ovulation and contraceptive failure.
Finally, in vitro data suggest that BMS-955176 may inhibit OATP1B1 and OATP1B3 and 
exposures to substrates of these transporters, such as HMG-CoA reductase inhibitors, may 
increase when co-administered with BMS-955176.
1.5
Overall Risk/Benefit Assessment
The preclinical and clinical safety data demonstrate that BMS-955176 administered at doses in 
this Phase 2b study (120, and 180 mg) should be well tolerated without a major clinically 
relevant impact on safety. Moreover, there have been no identified safety risks from 
completed/ongoing clinical studies to date.
The preclinical toxicology studies demonstrate two potential risks to subjects:
First, BMS-955176 is a selective developmental toxicant. Developmental toxicity (skeletal 
alterations in rats; cleft palate and reduced fetal body weights in mice) were observed in 
embryofetal development studies. In order to address this concern, subjects will be required to 
use two methods of contraception (as described in Section 3.3.1 Inclusion Criteria) and undergo 
routine urine pregnancy testing (as described in the T&E Tables in Section 5.1). Furthermore, 
due to results from Study AI468041 that demonstrates reduced exposures to the components of a 
combination oral hormonal contraceptive containing ethinyl estradiol and norgestimate when 
given concomitantly with BMS-955176, oral hormonal contraceptives cannot be used as a 
method of contraception by WOCBP in this study.
Second, single or repeat oral doses of BMS-955176 were associated with sporadic vomiting in 
dogs and unformed and/or liquid feces in rats and dogs. In rats at 10 mg/kg/day there were 
decreases in body weight and food consumption; in the stomach there was atrophy involving 
both parietal and chief cells, single-cell necrosis and regeneration in the glandular mucosa, and 
modest increases in serum gastrin values. At higher doses (100 mg/kg/day) in rats there were 
additional findings in the intestines (distended jejunum, ileum, and cecum; hyperplasia of the 
crypt epithelium in the jejunum; ulcers and erosions in the cecum; and decreased mucosal cell 
extrusion and increased mucus in the colon). 
Similar gastric changes were seen in dogs. At 20 mg/kg/day there was single-cell necrosis of the 
stomach glandular epithelium. At 3 mg/kg/day gastric changes showed chief cell depletion. 
Date: 28-Jan-2015
32
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
At 10 mg/kg/day changes in the stomach included: mucous cell hyperplasia correlating with 
increased thickness macroscopically, parietal cell depletion, single-cell necrosis of glandular 
epithelial cells, and modest increases in serum gastrin values. Unlike the rats, no changes were 
observed elsewhere in the alimentary canal including the gastroesophageal junction and the 
duodenum. There was no evidence of macrocytosis. Measurement of Total Protein and Albumin 
revealed no clinically relevant changes. The stomach histologic findings were BMS-955176 
dose- and duration dependent. In the 1-month studies, vomiting and fecal changes stopped soon 
after dosing cessation, and microscopic lesions in the stomach and/or intestines reversed 
completely within a 2-week treatment-free period. In the 6 month study in rats and the 9-month 
study in dogs, microscopic lesions in the stomach partially recovered after a 1 month treatment 
free period. The NOAEL was 1 mg/kg/day (AUC 64.9 mg•h/mL) in the 9-month study in dogs, 
and was not established in the 6-month study in rats. Investigative studies for gastric toxicity in 
rats and dogs indicated similar findings with both SDD and MC forms, and with no clear 
evidence that the gastric toxicity is a direct local effect of BMS-955176. The mechanism and 
clinical relevance of these gastrointestinal findings is unknown at present (see below).
A Phase 1 study (AI468001) in healthy volunteers evaluated single and multiple doses of 
BMS-955176 for 14-28 days both alone and in certain arms, in combination with ATV or RTV. 
Overall the safety data demonstrated that BMS-955176 was generally safe and well tolerated. 
A Phase 2a (AI468002) study in HIV-1 infected adults evaluated several doses of BMS-955176 
given alone or in combination with ATV RTV for 10-28 days. The preliminary results show 
acceptable safety and tolerability across all arms. There were no deaths, SAEs, or AEs leading to 
discontinuation. There were no clinically relevant changes in vital signs, lab parameters, or 
EKGs. Most of the AEs were Grade 1-2 and were most frequently due to hyperbilirubinemia 
(primarily observed in treatment arms with ATV). Of the GI AEs, most were attributable to 
diarrhea or loose/watery stools. Many of these events occurred in subjects who were randomized 
to an arm containing BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to 
headache and an increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia 
occurred in subjects also receiving ATV; moreover, the three arms with the highest average total 
bilirubin occurred in subjects receiving both BMS-955176 and ATV. Clinical changes/symptoms 
consistent with the GI findings from dogs and rats (described above) were not seen in the 
preliminary data set from short-term therapy with BMS-955176 in HIV-1 infected adults. 
In this treatment-experienced study population, we estimate GI safety multiples of 2× and 1×, 
(based on NOAEL in 9-month dog study), corresponding to projected human exposures at 
BMS-955176 doses of 120 and 180 mg.
While no clinically relevant GI safety signals have been observed in AI468001 or AI468002, in 
this clinical trial, subjects will undergo routine targeted and complete history/physical exams in 
addition to regular laboratory measurements (including CBC and chemistries). This will initially 
occur more frequently than in standard clinical practice and allow for increased vigilance for any 
potential GI toxicity. Guidance on the evaluation and management of potential GI toxicity is 
outlined in Section 6.7.1.4.
Date: 28-Jan-2015
33
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Subjects in this clinical study will benefit from receiving cART potentially containing 
BMS-955176. Preliminary data from the Phase 2a (Part A, B and C) study show a maximum 
median reduction in HIV-1 RNA (clades B and C) ranging from 1.3 to 1.7 log10 in the dose arms 
estimated to provide similar exposure to those in this current study. When BMS-955716 was 
combined with ATV RTV (Part B) this resulted in maximum median declines in HIV-1 RNA 
ranging from 1.9 to 2.2 log10. These results are generally similar to the antiviral effect 
demonstrated by other classes of ARVs. Thus, BMS-955176 should contribute with other ARVs 
substantially to form an effective cART regimen.
As with any antiretroviral study in HIV-1-infected subjects, there is a risk for the development of 
treatment failure and the development of drug resistance associated mutations to BMS-955176 
and/or other antiretrovirals. However, drug resistance to the maturation inhibitor would not be 
anticipated to result in cross-resistance to any other ARV class, including protease inhibitors.33
Ongoing analysis of preliminary data from the Phase 2a study is evaluating both emergent 
genotypic and phenotypic changes after short term monotherapy with BMS-955176. The use of 
three fully susceptible agents as a part of cART is expected to decrease the probability of 
virologic failure and drug resistance. Initially in this clinical trial, measurement of HIV-1 RNA 
will occur more frequently than in standard clinical practice which will allow for increased 
vigilance for the development of lack of efficacy/resistance. Finally, an analysis for virologic 
futility will occur at Week 24 (see Section 8.4.7).
As described earlier, treatment-experienced adults enrolled in Arms 3-4 may be exposed to a 
subtherapeutic regimen and may be at higher risk for virologic failure and the development of 
resistance. In order to decrease this probability, this clinical trial uses a two-stage design 
whereby enrollment in Arms 3-5 will be dependent upon the results of the Week 24 analyses in 
Stage 1 (whose two Arms contain ATV/r) and Study AI468038. This will minimize the risk of 
virologic failure and resistance to subjects enrolled in Arms 3-4 because clinical data will already 
have been generated using BMS-955176 with ATV/r (Arm 1) in Stage 1.
In-vitro studies show that BMS-955176 is expected to be active against a variety of HIV-1 clades 
albeit with EC50s 2-3 fold less toward HIV-1 clade AE compare to clade B (see Section 1.4.1). 
As described in Section 1.1.1, the only clinical data for BMS-955176 exists in HIV-1 clade B 
and C. The efficacy profile of BMS-955176 in other HIV-1 clades encountered in other 
geographical regions where this multinational Phase 2b trial will be conducted (eg, clae AE in
Thailand) is unknown. To mitigate the risk of randomizing subjects infected with HIV-1 with an 
unknown efficacy profile, the number of subjects with HIV-1 Clade AE will be stratified to 
ensure each treatment are has approximately the same number of HIV-1 clade AE infected 
subjects in their respective Stages and the maximum number of subjects with HIV-1 clade AE 
will be capped at approximately 3 per treatment arm.
Of note, the other ARVs used in this clinical trial have a known and acceptable risk benefit ratio 
and are frequently prescribed to HIV-1 infected adults as a part of standard of care.
Taken together, the clinical data to date show that BMS-955176 has potent antiretroviral activity 
and is generally safe and well tolerated in healthy volunteers and HIV-1 infected adults. These 
Date: 28-Jan-2015
34
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
factors should allow subjects to benefit from achieving viral suppression whilst taking a 
generally safe and well-tolerated new antiretroviral; additionally subjects in Arms 1, 3, and 4 
may benefit from a cART regimen that is nucleoside and nucleoside/booster sparing, 
respectively. Specifically, these subjects may benefit from improved bone mineral density, renal 
function, and lipid profiles. The risks, including teratogenicity, GI toxicity, and drug resistance, 
will be appropriately managed by following guidance in the study protocol.
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
2.2
Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure 
or product labeling information to be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate. 
Date: 28-Jan-2015
35
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form which will include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
1) Provide a copy of the consent form and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language 
must be non-technical and easily understood. 
2) Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study.
3) Obtain an informed consent signed and personally dated by the subject or the subject's 
legally acceptable representative and by the person who conducted the informed consent 
discussion.
4) Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
5) If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his 
or her informed consent during the study, consent must additionally be obtained from the 
subject.
6) Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject's willingness to continue participation in the study. This communication should be 
documented.
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to 
refuse participation in, or to be withdrawn from, the clinical study at any time should be 
considered by the investigator.
Date: 28-Jan-2015
36
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced HIV-1 subjects will be randomized to one of five treatment arms
(approximately 40 per arm) in a staged fashion.
Randomization will be stratified by HIV-1 Clade (AE versus Other). The number of subjects 
with HIV-1 Clade AE will be capped at a maximum of approximately 3 per treatment arm.
The totality of the data from the Week 24 analysis of Stage 1 and AI468038, including safety, 
efficacy and resistance, will be examined in conjunction with PK/PD modeling to determine if 
Stage 2 of the study will be initiated, and confirm the two doses of BMS-955176 for study in 
Stage 2.
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with: 

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
3.1.1
Screening
The screening period begins with the subject’s signature on the informed consent form (ICF).
The subject is then enrolled via the Interactive Voice Response System IVRS (or its web-based 
equivalent) See Section 4.4.
If the subject meets all eligibility criteria, the subject must be randomized within the 42 day 
screening period.
Date: 28-Jan-2015
37
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.1.2
Day 1/Baseline Visit
3.1.2.1
Day 1/Baseline Visit for Arms 1 and 2 - Stage 1
In Stage 1, approximately 80 subjects will be randomized 1:1 (approximately 40 per arm) to 
either of the treatment arms containing boosted atazanavir (ATV/r).
On the Day 1 Visit, subjects in Arms 1 and 2 will begin QD dosing with BMS-955176 or TDF, 
each in combination with ATV/r and DTG (see Section 4.5 for additional details of Selection and 
Timing of Dose).

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
3.1.2.2
Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2
In Stage 2, approximately 120 subjects will be randomized 1:1:1 (approximately 40 per arm) to 
either of the two BMS-955176 treatment arms containing ATV, or to the TDF Arm.
On the Day 1 Visit, subjects will begin QD dosing with BMS-955176 in combination with ATV 
and DTG, or TDF in combination with ATV/r and DTG (see Section 4.5 for additional details of 
Selection and Timing of Dose).

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r QD 300/100 mg + DTG 50 mg QD
3.1.3
Week 2 Intensive PK Visit
Subjects with anemia, defined as Hemoglobin < 11.0 g/dL, should be excluded from 
participation in the Week 2 Intensive PK Substudy.
Subjects in all arms will have the opportunity to participate in an elective Intensive PK Substudy 
visit at Week 2 (window for visit: Day 12-16). Approximately 60 subjects, 12 subjects from each 
arm, are expected to participate in the substudy; BMS may allow the substudy to over-enroll in 
an effort to have a sufficient number of complete datasets.
The series of 12 blood draws begins with pre-dose (0-hour) blood samples to be collected
approximately 24 hours (20-28 hrs) after the morning doses of study drugs that were taken on the 
day before. Ten more samplings are drawn through the 12-hr time point, with one final sampling 
collected at the 24-hr time point, requiring the subject to either remain overnight in the clinic, or 
to return the next morning; the final 24-hr sample will be collected prior to administration of the 
morning doses of study drugs (See Section 5.5.1).
PK Tools/Job Aids will be provided to assist with the proper sequencing of dosing and blood 
sample collections, as well as the collection of required data.
Date: 28-Jan-2015
38
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.1.4
Visits Week 4 - 96
Subjects are expected to be treated for the duration of 96 weeks. In each Stage, after Day 1 and 
the optional Intensive PK visit at Week 2, subjects will be required to attend 12 more in-clinic 
study visits over the 96-week treatment period, as follows:

Visits are conducted every 4 weeks from Week 4 through Week 16

Visits are conducted every 8 weeks from Week 24 through Week 48

Visits are conducted every 12 weeks from Week 60 through Week 96
Visits should be scheduled as an interval from the Day 1/Randomizaton date, and within a 
window of 5 days earlier or later.
Visits Week 4 - 24 should be conducted in the morning so that the blood is drawn as a 
pre-morning (pre-AM) dose collection, in order to meet the requirement for Sparse PK 
(see Section 5.5.2). One of these visits should meet the very specific timing requirements as 
outlined in Section 5.5.2.
Telephonic visits will be conducted with each subject at visit Weeks 20, 28, 36, 44, 54, 66, 78,
and 90 to conduct an adherence assessment and to continue retention efforts
3.1.5
Selection of the Continuation Dose of BMS-955176
3.1.5.1
Selection of the Continuation Dose, and the Switch for Stage 1
Once all subjects in Stage 1 have reached Week 24*, BMS will conduct an analysis of efficacy, 
safety, and resistance.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If Arm 1 meets 
criteria for Virologic Futility at Week 24, the clinical trial will be terminated.
The Week 24 analysis of Arms 1 and 2, combined with the Week 24 analysis of all Arms in the 
AI468038 study, will be used to select a Continuation Dose of BMS-955176 for Arm 1 in this 
study. Subjects in the BMS-955176 Treatment Arm 1 may subsequently be transitioned to a
selected Continuation Dose.
Subjects in the Arm containing TDF will continue with the TDF treatment regimen.
The assigned backbone will not change.
The result of the analyses from Stage 1 and Week 24 analysis from AI468038 will also trigger 
the start of Stage 2.
* If the Continuation Dose cannot be clearly identified using the Week 24 data, the study 
will continue in original fashion until an analysis of the Week 48 data can be performed 
and the Continuation Dose is selected. If a Continuation Dose cannot be selected based 
upon the Week 24 data, this does not preclude the ability to start recruitment of Stage 2.
After the Continuation Dose is selected, and once all of the logistics (eg, distribution of clinical 
drug supplies, activation of the new portion of the IVRS) have been completed globally, the 
Date: 28-Jan-2015
39
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
transition of the subjects in Arm 1 to the Continuation Dose will occur. It is anticipated that this 
transition will occur on or after all subjects have reached Week 48 (the earliest subjects to begin 
study treatment could be well beyond Week 48 when the switch to the Continuation Dose 
occurs).
3.1.5.2
Selection of the Continuation Dose, and the Switch for Stage 2
Once all subjects in Stage 2 have reached Week 24, BMS will conduct an analysis of efficacy, 
safety, and resistance.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If a BMS-955176 
dose arm meets criteria for Virologic Futility at Week 24, subjects in said arm will begin dosing 
with the next highest available remaining dose of BMS-955176.
The totality of data from AI468038 and AI468048 (Stages 1 and 2) will be used to select a 
Continuation Dose of BMS-955176 for Arms 3 and 4. Subjects in the BMS-955176 Treatment 
Arms 3 and 4 will subsequently be transitioned to a selected Continuation Dose. It is anticipated 
that this transition may occur on or after all subjects have reached Week 48, or it could occur 
sooner after Week 24.
The assigned backbone will not change.
Subjects in the arm containing TDF will continue with this assigned treatment regimen.
3.1.6
End of the study
The end of the study will occur when the last study visit has been completed, defined as the final 
subject completing their final study visit (expected to be a Week 96 or Early Termination visit).
The study design schematic is presented in Figure 3.1.6-1.
Date: 28-Jan-2015
40
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 3.1.6-1:
Study Design Schematic
Date: 28-Jan-2015
41
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.2
Post Study Access to Therapy
At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be 
eligible to receive BMS supplied study drug. Study drug will be provided via an extension of the 
study, a rollover study requiring approval by responsible health authority and ethics committee 
or through another mechanism at the discretion of BMS. BMS reserves the right to terminate 
access to BMS supplied study drug if any of the following occur: a) the marketing application is 
rejected by responsible health authority; b) the study is terminated due to safety concerns; c) the 
subject can obtain medication from a government sponsored or private health program; or 
d) therapeutic alternatives become available in the local market.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Ability to understand and sign a written informed consent form
2. Target Population
a) Antiretroviral treatment-experienced, defined as having documented evidence of having
failed, 1 or 2 regimens that include 2 or 3 classes of ARV (with or without documented 
resistance)
b) Confirmed Plasma HIV-1 RNA 400 copies/mL (First value from investigator; second 
value from screening test)
c) CD4+ T-cell count > 50 cells/mm3
d) Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, 
FC < 2.2; DTG; TDF)
e) Estimated Life expectancy 1 year
f)
Subject Re-enrollment: This study permits the re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / 
has not been treated). If re-enrolled, the subject must be re-consented and assigned a new 
PID.
3. Age and Reproductive Status
a) Males and non-pregnant females
b) At least 18 years of age, (or minimum age as determined by local regulatory or as legal 
requirements dictate)
c) Willingness to use approved highly effective methods of contraception (see below) to 
avoid pregnancy (female subjects who are WOCBP and male subjects who are sexually 
active with WOCBP)
d) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 
24 hours prior to the start of study drug.
Date: 28-Jan-2015
42
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
e) Women must not be breastfeeding
f)
WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug BMS-955176 plus 5 half-lives of study drug BMS-955176
(8 days) plus 30 days (duration of ovulatory cycle) for a total of 38 days post-treatment 
completion.
g) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug BMS-955176
plus 5 half-lives of the study drug BMS-955176 (8 days) plus 90 days (duration of sperm 
turnover) for a total of 98 days post-treatment completion.
h) Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However WOCBP must still undergo 
pregnancy testing as described in this section.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception. Highly effective methods of contraception 
have a failure rate of < 1% when used consistently and correctly.
At a minimum, subjects must agree to the use of two methods of contraception, with one method 
being highly effective and the other method being either highly effective or less effective as 
listed below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

Male condoms with spermicide34,35

Hormonal methods of contraception including combined oral contraceptive pills, vaginal 
ring, injectables, implants and intrauterine devices (IUDs) such as Mirena

For female study subjects who are WOCBP:
Study subjects who are WOCBP cannot use hormonal methods of contraception as 
one of the two methods of contraception because there are data that show a lack of 
effectiveness of systemic hormonal contraceptives in women taking BMS-955176
However, WOCBP can continue to use hormonal contraceptives, if necessary, in 
addition to 2 other non-hormonal methods of contraception (one of which must be 
highly effective)

For female partners of male study subjects (if they are WOCBP):
Hormonal methods of contraception may be used by male subject’s WOCBP partner. 
Female partners of male subjects participating in the study may use hormone based 
contraceptives as one of the acceptable methods of contraception since they will not 
be receiving BMS-955176

Nonhormonal IUDs, such as ParaGard

Tubal ligation
Date: 28-Jan-2015
43
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Vasectomy

Complete Abstinence*
*Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an 
acceptable form of contraception for all study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly effective contraception must be 
discussed in the event that the subject chooses to forego complete abstinence.
LESS EFFECTIVE METHODS OF CONTRACEPTION

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal sponge

Male Condom without spermicide 

Progestin only pills by male subject’s WOCBP partner

Female Condom*
* A male and female condom must not be used together
3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a) Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens
b) Resistance or partial resistance to any study drug
c) Three or more of the following PI mutations, historical or documented: M36I/V, 
M46I/L/T, G48M/V, I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M
d) Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S
e) Any major TDF mutation, historical or documented: K65R or T69ins
f)
Three or more of the following non-accessory thymidine analogue mutations (TAMs): 
M41L, D67N, K70R, L210W, T215Y/F, K219Q/E
g) Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI 
resistance), historical or documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, 
Y143C/H/R, E157Q
2. Medical History and Concurrent Diseases
a) A new AIDS defining condition diagnosed within the 30 days prior to screening
(see Appendix 2)
b) Any other clinical condition (including but not limited to active substance use) or prior 
therapy that, in the opinion of the Investigator, would make the subject unsuitable for the 
study; unable to comply with dosing requirements; or unable to comply with study visits; 
or a condition that could affect the absorption, distribution, metabolism or excretion of 
the drug.
Date: 28-Jan-2015
44
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3. Physical and Laboratory Test Findings
a) Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV 
Ab and HCV RNA)
b) ALT or AST > 3 × ULN
c) Alkaline Phosphatase > 5 × ULN
d) Bilirubin ≥ 1.5 × ULN
e) History of decompensated cirrhosis or active decompensated cirrhosis
f)
Hemoglobin < 8.0 g/dL
g) Platelets < 50,000 cells/mm3
h) Estimated eGFR < 60 mL/min (CKD-EPI formula)
i)
Confirmed QT value > 500 msec at Screening or Day 1
j)
Confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or 
Day 1
k) Confirmed PR Interval > 260 msec (severe first degree AV block) at Screening or Day 1
l)
Confirmed second or third degree heart block at Screening or Day 1
4. Allergies and Adverse Drug Reaction
a) Medications contraindicated for use with investigational/non-investigational study drugs 
(ATV, RTV, DTG, TDF);
or subjects with any known allergies to the 
investigational/non-investigational study drugs (ATV, RTV, DTG, TDF)
b) Current or anticipated treatment with any of the medications listed in Appendix 1, in 
addition to any medications that are contraindicated with ATV, RTV, DTG or TDF
c) Participation in an experimental drug and/or HIV-1 vaccine trial(s) within 30 days prior 
to Screening
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
A woman of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 years in the absence of other biological or physiological causes. In 
addition, females under the age of 55 years must have a serum follicle stimulating hormone, 
(FSH) level > 40 mIU/mL to confirm menopause.
Date: 28-Jan-2015
45
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. If the serum FSH level is > 40 mIU/mL at any time 
during the washout period, the woman can be considered postmenopausal:

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Refer to Appendix 1 which details prohibited and precautionary therapies during the study, 
including specifics about the use of antacids and hormonal methods of contraception.
3.4.2
Other Restrictions and Precautions
None.
3.5
Discontinuation of Subjects following any Treatment with Study Drug 
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject

Termination of the study by Bristol-Myers Squibb (BMS)

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Repeat non-adherence by the subject with the requirements of the protocol or treatment
(as determined by Investigator in consultation with the BMS Medical Monitor)

Evidence of Hepatitis B or C infection

Confirmed plasma HIV-1 RNA 1000 c/mL after Week 24

Confirmed plasma HIV-1 RNA 200 c/mL after Week 48

Emergence of genotypic and/or phenotypic resistance to any component of the study 
treatment regimen at any time after Screening

Subject requires switching to any other ARV

Development of pDILI (potential drug induced liver injury)
Date: 28-Jan-2015
46
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Confirmed QTcB or QTcF value > 500 msec

Confirmed second degree (Type II) or third degree AV block at any time during the study
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event. In most cases, the study drug will be permanently discontinued in 
an appropriate manner. If the investigator determines a possible favorable benefit/risk ratio that 
warrants continuation of study drug, a discussion between the investigator and the BMS Medical 
Monitor/designee must occur.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Section 5 (ie, perform an Early Termination [ET] visit). The only 
exception to this requirement is when a subject withdraws consent for all study procedures 
including post-treatment study follow-up (no such period exists in this study) or loses the ability 
to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either a 
psychiatric or physical illness).
If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post Study Drug Study Follow up
Subjects who discontinue study drug may continue to be followed.
Subject’s contact information will be collected/confirmed throughout the study so that subjects 
who discontinue study drug may continue to be followed for resolution of a pregnancy or SAE.
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug will remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. In 
the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
Date: 28-Jan-2015
47
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study. The site staff and representative will consult publicly available sources, such as public 
health registries and databases, in order to obtain updated contact information. If after all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
4
STUDY DRUG
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
Date: 28-Jan-2015
48
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 4-1:
Study Drugs for AI468048:
Product Description / 
Class and Dosage Form
Potency
IMP/Non-IMP
Blinded or 
Open Label
Packaging/ Appearance
Storage Conditions
(per label)
BMS-955176 
60 mga
IMP
Open Label
Bottle/
A white to off-white, biconvex, 
oval shaped film coated tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
BMS-955176
120 mga
IMP 
Open Label
Bottle/
A white to off-white, biconvex, 
capsule shaped tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
Tenofovir (TDF)
300 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Atazanavir (ATV)
200 mg
IMP
Open Label
Bottle/
Blue cap and blue body
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Atazanavir (ATV)
300 mg
IMP
Open Label
Bottle/
Red cap and blue body,
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Ritonavir (RTV)
100 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Dolutegravir (DTG)
50 mg
Non-IMP or 
IMP,
depending on 
country 
approval status.
Open Label
Various packaging configurations
Refer to label on
container or package insert.
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Date: 28-Jan-2015
49
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, investigational product(s) is/are: BMS-955176, ATV, and DTG (in countries 
where DTG has not been approved for use). These products will be supplied.
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be 
considered as non-investigational products.
In this protocol, noninvestigational product(s) is/are: TDF, RTV, and DTG (in countries where 
DTG is approved for use). These products will be supplied.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be 
dispensed and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
that includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations.
4.4
Method of Assigning Subject Identification
At the start of the screening period, the investigative staff will call the Assignment Center via an 
Interactive Voice Response System ([IVRS], or its web-based equivalent) designated by the 
sponsor to enroll the subject and to obtain a subject patient identification number (PID).
For subjects who meet the protocol eligibility criteria, the investigative staff will call the IVRS 
and subjects will start treatment.
Date: 28-Jan-2015
50
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Subjects will be randomly assigned in the staged fashion to one of the treatment arms, and 
stratified by HIV-1 Clade (AE versus Other), as described in Section 3 and as outlined in the 
AI468048 Study Schematic Figure 3.1.6-1.
Note: All efforts should be made to limit the possibility of randomizing subjects that do not start 
treatment. If a subject is randomized but does not receive study medication, the BMS study team 
must be notified immediately.
4.5
Selection and Timing of Dose for Each Subject
Subjects will be randomized into the treatment arms in a staged fashion described in Section 3.1.
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
4.5.1
Instructions for Dose Administration
4.5.1.1
General Instructions

Subjects should administer doses of each drug from only one bottle at a time, until that bottle 
is empty, before another bottle may be opened. 

Subjects will be required to complete Dosing Diaries so that drug administration can be 
accurately accounted. It is important that sites provide instructions to subjects for completion 
and obtain their acknowledgment that doing so provides critical information for the clinical 
trial.

Dosing times (and study appointment times) must be carefully considered through Week 24 
due to the requirements of the PK collection outlined in Section 5.5.
4.5.1.2
Specific Dosing Instructions for Initial Treatment Arm Assignment
In the morning, with a meal, subjects will take the following:

Arm 1: One pill each from bottles BMS-955176 120 mg, ATV, RTV, and DTG

Arm 2: One pill each from bottles TDF, ATV, RTV and DTG
Date: 28-Jan-2015
51
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Arm 3: One pill each from bottles BMS-955176 120 mg, DTG, and two pills from bottle
ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 4: One pill each from bottles BMS-955176 60 mg, BMS-955176 120 mg and DTG, and 
two pills from bottle ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 5: One pill each from bottles TDF, ATV, RTV and DTG
4.5.2
Dose Modifications
No dose adjustments or changes in intake frequency are allowed for any of the assigned study 
drugs in the protocol, except for the unique case of treatment-limiting renal toxicity which limits 
the use of the TDF. In the event of treatment-limiting renal toxicity, dose interval adjustments for 
TDF are permitted according to the local package insert/label, and only after the completion of 
the Week 2 Intensive PK optional Visit, if the subject is inclined to participate.
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Treatment Adherence to the treatment regimen will be critical to the conduct of this study. 
Adherence will be evaluated by the investigative staff at every treatment visit (including 
telephone contact visits) through interviews with the subjects and through examination of 
returned medication. It is expected that site staff attempt to have subjects maintain 90% 
treatment compliance or greater. Subjects should be instructed to bring all unused study 
medication back in the original container to each visit. Site staff are required to review Dosing 
Diaries completed by the subject, and to reinforce their use.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible Study Monitor unless study drug containers must be immediately destroyed as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:

On-site disposal practices must not expose humans to risks from the drug

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request
Date: 28-Jan-2015
52
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor must be documented

Accountability and disposal records are complete, up-to-date, and available for the Monitor 
to review throughout the clinical trial period
If conditions for destruction cannot be met the responsible Study Monitor will make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible Study Monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
Date: 28-Jan-2015
53
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)
Notes
Eligibility Assessments
Informed Consent
X
Call IVRS to Enroll the subject; PID assigned
X
Inclusion/Exclusion Criteria
X
Medical History
X
Includes historical CDC Class C Events
Non-Laboratory Safety Assessments
Full Physical Examination
X
See Section 5.3.1 for requirements
Vital Signs & Physical Measurements
X
See Section 5.3.1 for requirements
Pre-treatment events
X
Only CDC Class C events with onset during the Screening period
Serious Adverse Events Assessment
X
All SAEs that occur after the ICF has been signed should be reported
ECG
X
See Section 5.3.4 for requirements
Pregnancy Test
X
WOCBP
For females under age 55, an FSH level must be on record to confirm she 
is not a WOCBP if pregnancy testing is not being performed.
If positive urine, request serum hCG quant. on lab requisition.
Laboratory Assessments
Fasting Chemistry and Lipid Panel
X
Fasting overnight
Hematology
X
Urinalysis
X
Plasma HIV-1 RNA
X
This is the confirmatory HIV-1 RNA
(The first value is provided by the PI)
Date: 28-Jan-2015
54
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)
Notes
CD4+ and CD8+ T-cell count
X
HBV Surface Antigen
X
HCV Serology
X
Urine toxicology (drugs of abuse)
X
Could aid in the selection of appropriate study candidates.
Pharmacodiagnostic (PDx) samplea
X
Plasma collection to be banked for potential future use in development of 
novel predictive assay(s)
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
Complete set of test results may take up to 4 weeks.
PhenoSense Gag
X
Next Generation Seq. - Qs Gag
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
Molecular analysis at BMS WFD Discovery of baseline resistant samples 
and baseline sensitive controls in cases of subsequent on-treatment 
virologic failure
a By definition, a pharmacodiagnostic sample (PDx) is a pre-treatment test to determine whether or not a patient is likely to respond to a drug (ie, a predictive 
test). Based on the results of clinical studies with BMS-955176, BMS may have to develop a PDx assay. Thus, PDx samples obtained at Screening in this 
study would be used for that sole purpose.
Date: 28-Jan-2015
55
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Eligibility Assessments
Inclusion/Exclusion Criteria
X
Non-Laboratory Safety Assessments
Full Physical Examination
WK 12, 24, 48, 96/ET
See Section 5.3.1 for requirements
Targeted Physical Examination
X
WK 4, 8, 16, 32, 40, 60, 72, 84
See Section 5.3.1 for requirements
Vital Signs & Physical 
Measurements
X
X
See Section 5.3.1 for requirements
Adherence Assessments
X
X
Including review of Dosing Diaries
Pre-treatment Events
X
See Table 5.1-1
Adverse Events Assessments
X
X
X
Serious and Non-serious AEs
Concomitant Medications
X
X
X
See Section 5.3.3
ECG
X
WK 4, 12, 24, 48, 96/ET
See Section 5.3.4 for requirements
Pregnancy Test
X
X
X
For females under age 55, an FSH 
level must be on record to confirm 
she is not a WOCBP if pregnancy 
testing is not being performed.
If positive urine, request serum 
hCG quant. on lab requisition.
Date: 28-Jan-2015
56
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Provide WOCBP with Home 
Pregnancy test kit(s) to be used 
during the in-clinic visit interval
WK 16, 24, 32, 40,
48, 60, 72, 84
Provide One Kit at Weeks 16 - 40
Provide Two Kits at Weeks 48 - 84
WOCBP subjects perform test Q4 
weeks at home and report results to 
site.
Laboratory Assessments for Safety and Efficacy and Other Endpoints
Fasting Chemistry
X
X
Fasting overnight
Fasting Lipid Panel
X
WK 4, 12, 24, 48, 96/ET
Fasting overnight
Hematology
X
X
Urinalysis
X
X
Fractional Excretion of Phosphorous 
(FePO4)
(Urine creatinine and phosphorus, 
Plasma creatinine and phosphorus)
X
WK 48 and 96/ET
Plasma HIV-1 RNA
X
X
X
If collecting an HIV-1 RNA at an 
UNSCHEDULED visit, also collect 
samples for Resistance and 
Exploratory Resistance Testing
CD4 and CD8 T-cell counts
X
X
HBV Surface Antigen
WK 48 and 96/ET
HCV Serology
WK 48 and 96/ET
Positive HCV Ab will reflex to 
HCV RNA
Date: 28-Jan-2015
57
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
X
Samples stored and tested if needed
(ie, analyses of subjects if deemed 
clinically relevant)
See Section 5.4.2.2
PhenoSense Gag
X
X
Next Generation Seq. - Qs Gag
X
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
X
Samples stored and tested
retrospectively if needed (ie,
exploratory analyses for subjects if 
deemed clinically relevant)
Intensive PK sample collection
X
Use of PK Tools for data collection 
recommended.
See Section 5.5.1 for requirements
Sparse PK sample collection
WK 4, 8, 12, 16, 24
See Section 5.5.2 for requirements
Bone Biomarkers
(P1NP and CTX)
X
WK 12 and 24/ET
Serum collection
Renal Biomarkers
(2-microglobulin and creatinine)
X
WK 48 and 96/ET
Urine collection
Backup Serum and Plasma Sample
X
X
Samples stored and tested if needed
Date: 28-Jan-2015
58
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Outcomes Measures
EQ-5D-3L Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Health Outcomes Questionnaire
FAHI Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Functional Assessment of HIV 
Infection
Clinical Drug Supply
Call IVRS to Randomize
X
Dispense Study Drug
X
X
There is no dispensation at Week 96 
or ET.
Date: 28-Jan-2015
59
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory 
value). The Screening Period for this study is 42 days.
Any new result will override the previous result (ie, the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. Consultations 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant (eg, a previously failed inclusion criterion).
Rescreening is different than Retesting. Rescreening is the process of Re-enrollment and requires 
that all procedures be repeated in an entirely new screening period. Rescreening will also be 
allowed. If it is clinically reasonable, and upon Investigator assessment (and in consultation with 
the BMS Medical Monitor, if necessary), a subject may be rescreened multiple times during the 
entire course of the enrollment period. Therefore, subjects may be Rescreened, if, in the opinion 
of the Investigator, a current clinical outlook of the subjects seems favorable for study inclusion 
(and if the patient never received study medication in this trial).
The assigned patient identifier (PID) for the subject must be Screen Failed in the IVRS. A new 
call must be made to the IVRS for the assignment of a new PID for the subject, and all Screening 
parameters must be done again in reference to the new PID (See Section 3.3.1, Inclusion 
Criteria 2f). Subject must also be re-consented with the new PID.
5.2
Study Materials
The sponsor will provide each investigative site with the following:

BMS-955176 Investigator Brochure (IB) and any relevant safety addenda or updates

Protocol and any Amendments to the Protocol

Instructions for completing electronic Case Report Forms (eCRFs)

Laboratory Manual from the central laboratory

ECG Machines and manual

IVRS Worksheets to complete when calling the IVRS center to enroll, randomize, and 
discontinue subjects

Patient-reported Outcomes Questionnaires: EQ-5D-3L Health Outcome Questionnaire, FAHI 
(Functional Assessment of HIV Infection)

PK Tools/Job Aids that may be used for detailed instruction about the PK visits, and as a 
comprehensive source for documents of date/times of dosing and blood sampling

Dosing Diaries

Completion by subjects is required
Date: 28-Jan-2015
60
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Should include daily dose of study medications administered by subject, modified or 
missed

Site staff should review the diaries with the subject at each visit, and, in combination with 
detailed questioning, should be able to provide comprehensive information in the case 
report form, noting discrepancies in the subject’s file. Dosing Diaries should be 
maintained in the subject’s study file.
5.3
Safety Assessments
The investigative team should follow the protocol-specified scheduled of safety-related 
measurements. Only data for the procedures and assessments specified should be submitted to 
BMS on the case report form. Additional procedures and assessments may be performed as part 
of standard of care, however, data for these assessments should remain in the subject’s medical 
record and should not be submitted to BMS, unless specifically requested (ie, as part of an SAE).
5.3.1
Vital Signs and Physical Examinations
The schedule of vital signs, physical examinations, and targeted physical examinations is 
provided in Section 5.1 (Flow Chart/Time and Events Schedule). Vital signs include heart rate, 
blood pressure, respiration rate, and temperature and should be measured after the subject has 
been sitting/resting for at least 5 minutes. Physical measurements include height and weight. 
Targeted physical examinations will include examination of the heart, lungs, skin, abdomen, any 
symptomatic organ system, and general appearance.
5.3.2
Adverse Events
Subjects will be closely monitored throughout the study for any new or ongoing HIV-related 
diagnoses (Appendix 2) and/or adverse events. CDC Class C events that occur from the 
Screening Visit through Day 1 (prior to dosing), will be recorded as Pre-treatment Events. All 
events that occur after dosing on Day 1 will be recorded on the appropriate Adverse Event eCRF. 
Additional information on Adverse Events is provided in Section 6.
5.3.3
Concomitant Medication Assessment
All medications taken from the Screening Visit throughout the duration of the study will be 
reported. In addition, any prior therapy with antiretroviral drugs will be reported
(See Appendix 1 for Prohibited and Precautionary Therapies).
5.3.4
Electrocardiograms
The schedule of electrocardiograms (ECGs) is provided in Section 5.1 (Flow Chart/Time and 
Events Schedule). ECG machines will be provided by a central vendor who will also perform the
read/interpretation of the output.
5.4
Efficacy Assessments
5.4.1
Primary Efficacy Assessment
The primary assessment for efficacy is HIV-1 RNA through Week 24.
Date: 28-Jan-2015
61
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.1
Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing
A confirmatory HIV-1 RNA viral load should be obtained when:

HIV-1 RNA 40 c/mL if prior suppression 40 c/mL, or

> 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is 
40 c/mL
All efforts should be made to collect this sample within 2-4 weeks from the collection of the 
original sample.
When collecting a blood sample for HIV-1 RNA testing at an Unscheduled visit, samples should 
also be collected for the sets of Resistance and Exploratory Resistance Tests, so that the samples
are available should resistance testing be required or deemed necessary based on the result of the 
HIV-1 RNA test.
Table 5.4.1.1-1:
Management of Detectable HIV-1 RNA, based on Confirmed 
(2-4 weeks from original sample) or Consecutive HIV-1 RNA Resulta
Day 1 through Week 24
40 - 399 c/mL
Reinforce Adherence
400 c/mL
Consider the need for resistance testing, in consultation with BMS Medical Monitor.
Consider possible discontinuation of subject, in consultation with BMS Medical Monitor, and/or 
reinforce adherence.
After Week 24 through Week 48
40 - 399 c/mL
Reinforce Adherence
400 - 999 c/mL
Resistance testing will be performed.
If resistance has developed, subject must be discontinued.
If resistance has not developed, consider possible discontinuation of subject, in consultation with 
BMS Medical Monitor, and/or reinforce adherence.
1000 c/mL
Resistance testing will be performed.
Regardless of result of resistance tests, subject must be discontinued (see Section 3.5).
After Week 48
< 200 c/mL
Reinforce Adherence
200 c/mL
Subject must be discontinued (see Section 3.5). 
If 400 c/mL, consider the need for resistance testing, in consultation with BMS Medical 
Monitor.
a When discontinuation is required or otherwise warranted and resistance results are needed, subject may continue 
on study medication/on study until resistance testing results are available.
Date: 28-Jan-2015
62
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.2
Protocol Defined Virologic Failure
Protocol Defined Virologic Failure (PDVF) is defined by a subject meeting one of the following 
three criteria:
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir 
is 40 c/mL
2) Confirmed HIV-1 RNA 400 c/mL after Week 24
3) Failure to suppress last HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot 
window
In addition to the clinical management outlined in section 5.4.1.1, samples meeting criteria for 
PDVF will also be sent for resistance and exploratory resistance testing.
5.4.2
Secondary Efficacy Assessments
5.4.2.1
CD4+ and CD8+ T-Cells
CD4+ and CD8+ T-cells counts and percentages will be assessed using flow cytometry. The 
schedule of assessments is provided in Section 5.1 (Flow Chart/Time and Events Schedule). 
Procedures for samples collection and processing are provided in the central clinical laboratory 
manual.
5.4.2.2
Drug Resistance Testing
Plasma samples for viral drug resistance testing will be collected at Screening for all subjects and 
the HIV-1 drug resistance genotype will be analyzed to rule out resistance to any component of 
the study regimen or specific resistance mutations as outlined in Section 3.3.2, Exclusionary 
Criteria. At subsequent visits, samples for emergent drug resistance testing (both genotypic and 
phenotypic) will be collected and stored to be as outlined in Section 5.4.1.
5.5
Pharmacokinetic Assessments
It is extremely important to record the exact dose and time of the dose(s) taken the day prior to 
the visit/collection, and the exact date and time of the sample collection, even if drawn slightly 
off-schedule.
5.5.1
Intensive Pharmacokinetic Assessment
A subset of subjects (about 12 subjects per treatment group) will participate in an optional 
Intensive PK assessment at Week 2 (window Day 12-16).
Intensive PK samples collection in this study will provide for the assessment of BMS-955176, 
ATV, RTV, and DTG to support the secondary objective (to compare steady-state exposures of 
DTG when co-administered with BMS-955176 and ATV/RTV to DTG when co-administered 
with TDF and ATV/RTV).
Intensive PK sampling begins with a morning pre-dose (0 hour) sampling, ie, prior to the 
administration of the morning doses of the study drugs on the day of the visit. The sampling 
Date: 28-Jan-2015
63
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
should also begin 24 hours after the morning doses of the study drugs were taken the day prior to 
the visit.
The subsequent 11 time points include samplings through Hour 12, with the last sample collected 
at Hour 24. The subject will either stay overnight or will return to the clinic so that the final 
sample can be collected at Hour 24.
It is critical to capture the exact date and time of each PK sample collection, even if drawn 
slightly off-schedule. There is no specified collection window end for which any one time point 
should be abandoned as the schedule progresses. If a sample collection time point is missed/late 
and the next collection time point has not yet been reached, collect the missed time point, and 
record the exact time of that collection, then get back on track for the next time point/on-time 
collection.
Table 5.5.1-1 lists the sampling schedule to be followed for the assessment of intensive 
pharmacokinetics. Further details of PK blood collection and sample processing will be provided 
in the central clinical laboratory manual.
Table 5.5.1-1:
AI468048 Intensive Pharmacokinetic Sampling Schedule at Week 2
Time 
(Event)
Time 
(Relative to Dosing)
Hour: Min
PK
Blood Sample
Study Week 2
(window Day 12-16)
0 (morning pre-dose)
00:00
X
1 Hr
01:00
X
2 Hr
02:00
X
2.5 Hr
02:30
X
3 Hr
03:00
X
4 Hr
04:00
X
4.5 Hr
04:30
X
5 Hr
05:00
X
6 Hr
06:00
X
8 Hr
08:00
X
12 Hr
12:00
X
24 hr (morning pre-dose)
24:00
X
Date: 28-Jan-2015
64
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.5.2
Sparse Pharmacokinetic Assessments
All subjects will provide Sparse PK samples (as part of the regular blood collection) for the 
assessment of BMS-955176, ATV, RTV and DTG at visit Weeks 4- 24.
The visits Week 4 - 24 would need to be performed in the morning: Sparse samples must be 
collected as morning pre-dose (0 hour) samplings, ie, drawn prior to the morning doses taken on 
the day of the visit. 
Table 5.5.2-1:
AI468048 Sparse Pharmacokinetic Sampling Weeks 4 - 24
Time 
(Event)
Time 
(Relative to Dosing)
Hour: Min
PK
Blood Sample
Weeks 4 - 24
0 (morning pre-dose)
00:00
X
Of the five visits (Week 4 - 24), it is requested that the following guidelines are followed:
At any one visit Week 4 through Week 24, perform the blood collection for the visit as a 
pre-AM dose sampling that is 24-hours post-morning dose, ie, 24 hours after the morning 
doses of the study drugs were taken the day prior (20-28 hours) 
At the remaining four visits Week 4 through Week 24, the pre-AM dose blood collections may 
be done without any specific consideration to timing of previous dose administration, though 
it is critical that the exact date and time of the morning doses of study drug taken the day 
prior be accurately reported to the site
PK Samples need to be tested on an ongoing basis prior to the Week 24 database lock and 
analysis.
5.6
Biomarker Assessments
In this study, BMS is confirming the safety of BMS-955176 demonstrated in the Phase 2a study 
to date. The proposed sample population of treatment-experienced adults in Arms 3, 4, and 5, 
will provide a representation of the potential benefits of BMS-955176 on nucleoside and RTV 
based toxicities of interest (ie, renal toxicity, bone mineral density, and dyslipidemia): Arms 3 
and 4 relative to Arms 1, 2, and 5.
Specifically, to evaluate for renal toxicity we will evaluate clinically relevant parameters and 
biomarkers for glomerular and tubular toxicity, which may include but are not limited to: 
fractional excretion of phosphorous and urinary β2-microglobulin/creatinine, in all available 
subjects. To evaluate for bone-related toxicity, clinically relevant bone biomarkers for both 
formation and resorption will be evaluated in all available subjects. These may include but are 
not limited to: N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked 
C-telopeptide of Type 1 collagen (CTX). The bone and renal biomarkers will be collected and 
measured at time points specified in Table 5.1-2 Additionally, back-up plasma and serum 
samples (at Baseline, Week 24, and Week 48) will be obtained for potential future evaluation of 
the safety of BMS-955176.
Date: 28-Jan-2015
65
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Samples will be collected at the screening visit for HIV-1 Gag sequencing, phenotypic 
susceptibility (PhenoSense Gag) and potential pharmacodiagnostic analysis as specified in Table 
5.1-1. These samples may be analyzed, if deemed clinically relevant, as a predictive marker of 
clinical response.
Any remaining blood and urine specimens that are available after completion of the designated 
analyses may be used in the future for identification of potentially predictive or 
pharmacodynamic markers of study drug activity or to enhance the understanding around disease 
biology, except where prohibited by local laws or regulations.
5.7
Outcomes Research Assessments
Increases in CD4 counts and avoidance of opportunistic infections and other AIDS-defining 
illnesses have been shown in many studies to improve health related quality of life (HRQoL). To 
help assess whether use of BMS-955176 will result in a better quality of life outcome, both a 
disease specific quality of life assessment and a generic quality of life assessment will be 
administered. Disease specific instruments are more sensitive to disease specific changes in 
quality of life and are more likely to show improvement with new interventions. The generic 
instruments are needed because Health Technology Authorities often require use of these 
instruments for cost-effectiveness modeling.
The Functional Assessment of HIV (FAHI) is the disease specific instrument that will be used. 
The FAHI evaluates physical well-being, functional and global well-being, emotional 
well-being/living with HIV, social well-being and cognitive functioning. It yields a total score 
and individual subscale scores.
The EQ-5D-3L is the generic instrument that will be used. The EQ-5D-3L includes two parts: the 
EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L 
descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some 
problems, extreme problems. The EQ VAS records the respondents’ self-rated health on a 
100 point, vertical, visual analogue scale where the endpoints are labeled ‘Best imaginable health 
state’ and ‘Worst imaginable health state.’
5.8
Other Assessments 
We will obtain back-up plasma and serum samples for current/future evaluation of the efficacy, 
safety and tolerability of BMS-955176. 
Should any new safety signal develop during the course of the ongoing analysis of the Phase 2a 
trial, appropriate measures for evaluation and management will be incorporated into the design 
of the Phase 2b trial via a protocol amendment.
5.9
Results of Central Assessments
The following describes the centrally assessed parameters and the timing with which they will be 
shared with investigators, if pertinent. Some parameters are relevant to ongoing subject 
management during the study and will be provided to the site for such purpose, while others are 
Date: 28-Jan-2015
66
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
not relevant to subject management during the study and results may only be shared in a 
summarized way at the end of the study.

Samples sent to the central lab vendors for safety and efficacy assessments and that are tested 
real time will be provided to the sites as soon as results are available

The results of the read of each ECG will be sent to the site by the central ECG vendor as 
soon as results are available

Samples collected on-treatment for resistance testing will be tested if deemed clinically 
relevant (eg, if the development of resistance is suspected). If tested, results will be reported 
to the site

Other samples (including but not limited to biomarker assessments, exploratory resistance, 
pharmacodiagnostics) may not be tested immediately, and may only be tested if deemed 
clinically relevant. Results may be suppressed from laboratory reports and may not be 
provided to the sites

Individual PK results will not be reported to the site; the overall PK assessments will be 
included in the CSR

Individual assessments of the Outcomes research will not be reported to the site; the overall 
Outcomes assessments will be included in the CSR
6
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE). The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term "reasonable causal relationship" means there is evidence to suggest a causal 
relationship.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs).
Date: 28-Jan-2015
67
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
6.1
Serious Adverse Events
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

results in death

is life-threatening (defined as an event in which the subject was at risk of death at the time of 
the event; it does not refer to an event which hypothetically might have caused death if it 
were more severe)

requires inpatient hospitalization or causes prolongation of existing hospitalization 
(see NOTE below)

results in persistent or significant disability/incapacity

is a congenital anomaly/birth defect

is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above).
Examples of such events include, but are not limited to, intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization). Potential drug induced liver injury (DILI) is also considered an 
important medical event. (See Section 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must
be handled as
SAEs. 
(See Section 6.1.1 for reporting pregnancies).
NOTE:
The following hospitalizations are not considered SAEs in BMS clinical studies:

a visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason)

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
Date: 28-Jan-2015
68
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochure (IB) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
and within 30 days of discontinuation of dosing.
The investigator should report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure.
An SAE report should be completed for any event where doubt exists regarding its seriousness.
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship should be specified in the narrative section of the SAE Report Form.
SAEs, whether related or not related to study drug, and pregnancies, must be reported to BMS 
(or designee) within 24 hours. SAEs must be recorded on the SAE Report Form; pregnancies on 
a Pregnancy Surveillance Form (electronic or paper forms). The preferred method for SAE data 
reporting collection is through the eCRF. The paper SAE/pregnancy surveillance forms are only 
intended as a back-up option when the eCRF system is not functioning. In this case, the paper 
forms are to be transmitted via email or confirmed facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. The paper forms should be used and submitted immediately, only 
in the event the electronic system is unavailable for transmission. When paper forms are used, 
the original paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports should include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, a follow-up SAE report should be sent within 24 hours to the BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs should be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
Date: 28-Jan-2015
69
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (paper or electronic) as appropriate:

Any laboratory test result that is clinically significant or meets the definition of an SAE

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance 
Form to BMS Designee within 24 hours and in accordance with SAE reporting procedures 
described in Section 6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner 
(eg, dose tapering if necessary for subject safety).
In the rare event that the benefit of continuing study drug is thought to outweigh the risk, after 
consultation with BMS, the pregnant subject may continue study drug after a thorough 
discussion of benefits and risk with the subject.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated.
Date: 28-Jan-2015
70
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The investigator must immediately notify the BMS (or designee) Medical Monitor of this event 
and complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours 
and in accordance with SAE reporting procedures described in Section 6.1.1.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important.
All occurrences of overdose must be reported as an SAE (see Section 6.1.1 for reporting details).
6.6
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
Potential drug induced liver injury in HIV-1 mono-infected subjects is defined as:
1. AT (ALT or AST) elevation > 3 times upper limit of normal (ULN)
AND
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3. No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic
6.7
Other Safety Considerations
Any 
significant 
worsening
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
6.7.1
Toxicity Management
6.7.1.1
Management of Elevations in Liver Transaminases
The following Table 6.7.1.1-1 summarizes the management of elevations in liver transaminases:
Date: 28-Jan-2015
71
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.1-1:
Management of Elevations in Liver Transaminases Grade 
Level of AST or ALT Recommendationsa
Grade
Recommendation
Grade1
None
Grade 2
none
Grade 3
Confirm elevation, evaluate for potential causes (including but not limited to alcohol or 
other substance abuse, concomitant medications, reactivation of existing or de novo 
infection with hepatitis viruses) consult with BMS Medical Monitor or designate as soon as 
possible.
Grade 4
Interrupt all study medications, evaluate for potential causes (including but not limited to 
alcohol or other substance abuse, concomitant medications, reactivation of existing or de 
novo infection with hepatitis viruses), monitor values frequently and consult with BMS 
Medical Monitor or designate as soon as possible. If Grade 4 is deemed related to study 
medication the subject must be discontinued from the study. Otherwise, if reinstitution of 
study therapy is considered, please obtain approval from the BMS Medical Monitor or 
designate.
a If persisting (> Grade 1/2), evaluate for alternative etiologies, including alcohol use and viral hepatitis
6.7.1.2
Management of Renal Toxicity
Serum phosphate levels and creatinine clearance (CrCl; CCL: as calculated by the Cockcroft 
Gault Equation [see Appendix 4] or eGFR) should be monitored and managed as described in the 
Viread local package insert/label.29 Dose interval adjustments of TDF (Viread) are permitted, as 
described in Section 4.5.2.
6.7.1.3
Management of Hyperbilirubinemia
Most patients taking ATV experience asymptomatic elevations in indirect (unconjugated) 
bilirubin related to inhibition of UDP-glucuronosyl transferase (UGT). Hepatic transaminase 
elevations that occur with hyperbilirubinemia should be evaluated for alternative etiologies. Dose 
modification of ATV is not permitted. Subjects who experience unacceptable jaundice/scleral 
icterus should be discussed with the BMS Medical Monitor or designate to determine if subjects 
are to be discontinued from study. The investigator must contact the BMS Medical Monitor or 
designate prior to discontinuing any subject due to hyperbilirubinemia.
6.7.1.4
Gastrointestinal Toxicity Evaluation and Management Plan
Pre-clinical toxicology studies in rats and dogs (see Section 1.4.1.2) have suggested a potential 
for GI related toxicity with BMS-955176. This section provides general guidance to the 
Investigator on the evaluation and management of primarily upper gastrointestinal symptoms. 
The Investigator may contact the Medical Monitor to discuss evaluation and management 
(including interruption of ARVs or discontinuation of a subject) of any GI symptoms throughout 
the trial.
Date: 28-Jan-2015
72
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical trial. 
Nausea and Vomiting
The investigator should attempt to identify the etiology of these symptoms (and whether it 
is intraperitoneal, extraperitoneal, medication related, infection related, or due to a 
metabolic disorder).36 Medications can cause nausea and vomiting acutely. 
Dyspepsia
The Investigator should identify the presence of red flags (odynophagia, unexplained 
weight loss, recurrent vomiting, GI bleeding, jaundice, palpable mass or adenopathy, or 
family history of GI malignancy). Symptoms of dyspepsia could include early satiety, 
bloating, or belching. Additionally, atypical symptoms of dyspepsia could include: 
pharyngitis, asthma, bronchitis, hoarseness, chest pain, or abdominal pain. 
Ulcerative Disease
Symptoms suggestive of ulceration often are intermittent over a period of weeks to months 
and may be relieved by eating or antacid use;37 penetrating ulcers become more acute 
with localized pain and may not improve with food.38 The development of perforation 
may be indicated by severe diffuse abdominal pain. 
Other Clinical 
Syndromes
Additional diagnostic criteria for other GI disorders potentially encountered in the clinical 
trial are available elsewhere.39
PHYSICAL 
EXAMINATION
Physical examination should complement elements obtained from the history37
Acutely, the investigator may assess for signs of intravascular volume depletion 
(eg, orthostasis) and/or aspiration of vomitus as appropriate. Abdominal tenderness 
and guarding may indicate inflammation. The presence of fecal blood can indicate 
mucosal damage (eg, from an ulcer). Complete evaluation of dyspepsia should 
include an oral examination (poor dentition or pharyngeal erythema) and lungs for 
wheezing. 
DIAGNOSTIC 
EVALUATION AND 
MANAGEMENT
A major goal in the diagnostic evaluation of a subject with upper GI symptoms is to 
quickly arrive at a final diagnosis without exposing the subject to unnecessary 
(invasive) testing; Investigators should exercise good clinical judgment38 in this 
regard. A major goal of therapy is directed at correcting the underlying identifiable 
medical or surgical abnormalities. Consultation (eg, gastroenterologist) is 
recommended as clinically indicated.
Grade 1 symptoms
Subjects may be treated symptomatically. If subjects develop dyspepsia alone, generally 
only limited and direct diagnostic testing should be performed.37 If the subject has 
dyspepsia they should limit alcohol, caffeine, chocolate, tobacco, other contributing 
concomitant medications (eg, NSAIDs) and eating directly before bedtime. A variety of 
OTC medications are available to address constipation and diarrhea as indicated. Please 
refer to Appendix 1 for Prohibited and Precautionary Therapies.
Grade 2 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically indicated):

Serum chemistries and assessment of hemoglobin if not recently performed. 

Testing for Helicobacter pylori

Serologies (eg, celiac disease) 

PCR for viruses (eg, CMV)

Iron panel or Vitamin B12 level
Date: 28-Jan-2015
73
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
For subjects who develop dyspepsia or are infected with H. pylori the use of H2 
antagonists, PPIs, Sucralfate, and antacids are prohibited (see Appendix 1 Prohibited 
Medications). If such therapy is required, discontinuation from the trial is necessary. 
The use of antiemetic’s (eg, Prochlorperazine) can be utilized as indicated. Management 
should be targeted at addressing the underlying pathology.
Grade 3 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically indicated):

The testing outlined above in Grade 2

A fasting serum gastrin level can be obtained in cases of known ulcers refractory to 
therapy, a family history of the disease, or when surgery is required; of note, H. pylori
can increase gastrin levels.38

A barium swallow to detect ulcers 

CT to identify gastrointestinal inflammation and a penetrating or perforated ulcer. 

Upper endoscopy with biopsy as indicated in order to evaluate dyspepsia further (eg,
mucosal injury, new onset unexplained dyspepsia in subjects > 55 y/o, or the presence 
of red flags).
Management should be targeted at addressing the underlying pathology.
Grade 4 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically indicated):

The testing outlined above in Grade 2 and Grade 3

An acute abdominal series

If a perforated ulcer is clinically suspected, surgical consultation may be necessary
Initial management can include correction of hemodynamic and electrolyte abnormalities 
as clinically indicated. After stabilization, management should be targeted at addressing 
the underlying pathology.
a For Grade 2-4 symptoms if any ARV is thought to have a direct causal relationship to the patient’s 
gastrointestinal symptoms, the Investigator should consider discontinuing the subject from the study and 
performing an evaluation/management plan incorporating elements above. The Investigator can consider 
interruption of the potential offending ARV(s) but must balance this with the increased probability of 
development of viral resistance/lack of efficacy. As stated above, prior to discontinuing the subject from the 
study, attempts should be made to discuss with the BMS Medical Monitor unless the safety of the subject is 
acutely at risk.
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
This is an estimation study, without statistical testing, and hence there are no power 
considerations.
Date: 28-Jan-2015
74
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
It is expected that response rate for the primary endpoint for all five arms will be somewhere 
around 80%. With this response rate, and 40 subjects per arm, an exact 95% confidence interval 
would run from roughly 64% to 91%.
8.2
Populations for Analyses
The following definitions are used in this document:

Enrolled subjects: Subject who signed an informed consent form and were assigned a 
Patient Identification number (PID);

Randomized subjects: Enrolled subjects who received a treatment assignment from the 
IVRS;

Treated subjects: Randomized subjects who received at least 1 dose of BMS-955176 or 
TDF. 

Modified Intent to Treat Analysis Set: All randomized subjects who received at least 
1 dose of BMS-955176 or TDF (this is the same as all treated subjects)

Observed analysis set: A collection of subjects that have data within an interval of 
interest.
8.3
Endpoints
8.3.1
Primary Endpoint(s)Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Week 24. This will be assessed with the FDA snapshot algorithm. This uses 
the last on-treatment plasma HIV-1 RNA measurement, within an FDA-specified visit window, 
to determine response. 
8.3.2
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 
RNA < 200 c/mL at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with 
positive response defined as HIV-1 RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be 
assessed using the most recent version of the IAS-USA list of HIV-1 drug resistance 
mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells will be assessed using on-treatment laboratory results, and 
pre-specified visit windows

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly 
from the case report forms (CRFs). The summary will count the number of subjects that have 
at least one event
Date: 28-Jan-2015
75
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from 
the CRFs. The summary will count the number of subjects that have at least one event

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, 
collected at Week 2 from a subset of subjects
8.4
Analyses
In general, categorical variables are tabulated with counts and percents. Continuous variables are 
summarized with univariate statistics (eg, mean, median, standard error).
Longitudinal analyses use pre-defined visit week windows. Unless otherwise specified, windows 
around planned measurement times are constructed based on the midpoint between planned 
study visits (ie, half the duration of time between study visits), and data are summarized at each 
scheduled visit. 
For the calculation of descriptive statistics of observed data, subjects must have a baseline 
measurement to be evaluable for longitudinal tabulations of parameter values and changes from 
baseline. 
Tabulations of the following endpoints present the number of unique subjects with an event: 
protocol deviations; interruptions of study therapy; non-study medications; adverse events; and 
laboratory abnormalities. Thus, multiple occurrences of the same event are counted only once 
per subject.
8.4.1
Demographics and Baseline Characteristics
The following demographic and baseline characteristics will be summarized by treatment arm
and overall using the treated subjects:

Demographics: age, race, ethnicity, gender, geographic region;

Disease characteristics at baseline: plasma HIV-1 RNA level, CD4+ T-cell counts and 
percentages, CD8+ T-cell counts, HIV-1 subtype;

Laboratory tests at baseline;

Pre-treatment CDC Class C AIDS events;

Prior medications
8.4.2
Efficacy Analyses
The efficacy analyses will be based on the treated subjects.
Date: 28-Jan-2015
76
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
8.4.2.1
Primary Efficacy Analyses
The primary efficacy endpoint is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL 
at the Week 24 snapshot within each stage. This endpoint is assessed with the FDA snapshot 
algorithm. The primary analysis will be based on a modified ITT (mITT) approach. A sensitivity 
analysis will be conducted using an observed values approach. The two approaches will be 
implemented as follows:

Modified ITT: The numerator will be based on subjects with plasma HIV-1 RNA < 40 c/mL 
at Week 24. The denominator will be based on all treated subjects

Observed values: Similar to the mITT approach, the numerator will be based on subjects with 
plasma HIV-1 RNA < 40 c/mL at Week 24. However, the denominator will be based on the 
treated subjects with plasma HIV-1 RNA at Week 24
Response rates will be tabulated by treatment arm (within the stage) with exact binomial 95% 
confidence intervals.
Subgroup summaries will be provided to examine the impact of baseline viral load and HIV-1 
Clade (Clade AE versus Other) for both the mITT and the observed values approach. Other 
subgroup summaries may be provided to examine the impact of other important covariates such 
as CD4+ count, sex, geographic region, etc
8.4.2.2
Secondary Efficacy Analyses
The following secondary endpoints will be summarized by treatment arm:

Proportion of subjects with HIV-1 RNA < 40 c/mL at Week 48 and Week 96 using mITT 
and observed values

Proportion of subjects with HIV-1 RNA < 200 c/mL at Week 24, 48 and 96 using mITT and 
observed values

Change from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells over time

Newly emergent genotypic substitutions (using all on-treatment isolates) will be tabulated by 
treatment arm

The newly emergent phenotypic resistance profile (using all on-treatment isolates) will be 
tabulated by treatment arm
8.4.3
Safety Analyses
The investigators will determine the intensity of adverse events (AEs) and the relationship of 
AEs to study therapy. The investigators’ terms will be coded and grouped by system organ class 
using the latest version of the Medical Dictionary for Regulatory Activities (MedDRA) in 
production at BMS. AEs will be presented by system organ class and preferred term. 
Presentations will include both non-serious and serious adverse events, unless specified 
Date: 28-Jan-2015
77
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
otherwise. If a subject had an adverse event with different intensities over time, then only the 
greatest intensity will be reported.
Deaths will be listed for enrolled subjects without regard to onset.
In analyses of fasting lipids over time, values will be excluded after the start of serum lipid 
reducing agents.
The frequency of the following safety events will be summarized by treatment arm for treated 
subjects:

SAEs

AEs leading to discontinuation of study therapy

AEs by intensity

CDC Class C AIDS events

Laboratory abnormalities by toxicity grade
8.4.4
Pharmacokinetic Analyses
The following PK parameters will be summarized by treatment arm:

Cmax: maximum observed plasma concentration

Tmax: time of maximum observed plasma concentration

Ctau: observed plasma concentration at the end of a dosing interval (eg, concentration at 
24 hours)

C0: observed pre-dose plasma concentration

AUC(TAU) : area under the concentration-time curve in one dosing interval
8.4.4.1
Sparse Pharmacokinetic Analyses
Sparse pharmacokinetic data will be used in population PK, PK/PD and PK/VK analyses.
8.4.4.2
PK/PD and PK/VK Analyses
PK data obtained from this study will be pooled with data from other studies to perform an 
integrated population PK analysis, exposure-response analyses for selected safety and efficacy 
endpoints, and viral kinetic modeling of BMS-955176 in combination with other ARVs to 
support the on-going development of BMS-955176. These analyses will facilitate optimal dose 
selection for future Phase 3 studies. 
The population PK, exposure-response, and viral kinetic analyses will be reported separately.
8.4.5
Biomarker Analyses
Details about the biomarker analyses will be provided in the Statistical Analysis Plan (SAP).
8.4.6
Outcomes Research Analyses
Details about the outcomes research analyses will be provided in the SAP.
Date: 28-Jan-2015
78
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
8.4.7
Other Analyses (including Virologic Futility)
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 1 completes their Week 24 visit. This analysis will be conducted to evaluate whether the 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 1 (containing 
BMS-955176) to Arm 2 (containing TDF) will be made with one-sided, Fisher’s exact tests, 
conducted at the 0.01 probability level.
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 2 completes their Week 24 visit. This analysis will be conducted to evaluate whether a 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 3-4
(containing BMS-955176) to Arm 5 (containing TDF) will be made with one-sided, Fisher’s 
exact tests, conducted at the 0.01 probability level.
8.5
Interim Analyses
The first two interim analyses are scheduled to support the decision on initiating the second stage 
of this study. This decision will be based on the totality of the data, including: safety, efficacy 
and resistance data from this study; relevant data from other studies in the development program; 
and PK/PD modeling.
The first interim analysis will be conducted after approximately 50% of the randomized subjects
have completed 24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of 
SDTM (Study Data Tabulation Model) data (“level 1” data) to facilitate the development of 
models for: population pharmacokinetics; exposure-response relationships; and viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of 
therapy in Stage 1. This will be a complete analysis of the available efficacy, safety and 
resistance data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well 
as the recruiting time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If 
Stage 2 is initiated, and recruiting follows projected timelines, then it is anticipated that analyses 
will be conducted when:

The last subject in Arms 3, 4, and 5 completes the Week 24 visit

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4, and 5 completes the Week 96 visit
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
Date: 28-Jan-2015
79
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
deviation or change to the protocol without prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change 
will be submitted to:

IRB/IEC for review and approval/favorable opinion

BMS

Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
subject: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a 
schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the 
source documents:
In addition, the study may be evaluated by BMS internal auditors and government inspectors 
who must be allowed access to CRFs, source documents, other study files, and study facilities. 
BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to BMS.
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
Date: 28-Jan-2015
80
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records 
(EMRs/EHRs), adverse event tracking/reporting, protocol required assessments, and/or drug 
accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS.
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include the investigational product 
and the non-investigational product(s). Records or logs must comply with applicable regulations 
and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each subject, including unique subject identifiers

amount transferred to another area/site for dispensing or storage

nonstudy disposition (eg, lost, wasted)

amount destroyed at study site, if applicable

amount returned to BMS
Date: 28-Jan-2015
81
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

retain samples for bioavailability/bioequivalence, if applicable

dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS electronic data capture tool, electronic CRFs will be prepared for all 
data collection fields except for fields specific to SAEs and pregnancy, which will be reported on 
the paper or electronic SAE form and Pregnancy Surveillance form, respectively. Spaces may be 
left blank only in those circumstances permitted by study-specific CRF completion guidelines 
provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated by the investigator or qualified physician who is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form. For electronic CRFs, review 
and approval/signature is completed electronically through the BMS electronic data capture tool.
The investigator must retain a copy of the CRFs including records of the changes and 
corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements 
and must only access the BMS electronic data capture tool using the unique user account 
provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the 
following criteria:

External Principal Investigator designated at protocol development
Date: 28-Jan-2015
82
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

National Coordinating Investigator 

Study Steering Committee chair or their designee

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region 
or country)

Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study require approval by BMS prior to publication or presentation 
and must adhere to BMS’s publication requirements as set forth in the approved clinical trial 
agreement (CTA). All draft publications, including abstracts or detailed summaries of any 
proposed presentations, must be submitted to BMS at the earliest practicable time for review, but 
at any event not less than 30 days before submission or presentation unless otherwise set forth in 
the CTA. BMS shall have the right to delete any confidential or proprietary information 
contained in any proposed presentation or abstract and may delay publication for up to 60 days 
for purposes of filing a patent application.
Date: 28-Jan-2015
83
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete Abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Female subjects must continue 
to have pregnancy tests. Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject chooses to 
forego complete abstinence.
If two forms of contraception is required, Complete abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Subjects who choose complete 
abstinence are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. Acceptable 
alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as complete 
avoidance of heterosexual intercourse is an acceptable form of 
contraception for all study drugs. This also means that abstinence is the 
preferred and usual lifestyle of the patient. This does not mean periodic 
abstinence (eg, calendar, ovulation, symptothermal, profession of 
abstinence for entry into a clinical trial, post-ovulation methods) and 
withdrawal, which are not acceptable methods of contraception. Subjects 
who choose complete abstinence are not required to use a second method 
of contraception, but female subjects must continue to have pregnancy 
tests. Acceptable alternate methods of highly effective contraception must 
be discussed in the event that the subject chooses to forego complete 
abstinence
Date: 28-Jan-2015
84
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
11
LIST OF ABBREVIATIONS
Term
Definition
3TC
Lamivudine
AE
adverse event
AI
accumulation index
AIDS
Acquired Immunodeficiency Syndrome
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after the 
first dose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALT
alanine aminotransferase
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir
ATV/r
atazanavir boosted with ritonavir
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the time of 
the last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
A-V
atrioventricular
-HCG
beta-human chorionic gonadotrophin
BA/BE
bioavailability/bioequivalence
BID, bid
bis in die, twice daily
BCRP
Breast cancer reactive protein
BDC
Bile duct-cannulated
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
BVM
bevirimat
Date: 28-Jan-2015
85
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
c
copies
c/mL
copies per milliliter
C
Celsius
C12
concentration at 12 hours
C24
concentration at 24 hours
CA
capsid
cART
Combination antiretroviral therapy
Cavg
average concentration
Cexpected-tau
expected concentration in a dosing interval
CD
Cluster designation (CD4; CD8)
CDC
Centers for Disease Control
CFC
corrected fold change
CFR
Code of Federal Regulations 
CI
confidence interval
CrCl
creatinine clearance
CLR
renal clearance
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CMV
cytomegalovirus
CNS
Central nervous system
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
Css,avg
average steady-state plasma concentration
CSR
Clinical study report
Ct
Expected concentration at a certain time, usually at the end of an 
expected future dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctau
Concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctrough
Trough observed plasma concentration
CT
Computed tomography
Date: 28-Jan-2015
86
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
CTA
clinical trial agreement
CTX
Cross-linked C-telopeptide of Type 1 collagen
CYP
cytochrome p-450
D/C
discontinue
DDI
drug-drug interaction
DHHS
Department of Health and Human Services
dL
deciliter
DTG
dolutegravir
EC
Ethics committee
EC
effective concentration
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EFV
efavirenz
eg
exempli gratia (for example)
E-R
exposure-response
ESR
Expedited Safety Report
ET
Early termination or End of Treatment
EU
European Union
FAHI
Functional Assessment of HIV Infection
FDA
Food and Drug Administration
FDC
Fixed dose combination
FSH
follicle stimulating hormone
FTC
emtricitabine
g
gram
GFR
glomerular filtration rate
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
GSH
glutathione
Date: 28-Jan-2015
87
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
h; hr
hour
HAART
Highly active antiretroviral therapy
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCG
Human chorionic gonadotropin
HCV
hepatitis C virus
HCO3-
bicarbonate
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HR
heart rate
HRT
hormone replacement therapy
HS
Human serum
HuSA
Human serum albumin
IAS
International AIDS Society
IB
Investigator brochure
IC
Inhibitory concentration
ICD
International Classification of Diseases
ICF
informed consent form
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
INI
Integrase inhibitor
IP
investigational product
IRB
Institutional Review Board
IU
International Unit
IUD
intrauterine device
IV
intravenous
IVRS
interactive voice response system
Date: 28-Jan-2015
88
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
GALT
Gut associated lymphoid tissue
GI
gastrointestinal
kg
kilogram
L
liter
MAD
multiple ascending dose
MC
micronized crystalline
mg
milligram
MI
Maturation inhibitor
MIC
minimum inhibitory concentration
min
minute
mITT
Modified Intent to Treat
mL
milliliter
mmHg
millimeters of mercury
msec
millisecond
MOA
mechanism of action
g
microgram
M
micromolar
N
number of subjects or observations
N/A
not applicable
ng
nanogram
nM
nanomolar
NIMP
non-investigational medicinal products 
NNRTI
Non- nucleoside reverse transcriptase inhibitor
NOAEL
No observed adverse effect level
NOEL
No observed effect level
NRTI
nucleoside reverse transcriptase inhibitor
NSAID
nonsteroidal anti-inflammatory drug
pDILI
potential drug induced liver injury
PBMC
peripheral blood mononuclear cells
PCR
polymerase chain reaction
Date: 28-Jan-2015
89
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
PD
pharmacodynamics
PI
protease inhibitor
PDVF
Protocol-defined virologic criteria
PK
pharmacokinetics
PPI
proton pump inhibitor
PR
atrial depolarization to ventricular depolarization
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
QD, qd
quaque die, once daily
QRS
interval representing the time for ventricular depolarization
QT
Duration of ventricular electrical activity
QTcF
QT corrected for heart rate using Frederica’s formula
RAL
raltegravir
RBC
red blood cell
RNA
ribonucleic acid
RTV
ritonavir
SAD
single ascending dose
SDD
spray-dried dispersion
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SDTM
Study Data Tabulation Model
SOP
Standard Operating Procedures
SP1
spacer peptide 1
Subj
subject
STR
single tablet regimen
t
temperature
T
time
TDF
tenofovir
Date: 28-Jan-2015
90
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
TDF/FTC
Truvada (TDF 300 mg + FTC 200 mg)
TAO
Trial Access Online, the BMS implementation of an EDC capability
TAM
Thymidine analogue mutation
T-HALF
Half life
T-HALFeff_AUC
Effective elimination half life that explains the degree of AUC 
accumulation observed
Tmax, TMAX
time of maximum observed concentration
TR_AUC(0-T)
AUC(0-T) treatment ratio
TR_AUC(INF)
AUC(INF) treatment ratio
TR_Cmax
Cmax treatment ratio
UGT
UDP-glucuronosyltransferase
ULN
upper limit of normal
US
United States
VF
virologic failure
VK
Viral kinetics
VLP
Virus-like particles
WBC
white blood cell
WFD
Wallingford, Connecticut, USA
WHO
World Health Organization
Wk or WK
week
WOCBP
women of childbearing potential
Date: 28-Jan-2015
91
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
REFERENCES
1
WHO HIV Department. Global Summary of the AIDS Epidemic 2013. Available at: 
http://www.who.int/hiv/data/epi_core_dec2014.png?ua=1 Accessed 12/29/14
2
European AIDS Clinical Society. European Guidelines for treatment of HIV-infected adults 
in Europe (Oct 2013). http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf. 
Accessed Nov 30, 2013.
3
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services. 
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed Nov 
30, 2013.
4
United States Department of Health and Human Services, Food and Drug Administration, 
Center for Drug Evaluation and Research. Guidance for Industry Human Immunodeficiency 
Virus-1 Infection: Developing Antiretroviral Drugs for Treatment. (June 2013). Revision 1.
5
Gupta S.K., Lombaard J., Echevarria J., et. al. HIV NRTI BMS-986001 in Antiretroviral-
Naive Subjects: Week 24/49 Analyses. ICAAC 2014 Oral Abstract: H-642
6
Study AI468001 Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple 
Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of 
BMS-955176 in Healthy Subjects. Document Control No. 930071044
7
Study AI468002 Randomized, Placebo-Controlled, Multiple-Dose Study to Evaluate the 
Pharmacodynamics, Safety and Pharmacokinetics of BMS-955176 (Double-Blinded) and 
BMS-955176 with Atazanavir +/- Ritonavir (Open-Labelled) in HIV-1 Infected Subjects. 
Draft Document Control No. 930087017
8
Min 
S., 
Sloan 
L., 
DeJesus 
E., 
et. 
al. 
Antiviral 
activity, 
safety, 
and 
pharmacokinetics/pharmacodynamics 
of 
dolutegravir 
as 
10-day 
monotherapy 
in 
HIV-1-infected adults. AIDS 2011. 25(14):1737-45.
9
Walmsley SL., Antela A., Clumeck N., et. al. Dolutegravir plus abacavir-lamivudine for the 
treatment of HIV-1 infection. NEJM 2013 369(19):1807-18.
10
Raffi F., Jaeger H., Quiros-Roland E., et. al. Once-daily dolutegravir versus twice-daily 
raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week 
results from a randomised, double-blind, non-inferiority trial. Lancet ID. 2013 13(11): 
927-35.
11
Cahn P., Pozniak AL., Mingrone H,. et. al. Dolutegravir versus raltegravir in antiretroviral-
experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, 
double-blind, non-inferiority SAILING study. Lancet 2013 382(9893):700-8.
Date: 28-Jan-2015
92
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
Stellbrink HJ., Reynes J., Lazzarin A., Dolutegravir in antiretroviral-naive adults with 
HIV-1: 96-week results from a randomized dose-ranging study. AIDS 2013 27(11):1771-8.
13
Eron JJ., Clotet B., Durant J., Safety and efficacy of dolutegravir in treatment-experienced 
subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING 
Study. JID 2013 207(5): 740-748.
14
Sanne I, Piliero P, Squires K, Thiry A, Schnittman S. Results of a phase 2 clinical trial at 48 
weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at 
three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. 
J Acquir Immune Defic Syndr. Jan 1 2003;32(1):18-29.
15
Bertz RJ, Persson A, Chung E, et al. Pharmacokinetics and pharmacodynamics of atazanavir-
containing antiretroviral regimens, with or without ritonavir, in patients who are 
HIV-positive and treatment-naive. Pharmacotherapy. Mar 2013;33(3):284-294.
16
Molto J, Santos JR, Valle M, et al. Monitoring atazanavir concentrations with boosted or 
unboosted regimens in HIV-infected patients in routine clinical practice. Ther Drug Monit. 
Oct 2007;29(5):648-651.
17
Goutelle S, Baudry T, Gagnieu MC, et al. Pharmacokinetic-pharmacodynamic modeling of 
unboosted Atazanavir in a cohort of stable HIV-infected patients. Antimicrob Agents 
Chemother. Jan 2013;57(1):517-523.
18
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services. 
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed Nov 
30, 2013.
19
Malan DR, Krantz E, David N, Wirtz V, Hammond J, McGrath D. Efficacy and safety of 
atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy 
regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr. Feb 1 
2008;47(2):161-167.
20
Landman R, Diallo MB, Gueye NF, et al. Efficacy and safety of unboosted atazanavir in 
combination with lamivudine and didanosine in naive HIV type 1 patients in Senegal. AIDS 
Res Hum Retroviruses. May 2010;26(5):519-525.
21
Gianotti N, Seminari E, Guffanti M, et al. Evaluation of atazanavir Ctrough, atazanavir 
genotypic inhibitory quotient, and baseline HIV genotype as predictors of a 24-week 
virological response in highly drug-experienced, HIV-infected patients treated with 
unboosted atazanavir. New Microbiol. Apr 2005;28(2):119-125.
Date: 28-Jan-2015
93
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
22
Giuntini R, Martinelli C, Ricci E, et al. Efficacy and safety of boosted and unboosted 
atazanavir-containing antiretroviral regimens in real life: results from a multicentre cohort 
study. HIV Med. Jan 2010;11(1):40-45.
23
Two Drug Combination Studies with BMS-955176 and HIV Antiviral Agents. Version 1.0. 
June 2013. DCN 930071469
24
Song I., Borland J., Chen S. Effect of atazanavir and atazanavir/ritonavir on the 
pharmacokinetics of the next-generation HIV integrase inhibitor, S/GSK1349572. Br. J. 
Pharm. 2011 72(1):103-108
25 BMS-955176 Investigator Brochure, Version 2.0, July 2013 DCN 930056146
26 BMS-955176 Investigator Brochure, Version 3.0, April 17, 2014 DCN 930056146
27 Partial response to FDA “May Proceed” Letter dated 27 Sep 2013 for IND 118,936. Bristol-
Myers Squibb Company; Jan 2014. Document Control No. 930076507 2.0. Insert this 
additional reference: “Evaluation of cross-resistance of HIV-1 Maturation Inhibitor 
BMS-955176 toward HIV-1 protease inhibitor resistant viruses. Bristol-Myers Squibb 
Company; 30-Sept-2014. Document Control No. 930083565.”
28 Evaluation of Cross Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. Document Control No. 930083565
29 Gilead 
Sciences. 
Prescribing 
Information 
for 
TDF. 
Available 
at: 
http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/viread/viread_pi.pdf.
Accessed Dec 31, 2014
30
ViiV 
Healthcare. 
Prescribing 
Information 
for 
DTG. 
Available 
at: 
https://www.viivhealthcare.com/media/58599/us_tivicay.pdf. Accessed Dec 31, 2014.
31 BMS. 
Prescribing 
Information 
for 
ATV. 
Available 
at: 
http://packageinserts.bms.com/pi/pi_reyataz.pdf. Accessed Dec 31, 2014
32 AbbVie. 
Prescribing 
Information 
for 
RTV. 
Available 
at: 
http://www.rxabbvie.com/pdf/norvirtab_pi.pdf. Accessed Dec 31, 2014
33 Evaluation of Cross-Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. DCN 930083565
34
Kestelman P. et. al., Efficacy of the Simultaneous Use of Condoms and Spermicides Family 
Planning Perspectives.Vol 23 (5); October 1991.
35
Gabbay MB, Thomas J, Gibbs A, Hold P. A Randomized Crossover Trial of The Impact of 
Additional Spermicide on Condom Failure Rates. Sex Transm Dis 2008; 35: 862-8.
Date: 28-Jan-2015
94
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
36
Hasler WL Nausea, Vomiting, and Indigestion: Introduction. Chapter 39. Harrisons 
Principles of Internal Medicine 18th edition. 2012. McGraw Hill
37
Hasler WL and Owyang C Approach to the Patient with Gastrointestinal Disease. Chapter 
290. Harrisons Principles of Internal Medicine 18th edition. 2012. McGraw Hill
38
Soll AH and Graham DY. Peptic Ulcer Disease. Chapter 40. Textbook of Gastroenterology. 
5th edition. 2009. Blackwell Publishing
39
Rome Foundation. Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. 
Available: http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Accessed 
Dec 22 2014
Date: 28-Jan-2015
95
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 1
LISTINGS OF PROHIBITED AND PRECAUTIONARY
THERAPIES
General Notes: 

Guidelines for the use of drugs with established or other potentially significant drug 
interactions listed in the Package Inserts of the marketed ARV agents used by subjects 
participating in this study (Reyataz, Norvir, Viread, Tivicay) should be followed. 

Medications listed in the Package Inserts as contra-indicated with the other marketed ARV 
agents used by subjects participating in this study are not permitted. 

Any immunizations deemed appropriate by the subject’s physician are permitted provided 
that the immunization is given > 4 weeks from any HIV-1 RNA measurement.

A subject may not be co-enrolled in a concomitant trial unless it is approved by the Medical 
Monitor prior to randomization.
Prohibited Therapies
Drugs that should not be administered throughout the duration of the study:
Anticonvulsants: Carbamazepine, 
Phenobarbital, Phenytoin
Use with ATV may result in decreased ATV concentrations. Use 
of Carbamazepine may result in decreased DTG concentrations.
Oral Antifungals: Itraconazole, 
Posaconazole, and Voriconazole
Use with ATV can result in increased ATV concentrations
Antimycobacterials: Rifampin, 
Rifapentine, Rifabutin
These antimycobacterials decrease ATV plasma concentrations
and may decrease BMS-955176 plasma concentrations.
St. John’s wort
Use with ATV or DTG may result in loss of antiviral therapeutic 
effect
GI motility agent: Cisapride
Potential for serious and/or life threatening reactions such as 
cardiac arrhythmias
Pimozide
Potential for serious and/or life threatening reactions such as 
cardiac arrhythmias
Zetia (ezetimibe)
Ezetimibe is a substrate of OATP1B1 (of which BMS-955176 is 
an inhibitor in vitro).
Dofetilide
Use with DTG may result in the potential for increased Dofetilide 
plasma concentrations and the risk for serious and/or life 
threatening events
Alfuzosin
ATV increases Alfuzosin concentrations which can result in 
hypotension
Benzodiazepines: Triazolam and 
Midazolam
ATV can increase the concentration of these Benzodiazepines 
with the potential to increase sedation or respiratory depression
Ergot derivatives: 
Dihydroergotamine, ergotamine, 
ergonovine, methylergonovine
ATV can increase potential for ergot toxicity (e.g. peripheral 
vasospasm)
Date: 28-Jan-2015
96
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
HMG-CoA Reductase Inhibitors: 
Lovastatin, Simvastatin, 
Atorvastatin, Pitavastatin, 
Rosuvastatin, Pravastatin
Use with ATV may result in increased levels of HMG-CoA 
Reductase Inhibitors and potential for serious reactions such as 
myopathy
Antacids, H2 receptor angatonists, 
Proton Pump Inhibitors, Sucralfate
Use with ATV may result in decreased plasma concentrations of 
ATV. Use of Antacids containing Aluminium, Magnesium, or 
Calcium may result in decreased levels of DTG.
Macrolides: Clarithromycin
Use with ATV may result in increased Clarithromycin levels and 
QTc prolongation
Buprenorphine
Use with ATV may increase levels of Buprenorphine
Quetiapine
Use with ATV may increase levels of Quetiapine
Salmeterol
Use with ATV may result in increased levels of Salmeterol
Avanafil
Use with ATV may result in increased Avanafil levels
All drugs with antiretroviral 
activity other than those 
considered study therapy
Any drugs with antiretroviral activity not considered study 
therapy may interfere with the assessments of the study.
Precautionary Therapies
Drugs that should be administered with caution during the study:
Hormonal Contraceptives
Hormonal Contraceptives cannot be relied upon as a highly 
effective method of contraception. 
See Protocol Section 3.3.1, for more information on Highly 
Effective Methods of Contraception.
Antidepressants: Trazodone, 
Tricyclic Antidepressants (TCA)
Use with ATV/r may result in increased plasma concentrations of 
trazodone and TCA
Antimalarials: 
Atovaquone/Proguanil, Mefloquine
Use with ATV/r may result in decreased Atovaquone/Proguanil 
levels. The effect of Mefloquine on ATV/r is unknown.
Benzodiazepines: Alprazolam and 
Diazepam
ATV can increase the concentration of these Benzodiazepines 
Calcium Channel Blockers
Use with ATV may result in increased concentrations of CCB’s. 
Non-topical Corticosteroids: 
Budesonide, Fluticasone, 
Prednisone, Methylprednisolone, 
Prednisolone, Triamcinolone
Use with ATV/r may result in increased levels of glucocorticoids 
and adrenal insufficiency
Dexamethasone
Use with ATV may result in reduced levels of ATV.
Colchicine
Use with ATV may result in increased Colchicine levels
Metformin
Use with DTG may result in increased levels of metformin. 
A cation-containing (e.g. 
Magnesium) laxative
If used with DTG the laxative should be taken 2 hours before or 
6 hours after taking concomitant laxatives.
Date: 28-Jan-2015
97
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 2
AIDS-DEFINING DIAGNOSES
I.
PARASITIC INFECTIONS
Pneumocystis carinii (PC)
1011
PC pneumonia histologically proven.
1012
PC pneumonia, clinical diagnosis by the following specifications and confirmed HIV 
infection:
A history of dyspnea on exertion or non-productive cough of recent onset (within the past 
3 months).
AND
Chest X-ray evidence of diffuse bilateral interstitial or gallium scan evidence of diffuse 
bilateral pulmonary disease;
AND
Arterial blood gas analysis showing an arterial pO2 of < 70 mmHg or a low respiratory 
diffusing capacity (< 80% of predicted values) or an increase in the alveolar-arterial 
oxygen tension gradient;
AND
Successful response to appropriate therapy and no evidence of pneumonias of other 
etiologies.
1013
Pneumocystis carinii, histologically proven, at a site other than lungs.
Toxoplasmosis (in patients > 1 month old)
1021
Toxoplasmosis, clinical diagnosis (of brain only) by the following specifications and 
confirmed HIV infection:
Recent onset of a neurologic disease consistent with toxoplasmosis;
AND
Brain imaging evidence of a mass lesion (on computed tomography, nuclear magnetic 
resonance of radiography enhanced by injection of contrast medium);
AND
Serum antibody to toxoplasmosis and successful response to therapy for toxoplasmosis.
1022
Toxoplasmosis, of brain or internal organs other than liver, spleen or lymph nodes. 
Proven by microscopy.
Isosporiasis
1031
Isosporiasis causing chronic diarrhea of > 1 month. Proven by microscopy.
Date: 28-Jan-2015
98
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Cryptosporidiosis
1041
Cryptosporidiosis causing chronic diarrhea of > 1 month. Proven by microscopy.
II.
FUNGAL INFECTIONS
Candidiasis
2011
Candidiasis, Esophageal, definitive diagnosis by the following specifications:
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
2012
Candidiasis, Esophageal, presumptive diagnosis by the following specifications and 
confirmed HIV infection:
Recent onset of retrosternal pain on swallowing:
AND
Oral candidiasis diagnosed by the gross appearance of white patches or plaques on an 
erythematous base OR by the microscopic appearance of fungal mycelial filaments in an 
uncultured specimen scraped from the oral mucosa;
AND
Response to appropriate therapy.
2013
Candidiasis, Bronchial/Pulmonary, definitive diagnosis by the following specifications; 
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
Cryptococcosis
2022
Cryptococcosis, Extra-pulmonary, proven by microscopy (histology or cytology), culture 
or detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Histoplasmosis
2031
Histoplasmosis, Disseminated (at a site other than or in addition to lungs or cervical or 
hilar lymph nodes), proven by microscopy (histology or cytology), culture or detection of 
antigen in a specimen obtained directly from the tissues affected or a fluid from those 
tissues.
Coccidioidomycosis
2041
Coccidioidoidomycosis, Disseminated (at a site other than or in addition to lungs or 
cervical or hilar lymph nodes), proven by microscopy (histology or cytology), culture or 
detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Date: 28-Jan-2015
99
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
2042
Coccidioidomycosis, clear reactivation of prior infection, proven by microscopy 
(histology or cytology), culture or detection of antigen in a specimen obtained directly 
from the tissues affected or a fluid from those tissues.
III.
BACTERIAL INFECTIONS
Mycobacterium
3001
Mycobacterium (unidentified species). Presumptive diagnosis, by the following 
specifications and confirmed HIV infection.
Acid fast bacilli (AFB) positive stain of specimen obtained from endoscopic biopsy or 
from a normal sterile site other than lungs, skin or cervical or hilar lymph nodes. Species 
NOT identified by culture.
Mycobacterium tuberculosis
3011
Mycobacterium tuberculosis, Pulmonary, definitive diagnosis proven by culture, without 
evidence of upper respiratory infection symptoms of Mycobacterium tuberculosis that 
could account for the positive culture.
3012
Mycobacterium tuberculosis, definitive diagnosis proven by culture, of at least one extra 
pulmonary site regardless of concurrent pulmonary involvement.
3013
Mycobacterium tuberculosis, Disseminated, definitive diagnosis proven by culture.
Mycobacterium avium intracellulare
3022
MAI in Blood, proven by culture.
3023
MAI Colitis, proven by histology and culture. (This does not include MAI of the stool 
alone).
3024
MAI, Disseminated, at a site other than or in addition to lungs or cervical or hilar lymph 
nodes, proven by culture.
Mycobacterium Kansasii, Mycobacterium Scrofulaceum and Other Atypical 
Mycobacterium
3032
M. Kansasii, in Blood, proven by culture.
3033
M. Kansasii Colitis, proven by histology and culture. (NOT including positive M. 
Kansasii of stool alone).
3034
M. Kansasii, Disseminated, at a site other than or in addition to lungs, or cervical or hilar 
lymph nodes, proven by culture.
3035
M. Scrofulaceum or other Atypical Mycobacterium, proven by culture.
Salmonella
3041
Salmonella, recurrent Bacteremia (non-typhoid), proven by culture.
Date: 28-Jan-2015
100
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
IV.
VIRAL INFECTIONS
Cytomegalovirus
4011
CMV, Pneumonitis, pathologically or histologically confirmed. Serum antibody titer and 
culture alone is not sufficient for the diagnosis.
4012
CMV, Esophagitis, as diagnosed by histology, pathology or culture of an esophageal 
lesion. Serum antibody titer and culture of other than esophageal tissue is not sufficient 
for the diagnosis.
4013
CMV, Retinitis as evidenced by a characteristic appearance on serial ophthalmoscopic 
examinations (eg, discrete patches of retinal whitening with distinct borders, spreading in 
a centrifugal manner, following blood vessels, progressing over several months, 
frequently associated with retinal vasculitis, hemorrhage, and necrosis). Resolution of 
active disease leaves retinal scarring and atrophy with retinal pigment epithelial mottling.
4014
CMV, Colitis, as diagnosed by histology, pathology or culture of a colonic lesion. Serum 
antibody titer and culture of other than colonic tissue is not sufficient for the diagnosis.
4015
CMV, Encephalitis, as diagnosed by histology, pathology or culture of brain tissue or 
CSF. Serum antibody titer and culture of other than brain tissue or CSF is not sufficient 
for the diagnosis.
Herpes Simplex (in patients > 1 month old).
4021
HSV, Disseminated (but not encephalitis alone), proven by microscopy (histology or 
cytology), culture or detection of antigen in a specimen obtained directly from affected 
tissues.
4022
HSV, Esophagitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4023
HSV, Bronchitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4024
HSV, Pneumonitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for diagnosis.
4025
HSV, GI, other than mouth, throat, or peri-rectal, as diagnosed by microscopy (histology 
or cytology), culture or detection of antigen in a biopsy specimen obtained directly from 
affected tissue. Serological measurement and culture from other than the affected tissue is 
not sufficient for diagnosis.
Date: 28-Jan-2015
101
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4026
HSV, Mucocutaneous, ulcers persisting for 1 month despite appropriate therapy, as 
diagnosed by microscopy (histology or cytology), culture or detection of antigen in a 
biopsy specimen obtained directly from affected tissue. Serological measurement and 
culture from other than the affected tissue is not sufficient for the diagnosis.
Progressive Multifocal Leukoencephalopathy
4041
Progressive Multifocal Leukoencephalopathy, proven by microscopy.
VI.
NEOPLASTIC DISEASES
Kaposi’s Sarcoma
6011
Kaposi’s sarcoma, Mucocutaneous, proven by microscopy.
6012
Kaposi’s sarcoma. Mucocutaneous, presumptive diagnosis with characteristic gross 
appearance and confirmed HIV infection.
6013
Kaposi’s sarcoma, Visceral.
6014
Kaposi’s sarcoma, other than above.
Lymphoma of the Brain
6021
Primary Lymphoma of the brain at any age, proven by microscopy.
Non-Hodgkins Lymphoma
6031
Small Non-cleaved lymphoma (either Burkitt or non-Burkitt type).
6032
Immunoblastic sarcoma, equivalent to any of the following, although not necessarily all 
in combination: Immunoblastic lymphoma, large-cell lymphoma, diffuse histocytic 
lymphoma.
Cervical Carcinoma
6041
Histologically proven invasive carcinoma of the cervix.
VII.
OTHER CONDITIONS
HIV Dementia/Motor Defects
7011
HIV Dementia, clinical findings of disabling cognitive and/or motor dysfunction 
interfering with occupation or activities of daily living progressing over weeks to months, 
in the absence of a concurrent illness or condition other than HIV infection that could 
explain the findings. Method to rule out such concurrent illnesses and conditions must 
include cerebrospinal fluid examination and either brain imaging (computed tomography 
or magnetic resonance) or autopsy.
Slim Disease or HIV Wasting Syndrome
7021
HIV Wasting Syndrome, findings of profound involuntary weight loss > 10% of baseline 
body weight plus either chronic diarrhea (at least two loose stools per day for 30 days) 
or chronic weakness and documented fever (for 30 days, intermittent to constant) in the 
Date: 28-Jan-2015
102
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
absence of a concurrent illness or condition other than HIV infection that could explain 
the findings (eg, cancer, tuberculosis, cryptosporidiosis, or other specific enteritis).
7061
Recurrent pneumonia, acute onset within 12 months of most recent episode.
Date: 28-Jan-2015
103
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 3
DAIDS TOXICITY GRADES
Date: 28-Jan-2015
104
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
105
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
106
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
107
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
108
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
109
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
110
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
111
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
112
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
113
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
114
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
115
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
116
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
117
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
118
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
119
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
120
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
121
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
122
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
123
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Date: 28-Jan-2015
124
1.0
Approved
1.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 4
COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE
Online calculator:
http://nephron.com/cgi-bin/CGSI.cgi
Manual calculation:
Male:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg)
72 x Serum Creatinine (mg/dL)
Female:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg) x 0.85
72 x Serum Creatinine (mg/dL)
1 pound = 0.4536 kilograms
Date: 28-Jan-2015
125
1.0
Approved
1.0
v
930087072


PPD


Page:
1
Protocol Number:
AI468048
IND Number:
118,936
Ex-US
Non-IND
EUDRACT Number
N/A
Date:
28-Jan-2015
Revised Date:
19-Mar-2015
CLINICAL PROTOCOL AI468048
A Phase 2b Randomized, Active-Controlled, Staged, Open-Label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without 
Ritonavir) in Treatment-Experienced HIV-1 Infected Adults
Revised Protocol Number: 01
Incorporates Amendment(s): 04
Study Director/Central Medical Monitor
 DO, MPH
5 Research Parkway
Office 201D
Wallingford, CT  06492 USA
Telephone (office): 
Fax: 
24-hr Emergency Telephone Number
USA:
International: 
Bristol-Myers Squibb Research and Development
Virology Clinical Research and Development
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
5 Research Parkway
Wallingford, CT 06492
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
2.0
Approved
2.0
v
930087072
PPD
PPD
PPD
PPD
PPD


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
2
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (eg, amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved. References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a 
copy of this revised protocol to all study personnel under your supervision, and archive the 
previous versions.
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 01
19-Mar-2015
Incorporates Amendment 04
Amendment 04
19-Mar-2015
Incorporated information that more clarify the Week 24 data (consisting of 
efficacy, safety, and pharmacokinetic data) to be used to confirm the doses 
for Stage 2 and to trigger the start of Stage 2 of the study relative to other 
analyses conducted under the protocol for other purposes.
Removed the requirement that all Sparse PK samples need to be collected 
as pre-AM dose samplings.  Only one visit Weeks 4- 24 (as opposed to all 
visits Weeks 4 - 24) needs to be performed in the morning and to have the 
blood collected as a pre-AM dose sampling; (includes the deletion of 
Table 5.5.2-1).
Administrative changes.
Original 
Protocol
28-Jan-2015
Not applicable
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
SYNOPSIS
Clinical Protocol AI468048
Protocol Title: A Phase 2b Randomized, Active-Controlled, Staged, Open-label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without Ritonavir) in 
Treatment-Experienced HIV-1 Infected Adults
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): Subjects in each arm and per stage will begin QD dosing (in the morning, with a meal) with 
BMS-955176 in combination with atazanavir (ATV) [with or without ritonavir (RTV)] and dolutegravir (DTG), or 
tenofovir (TDF) in combination with atazanavir boosted with ritonavir (ATV/r) and DTG, for a duration of 
96 weeks.
Stage 1:

Arm 1: BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Study Phase: 2b
Research Hypothesis: This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with 
or without RTV) and DTG is efficacious, safe, and well-tolerated in HIV-1 infected treatment-experienced adults.
Objectives:
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg and a TDF 300 mg-containing arm, each when given in 
combination with ATV/r 300/100 and DTG 50 mg by determining the proportion of treatment-experienced 
subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when given in 
combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the antiviral efficacy of TDF 300 mg 
when given in combination with and ATV/r 300/100 mg and DTG 50 mg by determining the proportion of 
treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms (TDF + ATV/r + DTG), 
by determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms, by determining the 
proportion of treatment-experienced subjects with plasma HIV-1 RNA < 200 c/mL at Weeks 24, 48, 96
Revised Protocol No.: 01
Date: 19-Mar-2015
4
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess the emergence of HIV drug resistance in samples selected for drug resistance testing (according to 
criteria outlined in Protocol Section 5.4.1)

To assess efficacy of BMS-955176 Arms, and the TDF-containing Arms, by using the mean changes from 
baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by measuring frequency 
of SAEs and AEs leading to discontinuation

To assess disease progression as measured
by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV (with or without 
ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
Study Design: This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced subjects total will be randomized into the study. In Stage 1, approximately 80 subjects 
will be randomized 1:1 (approximately 40 per arm) to either of the treatment arms containing BMS-955176 or TDF 
in combination with boosted atazanavir (ATV/r) and DTG. In Stage 2, approximately 120 subjects will be 
randomized 1:1:1 (approximately 40 per arm) to either of the two BMS-955176 treatment arms containing
unboosted ATV and DTG, or to the TDF-containing Arm containing ATV/r and DTG. The randomization in both 
Stages will be stratified by HIV-1 Clade (AE versus Other). The number of subjects with HIV-1 Clade AE will be 
capped at a maximum of approximately 3 per arm.
Stage 1:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
A Continuation Dose of BMS-955176 will be selected based on Week 24 data from Stage 1 and from study 
AI468038 (BMS-955176 in ARV treatment-naive HIV-1 infected subjects) with which subjects in Stage 1, Arm 1 
may transition to for the remainder of the study. The transition may occur on or after Week 48.
The data from the Week 24 analysis for AI468038 and Stage 1, including safety, efficacy and pharmacokinetics, will 
be examined to trigger the start of Stage 2 and confirm the two doses of BMS-955176 for study in Stage 2.
After the Stage 2 Week 24 endpoint, a Continuation Dose of BMS-955176 will be selected based on data from 
Stages 1 and 2, and study AI468-038 with which subjects in Stage 2, Arms 3 and 4 will transition to for the 
remainder of the study. The switch in Stage 2 may occur sooner, between Week 24 and Week 48, or it may be after 
Week 48.
The assigned backbone for each arm, ATV and DTG, or ATV/r and DTG, will remain unaltered throughout the 
study.
All subjects in both stages are expected to receive study treatment for 96 weeks.
Revised Protocol No.: 01
Date: 19-Mar-2015
5
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Arm 2
TDF
300 mg QD
+ ATV/r + DTG
Day 1
Begin dosing
Arm 3
BMS-955176 
120 mg QD
+ ATV + DTG
1 Virologic Futility will be evaluated at Week 24 
(see Section 8.4.7).  
Results of Week 24 Stage 1 AI468-048 & AI468-038 
Confirm the Start of Stage 2   
Arm 4
BMS-955176 
180 mg QD
+ ATV + DTG
40
40
Week 2
Week 24
Week 24 Analysis1
Intensive PK subset
4 Based on totality of data from both studies the 
Continuation Dose for Arms 3 & 4 may be 
identified.  
Number
Randomized
STAGE 2
Week 96
Week 96 Analysis/End of Study
Week 48
Week 48 Analysis
The Switch to the Continuation Dose4,3     
is expected to occur on or after Week 48, 
but could occur sooner.
Arm 1
BMS-955176 
120 mg QD
+ ATV/r + DTG
Week 2
Number
Randomized
Week 24
Week 24 Analysis1
Day 1
Begin dosing
Intensive PK subset
40
40
Week 48
Week 96
Week 48 Analysis
Week 96 Analysis/End of Study
The Switch to             
the Continuation Dose2,3
may occur on or after 
Week 48 
STAGE 1
BMS-955176
Continuation Dose QD 
+ ATV/r + DTG
Arm 5
TDF
300 mg QD
+ ATV/r + DTG
40
3 The actual switch of subjects of BMS-955176 
subjects to that Continuation Dose may occur when 
all of the subjects have reached at least Week 48 
(though it could occur sooner in Stage 2).
BMS-955176
Continuation Dose QD
+ ATV + DTG
2 Based on Week 24 data from Arms 1 & 2 and 
from AI468-038, the Continuation Dose for 
Arm 1 may be identified.  
Revised Protocol No.: 01
Date: 19-Mar-2015
6
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Population:
Key Inclusion Criteria:

Men and non-pregnant women, at least 18 years of age (or minimum age as determined by local regulatory or as 
legal requirements dictate)

Antiretroviral treatment-experienced, defined as having documented evidence of having failed 1 or 2 regimens 
that include 2 or 3 classes of ARV (with or without documented resistance)

Confirmed Plasma HIV-1 RNA 400 copies/mL

CD4+ T-cell count > 50 cells/mm3

Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, FC < 2.2; DTG; TDF)
Key Exclusion Criteria:

Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens

Resistance or partial resistance to any study drug

Three or more of the following PI mutations, historical or documented: M36I/V, M46I/L/T, G48M/V, 
I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M

Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S

Any major TDF mutation, historical or documented: K65R or T69ins

Three or more of the following non-accessory thymidine analogue mutations (TAMs): M41L, D67N, K70R, 
L210W, T215Y/F, K219Q/E

Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI resistance), historical or 
documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, Y143C/H/R, E157Q

Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV Ab and HCV RNA)

ALT or AST > 3 × ULN

Alkaline Phosphatase > 5 × ULN

Bilirubin 1.5 × ULN

History of decompensated cirrhosis or active decompensated cirrhosis

Hemoglobin < 8.0 g/dL

Platelets < 50,000 cells/mm3
Study Drug: includes both Investigational
[Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for AI468048
Medication 
Potency 
IMP/Non-IMP 
BMS-955176 
60 mg or 120 mga
IMP
Tenofovir (TDF)
300 mg
Non-IMP
Atazanavir (ATV)
200 mg and 300 mg
IMP
Ritonavir (RTV)
100 mg
Non-IMP
Revised Protocol No.: 01
Date: 19-Mar-2015
7
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Drug for AI468048
Medication 
Potency 
IMP/Non-IMP 
Dolutegravir (DTG)
50 mg
IMP and Non-IMP, based on 
country approval status
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Study Assessments: Efficacy assessments will include plasma HIV-1 RNA measurements. Safety Assessments will 
include blood chemistry and hematology, ECGs, Physical Exams and Vital Signs, and assessment of non-serious 
AEs, SAEs and AEs leading to discontinuation.
Statistical Considerations:
Sample Size:
This is an estimation study, without statistical testing, and hence there are no power considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere around 80%. With this 
response rate, and 40 subjects per arm, an exact 95% confidence interval would run from roughly 64% to 91%.
Endpoints:
Primary Endpoint(s) for Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24. This will be assessed with the FDA snapshot algorithm. This uses the last on-treatment plasma HIV-1 
RNA measurement, within an FDA-specified visit window, to determine response
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 RNA < 200 c/mL 
at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with positive response defined as HIV-1 
RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be assessed using the 
most recent version of the IAS-USA list of HIV-1 drug resistance mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the percentage of 
CD4+ T-cells will be assessed using on-treatment laboratory results, and pre-specified visit windows

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly from the case report 
forms (CRFs). The summary will count the number of subjects that have at least one event.

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from the CRFs. The 
summary will count the number of subjects that have at least one event.

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, collected at Week 2 
from a subset of subjects.
Analyses:
There are two interim analyses scheduled before the start of Stage 2.
The first interim analysis will be conducted after approximately 50% of the randomized subjects have completed
24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of SDTM (Study Data Tabulation Model) 
Revised Protocol No.: 01
Date: 19-Mar-2015
8
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
data (“level 1” data) to facilitate the development of models for: population pharmacokinetics; exposure-response 
relationships; and, as available, viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of therapy in Stage 1. 
This will be an analysis of the available efficacy, safety, resistance and pharmacokinetic data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well as the recruiting 
time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If Stage 2 is initiated, and recruiting 
follows projected timelines, then it is anticipated that analyses will be conducted when:

The last subject in Arms 3, 4 and 5 completes the Week 24 visit

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4 and 5 completes the Week 96 visit
Revised Protocol No.: 01
Date: 19-Mar-2015
9
2.0
Approved
2.0
v
930087072


TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Study Rationale ................................................................................................. 
1.1.1 Rationale to support study design ............................................................ 
1.1.2 Rationale to support the dose selection ................................................... 
1.1.3 Rationale to support any drug combinations ........................................... 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objective .................................................................................... 
1.3.2 Secondary Objectives ............................................................................... 
1.3.3 Exploratory Objectives ............................................................................ 
1.4 Product Development Background ................................................................... 
1.4.1 Background Information BMS-955176 .................................................... 
1.4.1.1 Mechanism of Action....................................................................... 
1.4.1.2 Nonclinical studies .......................................................................... 
1.4.1.3 Clinical studies................................................................................ 
1.4.2 Background Information on TDF ............................................................ 
1.4.3 Background Information on DTG ............................................................ 
1.4.4 Background Information on ATV ............................................................. 
1.4.5 Background Information on RTV ............................................................. 
1.4.6 Drug-Drug Interactions ........................................................................... 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.1.1 Screening.................................................................................................. 
3.1.2 Day 1/Baseline Visit ................................................................................. 
3.1.2.1 Day 1/Baseline Visit for Arms 1 and 2 - Stage 1 ............................ 
3.1.2.2 Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2 ........................ 
3.1.3 Week 2 Intensive PK Visit ........................................................................ 
3.1.4 Visits Week 4 - 96 ..................................................................................... 
3.1.5 Selection of the Continuation Dose of BMS-955176 ............................... 
3.1.5.1 Selection of the Continuation Dose, and the Switch for Stage 1 .... 
3.1.5.2 Selection of the Continuation Dose, and the Switch for Stage 2 .... 
3.1.6 End of the study ........................................................................................ 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
1
3
4
10
14
14
14
16
19
21
21
21
21
22
22
22
22
23
28
31
31
31
32
32
32
35
35
36
36
37
37
38
38
38
38
39
39
40
40
40
41
43
43
43
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
10
2.0
Approved
2.0
v
930087072


3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Other Restrictions and Precautions ......................................................... 
3.5 Discontinuation of Subjects following any Treatment with Study Drug .......... 
3.6 Post Study Drug Study Follow up .................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Instructions for Dose Administration ...................................................... 
4.5.1.1 General Instructions ....................................................................... 
4.5.1.2 Specific Dosing Instructions for Initial Treatment Arm Assignment
...............................................................................................................
4.5.2 Dose Modifications .................................................................................. 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Vital Signs and Physical Examinations ................................................... 
5.3.2 Adverse Events ......................................................................................... 
5.3.3 Concomitant Medication Assessment ...................................................... 
5.3.4 Electrocardiograms ................................................................................. 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.1.1 Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing .................................................................................. 
5.4.1.2 Protocol Defined Virologic Failure ................................................ 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.4.2.1 CD4+ and CD8+ T-Cells ............................................................... 
5.4.2.2 Drug Resistance Testing ................................................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.5.1 Intensive Pharmacokinetic Assessment .................................................... 
5.5.2 Sparse Pharmacokinetic Assessments ...................................................... 
5.6 Biomarker Assessments .................................................................................... 
5.7 Outcomes Research Assessments ..................................................................... 
45
46
47
47
47
47
48
48
48
49
51
51
51
51
52
52
52
52
53
53
53
53
54
55
55
61
61
62
62
62
62
62
62
62
63
64
64
64
64
64
64
65
66
66
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
11
2.0
Approved
2.0
v
930087072


5.8 Other Assessments ............................................................................................ 
5.9 Results of Central Assessments ........................................................................ 
6 ADVERSE EVENTS ................................................................................................. 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) ..................................................... 
6.7 Other Safety Considerations ............................................................................. 
6.7.1 Toxicity Management ............................................................................... 
6.7.1.1 Management of Elevations in Liver Transaminases ....................... 
6.7.1.2 Management of Renal Toxicity ....................................................... 
6.7.1.3 Management of Hyperbilirubinemia ............................................... 
6.7.1.4 Gastrointestinal Toxicity Evaluation and Management Plan ......... 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s)Stage 1 and Stage 2 ................................................. 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Primary Efficacy Analyses .............................................................. 
8.4.2.2 Secondary Efficacy Analyses .......................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.4.1 Sparse Pharmacokinetic Analyses .................................................. 
8.4.4.2 PK/PD and PK/VK Analyses .......................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Other Analyses (including Virologic Futility) ......................................... 
8.5 Interim Analyses ............................................................................................... 
9 STUDY MANAGEMENT ........................................................................................ 
9.1 Compliance ....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
67
67
68
68
69
70
70
70
71
71
72
72
72
72
73
73
73
75
75
75
75
76
76
76
76
77
77
77
78
78
78
79
79
79
79
79
79
80
80
80
81
81
81
82
82
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
12
2.0
Approved
2.0
v
930087072


9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10 GLOSSARY OF TERMS ........................................................................................ 
11 LIST OF ABBREVIATIONS .................................................................................. 
12 REFERENCES ........................................................................................................ 
APPENDIX 1 LISTINGS OF PROHIBITED AND PRECAUTIONARY 
THERAPIES ........................................................................................................... 
APPENDIX 2 AIDS-DEFINING DIAGNOSES.......................................................... 
APPENDIX 3 DAIDS TOXICITY GRADES .............................................................. 
APPENDIX 4 COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE .................................................................................... 
82
83
83
85
86
93
97
99
105
126
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
13
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
1
INTRODUCTION AND STUDY RATIONALE
1.1
Study Rationale
Despite advances in prevention and care, HIV/AIDS remains a significant epidemic in both the 
US and worldwide. AIDS remains the 6th leading cause of death, internationally. Globally, 
approximately 35 million people were living with HIV infection in 2013.1 A number of these 
patients include those who are treatment-experienced. Note: the use of the term 
“treatment-experienced” herein refers to subjects who have failed at least one or two 
antiretroviral (ARV) regimens and who may be harboring drug resistant virus (current or 
archived) to at least one drug class.
In contrast to current HIV treatment guidelines for treatment-naïve patients, the recommended 
composition of combination
antiretroviral therapy (cART) is far less uniform for 
treatment-experienced subjects.2,3 The level of detail in the DHHS and EACS guidelines leads to 
a lack of uniformity in treatment for patients in later lines of therapy. Moreover, drug related 
toxicities (both short and longer term) in treatment-experienced subjects necessitate vigilance 
and continued monitoring. Thus, there is a need for new and efficacious agents with novel 
mechanisms of action (MOA) and favorable safety/tolerability profiles. Given the aging HIV-1 
infected population and overall fewer number of ARV options for treatment-experienced 
patients, there is a need for a more simplified regimen that may have a better long-term safety 
profile such as that of a nucleoside- and booster-sparing cART regimen. As discussed below, this 
study 
evaluates 
the 
merits 
of 
a 
nucleoside-sparing 
cART 
regimen 
and 
a 
nucleoside/booster-sparing cART regimen in Stage 1 and 2, respectively.
Given the aforementioned challenges with existing treatment in ARV treatment-experienced 
adults, the two primary objectives of this two stage, Phase 2b study are to: 1) To study the 
efficacy of one dose (120 mg) of BMS-955176 (a novel HIV-1 maturation inhibitor) when given 
in combination with atazanavir boosted with ritonavir (ATV/r) 300/100 mg and dolutegravir 
(DTG) 50 mg in Stage 1, and 2) to study the efficacy of two doses (120 and 180 mg) of 
BMS-955176 when given in combination with unboosted ATV 400 mg and dolutegravir (DTG) 
50 mg in Stage 2.
Ultimately this Phase 2b clinical trial will provide supportive data in the context of a therapeutic 
dose of BMS-955176 and the clinical safety/efficacy/resistance of the proposed component(s) of 
a single tablet regimen (STR, that is also a nucleoside/ritonavir sparing ARV strategy) for 
Phase 3 trial development in HIV-1 infected treatment-experienced subjects. Specifically, two 
arms in Stage 2 will contain the individual ARV components of a potential STR: BMS-955176, 
ATV, and DTG.
1.1.1
Rationale to support study design
This Phase 2b open-label clinical trial design is in general agreement with published Food and 
Drug 
Administration 
(FDA)
guidance.4
Initially,
in 
Stage 
1, 
approximately 
80 treatment-experienced HIV-1 infected subjects will be randomized 1:1 (approximately 40 per 
treatment group) to one experimental arm (Arm 1) and a TDF-containing arm (Arm 2) 
Revised Protocol No.: 01
Date: 19-Mar-2015
14
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
(see Figure 3.1.6-1) to accomplish this study’s Stage 1 primary study objective: to study the 
efficacy of one dose (120 mg) of BMS-955176 when given in combination with ATV/r 
(300/100 mg) and DTG (50 mg). At the Week 24 primary endpoint of Stage 1 and AI468038, 
Bristol-Myers Squibb (BMS) will conduct an analysis of efficacy, safety, and pharmacokinetics; 
this analysis will be used to select a continuation dose for BMS-955176 in Arm 1 of study 
AI468048, trigger the start of Stage 2 of study in AI468048, and confirm the two doses of 
BMS-955176 for study in Stage 2 of study AI468048. Note, AI468038 is a concurrent Phase 2b 
study in HIV-1 infected treatment naive adults; the primary objective is to evaluate three doses 
of BMS-955176 (60, 120, and 180 mg) and EFV when given in combination with TDF/FTC by 
determining the proportion of subjects with HIV-1 RNA < 40 c/mL at Week 24.
To mitigate the clinical concerns of a potential subtherapeutic regimen and the subsequent 
development of virologic failure/resistance, the clinical trial design will contain a second stage. 
Specifically in Stage 2, approximately 120 additional treatment-experienced HIV-1 infected 
subjects will begin randomization 1:1:1 (approximately 40 per treatment group) to Arms 3, 4,
and 5 based upon the results of two concurrent analyses:

Results of the Week 24 analysis in Stage 1, including an analysis for virologic futility (see 
Section 8.4.7)

Results of the Week 24 analysis in AI468038 (treatment-naïve HIV-1 infected adults)
Thus, Stage 2 (Arms 3, 4, and 5) will not enroll if the likelihood of a subtherapeutic regimen 
(in Arms 3 and 4) is high based upon the results of the Week 24 analyses from either AI468038 
or Stage 1 of AI468048. Note, subjects in Arm 5 (Stage 2) will receive the same ARV regimen 
as subjects in Arm 2 (Stage 1); Arm 5 in Stage 2 exists to maintain similar baseline demographic 
and clinical characteristics among subjects who are randomized to the three Arms in Stage 2. 
This staged design allows Stage 2 (Arms 3, 4, and 5) to begin recruitment in a clinically 
de-risked fashion and accomplish this study’s Stage 2 primary study objective: to study the 
efficacy of two doses (120 mg and 180 mg) of BMS-955176 when given in combination with 
unboosted ATV 400 mg and DTG 50 mg. Ultimately, the totality of data from the Week 24 
primary endpoint of Stage 2 (Arms 3, 4, and 5), Stage 1 (Arms 1 and 2), and all arms in the 
AI468038 study will be used to select a continuation dose for BMS-955176 in Arms 3 and 4 of 
study AI468048. Across all five arms of this study, subjects will receive treatment with three 
fully-active ARVs (see Section 1.1.3, Rationale to support any drug combinations). Ultimately, 
subjects in experimental Arms 1, 3, and 4 will be given a continuation dose of BMS-955176 
which has acceptable efficacy, safety, and tolerability (see Figure 3.1.6-1) for subsequent 
development in HIV-1 treatment-experienced adults. 
In a recent clinical trial approximately 95% of randomized subjects were noted to be infected 
with HIV-1 clades B, C, and AE.5 Based on in-vitro studies, BMS-955176 is expected to be 
active against a variety of clades albeit with EC50s approximately 2-3 fold less toward HIV-1 
clade AE compared to clade B (see Section 1.4.1). Since the Phase 2a study AI468002 did not 
include any subjects infected with HIV-1 clade AE (see Section 1.4.1.3), this multinational 
Revised Protocol No.: 01
Date: 19-Mar-2015
15
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Phase 2b trial will stratify randomization to ensure each treatment arm has approximately the 
same number of HIV-1 clade AE infected subjects in their respective Stages and cap the number 
of HIV-1 clade AE subjects to a maximum of approximately 3 per treatment arm. The study 
duration is expected to be 96 weeks in length to assess durability of response and longer term 
safety and tolerability.
1.1.2
Rationale to support the dose selection
Phase 1 and Phase 2a clinical trials (AI4680016 and AI4680027) investigating BMS-955176 
utilized a spray-dried dispersion (SDD) suspension. However, this Phase 2b study will utilize a 
micronized crystalline (MC) tablet.
In the concomitant dose-finding Phase 2b study in HIV-1 infected treatment naive adults for 
BMS-955176 (AI468038), doses of BMS-955176 of 60 mg, 120 mg, and 180 mg MC tablet are 
proposed for assessment. These doses are based upon modeling and simulation and formulation 
considerations. A population pharmacokinetic model was developed using single dose 
(10 mg - 120 mg SDD) and multiple dose (10 mg to 80 mg SDD) data in healthy subjects 
(AI468001) as well as multiple dose data in HIV-1 clade B-infected subjects (5 mg to 120 mg
SDD for 10 days, AI468002). An exposure-response analysis was conducted using data from 
Part A of the Phase 2a clinical trial where HIV-1 clade B infected subjects received 
BMS-955176 monotherapy (Dose range: 5 - 120 mg) for 10 days. The exposure-response 
relationship was assessed via an Emax model using observed BMS-955176 steady state Cmin. The 
primary endpoint was predicted maximum viral load decline from baseline.
Steady state BMS-955176 Cmin values in HIV-infected subjects administered MC tablet with 
food were projected according to the following data and assumptions:

Exposures in HIV-infected subjects are 35% less than normal healthy volunteers based on 
observations from AI468001 and AI468002 study

Single dose data projected to multiple dose using accumulation index from AI468001 study

BMS-955176 exposures from the MC tablet formulation with food were projected based on 
studies AI468001 and AI468034. The impact of food on the 60 mg MC tablet dose was 
assumed to be that observed for the 40 mg MC suspension formulation in AI468001. 
Exposures to BMS-955176 120 mg MC tablet with food were determined from observed data 
in Study AI468034, where BMS-955176 C24 increased approximately 70% when 120 mg 
MC tablet was given with a high fat meal, relative to fasted conditions. Finally, exposures to 
BMS-955176 180 mg MC tablet with food were assumed to be 1.5-times that of 120 mg MC 
tablet with food
Figure 1.1.2-1 depicts the simulated maximum viral load decline in HIV-infected subjects 
administered BMS-955176 MC tablet under fed conditions.
Revised Protocol No.: 01
Date: 19-Mar-2015
16
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 1.1.2-1:
Simulated Maximum Viral Load Decline from Baseline Under Fed 
Conditions1
1 Solid lines are 10th and 90th percentiles and the median of simulated data, shaded area is the 90% confidence 
interval of simulated data, vertical solid lines are the 25th to 75th percentile of the simulated steady state 
BMS-955176 Cmin for the 60 mg MC tablet dose, vertical dotted lines are the 25th to 75th percentile of the 
simulated steady state BMS-955176 Cmin for the 120 mg MC tablet dose, and vertical dashed and dotted lines 
are the 25th to 75th percentile of the simulated steady state BMS-955176 Cmin for the 180 mg MC tablet dose.
While baseline EC90 was not a covariate included in the model due to the lack of significance; 
this covariate, among others, was considered marginally significant and it is possible this 
covariate will become important with additional data.
Although data from AI468002 Part C (in HIV-1 clade C infected subjects) were not included in 
the exposure-response assessment described above, BMS-955176 doses 40 mg SDD once daily 
demonstrated median maximal reductions in HIV-1 RNA > 1 log10 in both clade B and clade C 
HIV-1-infected subjects (see Section 1.4.1.3); thus, doses of BMS-955176 60 mg, 120 mg, and 
180 mg are expected to yield a similar response in HIV-1 infected subjects of either clade.
Because the lowest dose assessed in AI468038 (BMS-955176 60 mg) has the potential for a 
suboptimal antiviral response and possible development of resistance, BMS-955176 120 mg in 
combination with ATV/r and DTG will be assessed in Stage 1 of this study. Based on previous 
data that demonstrated exposures to BMS-955176 increase approximately 50% when given in 
combination with RTV, exposures to BMS-955176 120 mg given in combination with ATV/r are 
expected to result in exposures similar to BMS-955176 180 mg given without RTV. Finally, 
BMS-955176 180 mg will not be used in Stage 1 because exposures (when administered with 
RTV) are expected to exceed those previously studied in clinical trials.
Revised Protocol No.: 01
Date: 19-Mar-2015
17
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.1.2-1 depicts the projected exposure multiples of BMS-955176 60 mg, 120 mg, and 
180 mg MC tablet with food at the NOAEL for pre-clinical findings of interest.
Table 1.1.2-1:
Exposure Multiples of BMS-955176 at NOAELa
Species/ Study 
NOAEL
Multiples
Dose 
(mg/kg/d)
Exposure
PK 
Parameter
60 mg
120 mg
180 mg
Rat/6-month (stomach 
histologic changes) 
No NOAEL
AUC
---
---
---
Dog/9-month (stomach 
histologic changes) 
1
AUC:
64.9 gh/mL
AUC 
3
2
1
Dog/1-month (heart rate)
20
Cmax:
17.8 g/mL 
Cmax
19
10
5
Dog/ Cardiovascular 
telemetry (heart rate) 
2
Cp:
1.93 g/mL 
Cmax
2
1
0.5
Mouse/EFD 
45
AUC:
197 gh/mL 
AUC
10
6
3
a Exposure multiple = animal value ÷ human value. Projected human Cmax values are 0.94, 1.79, and 3.61 g/mL 
and steady state AUC values are 19.3, 35.8, and 69.2 g•h/mL at 60, 120, and 180 mg in HIV-1 subjects 
receiving BMS-955176 MC tablets with high fat meal, respectively. High fat meal provides the highest exposure 
relative to other meal types or fasted state.
With regard to heart rate and the NOAEL of 1.93 g/mL observed in the cardiovascular 
telemetry study in dogs (N=2), it is noted that the projected exposure multiple is 1 at a dose of 
120 mg MC tablet in HIV-infected subjects. However, to date, there have been no clinically 
meaningful changes in heart rate observed in subjects treated with BMS-955176 up to 28 days
(in Part B of the Phase 2a study). With regard to stomach histologic changes, no NOAEL could 
be established based on the 6-month rat study and the projected exposure multiples from the 
9-month dog study are relatively low (eg, 2-fold at the 120 mg MC tablet dose). Despite these 
preclinical findings, a dose of BMS-955176 120mg MC tablet will provide exposures in this 
study which are expected to be generally safe and well tolerated based on existing clinical data 
(see Section 1.4.1).
Data from Study AI468034 demonstrated that BMS-955176 120 mg MC tablet AUC increased 
53% when given with a high fat meal, relative to fasted conditions. Furthermore, preliminary 
data from Study AI468049 demonstrated that a light meal, a standard meal, and a high fat meal 
increased BMS-955176 180 mg MC tablet AUC 1.8-, 2.1-, and 2.5-fold, respectively, relative to 
fasted conditions. Taken together, these data suggest that exposures to BMS-955176 MC tablet 
at doses up to 180 mg increase in a linear fashion when given with food and that similar 
exposures are observed regardless of meal type.
Revised Protocol No.: 01
Date: 19-Mar-2015
18
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In total, BMS-955176 120 mg is expected to be safe, well-tolerated, and efficacious in Stage 1 
and will inform the selection of a Stage 1 continuation dose and aspects of Stage 2 (as described 
in detail within Section 1.1.1).
The doses of BMS-955176 in Stage 2 will be confirmed based upon the Week 24 analyses
(efficacy, safety, and pharmacokinetics) of both Stage 1 and Study AI468038. As described in 
this protocol, the doses in Stage 2 are proposed to be BMS-955176 120 mg and 180 mg in Arms 
3 and 4, respectively.
1.1.3
Rationale to support any drug combinations
This study co-administers BMS-955176, with unboosted ATV 400 mg QD or ATV/r 300/100 mg
QD, and DTG 50 mg. The drug combinations within this clinical trial design will provide 
supportive data in the context of a therapeutic dose of BMS-955176 and the clinical 
safety/efficacy/resistance of the proposed components (Stage 2, Arms 3 and 4) of a single tablet 
regimen (STR) for Phase 3 trial development. Ultimately, BMS will seek approval of
BMS-955176 for use in treatment-experienced HIV-1 infected adults (including either a STR; 
FDC; and/or monoentity). 
The rationale for using a backbone of ATV and DTG in this treatment-experienced patient 
population is based upon established safety, efficacy, and tolerability of the individual 
components. DTG alone provides a 2.46 log10 c/mL reduction in HIV-1 RNA when administered 
as monotherapy for 10 days.8 Furthermore, DTG has been recently approved and is generally 
safe.9,10,11,12,13 Lastly, ATV/r is often used in treatment-experienced adults’ second-line therapies 
or beyond (for example, in individuals who may have failed an non-nucleoside reverse 
transcriptase inhibitor (NNRTI) and/or integrase inhibitor (INI) based regimen).2,4
This Phase 2b design allows treatment-experienced adults in the experimental Arms to be 
exposed to three fully active ARVs (from three classes). Subjects will benefit from each ARV 
(except
RTV) independently providing a > 1 log10
c/mL decrease in HIV-1 RNA
(see Section 1.4.1.3 for details on Phase 2a results [AI468002]). BMS expects the combination of 
two agents (unboosted ATV and DTG) with one investigational agent (BMS-955176) to provide 
a generally improved safety/tolerability profile relative to the respective arm containing ATV/r 
(Arms 3 and 4 relative to Arm 1, respectively) or TDF (Arms 3 and 4 relative to Arm 5, 
respectively).
There is a potential risk of a subtherapeutic regimen to treatment-experienced subjects enrolled 
in Arms 3 and 4 since unboosted ATV is only approved for use in treatment-naïve HIV infected 
adults (within the US) and the therapeutic dose of BMS-955176 has not been established.
Unboosted ATV (400 mg) in treatment-naïve adults results in a 1.41 log10 c/mL reduction in 
HIV-1 RNA after two weeks of monotherapy.14 Despite the monotherapy based reduction in 
HIV-1 RNA, pharmacokinetic data of unboosted ATV in prospective clinical trials,15
cross-sectional,16 and retrospective analyses17 generally supports the finding of DHHS defined 
subtherapeutic ATV levels (< 150 ng/mL) in patients.18
Revised Protocol No.: 01
Date: 19-Mar-2015
19
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In a randomized, open-label clinical trial, ATV/r has demonstrated non-inferiority to unboosted 
ATV (TLVOR: 75% vs 70% VR-OC: 87% vs 76%, respectively), similar declines in HIV-1 
RNA (approx -3.1 log10 c/mL), and increase in CD4 cell counts within treatment-naïve adults. 
However, the unboosted ATV arm had an increased number of subjects with emerging ATV and 
lamivudine (3TC) resistance. In particular, the difference in nucleoside/nucleotide reverse 
transcriptase inhibitor (NRTI) resistance was markedly greater in the unboosted ATV compared 
to RTV boosted ATV arm.19 Of note, in this clinical trial (AI468048) NRTIs are not used in the 
experimental Arms 1, 3, and 4. Similar single arm, prospective studies have replicated the viral 
efficacy and immunologic response using unboosted ATV in treatment-naïve HIV infected 
adults.20
Insights from limited data regarding the use of unboosted ATV in treatment-experienced adults 
have demonstrated a viral decay ranging from -1.4 to -2.7 log10 c/mL over 24 weeks of therapy 
in combination with NRTIs (such as TDF, 3TC, and didanosine).21 Also, observational data 
(mean: 24 months of follow-up) has shown similar percentages of subjects with their last HIV 
RNA being undetectable (80% vs 83%) after receiving unboosted and RTV boosted ATV, 
respectively.22
Taking the key findings from studies of ATV in both treatment-naïve and treatment-experienced 
HIV infected adults, Arms 3 and 4 containing unboosted ATV may have the potential for 
increased resistance (relative to Arm 1 containing RTV boosted ATV) and the development of 
virologic failure. However, several other factors must be taken into consideration. First, these 
Arms will use three potent (> 1 log10
c/mL) ARVs in combination. Moreover, 
treatment-experienced subjects who have failed one or two prior regimens are likely to be either 
naïve to ATV treatment (prior NNRTI- and/or INI-class failure) or will need to be fully 
susceptible to approved ARVs (including unboosted ATV, see Section 3.3.2). Second, both the 
combination of ATV and DTG with BMS-955176 independently have demonstrated additivity to 
synergy in-vitro23 (see Section 1.4.1.3 for clinical data on the combination of ATV and 
BMS-955176). Third, unboosted ATV increases the geometric mean ratio of Ctrough for DTG by 
a factor of 2.8.24 Fourth, in normal healthy volunteers, multiple dose administration of 
BMS-955176 40 mg (SDD suspension formulation) with ATV 400 mg for 14 days resulted in an 
approximate 25% increase in the AUC(TAU) of BMS-955176 administration alone25 and 
preliminary PK data from the Phase 2a (AI468002) demonstrated that BMS-955176 AUC(TAU) 
increased approximately 37% and 52% when ATV was combined with BMS-955176 40 and 
80 mg (SDD suspension formulation), respectively, relative to administration of BMS-955176 
alone. It is clinically unclear whether higher exposures of DTG and BMS-955176 would lead to 
a decreased incidence of unboosted ATV resistance in the context of Arms 3 and 4 
(BMS-955176 120 and 180 mg + ATV + DTG). Combined with these factors, BMS proposes to 
mitigate the potential risk of increased resistance by 1) studying two doses of BMS-955176 
(120 and 180 mg) in combination with unboosted ATV and DTG, and 2) using a two stage 
clinical trial design with Stage 2 (Arms 3, 4, and 5) enrolling after the Week 24 analysis
(efficacy, safety, and pharmacokinetics) of Stage 1 (Arms 1 and 2) and AI468038 are completed, 
and 3) only enrolling subjects who are susceptible to study medication (including unboosted 
Revised Protocol No.: 01
Date: 19-Mar-2015
20
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
ATV) (see Section 1.1.1, Rationale to support study design). This risk mitigation is employed to
increase the probability of establishing clinical efficacy (number of responders at the Week 24) 
in treatment-experienced HIV-1 infected adults.
BMS expects BMS-955176 120 and 180 mg given with unboosted atazanavir to be generally 
safe and well-tolerated. Subjects in Arms 3 and 4 treated with unboosted ATV would potentially 
benefit from a more favorable lipid profile, fewer gastrointestinal (GI) side effects, and 
decreased indirect hyperbilirubinemia. In total, the potential clinical risks for subjects 
randomized to Arms 3 and 4 in Stage 2 do not outweigh the potential benefits of a Nucleoside-
and Booster-sparing cART regimen that may offer both efficacy and long-term safety (including 
but not limited to improved bone mineral density, improved renal function, and improved lipid 
profile). Please see Section 1.5 for further details on the overall risk/benefit assessment.
1.2
Research Hypothesis 
This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with or 
without RTV)
and DTG
is efficacious, safe, and well-tolerated
in HIV-1 infected 
treatment-experienced adults.
1.3
Objectives(s)
1.3.1
Primary Objective
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg, and a TDF 300 mg-containing arm,
each when given in combination with ATV/r 300/100 mg and DTG 50 mg by determining 
the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when 
given in combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the 
antiviral efficacy of TDF 300 mg when given in combination with ATV/r 300/100 mg and 
DTG 50 mg by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
1.3.2
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms (TDF + 
ATV/r + DTG), by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms, by 
determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA 
< 200 c/mL at Weeks 24, 48, 96

To assess the emergence of HIV drug resistance in samples selected for drug resistance 
testing (according to criteria outlined in Section 5.4.1)
Revised Protocol No.: 01
Date: 19-Mar-2015
21
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess efficacy of BMS-955176 Arms, and the TDF-containing Arms, by using the mean 
changes from baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ 
T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by 
measuring frequency of SAEs and AEs leading to discontinuation

To assess disease progression as measured by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV 
(with or without ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
1.3.3
Exploratory Objectives

To determine the effect of BMS-955176 Arms, and the TDF-containing Arms, on renal 
clinical parameters and biomarkers through Weeks 48 and 96

To determine the effect of BMS-955176 Arms, and the TDF-containing Arms, on bone 
biomarkers through Weeks 12 and 24

To assess the impact of baseline (pre-therapy) Gag polymorphisms on the efficacy of 
BMS-955176 Arms by determining the proportion of treatment-experienced subjects with 
plasma HIV-1 RNA < 40 c/mL, HIV-1 RNA < 200 c/mL, and the changes from baseline in 
log10 HIV-1 RNA at Weeks 24, 48 and 96, by baseline polymorphisms

To characterize the steady-state plasma PK of DTG when co-administered with BMS-955176 
and ATV (with or without RTV) in treatment-experienced subjects. The effect of 
BMS-955176 on DTG PK in the presence of ATV (without RTV) may be assessed relative to 
historical data

To compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV

To characterize the PK of ATV when co-administered with DTG and BMS-955176, with or 
without RTV

To explore PK/PD and PK/viral kinetic (VK) relationships between BMS-955176, ATV, 
and/or DTG exposure and both efficacy and safety endpoints

To assess the impact of the study therapies on health-related quality of life measures
1.4
Product Development Background
1.4.1
Background Information BMS-955176
1.4.1.1
Mechanism of Action
BMS-955176 is an HIV-1 maturation inhibitor (MI), a novel class of anti-HIV-1 drugs that 
prevents the maturation of HIV-1 virions by binding near a key structural element within the Gag 
polyprotein that is required for virion maturation and assembly. Maturation inhibitors block the 
last protease cleavage event between Gag protein segments designated as capsid (CA) protein 
p24 (p24) and spacer peptide 1 (SP1), resulting in the release of immature noninfectious virus 
particles. BMS-955176 has excellent potency and broad spectrum activity, and mechanism of 
Revised Protocol No.: 01
Date: 19-Mar-2015
22
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
action studies indicate that BMS-955176 is a true MI, with a mechanism of action distinct from 
current antiretroviral agents.26 Development of BMS-955176 could potentially lead to novel 
HIV-1 treatment regimens in treatment-experienced HIV-1 patients.
1.4.1.2
Nonclinical studies
Nonclinical Pharmacology and Microbiology
BMS-955176 specifically inhibits HIV-1 protease cleavage at the CA(p24)/SP1 junction within 
the Gag protein in both HIV-1-infected cells and purified HIV-1 Gag virus-like particles (VLPs). 
Radiolabeled BMS-955176 specifically binds to purified HIV-1 Gag VLPs, and its binding is 
dose-dependently inhibited by related MIs and is reversible. BMS-955176 does not directly 
inhibit HIV-1 protease nor bind to a small HIV-1 protease peptide substrate. These results 
indicate that BMS-955176 inhibits late in the HIV-1 life cycle by specific binding to immature 
capsid structures at or near the CA(p24)/SP1 junction, thereby inhibiting cleavage at that 
particular site. In cell culture, the range of values for the concentration producing 50% effect 
(EC50) of BMS-955176 against 7 common laboratory strains of HIV-1 was 1.6 to 10.5 nM 
(mean = 6.0 3.5 nM). Using a reverse transcriptase readout, a phenotyping analysis of 
93 subtype B viruses whose genotypes are representative of 96% of the diversity (found in the 
Los Alamos National Laboratory [LANL] database) in Gag sequences indicates that the mean 
EC50 of this cohort was 2.7 1.9 nM, with a median value of 2.2 nM and a range between 0.6 to 
12 nM. A similar analysis of 23 isolates of subtype C viruses found a mean EC50 of 
6.1 3.1 nM, a median value of 5.6 nM, and a range from 2.5 to 16 nM. When evaluated against 
clinical isolates in peripheral blood mononuclear cells (PBMCs), BMS-955176 exhibited a mean 
EC50 of 24 24 nM against a cohort (N = 22) of subtype B viruses. Activity was also observed 
against viruses from subtypes A, C, D, F, and G, with average EC50 values for 96% of tested 
isolates (N = 41) between 5.9 and 87 nM. Clinical isolates from the CRF01_AE subtype were 
approximately 2- to 3-fold less susceptible to BMS-955176 (average EC50 77 nM, N = 7) 
viruses. BMS-955176 was active against 1 of 3 human immunodeficiency virus type-2 (HIV-2)
isolates (EC50 = 15 nM). BMS-955176 retains complete activity against reverse transcriptase 
(RT), protease, and integrase inhibitor-resistant viruses, with EC50 values similar to wild-type 
(wt) viruses, while the potency of currently approved nucleotide/nucleoside reverse transcriptase 
inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors 
(PIs), and integrase inhibitors (INIs) was undiminished when tested against viruses with reduced 
susceptibility to BMS-955176. BMS-955176 maintained activity against a panel of PI-resistant 
isolates from PI-treated subjects harboring a variety of major and minor PI-resistance
determinants in both protease and Gag.27,28 Protein binding to 100% human serum (HS) was 
86%, and in the presence of 40% HS supplemented with additional human serum albumin 
(HuSA) to match physiologic concentrations, BMS-955176 exhibited an approximately 4-fold 
reduction of antiviral activity. Selection for resistance to BMS-955176 in cell culture identified
changes that map to amino acids adjacent to the CA(p24)/SP1 cleavage site. These include an 
amino acid substitution of A364V or a combination of V362I with secondary changes (V370A, 
A374P or I376V). In vitro, virus with the A364V change exhibited a drastic loss of susceptibility 
to BMS-955176 (>100-fold), while the V362I plus secondary change-containing viruses were 
Revised Protocol No.: 01
Date: 19-Mar-2015
23
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
generally less sensitive to BMS-955176 (median EC50 25 nM, range 7.1 to 167 nM). In 2-drug 
combination studies with representative drugs from NRTI, NNRTI, PI, and INI classes, all 
combinations produced additive to synergistic effects, suggesting that BMS-955176 should be 
amenable for use in combination with any of these agents.
Bevirimat (BVM), a first-generation MI, demonstrated proof of concept and dose-dependent 
anti-HIV-1 potency in both Phase 1 and Phase 2 clinical studies. Patients infected with HIV-1 
sensitive to BVM demonstrated an approximate 1.2 log10 decline in HIV-1 RNA. However, 
approximately 50% of patients harboring naturally occurring polymorphisms located close to the 
CA(p24)/SP1 cleavage site showed a significantly reduced response to BVM treatment. In 
addition, BVM exhibited a large reduction in antiretroviral activity in the presence of human 
serum. BMS-955176 was developed to address the key flaws of BVM by providing improved 
coverage of BVM-resistant polymorphic variants and improved potency in serum. BMS-955176 
has been shown to be active against viruses with resistance from all marketed ARVs, and to 
possess a low serum effect. Development of BMS-955176 could potentially lead to novel HIV-1 
treatment regimens in treatment-experienced HIV-1 patients.
Nonclinical Pharmacokinetics
The absolute oral bioavailability of BMS-955176 was low (3.89% to 26.8%) in all preclinical 
species (mice, rats, dogs, and monkeys). In the dog, though there was a positive food effect and 
no pH dependent absorption, upon repeat dosing a less than dose-proportional increase in 
exposure was observed. BMS-955176 distributed preferentially into the duodenum, liver, and 
lymph nodes with little penetration into the brain. Protein binding was 86.1% in human serum 
and 78% to 94% in animal sera
In human in vitro systems, the metabolism of BMS-955176 was primarily mediated via 
cytochrome P450 (CYP)3A4. In vivo in rats, dogs, and monkeys, BMS-955176 was the 
predominant drug-related component in plasma following a single oral dose of BMS-955176. 
BMS-955176 was eliminated principally via metabolism followed by excretion in bile with little 
renal excretion. 
In vitro, BMS-955176 was an inhibitor of CYP2C8 (concentration at which 50% inhibition 
observed [IC50] = 28.5 M), CYP3A4 (IC50 = 32 M), and uridine diphosphate 
glucuronosyltransferase (UGT)1A1 (IC50 = 20 M) enzymes. No P-gp inhibition or 
time-dependent inhibition of CYPs was observed. BMS-955176 was not an inducer of CYP1A2, 
CYP2B6, or CYP3A4. The steady state Cmax of BMS-955176 180 mg tablet in HIV-infected 
patients with food is projected to be approximately 5.2 M. Thus, the potential exists for 
BMS-955176 to inhibit CYP2C8, CYP3A4, and/or UGT1A1 in vivo and increase exposures to 
co-administered drugs that are metabolized by these enzymes. Furthermore the potential exists 
for drug-drug interactions (DDI) if BMS-955176 is co-administered either with an inhibitor or 
inducer of CYP3A4 or P-gp.
BMS-955176 was a substrate of mouse P-glycoprotein (P-gp) based on higher bioavailability in 
P-gp knock-out mice when BMS-955176 was co-administered with elacridar, a potent inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
24
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
of P-gp and breast cancer resistance protein (BCRP). BMS-955176 could not be reliably assessed 
as a substrate for human P-gp due to nonspecific binding and low solubility. In vitro, 
BMS-955176 inhibited organic anion transporting polypeptide (OATP)1B1 and OATP1B3 
(IC50 5.3 and 4 M, respectively), but was not an inhibitor of P gp, sodium taurocholate 
cotransporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multiple 
drug-resistance protein (MRP)2, and bile salt export pump (BSEP). These findings suggest a 
potential for DDI between BMS-955176 (as the perpetrator) and substrates of OATP1B1 and 
OATP1B3, but not with those of P-gp, NTCP, OAT1, OAT3, MRP2, and BSEP. Furthermore, 
the potential exists for drug-drug interactions (DDI) if BMS-955176 is co-administered either 
with an inhibitor or inducer of CYP3A4 or P-gp. Preliminary data indicate that BMS-955176 
does not inhibit OCT2, a transporter that is inhibited by dolutegravir (DTG), a drug with which 
BMS-955176 is planned to be co-administered.
Nonclinical Toxicology
The toxicity profile of BMS-955176 was evaluated in single- and repeat-dose toxicity, 
genotoxicity, phototoxicity, safety pharmacology, sensitization, reproductive toxicity and 
embryo-fetal development studies. The scope of the toxicologic evaluation for BMS-955176
supports its proposed clinical use for HIV-1 infection. Unless otherwise mentioned, all animal 
studies were dosed by the oral route with an aqueous methylcellulose suspension of a 
BMS-955176 spray-dried dispersion (SDD). 
BMS-955176 was not phototoxic, mutagenic, or clastogenic in vitro and was not genotoxic in a 
rat micronucleus assay at 300 mg/kg/day (AUC 279 g·h/mL). BMS-955176 was not a skin 
sensitizer in the local lymph node assay in the mouse. BMS-955176 had a low potential (IC50 or 
EC50 > 5 M [> 3.45 µg/mL]) for in vitro off-target interactions on a broad range of enzymes, 
transporters, and receptors, including cardiac ion channels. 
In safety pharmacology evaluations in rats, there were no respiratory findings and no direct 
central nervous system (CNS) findings. Decreases in motor activity, arousal, and rearing were 
considered secondary to general toxicity (ie, body weight decreases).
Cardiovascular safety pharmacology evaluations were conducted in rabbits, rats, and dogs. In the 
definitive oral single-dose cardiovascular safety study in conscious telemeterized dogs, blood 
pressure and electrocardiogram were was unaffected at 20 mg/kg; however, increases in heart 
rate (mean 33% to 57% of pretest vehicle) were observed at 8 and 20 mg/kg. The increase in 
heart rate at these doses was primarily due to increases in 2 dogs at each dose that had higher 
plasma concentrations (12.83 g/mL) relative to the dogs without effects on heart rate 
(6.81 g/mL). The no-observed-effect level (NOEL) for cardiovascular effects in dogs was 
2 mg/kg (plasma concentration of 1.93 µg/mL). Importantly, there was no change in heart rate at 
20 mg/kg/day at higher plasma concentrations (Cmax 17.8 µg/mL) in the 1-month study in 
dogs (below). 
Taken together, BMS-955176 has low potential for respiratory, CNS, and cardiovascular effects 
and no cardiovascular effects have been observed in humans to date.
Revised Protocol No.: 01
Date: 19-Mar-2015
25
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Two-week, 1-month, and 6-month studies were conducted in rats. As the 2-week study was of 
limited scope, only the 1-month and 6-month studies are presented in this summary. 
BMS-955176 was administered for 1 month at doses of 30, 100, or 300 mg/kg/day. While there
was no mortality at 100 mg/kg/day, the high dose of 300 mg/kg/day was associated with 
pronounced signs of clinical toxicity and early euthanasia of all the rats at that dose level on 
Days 8 to 9. The dose of 30 mg/kg/day was tolerated. The intermediate dose of 100 mg/kg/day 
(AUC 357 g·h/mL) resulted in dose-limiting toxicity including persistent reduction in food 
consumption and body weights. A number of minor hematology (including red cell parameter 
changes with no consistent effect on the erythron) and serum chemistry changes (including 
increased alkaline phosphatase and alanine aminotransferase) without correlating histologic liver 
findings) occurred at 30 and 100 mg/kg/day; these changes were considered not adverse due to 
small magnitude, occurrence only in 1 sex, and lack of microscopic correlates, and most were 
secondary to decreases in food consumption and body weight. Dose-related gastrointestinal 
toxicity was primarily characterized by morphologic changes in the stomach at 100 mg/kg/day 
and the stomach and small and large intestines at 300 mg/kg/day. At the end of the 2-week 
postdose recovery period, there was complete recovery of all BMS-955176-related findings at 
30 mg/kg/day. At 100 mg/kg/day, all findings recovered with the exception of increased red cell 
distribution width in females, minimally higher (1.94×) ALT activity in 1 male without any 
histologic correlates, and decreased mean prostate gland (with seminal vesicles) weights. The 
low dose of 30 mg/kg/day (AUC 113.5 g·h/mL) was considered the no-observed-adverse-effect 
level (NOAEL) because the body weight and food consumption changes were minimal and 
transient and there were no BMS-955176-related morphologic changes.
In a 6-month oral toxicity study in rats with 1-month recovery period, BMS-955176 was 
administered at doses of 10, 25, or 50 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month rat study and occurred at all doses (10 mg/kg/day; 
AUC 71 gh/mL). Findings included decreased body weight, food consumption, and in the 
stomach, minimal to marked atrophy involving both parietal and chief cells, minimal to mild 
single-cell necrosis and minimal regeneration in the glandular mucosa, which were partially 
reversible at the end of the 1-month recovery period. A NOAEL was not established in this 
study.
Five-day, 1-month, and 9-month repeat-dose studies were conducted in dogs. As the 5-day 
toxicokinetics and tolerability studies were of limited scope, only the 1-month and 9-month
studies are presented here. In the 1-month study, BMS-955176 was administered at doses of 2, 8, 
or 20 mg/kg/day. Increased incidences of sporadic vomiting and liquid, yellow, and/or mucoid 
feces occurred at all doses, but had no apparent effect on the overall health of these animals. 
At 20 mg/kg/day, additional findings included occasional decreases in food consumption in a 
few animals, loss of body weight (up to 8%) in 2 females, a minimal increase in serum ALT 
activity (2.10× pretest) in 1 female with no microscopic correlates, and minimal single-cell 
necrosis of stomach glandular epithelium. All BMS-955176-related changes were fully 
reversible by the end of the 2-week recovery period. The dose of 8 mg/kg/day was considered a 
NOAEL (AUC 219.5 g·h/mL) since the sporadic clinical observations had no adverse effects 
Revised Protocol No.: 01
Date: 19-Mar-2015
26
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
on the general health of the animals and there were no BMS-955176-related morphologic 
changes. 
In a 9-month oral toxicity study in dogs with 1-month recovery period, BMS-955176 was 
administered at 0 (vehicle), 1, 3, or 10 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month dog
study
and
occurred at doses 3 mg/kg/day 
(AUC 135 gh/mL). Findings included salivation (only males at 10 mg/kg/day), fur thinness 
(males), thin appearance, and abnormal feces (yellow, liquid, pale and/or mucoid) that occurred 
sporadically throughout the study; increases in mean food consumption; minimal to marked chief 
cell depletion in the glandular stomach. Additional findings at 10 mg/kg/day included thin 
appearance that correlated with decreases in body weight in food consumption; occasional 
vomitus in males; in the stomach, minimal to moderate mucous cell hyperplasia (often associated 
with glandular dilatation) correlating with increased thickness macroscopically (males only) and 
minimal to marked parietal cell depletion and single-cell necrosis of glandular epithelial cells; 
and increases in serum gastrin values (1.31 to 4.56× highest control value) for several dogs that
may have reflected the reductions in gastric parietal cells. The NOAEL was 1 mg/kg/day 
(AUC 64.9 gh/mL).
The embryo-fetal development (EFD) studies were conducted in 3 species (rabbits, rats, and 
mice) instead of the standard 2 species due to poor maternal tolerability and inability to achieve 
adequate systemic exposures in rabbits.
In a definitive EFD study in pregnant mice, BMS-955176 was administered at doses of 15, 45, or 
150 mg/kg/day from gestation day (GD) 6 through 15. BMS-955176 was a selective 
developmental toxicant in mice. Dose of 100 mg/kg/day was associated with an increase in 
embryo-fetal lethality (cumulative postimplantation losses of 11.5%, relative to 3.9% in control 
litters, attributed to increased incidences of dead fetuses, early resorptions and late resorptions). 
Cleft palate and exencephaly were observed in a few fetuses; additionally, marginal reductions in 
fetal body weight (5% relative to control values) were observed. There was no maternal toxicity 
at any dose tested. The developmental NOAEL was 45 mg/kg/day (AUC 213 g·h/mL).
In a definitive EFD study in pregnant rats, BMS-955176 was administered at doses of 10, 30, or 
100 mg/kg/day from GD 6 through 15. BMS-955176 was not a selective developmental toxicant. 
Developmental toxicity (reduced fetal body weights, increases in fetal alterations, and reduced 
fetal ossification) occurred only at 100 mg/kg/day; whereas, maternal toxicity (clinical 
observations, reduced body weights, and reduced food consumption) was observed at 
30 mg/kg/day. The developmental NOAEL was 30 mg/kg/day (AUC 114 gh/mL). 
In an EFD study in pregnant rabbits, BMS-955176 was administered at a dose of 80 mg/kg/day 
from GD 7 through 19. BMS-955176 was not a developmental toxicant in rabbits at 
80 mg/kg/day (AUC 3.26 gh/mL), at which reductions in maternal food consumption and 
weight gain were observed.
In the fertility and early embryonic development study in rats, BMS-955176 was evaluated at 
doses of 10, 30, or 100/60 mg/kg/day in males and females. BMS-955176 did not affect 
Revised Protocol No.: 01
Date: 19-Mar-2015
27
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
reproduction or early embryonic development at doses 100 mg/kg/day that produced overt 
toxicity. The reproductive NOAEL was 100/60 mg/kg/day (AUC 210 g•h/mL) in male rats and
100 mg/kg/day (AUC 458 g•h/mL) in female rats.
Overall, results from the nonclinical toxicology studies demonstrate that BMS-955176 has a low 
potential for cardiovascular effects, is toxic to the gastrointestinal tract, and is a selective 
developmental toxicant. Clinical monitoring of vital signs (heart rate, systolic and diastolic blood 
pressure) and for gastrointestinal adverse events (AEs) (eg, nausea, vomiting, diarrhea, or fecal 
changes), along with screening for potential renal tubular injury, have not indicated any potential 
for these AEs in Phase 1 or proof of concept (POC) studies in humans. Clinical protocols will 
ensure that appropriate contraceptive measures will be followed to minimize the risk of 
pregnancy while enrolling women of child-bearing potential (WOCBP) males subjects who are 
sexually active with (see Section 3.3.1 Inclusion Criteria).
1.4.1.3
Clinical studies
Phase 1
The safety, tolerability, and PK of BMS-955176 were evaluated in a randomized, double-blind, 
placebo-controlled, sequential single ascending dose (SAD, 10-120 mg) and multiple ascending 
dose (MAD, 10-80 mg QD for 14-28 days) study in healthy subjects (AI468001). No SAEs, 
deaths, or discontinuations related to study drug occurred. No clinically meaningful trends were 
observed in vital signs, physical exam findings, laboratory values, or ECGs. Following 
single-dose and multiple-dose administration of BMS-955176, a slightly less than 
dose-proportional increase in Cmax and AUC(INF) was observed over the dose ranges studied. 
Steady state was reached in approximately 7 days following multiple-dose once daily 
administration of BMS-955176. The half life (T-HALF) of BMS-955176 is approximately 
35 hours. 
Study AI468034 assessed the relative bioavailability and dose proportionality of BMS-955176 
MC tablet - the formulation that will be used in the current study. Relative to 80 mg SDD 
suspension, the bioavailability of BMS-955176 120 mg MC tablet was approximately 23% 
lower. Furthermore, consistent with the low solubility of BMS-955176, considerable overlap in 
exposures was observed between 60 mg, 120 mg and 180 mg MC tablet, when given under 
fasted conditions. The impact of food on exposures to BMS-955176 120 mg MC tablet was 
assessed in Study AI468034 as well; a high fat meal increased BMS-955176 AUC approximately 
50% with negligible impact on BMS-955176 Cmax.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose. Preliminary safety 
Revised Protocol No.: 01
Date: 19-Mar-2015
28
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
results from AI468049 indicate that GI adverse events (eg, nausea, vomiting, loose stools) only 
occurred in the fed arms (where the BMS-955176 exposures were higher) relative to the fasted 
arms.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose.
Phase 2a
A randomized, double-blind, placebo-controlled proof of concept study in HIV subjects has 
completed enrollment and is undergoing analysis (AI468002). The three parts of this study were: 
1) Part A evaluated doses of 5, 10, 20, 40, 80, and 120 mg of BMS-955176 (SDD suspension) 
given for 10 days in HIV-1 clade B infected subjects, 2) Part B compared the antiviral activity of 
BMS-955176 (SDD suspension) administered with ATV (with or without RTV) against standard 
of care (TDF + FTC + ATV/r) for 28 days in HIV-1 clade B infected subjects, and 3) Part C 
evaluated BMS-955176 40 and 120 mg (SDD suspension) given for 10 days in HIV-1 clade C 
infected subjects. See Table 1.4.1.3-1 for baseline demographics. 
Preliminary results from the Phase 2a study (AI468002) in HIV-1 (clade B and C only) infected 
adults showed that at effective doses, a maximum median reduction in HIV-1 RNA ranging from 
1.3 to 1.7 log10 was observed. In the Phase 2b study BMS-955176 doses estimated to provide 
similar exposure to effective doses in the Phase 2a study will be used. Moreover, when 
BMS-955176 was combined with ATV RTV, these combinations resulted in maximum median 
declines in HIV-1 RNA ranging from 1.9 to 2.2 log10 (see Table 1.4.1.3-2). These results are 
generally similar to the antiviral effect demonstrated by other classes of ARVs in short-term
monotherapy trials, and thus BMS-955176 should contribute substantially with other ARVs to 
form an effective cART regimen. Lastly, preliminary safety data show acceptable safety and 
tolerability across all Phase 2a arms. Most AEs were Grade 1-2 and were most frequently due to 
an indirect hyperbilirubinemia; the levels seen with BMS-955176 and ATV/r were similar to 
those seen with ATV/r combined with TDF/FTC. The arms containing BMS-955176 and 
unboosted ATV had bilirubin levels that were approximately half of those observed in the arms
containing ATV/r. Last, arms containing BMS-955176 alone did not show elevated bilirubin
levels. Many of these events occurred in subjects who were randomized to an arm containing 
BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to headache and an 
increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia occurred in subjects also 
receiving ATV.
Revised Protocol No.: 01
Date: 19-Mar-2015
29
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.4.1.3-1:
Phase 2a Baseline Demographics and Characteristics of Subjects 
(Preliminary Results)
Treatment Arm
Subjects
(n)
Median 
age
Male
White
Median 
HIV 
RNA 
(log10
c/ml)
Median 
CD4 
(cells/mm3)
Part A (Clade B, 10 days 
monotherapy)
BMS-955176 5 mg
8
43.5
8 (100)
6 (75.0)
4.09
437
BMS-955176 10 mg
8
39
7 (87.5)
7 (87.5)
4.02
539
BMS-955176 20 mg
8
33
8 (100)
8 (100)
3.59
512
BMS-955176 40 mg
8
38
8 (100)
8 (100)
4.03
536
BMS-955176 80 mg
8
31.5
8 (100)
8 (100)
3.82
504
BMS-955176 120 mg
8
37.5
8 (100)
8 (100)
3.84
498
Placebo
12
36
12 
(100)
12 
(100)
3.98
458
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
8
32.5
8 (100)
6 (75)
4.04
581
BMS-955176 40 mg + ATV 300 mg + 
RTV 100 mg
8
34
8 (100)
8 (100)
4.45
480
BMS-955176 80 mg + ATV 400 mg
8
31.5
8 (100)
7 (87.5)
4.15
549
Truvada® + ATV 300 mg + RTV 
100 mg
4
32.5
4 (100)
4 (100)
4.12
427.5
Part C (Clade C, 10 days 
monotherapy)
BMS-955176 40 mg
7
35
4 (57.1)
2 (28.6)
4.53
554
Placebo
2
38.5
2 (100)
0 (0)
3.78
304
Table 1.4.1.3-2:
Maximum Decline Log10 HIV-1 RNA (Preliminary Results)
Treatment 
Mean 
S.D. 
Median 
Max
Min
Part A (Clade B, 10 days monotherapy)
BMS-955176 5 mg
-0.49
0.217
-0.498
-0.78
-0.22
BMS-955176 10 mg
-1.05
0.351
-0.976
-1.76
-0.64
BMS-955176 20 mg
-1.17
0.645
-1.115
-2.12
-0.13
BMS-955176 40 mg
-1.55
0.352
-1.701
-1.88
-0.93
BMS-955176 80 mg
-1.52
0.257
-1.555
-1.82
-1.04
Revised Protocol No.: 01
Date: 19-Mar-2015
30
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.4.1.3-2:
Maximum Decline Log10 HIV-1 RNA (Preliminary Results)
Treatment 
Mean 
S.D. 
Median 
Max
Min
BMS-955176 120 mg
-1.53
0.478
-1.654
-2.07
-0.83
Placebo
-0.48
0.581
-0.381
-1.46
0.56
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
-1.89
0.273
-1.858
-2.37
-1.49
BMS-955176 40 mg + ATV 300 mg + RTV 100 
mg
-2.22
0.676
-2.202
-3.52
-1.24
BMS-955176 80 mg + ATV 400 mg
-2.3
0.307
-2.228
-2.68
-1.87
Truvada® + ATV 300 mg + RTV 100 mg
-2.41
0.495
-2.39
-3.04
-1.83
Part C (Clade C, 10 days monotherapy)
BMS-955176 40 mg
-1.5
0.439
-1.285
-2.03
-1.04
Placebo
0.12
0.141
0.12
0.02
0.22
The pharmacokinetics of BMS-955176 were assessed in HIV-1 infected subjects in AI468002. 
Overall, exposures to BMS-955176 are approximately 30% to 35% lower in HIV-1-infected 
subjects compared to healthy subjects administered the same doses and formulation of 
BMS-955176. Furthermore, exposures to BMS-955176 increased in a generally linear fashion up 
to 40 mg, with a less than dose proportional increase in exposures between 40 mg and 80 mg, 
and considerable overlap in exposures between 80 mg and 120 mg.
1.4.2
Background Information on TDF
Tenofovir disoproxil fumarate (TDF) is an analog of the nucleotide adenosine 
5’-monophosphate. TDF inhibits HIV-1 reverse transcriptase and is indicated in combination 
with other ARVs for the treatment of HIV-1 infection. The most common adverse reactions 
include rash, diarrhea, headache, pain, depression, asthenia, and nausea. Clinicians are warned 
about new onset or worsening renal impairment, decreases in bone density, and immune 
reconstitution syndrome. For more information concerning TDF, please refer to the 
TDF/Viread® SmPC or TDF/Viread® USPI.29
1.4.3
Background Information on DTG
Dolutegravir (DTG) is a HIV-1 integrase strand transfer inhibitor indicated in combination with 
other ARVs for the treatment of HIV-1 infection. The most common adverse reactions of 
moderate to severe intensity include insomnia, fatigue, and headache. Clinicians are warned 
about immune reconstitution syndrome. For more information concerning DTG, please refer to 
the DTG/Tivicay SmPC or the DTG/Tivicay USPI.30
1.4.4
Background Information on ATV 
Atazanavir is a protease inhibitor indicated for use in combination with other ARVs for the 
treatment of HIV-1 infection. The
most common adverse reactions include nausea, 
Revised Protocol No.: 01
Date: 19-Mar-2015
31
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
jaundice/scleral icterus, rash, headache, abdominal pain, vomiting, insomnia, peripheral 
neurologic symptoms, dizziness, myalgia, diarrhea, depression, and fever. Clinicians are warned 
about hyperbilirubinemia, nephrolithiasis, and cholelithiasis. For more information concerning 
ATV please refer to the ATV/Reyataz® SmPC or ATV/Reyataz® USPI.31
1.4.5
Background Information on RTV
Ritonavir is a protease inhibitor indicated in combination with other ARVs for the treatment of 
HIV-1 infection. The most frequently reported adverse drug reactions with RTV alone or in 
combination with other ARVs include diarrhea, nausea, vomiting, abdominal pain, paresthesia, 
rash, and fatigue/asthenia. Clinicians are warned about total cholesterol and triglyceride 
elevations. For more information concerning RTV please refer to the RTV/Norvir® SmPC or 
RTV/Norvir® USPI.32
1.4.6
Drug-Drug Interactions
In AI468001, coadministration of BMS-955176 as a single dose following two doses of 100 mg 
RTV resulted in an approximate 48% increase in BMS-955176 AUC(INF), consistent with 
inhibition of CYP3A4 and/or P-gp. Multiple-dose administration of BMS-955176 with daily 
400 mg ATV and a standard meal for 14 days resulted in a modest (~25%) increase in the 
BMS-955176 AUC(TAU).
Study AI468005 assessed the two-way interaction between BMS-955176 40 mg (administered as 
an SDD suspension) and TDF at steady state in healthy subjects. Relative to administration of 
each drug alone, neither BMS-955176 nor TDF exposures were meaningfully impacted upon 
coadministration.
Study AI468041 assessed the impact of BMS-955176 80 mg (administered as an SDD 
suspension) on the pharmacokinetics of the components of a combined oral contraceptive 
containing ethinyl estradiol (EE) and norgestimate (NGM). Exposures to both EE and 
norelgestromin (NGMN), the active metabolite of NGM were reduced in the presence of 
BMS-955176. Furthermore, one subject had a serum progesterone level > 300 ng/dL while 
BMS-955176 and the oral contraceptive were concomitantly administered, indicative of 
ovulation and contraceptive failure.
Finally, in vitro data suggest that BMS-955176 may inhibit OATP1B1 and OATP1B3 and 
exposures to substrates of these transporters, such as HMG-CoA reductase inhibitors, may 
increase when co-administered with BMS-955176.
1.5
Overall Risk/Benefit Assessment
The preclinical and clinical safety data demonstrate that BMS-955176 administered at doses in 
this Phase 2b study (120, and 180 mg) should be well tolerated without a major clinically 
relevant impact on safety. Moreover, there have been no identified safety risks from 
completed/ongoing clinical studies to date.
Revised Protocol No.: 01
Date: 19-Mar-2015
32
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The preclinical toxicology studies demonstrate two potential risks to subjects:
First, BMS-955176 is a selective developmental toxicant. Developmental toxicity (skeletal 
alterations in rats; cleft palate and reduced fetal body weights in mice) were observed in 
embryofetal development studies. In order to address this concern, subjects will be required to 
use two methods of contraception (as described in Section 3.3.1 Inclusion Criteria) and undergo 
routine urine pregnancy testing (as described in the T&E Tables in Section 5.1). Furthermore, 
due to results from Study AI468041 that demonstrates reduced exposures to the components of a 
combination oral hormonal contraceptive containing ethinyl estradiol and norgestimate when 
given concomitantly with BMS-955176, oral hormonal contraceptives cannot be used as a 
method of contraception by WOCBP in this study.
Second, single or repeat oral doses of BMS-955176 were associated with sporadic vomiting in 
dogs and unformed and/or liquid feces in rats and dogs. In rats at 10 mg/kg/day there were 
decreases in body weight and food consumption; in the stomach there was atrophy involving 
both parietal and chief cells, single-cell necrosis and regeneration in the glandular mucosa, and 
modest increases in serum gastrin values. At higher doses (100 mg/kg/day) in rats there were 
additional findings in the intestines (distended jejunum, ileum, and cecum; hyperplasia of the 
crypt epithelium in the jejunum; ulcers and erosions in the cecum; and decreased mucosal cell 
extrusion and increased mucus in the colon). 
Similar gastric changes were seen in dogs. At 20 mg/kg/day there was single-cell necrosis of the
stomach glandular epithelium. At 3 mg/kg/day gastric changes showed chief cell depletion. 
At 10 mg/kg/day changes in the stomach included: mucous cell hyperplasia correlating with 
increased thickness macroscopically, parietal cell depletion, single-cell necrosis of glandular 
epithelial cells, and modest increases in serum gastrin values. Unlike the rats, no changes were 
observed elsewhere in the alimentary canal including the gastroesophageal junction and the 
duodenum. There was no evidence of macrocytosis. Measurement of Total Protein and Albumin 
revealed no clinically relevant changes. The stomach histologic findings were BMS-955176 
dose- and duration dependent. In the 1-month studies, vomiting and fecal changes stopped soon 
after dosing cessation, and microscopic lesions in the stomach and/or intestines reversed 
completely within a 2-week treatment-free period. In the 6 month study in rats and the 9-month 
study in dogs, microscopic lesions in the stomach partially recovered after a 1 month treatment 
free period. The NOAEL was 1 mg/kg/day (AUC 64.9 mg•h/mL) in the 9-month study in dogs, 
and was not established in the 6-month study in rats. Investigative studies for gastric toxicity in 
rats and dogs indicated similar findings with both SDD and MC forms, and with no clear 
evidence that the gastric toxicity is a direct local effect of BMS-955176. The mechanism and 
clinical relevance of these gastrointestinal findings is unknown at present (see below).
A Phase 1 study (AI468001) in healthy volunteers evaluated single and multiple doses of 
BMS-955176 for 14-28 days both alone and in certain arms, in combination with ATV or RTV. 
Overall the safety data demonstrated that BMS-955176 was generally safe and well tolerated. 
A Phase 2a (AI468002) study in HIV-1 infected adults evaluated several doses of BMS-955176 
given alone or in combination with ATV RTV for 10-28 days. The preliminary results show 
Revised Protocol No.: 01
Date: 19-Mar-2015
33
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
acceptable safety and tolerability across all arms. There were no deaths, SAEs, or AEs leading to 
discontinuation. There were no clinically relevant changes in vital signs, lab parameters, or 
EKGs. Most of the AEs were Grade 1-2 and were most frequently due to hyperbilirubinemia 
(primarily observed in treatment arms with ATV). Of the GI AEs, most were attributable to 
diarrhea or loose/watery stools. Many of these events occurred in subjects who were randomized 
to an arm containing BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to 
headache and an increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia 
occurred in subjects also receiving ATV; moreover, the three arms with the highest average total 
bilirubin occurred in subjects receiving both BMS-955176 and ATV. Clinical changes/symptoms 
consistent with the GI findings from dogs and rats (described above) were not seen in the 
preliminary data set from short-term therapy with BMS-955176 in HIV-1 infected adults. 
In this treatment-experienced study population, we estimate GI safety multiples of 2× and 1×, 
(based on NOAEL in 9-month dog study), corresponding to projected human exposures at 
BMS-955176 doses of 120 and 180 mg.
While no clinically relevant GI safety signals have been observed in AI468001 or AI468002, in 
this clinical trial, subjects will undergo routine targeted and complete history/physical exams in 
addition to regular laboratory measurements (including CBC and chemistries). This will initially 
occur more frequently than in standard clinical practice and allow for increased vigilance for any 
potential GI toxicity. Guidance on the evaluation and management of potential GI toxicity is 
outlined in Section 6.7.1.4.
Subjects in this clinical study will benefit from receiving cART potentially containing 
BMS-955176. Preliminary data from the Phase 2a (Part A, B and C) study show a maximum 
median reduction in HIV-1 RNA (clades B and C) ranging from 1.3 to 1.7 log10 in the dose arms 
estimated to provide similar exposure to those in this current study. When BMS-955716 was 
combined with ATV RTV (Part B) this resulted in maximum median declines in HIV-1 RNA 
ranging from 1.9 to 2.2 log10. These results are generally similar to the antiviral effect 
demonstrated by other classes of ARVs. Thus, BMS-955176 should contribute with other ARVs 
substantially to form an effective cART regimen.
As with any antiretroviral study in HIV-1-infected subjects, there is a risk for the development of 
treatment failure and the development of drug resistance associated mutations to BMS-955176 
and/or other antiretrovirals. However, drug resistance to the maturation inhibitor would not be 
anticipated to result in cross-resistance to any other ARV class, including protease inhibitors.33
Ongoing analysis of preliminary data from the Phase 2a study is evaluating both emergent 
genotypic and phenotypic changes after short term monotherapy with BMS-955176. The use of 
three fully susceptible agents as a part of cART is expected to decrease the probability of 
virologic failure and drug resistance. Initially in this clinical trial, measurement of HIV-1 RNA 
will occur more frequently than in standard clinical practice which will allow for increased 
vigilance for the development of lack of efficacy/resistance. Finally, an analysis for virologic 
futility will occur at Week 24 (see Section 8.4.7).
Revised Protocol No.: 01
Date: 19-Mar-2015
34
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
As described earlier, treatment-experienced adults enrolled in Arms 3-4 may be exposed to a 
subtherapeutic regimen and may be at higher risk for virologic failure and the development of 
resistance. In order to decrease this probability, this clinical trial uses a two-stage design 
whereby enrollment in Arms 3-5 will be dependent upon the results of the Week 24 analyses
(efficacy, safety, and pharmacokinetics) in Stage 1 and Study AI468038. This will minimize the 
risk of virologic failure and resistance to subjects enrolled in Arms 3-4 because clinical data will 
already have been generated using BMS-955176 with ATV/r (Arm 1) in Stage 1.
In-vitro studies show that BMS-955176 is expected to be active against a variety of HIV-1 clades 
albeit with EC50s 2-3 fold less toward HIV-1 clade AE compare to clade B (see Section 1.4.1). 
As described in Section 1.1.1, the only clinical data for BMS-955176 exists in HIV-1 clade B 
and C. The efficacy profile of BMS-955176 in other HIV-1 clades encountered in other 
geographical regions where this multinational Phase 2b trial will be conducted (eg, clade AE in 
Thailand) is unknown. To mitigate the risk of randomizing subjects infected with HIV-1 with an 
unknown efficacy profile, the number of subjects with HIV-1 Clade AE will be stratified to 
ensure each treatment are has approximately the same number of HIV-1 clade AE infected 
subjects in their respective Stages and the maximum number of subjects with HIV-1 clade AE 
will be capped at approximately 3 per treatment arm.
Of note, the other ARVs used in this clinical trial have a known and acceptable risk benefit ratio 
and are frequently prescribed to HIV-1 infected adults as a part of standard of care.
Taken together, the clinical data to date show that BMS-955176 has potent antiretroviral activity 
and is generally safe and well tolerated in healthy volunteers and HIV-1 infected adults. These 
factors should allow subjects to benefit from achieving viral suppression whilst taking a 
generally safe and well-tolerated new antiretroviral; additionally subjects in Arms 1, 3, and 4 
may benefit from a cART regimen that is nucleoside and nucleoside/booster sparing, 
respectively. Specifically, these subjects may benefit from improved bone mineral density, renal 
function, and lipid profiles. The risks, including teratogenicity, GI toxicity, and drug resistance, 
will be appropriately managed by following guidance in the study protocol.
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, 
Revised Protocol No.: 01
Date: 19-Mar-2015
35
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
2.2
Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure 
or product labeling information to be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form which will include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
1) Provide a copy of the consent form and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language 
must be non-technical and easily understood. 
2) Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study.
3) Obtain an informed consent signed and personally dated by the subject or the subject's 
legally acceptable representative and by the person who conducted the informed consent 
discussion.
4) Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
Revised Protocol No.: 01
Date: 19-Mar-2015
36
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5) If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his 
or her informed consent during the study, consent must additionally be obtained from the 
subject.
6) Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject's willingness to continue participation in the study. This communication should be 
documented.
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to 
refuse participation in, or to be withdrawn from, the clinical study at any time should be 
considered by the investigator.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced HIV-1 subjects will be randomized to one of five treatment arms
(approximately 40 per arm) in a staged fashion.
Randomization will be stratified by HIV-1 Clade (AE versus Other). The number of subjects 
with HIV-1 Clade AE will be capped at a maximum of approximately 3 per treatment arm.
The data from the Week 24 analysis of Stage 1 and AI468038, including safety, efficacy and 
pharmacokinetics, will be examined to trigger the start of Stage 2 and confirm the two doses of 
BMS-955176 for study in Stage 2.
Revised Protocol No.: 01
Date: 19-Mar-2015
37
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with: 

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
3.1.1
Screening
The screening period begins with the subject’s signature on the informed consent form (ICF).
The subject is then enrolled via the Interactive Voice Response System IVRS (or its web-based 
equivalent) See Section 4.4.
If the subject meets all eligibility criteria, the subject must be randomized within the 42 day 
screening period.
3.1.2
Day 1/Baseline Visit
3.1.2.1
Day 1/Baseline Visit for Arms 1 and 2 - Stage 1
In Stage 1, approximately 80 subjects will be randomized 1:1 (approximately 40 per arm) to 
either of the treatment arms containing boosted atazanavir (ATV/r).
On the Day 1 Visit, subjects in Arms 1 and 2 will begin QD dosing with BMS-955176 or TDF, 
each in combination with ATV/r and DTG (see Section 4.5 for additional details of Selection and 
Timing of Dose).

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
3.1.2.2
Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2
In Stage 2, approximately 120 subjects will be randomized 1:1:1 (approximately 40 per arm) to 
either of the two BMS-955176 treatment arms containing ATV, or to the TDF Arm.
Revised Protocol No.: 01
Date: 19-Mar-2015
38
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
On the Day 1 Visit, subjects will begin QD dosing with BMS-955176 in combination with ATV 
and DTG, or TDF in combination with ATV/r and DTG (see Section 4.5 for additional details of 
Selection and Timing of Dose).

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r QD 300/100 mg + DTG 50 mg QD
3.1.3
Week 2 Intensive PK Visit
Subjects with anemia, defined as Hemoglobin < 11.0 g/dL, should be excluded from 
participation in the Week 2 Intensive PK Substudy.
Subjects in all arms will have the opportunity to participate in an elective Intensive PK Substudy 
visit at Week 2 (window for visit: Day 12-16). Approximately 60 subjects, 12 subjects from each 
arm, are expected to participate in the substudy; BMS may allow the substudy to over-enroll in 
an effort to have a sufficient number of complete datasets.
The series of 12 blood draws begins with pre-dose (0-hour) blood samples to be collected
approximately 24 hours (20-28 hrs) after the morning doses of study drugs that were taken on the 
day before. Ten more samplings are drawn through the 12-hr time point, with one final sampling 
collected at the 24-hr time point, requiring the subject to either remain overnight in the clinic, or 
to return the next morning; the final 24-hr sample will be collected prior to administration of the 
morning doses of study drugs (See Section 5.5.1).
PK Tools/Job Aids will be provided to assist with the proper sequencing of dosing and blood 
sample collections, as well as the collection of required data.
3.1.4
Visits Week 4 - 96
Subjects are expected to be treated for the duration of 96 weeks. In each Stage, after Day 1 and 
the optional Intensive PK visit at Week 2, subjects will be required to attend 12 more in-clinic 
study visits over the 96-week treatment period, as follows:

Visits are conducted every 4 weeks from Week 4 through Week 16

Visits are conducted every 8 weeks from Week 24 through Week 48

Visits are conducted every 12 weeks from Week 60 through Week 96
Visits should be scheduled as an interval from the Day 1/Randomization date, and within a 
window of 5 days earlier or later.
One of the visits Week 4 - 24 should meet the very specific timing requirements as outlined in 
Section 5.5.2 for a pre-AM dose blood collection.
Telephonic visits will be conducted with each subject at visit Weeks 20, 28, 36, 44, 54, 66, 78,
and 90 to conduct an adherence assessment and to continue retention efforts
Revised Protocol No.: 01
Date: 19-Mar-2015
39
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.1.5
Selection of the Continuation Dose of BMS-955176
3.1.5.1
Selection of the Continuation Dose, and the Switch for Stage 1
Once all subjects in Stage 1 have reached Week 24*, BMS will conduct an interim analysis of 
efficacy, safety, resistance and pharmacokinetics.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If Arm 1 meets 
criteria for Virologic Futility at Week 24, the clinical trial will be terminated.
The Week 24 analysis of Arms 1 and 2, combined with the Week 24 analysis of all Arms in the 
AI468038 study, will be used to select a Continuation Dose of BMS-955176 for Arm 1 in this 
study. Subjects in the BMS-955176 Treatment Arm 1 may subsequently be transitioned to a
selected Continuation Dose.
Subjects in the Arm containing TDF will continue with the TDF treatment regimen.
The assigned backbone will not change.
The Week 24 efficacy, safety, and pharmacokinetic analyses from Stage 1 and study AI468038 
will also trigger the start of Stage 2.
* If the Continuation Dose cannot be clearly identified using the Week 24 data, the study 
will continue in original fashion until an analysis of the Week 48 data can be performed 
and the Continuation Dose is selected. If a Continuation Dose cannot be selected based 
upon the Week 24 data, this does not preclude the ability to start recruitment of Stage 2.
After the Continuation Dose is selected, and once all of the logistics (eg, distribution of clinical 
drug supplies, activation of the new portion of the IVRS) have been completed globally, the 
transition of the subjects in Arm 1 to the Continuation Dose will occur. It is anticipated that this 
transition will occur on or after all subjects have reached Week 48 (the earliest subjects to begin 
study treatment could be well beyond Week 48 when the switch to the Continuation Dose 
occurs).
3.1.5.2
Selection of the Continuation Dose, and the Switch for Stage 2
Once all subjects in Stage 2 have reached Week 24, BMS will conduct an analysis of efficacy, 
safety, resistance and pharmacokinetics.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If a BMS-955176 
dose arm meets criteria for Virologic Futility at Week 24, subjects in said arm will begin dosing 
with the next highest available remaining dose of BMS-955176.
The data from AI468038 and AI468048 (Stages 1 and 2) will be used to select a Continuation 
Dose of BMS-955176 for Arms 3 and 4. Subjects in the BMS-955176 Treatment Arms 3 and 4 
will subsequently be transitioned to a selected Continuation Dose. It is anticipated that this 
transition may occur on or after all subjects have reached Week 48, or it could occur sooner after 
Week 24.
The assigned backbone will not change.
Subjects in the arm containing TDF will continue with this assigned treatment regimen.
Revised Protocol No.: 01
Date: 19-Mar-2015
40
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.1.6
End of the study
The end of the study will occur when the last study visit has been completed, defined as the final 
subject completing their final study visit (expected to be a Week 96 or Early Termination visit).
The study design schematic is presented in Figure 3.1.6-1.
Revised Protocol No.: 01
Date: 19-Mar-2015
41
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 3.1.6-1:
Study Design Schematic
Arm 2
TDF
300 mg QD
+ ATV/r + DTG
Day 1
Begin dosing
Arm 3
BMS-955176 
120 mg QD
+ ATV + DTG
1 Virologic Futility will be evaluated at Week 24 
(see Section 8.4.7).  
Results of Week 24 Stage 1 AI468-048 & AI468-038 
Confirm the Start of Stage 2   
Arm 4
BMS-955176 
180 mg QD
+ ATV + DTG
40
40
Week 2
Week 24
Week 24 Analysis1
Intensive PK subset
4 Based on totality of data from both studies the 
Continuation Dose for Arms 3 & 4 may be 
identified.  
Number
Randomized
STAGE 2
Week 96
Week 96 Analysis/End of Study
Week 48
Week 48 Analysis
The Switch to the Continuation Dose4,3     
is expected to occur on or after Week 48, 
but could occur sooner.
Arm 1
BMS-955176 
120 mg QD
+ ATV/r + DTG
Week 2
Number
Randomized
Week 24
Week 24 Analysis1
Day 1
Begin dosing
Intensive PK subset
40
40
Week 48
Week 96
Week 48 Analysis
Week 96 Analysis/End of Study
The Switch to             
the Continuation Dose2,3
may occur on or after 
Week 48 
STAGE 1
BMS-955176
Continuation Dose QD 
+ ATV/r + DTG
Arm 5
TDF
300 mg QD
+ ATV/r + DTG
40
3 The actual switch of subjects of BMS-955176 
subjects to that Continuation Dose may occur when 
all of the subjects have reached at least Week 48 
(though it could occur sooner in Stage 2).
BMS-955176
Continuation Dose QD
+ ATV + DTG
2 Based on Week 24 data from Arms 1 & 2 and 
from AI468-038, the Continuation Dose for 
Arm 1 may be identified.  
Revised Protocol No.: 01
Date: 19-Mar-2015
42
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.2
Post Study Access to Therapy
At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be 
eligible to receive BMS supplied study drug. Study drug will be provided via an extension of the 
study, a rollover study requiring approval by responsible health authority and ethics committee 
or through another mechanism at the discretion of BMS. BMS reserves the right to terminate 
access to BMS supplied study drug if any of the following occur: a) the marketing application is 
rejected by responsible health authority; b) the study is terminated due to safety concerns; c) the 
subject can obtain medication from a government sponsored or private health program; or 
d) therapeutic alternatives become available in the local market.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Ability to understand and sign a written informed consent form
2. Target Population
a) Antiretroviral treatment-experienced, defined as having documented evidence of having
failed, 1 or 2 regimens that include 2 or 3 classes of ARV (with or without documented 
resistance)
b) Confirmed Plasma HIV-1 RNA 400 copies/mL (First value from investigator; second 
value from screening test)
c) CD4+ T-cell count > 50 cells/mm3
d) Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, 
FC < 2.2; DTG; TDF)
e) Estimated Life expectancy 1 year
f)
Subject Re-enrollment: This study permits the re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / 
has not been treated). If re-enrolled, the subject must be re-consented and assigned a new 
PID.
3. Age and Reproductive Status
a) Males and non-pregnant females
b) At least 18 years of age, (or minimum age as determined by local regulatory or as legal 
requirements dictate)
c) Willingness to use approved highly effective methods of contraception (see below) to 
avoid pregnancy (female subjects who are WOCBP and male subjects who are sexually 
active with WOCBP)
d) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 
24 hours prior to the start of study drug.
Revised Protocol No.: 01
Date: 19-Mar-2015
43
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
e) Women must not be breastfeeding
f)
WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug BMS-955176 plus 5 half-lives of study drug BMS-955176
(8 days) plus 30 days (duration of ovulatory cycle) for a total of 38 days post-treatment 
completion.
g) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug BMS-955176
plus 5 half-lives of the study drug BMS-955176 (8 days) plus 90 days (duration of sperm 
turnover) for a total of 98 days post-treatment completion.
h) Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However WOCBP must still undergo 
pregnancy testing as described in this section.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception. Highly effective methods of contraception 
have a failure rate of < 1% when used consistently and correctly.
At a minimum, subjects must agree to the use of two methods of contraception, with one method 
being highly effective and the other method being either highly effective or less effective as 
listed below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

Male condoms with spermicide34,35

Hormonal methods of contraception including combined oral contraceptive pills, vaginal 
ring, injectables, implants and intrauterine devices (IUDs) such as Mirena

For female study subjects who are WOCBP:
Study subjects who are WOCBP cannot use hormonal methods of contraception as 
one of the two methods of contraception because there are data that show a lack of 
effectiveness of systemic hormonal contraceptives in women taking BMS-955176
However, WOCBP can continue to use hormonal contraceptives, if necessary, in 
addition to 2 other non-hormonal methods of contraception (one of which must be 
highly effective)

For female partners of male study subjects (if they are WOCBP):
Hormonal methods of contraception may be used by male subject’s WOCBP partner. 
Female partners of male subjects participating in the study may use hormone based 
contraceptives as one of the acceptable methods of contraception since they will not 
be receiving BMS-955176

Nonhormonal IUDs, such as ParaGard

Tubal ligation
Revised Protocol No.: 01
Date: 19-Mar-2015
44
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Vasectomy

Complete Abstinence*
*Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an 
acceptable form of contraception for all study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly effective contraception must be 
discussed in the event that the subject chooses to forego complete abstinence.
LESS EFFECTIVE METHODS OF CONTRACEPTION

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal sponge

Male Condom without spermicide 

Progestin only pills by male subject’s WOCBP partner

Female Condom*
* A male and female condom must not be used together
3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a) Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens
b) Resistance or partial resistance to any study drug
c) Three or more of the following PI mutations, historical or documented: M36I/V, 
M46I/L/T, G48M/V, I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M
d) Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S
e) Any major TDF mutation, historical or documented: K65R or T69ins
f)
Three or more of the following non-accessory thymidine analogue mutations (TAMs): 
M41L, D67N, K70R, L210W, T215Y/F, K219Q/E
g) Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI 
resistance), historical or documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, 
Y143C/H/R, E157Q
2. Medical History and Concurrent Diseases
a) A new AIDS defining condition diagnosed within the 30 days prior to screening
(see Appendix 2)
b) Any other clinical condition (including but not limited to active substance use) or prior 
therapy that, in the opinion of the Investigator, would make the subject unsuitable for the 
study; unable to comply with dosing requirements; or unable to comply with study visits; 
or a condition that could affect the absorption, distribution, metabolism or excretion of 
the drug.
Revised Protocol No.: 01
Date: 19-Mar-2015
45
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3. Physical and Laboratory Test Findings
a) Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV 
Ab and HCV RNA)
b) ALT or AST > 3 × ULN
c) Alkaline Phosphatase > 5 × ULN
d) Bilirubin ≥ 1.5 × ULN
e) History of decompensated cirrhosis or active decompensated cirrhosis
f)
Hemoglobin < 8.0 g/dL
g) Platelets < 50,000 cells/mm3
h) Estimated eGFR < 60 mL/min (CKD-EPI formula)
i)
Confirmed QT value > 500 msec at Screening or Day 1
j)
Confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or 
Day 1
k) Confirmed PR Interval > 260 msec (severe first degree AV block) at Screening or Day 1
l)
Confirmed second or third degree heart block at Screening or Day 1
4. Allergies and Adverse Drug Reaction
a) Medications contraindicated for use with investigational/non-investigational study drugs
(ATV, RTV, DTG, TDF);
or subjects with any known allergies to the 
investigational/non-investigational study drugs (ATV, RTV, DTG, TDF)
b) Current or anticipated treatment with any of the medications listed in Appendix 1, in 
addition to any medications that are contraindicated with ATV, RTV, DTG or TDF
c) Participation in an experimental drug and/or HIV-1 vaccine trial(s) within 30 days prior 
to Screening
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
A woman of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 years in the absence of other biological or physiological causes. In 
addition, females under the age of 55 years must have a serum follicle stimulating hormone, 
(FSH) level > 40 mIU/mL to confirm menopause.
Revised Protocol No.: 01
Date: 19-Mar-2015
46
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. If the serum FSH level is > 40 mIU/mL at any time 
during the washout period, the woman can be considered postmenopausal:

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Refer to Appendix 1 which details prohibited and precautionary therapies during the study, 
including specifics about the use of antacids and hormonal methods of contraception.
3.4.2
Other Restrictions and Precautions
None.
3.5
Discontinuation of Subjects following any Treatment with Study Drug 
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject

Termination of the study by Bristol-Myers Squibb (BMS)

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Repeat non-adherence by the subject with the requirements of the protocol or treatment
(as determined by Investigator in consultation with the BMS Medical Monitor)

Evidence of Hepatitis B or C infection

Confirmed plasma HIV-1 RNA 1000 c/mL after Week 24

Confirmed plasma HIV-1 RNA 200 c/mL after Week 48

Emergence of genotypic and/or phenotypic resistance to any component of the study 
treatment regimen at any time after Screening

Subject requires switching to any other ARV

Development of pDILI (potential drug induced liver injury)
Revised Protocol No.: 01
Date: 19-Mar-2015
47
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Confirmed QTcB or QTcF value > 500 msec

Confirmed second degree (Type II) or third degree AV block at any time during the study
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event. In most cases, the study drug will be permanently discontinued in 
an appropriate manner. If the investigator determines a possible favorable benefit/risk ratio that 
warrants continuation of study drug, a discussion between the investigator and the BMS Medical 
Monitor/designee must occur.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Section 5 (ie, perform an Early Termination [ET] visit). The only 
exception to this requirement is when a subject withdraws consent for all study procedures 
including post-treatment study follow-up (no such period exists in this study) or loses the ability 
to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either a 
psychiatric or physical illness).
If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post Study Drug Study Follow up
Subjects who discontinue study drug may continue to be followed.
Subject’s contact information will be collected/confirmed throughout the study so that subjects 
who discontinue study drug may continue to be followed for resolution of a pregnancy or SAE.
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug will remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. In 
the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
Revised Protocol No.: 01
Date: 19-Mar-2015
48
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study. The site staff and representative will consult publicly available sources, such as public 
health registries and databases, in order to obtain updated contact information. If after all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
4
STUDY DRUG
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
Revised Protocol No.: 01
Date: 19-Mar-2015
49
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 4-1:
Study Drugs for AI468048:
Product Description / 
Class and Dosage Form
Potency
IMP/Non-IMP
Blinded or 
Open Label
Packaging/ Appearance
Storage Conditions
(per label)
BMS-955176 
60 mga
IMP
Open Label
Bottle/
A white to off-white, biconvex, 
oval shaped film coated tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
BMS-955176
120 mga
IMP 
Open Label
Bottle/
A white to off-white, biconvex, 
capsule shaped tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
Tenofovir (TDF)
300 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Atazanavir (ATV)
200 mg
IMP
Open Label
Bottle/
Blue cap and blue body
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Atazanavir (ATV)
300 mg
IMP
Open Label
Bottle/
Red cap and blue body,
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Ritonavir (RTV)
100 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Dolutegravir (DTG)
50 mg
Non-IMP or 
IMP,
depending on 
country 
approval status.
Open Label
Various packaging configurations
Refer to label on
container or package insert.
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Revised Protocol No.: 01
Date: 19-Mar-2015
50
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, investigational product(s) is/are: BMS-955176, ATV, and DTG (in countries 
where DTG has not been approved for use). These products will be supplied.
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be 
considered as non-investigational products.
In this protocol, noninvestigational product(s) is/are: TDF, RTV, and DTG (in countries where 
DTG is approved for use). These products will be supplied.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be 
dispensed and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
that includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations.
4.4
Method of Assigning Subject Identification
At the start of the screening period, the investigative staff will call the Assignment Center via an 
Interactive Voice Response System ([IVRS], or its web-based equivalent) designated by the 
sponsor to enroll the subject and to obtain a subject patient identification number (PID).
For subjects who meet the protocol eligibility criteria, the investigative staff will call the IVRS 
and subjects will start treatment.
Revised Protocol No.: 01
Date: 19-Mar-2015
51
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Subjects will be randomly assigned in the staged fashion to one of the treatment arms, and 
stratified by HIV-1 Clade (AE versus Other), as described in Section 3 and as outlined in the 
AI468048 Study Schematic Figure 3.1.6-1.
Note: All efforts should be made to limit the possibility of randomizing subjects that do not start 
treatment. If a subject is randomized but does not receive study medication, the BMS study team 
must be notified immediately.
4.5
Selection and Timing of Dose for Each Subject
Subjects will be randomized into the treatment arms in a staged fashion described in Section 3.1.
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
4.5.1
Instructions for Dose Administration
4.5.1.1
General Instructions

Subjects should administer doses of each drug from only one bottle at a time, until that bottle 
is empty, before another bottle may be opened. 

Subjects will be required to complete Dosing Diaries so that drug administration can be 
accurately accounted. It is important that sites provide instructions to subjects for completion 
and obtain their acknowledgment that doing so provides critical information for the clinical 
trial.

Dosing times (and study appointment times) must be carefully considered through Week 24 
due to the requirements of the PK collection outlined in Section 5.5.
4.5.1.2
Specific Dosing Instructions for Initial Treatment Arm Assignment
In the morning, with a meal, subjects will take the following:

Arm 1: One pill each from bottles BMS-955176 120 mg, ATV, RTV, and DTG

Arm 2: One pill each from bottles TDF, ATV, RTV and DTG
Revised Protocol No.: 01
Date: 19-Mar-2015
52
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Arm 3: One pill each from bottles BMS-955176 120 mg, DTG, and two pills from bottle
ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 4: One pill each from bottles BMS-955176 60 mg, BMS-955176 120 mg and DTG, and 
two pills from bottle ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 5: One pill each from bottles TDF, ATV, RTV and DTG
4.5.2
Dose Modifications
No dose adjustments or changes in intake frequency are allowed for any of the assigned study 
drugs in the protocol, except for the unique case of treatment-limiting renal toxicity which limits 
the use of the TDF. In the event of treatment-limiting renal toxicity, dose interval adjustments for 
TDF are permitted according to the local package insert/label, and only after the completion of 
the Week 2 Intensive PK optional Visit, if the subject is inclined to participate.
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Treatment Adherence to the treatment regimen will be critical to the conduct of this study. 
Adherence will be evaluated by the investigative staff at every treatment visit (including 
telephone contact visits) through interviews with the subjects and through examination of 
returned medication. It is expected that site staff attempt to have subjects maintain 90% 
treatment compliance or greater. Subjects should be instructed to bring all unused study 
medication back in the original container to each visit. Site staff are required to review Dosing 
Diaries completed by the subject, and to reinforce their use.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible Study Monitor unless study drug containers must be immediately destroyed as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:

On-site disposal practices must not expose humans to risks from the drug

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request
Revised Protocol No.: 01
Date: 19-Mar-2015
53
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor must be documented

Accountability and disposal records are complete, up-to-date, and available for the Monitor 
to review throughout the clinical trial period
If conditions for destruction cannot be met the responsible Study Monitor will make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible Study Monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
Revised Protocol No.: 01
Date: 19-Mar-2015
54
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)
Notes
Eligibility Assessments
Informed Consent
X
Call IVRS to Enroll the subject; PID assigned
X
Inclusion/Exclusion Criteria
X
Medical History
X
Includes historical CDC Class C Events
Non-Laboratory Safety Assessments
Full Physical Examination
X
See Section 5.3.1 for requirements
Vital Signs & Physical Measurements
X
See Section 5.3.1 for requirements
Pre-treatment events
X
Only CDC Class C events with onset during the Screening period
Serious Adverse Events Assessment
X
All SAEs that occur after the ICF has been signed should be reported
ECG
X
See Section 5.3.4 for requirements
Pregnancy Test
X
WOCBP
For females under age 55, an FSH level must be on record to confirm she 
is not a WOCBP if pregnancy testing is not being performed.
If positive urine, request serum hCG quant. on lab requisition.
Laboratory Assessments
Fasting Chemistry and Lipid Panel
X
Fasting overnight
Hematology
X
Urinalysis
X
Plasma HIV-1 RNA
X
This is the confirmatory HIV-1 RNA
(The first value is provided by the PI)
Revised Protocol No.: 01
Date: 19-Mar-2015
55
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)
Notes
CD4+ and CD8+ T-cell count
X
HBV Surface Antigen
X
HCV Serology
X
Urine toxicology (drugs of abuse)
X
Could aid in the selection of appropriate study candidates.
Pharmacodiagnostic (PDx) samplea
X
Plasma collection to be banked for potential future use in development of 
novel predictive assay(s)
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
Complete set of test results may take up to 4 weeks.
PhenoSense Gag
X
Next Generation Seq. - Qs Gag
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
Molecular analysis at BMS WFD Discovery of baseline resistant samples 
and baseline sensitive controls in cases of subsequent on-treatment 
virologic failure
a By definition, a pharmacodiagnostic sample (PDx) is a pre-treatment test to determine whether or not a patient is likely to respond to a drug (ie, a predictive 
test). Based on the results of clinical studies with BMS-955176, BMS may have to develop a PDx assay. Thus, PDx samples obtained at Screening in this 
study would be used for that sole purpose.
Revised Protocol No.: 01
Date: 19-Mar-2015
56
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Eligibility Assessments
Inclusion/Exclusion Criteria
X
Non-Laboratory Safety Assessments
Full Physical Examination
WK 12, 24, 48, 96/ET
See Section 5.3.1 for requirements
Targeted Physical Examination
X
WK 4, 8, 16, 32, 40, 60, 72, 84
See Section 5.3.1 for requirements
Vital Signs & Physical 
Measurements
X
X
See Section 5.3.1 for requirements
Adherence Assessments
X
X
Including review of Dosing Diaries
Pre-treatment Events
X
See Table 5.1-1
Adverse Events Assessments
X
X
X
Serious and Non-serious AEs
Concomitant Medications
X
X
X
See Section 5.3.3
ECG
X
WK 4, 12, 24, 48, 96/ET
See Section 5.3.4 for requirements
Pregnancy Test
X
X
X
For females under age 55, an FSH 
level must be on record to confirm 
she is not a WOCBP if pregnancy 
testing is not being performed.
If positive urine, request serum 
hCG quant. on lab requisition.
Revised Protocol No.: 01
Date: 19-Mar-2015
57
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Provide WOCBP with Home 
Pregnancy test kit(s) to be used 
during the in-clinic visit interval
WK 16, 24, 32, 40,
48, 60, 72, 84
Provide One Kit at Weeks 16 - 40
Provide Two Kits at Weeks 48 - 84
WOCBP subjects perform test Q4 
weeks at home and report results to 
site.
Laboratory Assessments for Safety and Efficacy and Other Endpoints
Fasting Chemistry
X
X
Fasting overnight
Fasting Lipid Panel
X
WK 4, 12, 24, 48, 96/ET
Fasting overnight
Hematology
X
X
Urinalysis
X
X
Fractional Excretion of Phosphorous 
(FePO4)
(Urine creatinine and phosphorus, 
Serum creatinine and phosphorus)
X
WK 48 and 96/ET
Plasma HIV-1 RNA
X
X
X
If collecting an HIV-1 RNA at an 
UNSCHEDULED visit, also collect 
samples for Resistance and 
Exploratory Resistance Testing
CD4 and CD8 T-cell counts
X
X
HBV Surface Antigen
WK 48 and 96/ET
HCV Serology
WK 48 and 96/ET
Positive HCV Ab will reflex to 
HCV RNA
Revised Protocol No.: 01
Date: 19-Mar-2015
58
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
X
Samples stored and tested if needed
(ie, analyses of subjects if deemed 
clinically relevant)
See Section 5.4.2.2
PhenoSense Gag
X
X
Next Generation Seq. - Qs Gag
X
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
X
Samples stored and tested
retrospectively if needed (ie,
exploratory analyses for subjects if 
deemed clinically relevant)
Intensive PK sample collection
X
Use of PK Tools for data collection 
recommended.
See Section 5.5.1 for requirements
Sparse PK sample collection
WK 4, 8, 12, 16, 24
See Section 5.5.2 for requirements
Bone Biomarkers
(P1NP and CTX)
X
WK 12 and 24/ET
Serum collection
Renal Biomarkers
(2-microglobulin and creatinine)
X
WK 48 and 96/ET
Urine collection
Backup Serum and Plasma Sample
X
X
Samples stored and tested if needed
Revised Protocol No.: 01
Date: 19-Mar-2015
59
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Outcomes Measures
EQ-5D-3L Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Health Outcomes Questionnaire
FAHI Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Functional Assessment of HIV 
Infection
Clinical Drug Supply
Call IVRS to Randomize
X
Dispense Study Drug
X
X
There is no dispensation at Week 96 
or ET.
Revised Protocol No.: 01
Date: 19-Mar-2015
60
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory 
value). The Screening Period for this study is 42 days.
Any new result will override the previous result (ie, the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. Consultations 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant (eg, a previously failed inclusion criterion).
Rescreening is different than Retesting. Rescreening is the process of Re-enrollment and requires 
that all procedures be repeated in an entirely new screening period. Rescreening will also be 
allowed. If it is clinically reasonable, and upon Investigator assessment (and in consultation with 
the BMS Medical Monitor, if necessary), a subject may be rescreened multiple times during the 
entire course of the enrollment period. Therefore, subjects may be Rescreened, if, in the opinion 
of the Investigator, a current clinical outlook of the subjects seems favorable for study inclusion 
(and if the patient never received study medication in this trial).
The assigned patient identifier (PID) for the subject must be Screen Failed in the IVRS. A new 
call must be made to the IVRS for the assignment of a new PID for the subject, and all Screening 
parameters must be done again in reference to the new PID (See Section 3.3.1, Inclusion 
Criteria 2f). Subject must also be re-consented with the new PID.
5.2
Study Materials
The sponsor will provide each investigative site with the following:

BMS-955176 Investigator Brochure (IB) and any relevant safety addenda or updates

Protocol and any Amendments to the Protocol

Instructions for completing electronic Case Report Forms (eCRFs)

Laboratory Manual from the central laboratory

ECG Machines and manual

IVRS Worksheets to complete when calling the IVRS center to enroll, randomize, and 
discontinue subjects

Patient-reported Outcomes Questionnaires: EQ-5D-3L Health Outcome Questionnaire, FAHI 
(Functional Assessment of HIV Infection)

PK Tools/Job Aids that may be used for detailed instruction about the PK visits, and as a 
comprehensive source for documents of date/times of dosing and blood sampling

Dosing Diaries

Completion by subjects is required
Revised Protocol No.: 01
Date: 19-Mar-2015
61
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Should include daily dose of study medications administered by subject, modified or 
missed

Site staff should review the diaries with the subject at each visit, and, in combination with 
detailed questioning, should be able to provide comprehensive information in the case 
report form, noting discrepancies in the subject’s file. Dosing Diaries should be 
maintained in the subject’s study file.
5.3
Safety Assessments
The investigative team should follow the protocol-specified scheduled of safety-related 
measurements. Only data for the procedures and assessments specified should be submitted to 
BMS on the case report form. Additional procedures and assessments may be performed as part 
of standard of care, however, data for these assessments should remain in the subject’s medical 
record and should not be submitted to BMS, unless specifically requested (ie, as part of an SAE).
5.3.1
Vital Signs and Physical Examinations
The schedule of vital signs, physical examinations, and targeted physical examinations is 
provided in Section 5.1 (Flow Chart/Time and Events Schedule). Vital signs include heart rate, 
blood pressure, respiration rate, and temperature and should be measured after the subject has 
been sitting/resting for at least 5 minutes. Physical measurements include height and weight. 
Targeted physical examinations will include examination of the heart, lungs, skin, abdomen, any 
symptomatic organ system, and general appearance.
5.3.2
Adverse Events
Subjects will be closely monitored throughout the study for any new or ongoing HIV-related 
diagnoses (Appendix 2) and/or adverse events. CDC Class C events that occur from the 
Screening Visit through Day 1 (prior to dosing), will be recorded as Pre-treatment Events. All 
events that occur after dosing on Day 1 will be recorded on the appropriate Adverse Event eCRF. 
Additional information on Adverse Events is provided in Section 6.
5.3.3
Concomitant Medication Assessment
All medications taken from the Screening Visit throughout the duration of the study will be 
reported. In addition, any prior therapy with antiretroviral drugs will be reported
(See Appendix 1 for Prohibited and Precautionary Therapies).
5.3.4
Electrocardiograms
The schedule of electrocardiograms (ECGs) is provided in Section 5.1 (Flow Chart/Time and 
Events Schedule). ECG machines will be provided by a central vendor who will also perform the
read/interpretation of the output.
5.4
Efficacy Assessments
5.4.1
Primary Efficacy Assessment
The primary assessment for efficacy is HIV-1 RNA through Week 24.
Revised Protocol No.: 01
Date: 19-Mar-2015
62
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.1
Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing
A confirmatory HIV-1 RNA viral load should be obtained when:

HIV-1 RNA 40 c/mL if prior suppression 40 c/mL, or

> 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is 
40 c/mL
All efforts should be made to collect this sample within 2-4 weeks from the collection of the 
original sample.
When collecting a blood sample for HIV-1 RNA testing at an Unscheduled visit, samples should 
also be collected for the sets of Resistance and Exploratory Resistance Tests, so that the samples
are available should resistance testing be required or deemed necessary based on the result of the 
HIV-1 RNA test.
Table 5.4.1.1-1:
Management of Detectable HIV-1 RNA, based on Confirmed 
(2-4 weeks from original sample) or Consecutive HIV-1 RNA 
Resulta
Day 1 through Week 24
40 - 399 c/mL
Reinforce Adherence
400 c/mL
Consider the need for resistance testing, in consultation with BMS Medical Monitor.
Consider possible discontinuation of subject, in consultation with BMS Medical Monitor, 
and/or reinforce adherence.
After Week 24 through Week 48
40 - 399 c/mL
Reinforce Adherence
400 - 999 c/mL
Resistance testing will be performed.
If resistance has developed, subject must be discontinued.
If resistance has not developed, consider possible discontinuation of subject, in consultation 
with BMS Medical Monitor, and/or reinforce adherence.
1000 c/mL
Resistance testing will be performed.
Regardless of result of resistance tests, subject must be discontinued (see Section 3.5).
After Week 48
< 200 c/mL
Reinforce Adherence
200 c/mL
Subject must be discontinued (see Section 3.5). 
If 400 c/mL, consider the need for resistance testing, in consultation with BMS Medical 
Monitor.
a When discontinuation is required or otherwise warranted and resistance results are needed, subject may continue 
on study medication/on study until resistance testing results are available.
Revised Protocol No.: 01
Date: 19-Mar-2015
63
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.2
Protocol Defined Virologic Failure
Protocol Defined Virologic Failure (PDVF) is defined by a subject meeting one of the following 
three criteria:
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir 
is 40 c/mL
2) Confirmed HIV-1 RNA 400 c/mL after Week 24
3) Failure to suppress last HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot 
window
In addition to the clinical management outlined in section 5.4.1.1, samples meeting criteria for 
PDVF will also be sent for resistance and exploratory resistance testing.
5.4.2
Secondary Efficacy Assessments
5.4.2.1
CD4+ and CD8+ T-Cells
CD4+ and CD8+ T-cells counts and percentages will be assessed using flow cytometry. The 
schedule of assessments is provided in Section 5.1 (Flow Chart/Time and Events Schedule). 
Procedures for samples collection and processing are provided in the central clinical laboratory 
manual.
5.4.2.2
Drug Resistance Testing
Plasma samples for viral drug resistance testing will be collected at Screening for all subjects and 
the HIV-1 drug resistance genotype will be analyzed to rule out resistance to any component of 
the study regimen or specific resistance mutations as outlined in Section 3.3.2, Exclusionary 
Criteria. At subsequent visits, samples for emergent drug resistance testing (both genotypic and 
phenotypic) will be collected and stored to be as outlined in Section 5.4.1.
5.5
Pharmacokinetic Assessments
It is extremely important to record the exact dose and time of the dose(s) taken the day prior to 
the visit/collection, and the exact date and time of the sample collection, even if drawn slightly 
off-schedule.
5.5.1
Intensive Pharmacokinetic Assessment
A subset of subjects (about 12 subjects per treatment group) will participate in an optional 
Intensive PK assessment at Week 2 (window Day 12-16).
Intensive PK samples collected in this study will provide for the assessment of BMS-955176, 
ATV, RTV, and DTG to support the secondary and exploratory objectives (to characterize the 
PK of BMS-955176, DTG, and ATV (with or without RTV) when given in combination, and to 
compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV).
Intensive PK sampling begins with a morning pre-dose (0 hour) sampling, ie, prior to the 
administration of the morning doses of the study drugs on the day of the visit. The sampling 
Revised Protocol No.: 01
Date: 19-Mar-2015
64
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
should also begin 24 hours after the morning doses of the study drugs that were taken the day 
prior to the visit.
The subsequent 11 time points include samplings through Hour 12, with the last sample collected 
at Hour 24. The subject will either stay overnight or will return to the clinic so that the final 
sample can be collected at Hour 24.
It is critical to capture the exact date and time of each PK sample collection, even if drawn 
slightly off-schedule. There is no specified collection window end for which any one time point 
should be abandoned as the schedule progresses. If a sample collection time point is missed/late 
and the next collection time point has not yet been reached, collect the missed time point, and 
record the exact time of that collection, then get back on track for the next time point/on-time 
collection.
Table 5.5.1-1 lists the sampling schedule to be followed for the assessment of intensive 
pharmacokinetics. Further details of PK blood collection and sample processing will be provided 
in the central clinical laboratory manual.
Table 5.5.1-1:
AI468048 Intensive Pharmacokinetic Sampling Schedule at Week 2
Time 
(Event)
Time 
(Relative to Dosing)
Hour: Min
PK
Blood Sample
Study Week 2
(window Day 12-16)
0 (morning pre-dose)
00:00
X
1 Hr
01:00
X
2 Hr
02:00
X
2.5 Hr
02:30
X
3 Hr
03:00
X
4 Hr
04:00
X
4.5 Hr
04:30
X
5 Hr
05:00
X
6 Hr
06:00
X
8 Hr
08:00
X
12 Hr
12:00
X
24 hr (morning pre-dose)
24:00
X
5.5.2
Sparse Pharmacokinetic Assessments
All subjects will provide Sparse PK samples (as part of the regular blood collection) for the 
assessment of BMS-955176, ATV, RTV and DTG at visit Weeks 4- 24.
Revised Protocol No.: 01
Date: 19-Mar-2015
65
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Of the five visits (Week 4 - 24), it is requested that the following guidelines are followed:

At any one visit Week 4 through Week 24, the Sparse PK sample must be collected 
approximately 24 hours (between 20 and 28 hours) after the dose that was taken the morning 
before and before the morning dose is taken on the day of the visit

At the remaining four visits Week 4 through Week 24, the blood collections may be done 
without any specific consideration to timing of previous dose administration (taken either the 
day before the visit or on the day of the visit), though it is critical that the date and time of the 
most previous dose of study drug is recorded in the eCRF so that the exact interval between 
dose and blood sampling can be calculated for accurate PK analysis
PK Samples need to be tested on an ongoing basis prior to the Week 24 database lock and 
analysis.
5.6
Biomarker Assessments
In this study, BMS is confirming the safety of BMS-955176 demonstrated in the Phase 2a study 
to date. The proposed sample population of treatment-experienced adults in Arms 3, 4, and 5, 
will provide a representation of the potential benefits of BMS-955176 on nucleoside and RTV 
based toxicities of interest (ie, renal toxicity, bone mineral density, and dyslipidemia): Arms 3 
and 4 relative to Arms 1, 2, and 5.
Specifically, to evaluate for renal toxicity we will evaluate clinically relevant parameters and 
biomarkers for glomerular and tubular toxicity, which may include but are not limited to: 
fractional excretion of phosphorous and urinary β2-microglobulin/creatinine, in all available 
subjects. To evaluate for bone-related toxicity, clinically relevant bone biomarkers for both 
formation and resorption will be evaluated in all available subjects. These may include but are 
not limited to: N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked 
C-telopeptide of Type 1 collagen (CTX). The bone and renal biomarkers will be collected and 
measured at time points specified in Table 5.1-2 Additionally, back-up plasma and serum 
samples (at Baseline, Week 24, and Week 48) will be obtained for potential future evaluation of 
the safety of BMS-955176.
Samples will be collected at the screening visit for HIV-1 Gag sequencing, phenotypic 
susceptibility (PhenoSense Gag) and potential pharmacodiagnostic analysis as specified in Table 
5.1-1. These samples may be analyzed, if deemed clinically relevant, as a predictive marker of 
clinical response.
Any remaining blood and urine specimens that are available after completion of the designated 
analyses may be used in the future for identification of potentially predictive or 
pharmacodynamic markers of study drug activity or to enhance the understanding around disease 
biology, except where prohibited by local laws or regulations.
5.7
Outcomes Research Assessments
Increases in CD4 counts and avoidance of opportunistic infections and other AIDS-defining 
illnesses have been shown in many studies to improve health related quality of life (HRQoL). To 
Revised Protocol No.: 01
Date: 19-Mar-2015
66
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
help assess whether use of BMS-955176 will result in a better quality of life outcome, both a 
disease specific quality of life assessment and a generic quality of life assessment will be 
administered. Disease specific instruments are more sensitive to disease specific changes in 
quality of life and are more likely to show improvement with new interventions. The generic 
instruments are needed because Health Technology Authorities often require use of these 
instruments for cost-effectiveness modeling.
The Functional Assessment of HIV (FAHI) is the disease specific instrument that will be used. 
The FAHI evaluates physical well-being, functional and global well-being, emotional 
well-being/living with HIV, social well-being and cognitive functioning. It yields a total score 
and individual subscale scores.
The EQ-5D-3L is the generic instrument that will be used. The EQ-5D-3L includes two parts: the 
EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L 
descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some 
problems, extreme problems. The EQ VAS records the respondents’ self-rated health on a 
100 point, vertical, visual analogue scale where the endpoints are labeled ‘Best imaginable health 
state’ and ‘Worst imaginable health state.’
5.8
Other Assessments 
We will obtain back-up plasma and serum samples for current/future evaluation of the efficacy, 
safety and tolerability of BMS-955176. 
Should any new safety signal develop during the course of the ongoing analysis of the Phase 2a 
trial, appropriate measures for evaluation and management will be incorporated into the design 
of the Phase 2b trial via a protocol amendment.
5.9
Results of Central Assessments
The following describes the centrally assessed parameters and the timing with which they will be 
shared with investigators, if pertinent. Some parameters are relevant to ongoing subject 
management during the study and will be provided to the site for such purpose, while others are 
not relevant to subject management during the study and results may only be shared in a 
summarized way at the end of the study.

Samples sent to the central lab vendors for safety and efficacy assessments and that are tested 
real time will be provided to the sites as soon as results are available

The results of the read of each ECG will be sent to the site by the central ECG vendor as 
soon as results are available

Samples collected on-treatment for resistance testing will be tested if deemed clinically 
relevant (eg, if the development of resistance is suspected). If tested, results will be reported 
to the site

Other samples (including but not limited to biomarker assessments, exploratory resistance, 
pharmacodiagnostics) may not be tested immediately, and may only be tested if deemed 
clinically relevant. Results may be suppressed from laboratory reports and may not be 
provided to the sites
Revised Protocol No.: 01
Date: 19-Mar-2015
67
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Individual PK results will not be reported to the site; the overall PK assessments will be 
included in the CSR

Individual assessments of the Outcomes research will not be reported to the site; the overall 
Outcomes assessments will be included in the CSR
6
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE). The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term "reasonable causal relationship" means there is evidence to suggest a causal 
relationship.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs).
6.1
Serious Adverse Events
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

results in death

is life-threatening (defined as an event in which the subject was at risk of death at the time of 
the event; it does not refer to an event which hypothetically might have caused death if it 
were more severe)

requires inpatient hospitalization or causes prolongation of existing hospitalization 
(see NOTE below)

results in persistent or significant disability/incapacity

is a congenital anomaly/birth defect

is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above).
Examples of such events include, but are not limited to, intensive treatment in an emergency 
Revised Protocol No.: 01
Date: 19-Mar-2015
68
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization). Potential drug induced liver injury (DILI) is also considered an 
important medical event. (See Section 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must
be handled as
SAEs. 
(See Section 6.1.1 for reporting pregnancies).
NOTE:
The following hospitalizations are not considered SAEs in BMS clinical studies:

a visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason)

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochure (IB) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
and within 30 days of discontinuation of dosing.
The investigator should report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure.
An SAE report should be completed for any event where doubt exists regarding its seriousness.
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship should be specified in the narrative section of the SAE Report Form.
Revised Protocol No.: 01
Date: 19-Mar-2015
69
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
SAEs, whether related or not related to study drug, and pregnancies, must be reported to BMS 
(or designee) within 24 hours. SAEs must be recorded on the SAE Report Form; pregnancies on 
a Pregnancy Surveillance Form (electronic or paper forms). The preferred method for SAE data 
reporting collection is through the eCRF. The paper SAE/pregnancy surveillance forms are only 
intended as a back-up option when the eCRF system is not functioning. In this case, the paper 
forms are to be transmitted via email or confirmed facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. The paper forms should be used and submitted immediately, only 
in the event the electronic system is unavailable for transmission. When paper forms are used, 
the original paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports should include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, a follow-up SAE report should be sent within 24 hours to the BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs should be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (paper or electronic) as appropriate:
Revised Protocol No.: 01
Date: 19-Mar-2015
70
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Any laboratory test result that is clinically significant or meets the definition of an SAE

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance 
Form to BMS Designee within 24 hours and in accordance with SAE reporting procedures 
described in Section 6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner 
(eg, dose tapering if necessary for subject safety).
In the rare event that the benefit of continuing study drug is thought to outweigh the risk, after 
consultation with BMS, the pregnant subject may continue study drug after a thorough 
discussion of benefits and risk with the subject.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated.
The investigator must immediately notify the BMS (or designee) Medical Monitor of this event 
and complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours 
and in accordance with SAE reporting procedures described in Section 6.1.1.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important.
All occurrences of overdose must be reported as an SAE (see Section 6.1.1 for reporting details).
Revised Protocol No.: 01
Date: 19-Mar-2015
71
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
6.6
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
Potential drug induced liver injury in HIV-1 mono-infected subjects is defined as:
1. AT (ALT or AST) elevation > 3 times upper limit of normal (ULN)
AND
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3. No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic
6.7
Other Safety Considerations
Any 
significant 
worsening
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
6.7.1
Toxicity Management
6.7.1.1
Management of Elevations in Liver Transaminases
The following Table 6.7.1.1-1 summarizes the management of elevations in liver transaminases:
Table 6.7.1.1-1:
Management of Elevations in Liver Transaminases Grade Level of 
AST or ALT Recommendationsa
Grade
Recommendation
Grade1
None
Grade 2
none
Grade 3
Confirm elevation, evaluate for potential causes (including but not limited to alcohol or other 
substance abuse, concomitant medications, reactivation of existing or de novo infection with 
hepatitis viruses) consult with BMS Medical Monitor or designate as soon as possible.
Grade 4
Interrupt all study medications, evaluate for potential causes (including but not limited to alcohol 
or other substance abuse, concomitant medications, reactivation of existing or de novo infection 
with hepatitis viruses), monitor values frequently and consult with BMS Medical Monitor or 
designate as soon as possible. If Grade 4 is deemed related to study medication the subject must 
be discontinued from the study. Otherwise, if reinstitution of study therapy is considered, please
obtain approval from the BMS Medical Monitor or designate.
a If persisting (> Grade 1/2), evaluate for alternative etiologies, including alcohol use and viral hepatitis
Revised Protocol No.: 01
Date: 19-Mar-2015
72
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
6.7.1.2
Management of Renal Toxicity
Serum phosphate levels and creatinine clearance (CrCl; CCL: as calculated by the Cockcroft 
Gault Equation [see Appendix 4] or eGFR) should be monitored and managed as described in the 
Viread local package insert/label.29 Dose interval adjustments of TDF (Viread) are permitted, as 
described in Section 4.5.2.
6.7.1.3
Management of Hyperbilirubinemia
Most patients taking ATV experience asymptomatic elevations in indirect (unconjugated) 
bilirubin related to inhibition of UDP-glucuronosyl transferase (UGT). Hepatic transaminase 
elevations that occur with hyperbilirubinemia should be evaluated for alternative etiologies. Dose 
modification of ATV is not permitted. Subjects who experience unacceptable jaundice/scleral 
icterus should be discussed with the BMS Medical Monitor or designate to determine if subjects 
are to be discontinued from study. The investigator must contact the BMS Medical Monitor or 
designate prior to discontinuing any subject due to hyperbilirubinemia.
6.7.1.4
Gastrointestinal Toxicity Evaluation and Management Plan
Pre-clinical toxicology studies in rats and dogs (see Section 1.4.1.2) have suggested a potential 
for GI related toxicity with BMS-955176. This section provides general guidance to the 
Investigator on the evaluation and management of primarily upper gastrointestinal symptoms. 
The Investigator may contact the Medical Monitor to discuss evaluation and management 
(including interruption of ARVs or discontinuation of a subject) of any GI symptoms throughout 
the trial.
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical 
trial. 
Nausea and Vomiting
The investigator should attempt to identify the etiology of these symptoms (and whether 
it is intraperitoneal, extraperitoneal, medication related, infection related, or due to a 
metabolic disorder).36 Medications can cause nausea and vomiting acutely. 
Dyspepsia
The Investigator should identify the presence of red flags (odynophagia, unexplained 
weight loss, recurrent vomiting, GI bleeding, jaundice, palpable mass or adenopathy, or 
family history of GI malignancy). Symptoms of dyspepsia could include early satiety, 
bloating, or belching. Additionally, atypical symptoms of dyspepsia could include: 
pharyngitis, asthma, bronchitis, hoarseness, chest pain, or abdominal pain. 
Ulcerative Disease
Symptoms suggestive of ulceration often are intermittent over a period of weeks to 
months and may be relieved by eating or antacid use;37 penetrating ulcers become more 
acute with localized pain and may not improve with food.38 The development of 
perforation may be indicated by severe diffuse abdominal pain. 
Other Clinical 
Syndromes
Additional diagnostic criteria for other GI disorders potentially encountered in the 
clinical trial are available elsewhere.39
Revised Protocol No.: 01
Date: 19-Mar-2015
73
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical 
trial. 
PHYSICAL 
EXAMINATION
Physical examination should complement elements obtained from the history37
Acutely, the investigator may assess for signs of intravascular volume depletion 
(eg, orthostasis) and/or aspiration of vomitus as appropriate. Abdominal 
tenderness and guarding may indicate inflammation. The presence of fecal blood 
can indicate mucosal damage (eg, from an ulcer). Complete evaluation of dyspepsia 
should include an oral examination (poor dentition or pharyngeal erythema) and 
lungs for wheezing. 
DIAGNOSTIC 
EVALUATION 
AND 
MANAGEMENT
A major goal in the diagnostic evaluation of a subject with upper GI symptoms is 
to quickly arrive at a final diagnosis without exposing the subject to unnecessary 
(invasive) testing; Investigators should exercise good clinical judgment38 in this 
regard. A major goal of therapy is directed at correcting the underlying 
identifiable medical or surgical abnormalities. Consultation (eg, gastroenterologist) 
is recommended as clinically indicated.
Grade 1 symptoms
Subjects may be treated symptomatically. If subjects develop dyspepsia alone, generally 
only limited and direct diagnostic testing should be performed.37 If the subject has 
dyspepsia they should limit alcohol, caffeine, chocolate, tobacco, other contributing 
concomitant medications (eg, NSAIDs) and eating directly before bedtime. A variety of 
OTC medications are available to address constipation and diarrhea as indicated. Please 
refer to Appendix 1 for Prohibited and Precautionary Therapies.
Grade 2 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

Serum chemistries and assessment of hemoglobin if not recently performed. 

Testing for Helicobacter pylori

Serologies (eg, celiac disease) 

PCR for viruses (eg, CMV)

Iron panel or Vitamin B12 level
For subjects who develop dyspepsia or are infected with H. pylori the use of H2 
antagonists, PPIs, Sucralfate, and antacids are prohibited (see Appendix 1 Prohibited 
Medications). If such therapy is required, discontinuation from the trial is necessary. 
The use of antiemetic’s (eg, Prochlorperazine) can be utilized as indicated. Management 
should be targeted at addressing the underlying pathology.
Grade 3 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

The testing outlined above in Grade 2

A fasting serum gastrin level can be obtained in cases of known ulcers refractory to 
therapy, a family history of the disease, or when surgery is required; of note, H. 
pylori can increase gastrin levels.38

A barium swallow to detect ulcers 

CT to identify gastrointestinal inflammation and a penetrating or perforated ulcer. 
Revised Protocol No.: 01
Date: 19-Mar-2015
74
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical 
trial. 

Upper endoscopy with biopsy as indicated in order to evaluate dyspepsia further 
(eg, mucosal injury, new onset unexplained dyspepsia in subjects > 55 y/o, or the 
presence of red flags).
Management should be targeted at addressing the underlying pathology.
Grade 4 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

The testing outlined above in Grade 2 and Grade 3

An acute abdominal series

If a perforated ulcer is clinically suspected, surgical consultation may be necessary
Initial management can include correction of hemodynamic and electrolyte 
abnormalities as clinically indicated. After stabilization, management should be targeted 
at addressing the underlying pathology.
a For Grade 2-4 symptoms if any ARV is thought to have a direct causal relationship to the patient’s 
gastrointestinal symptoms, the Investigator should consider discontinuing the subject from the study and 
performing an evaluation/management plan incorporating elements above. The Investigator can consider 
interruption of the potential offending ARV(s) but must balance this with the increased probability of 
development of viral resistance/lack of efficacy. As stated above, prior to discontinuing the subject from the 
study, attempts should be made to discuss with the BMS Medical Monitor unless the safety of the subject is 
acutely at risk.
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
This is an estimation study, without statistical testing, and hence there are no power 
considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere 
around 80%. With this response rate, and 40 subjects per arm, an exact 95% confidence interval 
would run from roughly 64% to 91%.
8.2
Populations for Analyses
The following definitions are used in this document:

Enrolled subjects: Subject who signed an informed consent form and were assigned a 
Patient Identification number (PID);
Revised Protocol No.: 01
Date: 19-Mar-2015
75
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Randomized subjects: Enrolled subjects who received a treatment assignment from the 
IVRS;

Treated subjects: Randomized subjects who received at least 1 dose of BMS-955176 or 
TDF. (Also referred to as the mITT analysis set)
8.3
Endpoints
8.3.1
Primary Endpoint(s)Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Week 24. This will be assessed with the FDA snapshot algorithm. This uses 
the last on-treatment plasma HIV-1 RNA measurement, within an FDA-specified visit window, 
to determine response. 
8.3.2
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 
RNA < 200 c/mL at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with 
positive response defined as HIV-1 RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be 
assessed using the most recent version of the IAS-USA list of HIV-1 drug resistance 
mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells will be assessed using on-treatment laboratory results, and 
pre-specified visit windows

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly 
from the case report forms (CRFs). The summary will count the number of subjects that have 
at least one event

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from 
the CRFs. The summary will count the number of subjects that have at least one event

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, 
collected at Week 2 from a subset of subjects
8.4
Analyses
In general, categorical variables are tabulated with counts and percents. Continuous variables are 
summarized with univariate statistics (eg, mean, median, standard error).
Longitudinal analyses use pre-defined visit week windows. Unless otherwise specified, windows 
around planned measurement times are constructed based on the midpoint between planned 
study visits (ie, half the duration of time between study visits), and data are summarized at each 
scheduled visit. 
Revised Protocol No.: 01
Date: 19-Mar-2015
76
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
For the calculation of descriptive statistics of observed data, subjects must have a baseline 
measurement to be evaluable for longitudinal tabulations of parameter values and changes from 
baseline. 
Tabulations of the following endpoints present the number of unique subjects with an event: 
protocol deviations; interruptions of study therapy; non-study medications; adverse events; and 
laboratory abnormalities. Thus, multiple occurrences of the same event are counted only once 
per subject.
8.4.1
Demographics and Baseline Characteristics
The following demographic and baseline characteristics will be summarized by treatment arm
and overall using the treated subjects:

Demographics: age, race, ethnicity, gender, geographic region;

Disease characteristics at baseline: plasma HIV-1 RNA level, CD4+ T-cell counts and 
percentages, CD8+ T-cell counts, HIV-1 subtype;

Laboratory tests at baseline;

Pre-treatment CDC Class C AIDS events;

Prior medications
8.4.2
Efficacy Analyses
The efficacy analyses will be based on the treated subjects.
8.4.2.1
Primary Efficacy Analyses
The primary efficacy endpoint is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL 
at the Week 24 snapshot within each stage. This endpoint is assessed with the FDA snapshot 
algorithm. The primary analysis will be based on a modified ITT (mITT) approach. A sensitivity 
analysis will be conducted using an observed values approach. The two approaches will be 
implemented as follows:

Modified ITT: The numerator will be based on subjects with plasma HIV-1 RNA < 40 c/mL 
at Week 24. The denominator will be based on all treated subjects

Observed values: Similar to the mITT approach, the numerator will be based on subjects with 
plasma HIV-1 RNA < 40 c/mL at Week 24. However, the denominator will be based on the 
treated subjects with plasma HIV-1 RNA at Week 24
Response rates will be tabulated by treatment arm (within the stage) with exact binomial 95% 
confidence intervals.
Subgroup summaries will be provided to examine the impact of baseline viral load and HIV-1 
Clade (Clade AE versus Other) for both the mITT and the observed values approach. Other 
subgroup summaries may be provided to examine the impact of other important covariates such 
as CD4+ count, sex, geographic region, etc
Revised Protocol No.: 01
Date: 19-Mar-2015
77
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
8.4.2.2
Secondary Efficacy Analyses
The following secondary endpoints will be summarized by treatment arm:

Proportion of subjects with HIV-1 RNA < 40 c/mL at Week 48 and Week 96 using mITT 
and observed values

Proportion of subjects with HIV-1 RNA < 200 c/mL at Week 24, 48 and 96 using mITT and 
observed values

Change from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells over time

Newly emergent genotypic substitutions (using all on-treatment isolates) will be tabulated by 
treatment arm

The newly emergent phenotypic resistance profile (using all on-treatment isolates) will be 
tabulated by treatment arm
8.4.3
Safety Analyses
The investigators will determine the intensity of adverse events (AEs) and the relationship of 
AEs to study therapy. The investigators’ terms will be coded and grouped by system organ class 
using the latest version of the Medical Dictionary for Regulatory Activities (MedDRA) in 
production at BMS. AEs will be presented by system organ class and preferred term. 
Presentations will include both non-serious and serious adverse events, unless specified 
otherwise. If a subject had an adverse event with different intensities over time, then only the 
greatest intensity will be reported.
Deaths will be listed for enrolled subjects without regard to onset.
In analyses of fasting lipids over time, values will be excluded after the start of serum lipid 
reducing agents.
The frequency of the following safety events will be summarized by treatment arm for treated 
subjects:

SAEs

AEs leading to discontinuation of study therapy

AEs by intensity

CDC Class C AIDS events

Laboratory abnormalities by toxicity grade
8.4.4
Pharmacokinetic Analyses
The following PK parameters will be summarized by treatment arm:

Cmax: maximum observed plasma concentration

Tmax: time of maximum observed plasma concentration
Revised Protocol No.: 01
Date: 19-Mar-2015
78
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Ctau: observed plasma concentration at the end of a dosing interval (eg, concentration at 
24 hours)

C0: observed pre-dose plasma concentration

AUC(TAU) : area under the concentration-time curve in one dosing interval
8.4.4.1
Sparse Pharmacokinetic Analyses
Sparse pharmacokinetic data will be used in population PK, PK/PD and, as available, PK/VK 
analyses.
8.4.4.2
PK/PD and PK/VK Analyses
PK data obtained from this study will be pooled with data from other studies to perform an 
integrated population PK analysis, exposure-response analyses for selected safety and efficacy 
endpoints, and, as available, viral kinetic modeling of BMS-955176 in combination with other 
ARVs to support the on-going development of BMS-955176. These analyses will facilitate 
optimal dose selection for future Phase 3 studies. 
The population PK, exposure-response, and, as available, viral kinetic analyses, will be reported 
separately.
8.4.5
Biomarker Analyses
Details about the biomarker analyses will be provided in the Statistical Analysis Plan (SAP).
8.4.6
Outcomes Research Analyses
Details about the outcomes research analyses will be provided in the SAP.
8.4.7
Other Analyses (including Virologic Futility)
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 1 completes their Week 24 visit. This analysis will be conducted to evaluate whether the 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 1 (containing 
BMS-955176) to Arm 2 (containing TDF) will be made with one-sided, Fisher’s exact tests, 
conducted at the 0.01 probability level.
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 2 completes their Week 24 visit. This analysis will be conducted to evaluate whether a 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 3-4
(containing BMS-955176) to Arm 5 (containing TDF) will be made with one-sided, Fisher’s 
exact tests, conducted at the 0.01 probability level.
8.5
Interim Analyses
There are two interim analyses scheduled before the start of Stage 2.
Revised Protocol No.: 01
Date: 19-Mar-2015
79
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The first interim analysis will be conducted after approximately 50% of the randomized subjects
have completed 24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of 
SDTM (Study Data Tabulation Model) data (“level 1” data) to facilitate the development of 
models for: population pharmacokinetics; exposure-response relationships; and, as available,
viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of 
therapy in Stage 1. This will be an analysis of the available efficacy, safety, resistance and 
pharmacokinetic data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well 
as the recruiting time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If 
Stage 2 is initiated, and recruiting follows projected timelines, then it is anticipated that analyses 
will be conducted when:

The last subject in Arms 3, 4, and 5 completes the Week 24 visit

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4, and 5 completes the Week 96 visit
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
deviation or change to the protocol without prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change 
will be submitted to:

IRB/IEC for review and approval/favorable opinion

BMS

Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
subject: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
Revised Protocol No.: 01
Date: 19-Mar-2015
80
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a 
schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the 
source documents:
In addition, the study may be evaluated by BMS internal auditors and government inspectors 
who must be allowed access to CRFs, source documents, other study files, and study facilities. 
BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to BMS.
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records 
(EMRs/EHRs), adverse event tracking/reporting, protocol required assessments, and/or drug 
accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
Revised Protocol No.: 01
Date: 19-Mar-2015
81
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
9.2
Records
9.2.1
Records Retention
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS.
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include the investigational product 
and the non-investigational product(s). Records or logs must comply with applicable regulations 
and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each subject, including unique subject identifiers

amount transferred to another area/site for dispensing or storage

nonstudy disposition (eg, lost, wasted)

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for bioavailability/bioequivalence, if applicable

dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
Revised Protocol No.: 01
Date: 19-Mar-2015
82
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS electronic data capture tool, electronic CRFs will be prepared for all 
data collection fields except for fields specific to SAEs and pregnancy, which will be reported on 
the paper or electronic SAE form and Pregnancy Surveillance form, respectively. Spaces may be 
left blank only in those circumstances permitted by study-specific CRF completion guidelines 
provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated by the investigator or qualified physician who is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form. For electronic CRFs, review 
and approval/signature is completed electronically through the BMS electronic data capture tool.
The investigator must retain a copy of the CRFs including records of the changes and 
corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements 
and must only access the BMS electronic data capture tool using the unique user account 
provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the 
following criteria:

External Principal Investigator designated at protocol development

National Coordinating Investigator 

Study Steering Committee chair or their designee

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region or 
country)

Other criteria (as determined by the study team)
Revised Protocol No.: 01
Date: 19-Mar-2015
83
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study require approval by BMS prior to publication or presentation 
and must adhere to BMS’s publication requirements as set forth in the approved clinical trial 
agreement (CTA). All draft publications, including abstracts or detailed summaries of any 
proposed presentations, must be submitted to BMS at the earliest practicable time for review, but 
at any event not less than 30 days before submission or presentation unless otherwise set forth in 
the CTA. BMS shall have the right to delete any confidential or proprietary information 
contained in any proposed presentation or abstract and may delay publication for up to 60 days 
for purposes of filing a patent application.
Revised Protocol No.: 01
Date: 19-Mar-2015
84
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete Abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Female subjects must continue 
to have pregnancy tests. Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject chooses to 
forego complete abstinence.
If two forms of contraception is required, Complete abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Subjects who choose complete 
abstinence are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. Acceptable 
alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as complete 
avoidance of heterosexual intercourse is an acceptable form of 
contraception for all study drugs. This also means that abstinence is the 
preferred and usual lifestyle of the patient. This does not mean periodic 
abstinence (eg, calendar, ovulation, symptothermal, profession of 
abstinence for entry into a clinical trial, post-ovulation methods) and 
withdrawal, which are not acceptable methods of contraception. Subjects 
who choose complete abstinence are not required to use a second method 
of contraception, but female subjects must continue to have pregnancy 
tests. Acceptable alternate methods of highly effective contraception must 
be discussed in the event that the subject chooses to forego complete 
abstinence
Revised Protocol No.: 01
Date: 19-Mar-2015
85
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
11
LIST OF ABBREVIATIONS
Term
Definition
3TC
Lamivudine
AE
adverse event
AI
accumulation index
AIDS
Acquired Immunodeficiency Syndrome
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after the 
first dose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALT
alanine aminotransferase
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir
ATV/r
atazanavir boosted with ritonavir
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the time of 
the last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
A-V
atrioventricular
-HCG
beta-human chorionic gonadotrophin
BA/BE
bioavailability/bioequivalence
BID, bid
bis in die, twice daily
BCRP
Breast cancer reactive protein
BDC
Bile duct-cannulated
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
BVM
bevirimat
Revised Protocol No.: 01
Date: 19-Mar-2015
86
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
c
copies
c/mL
copies per milliliter
C
Celsius
C12
concentration at 12 hours
C24
concentration at 24 hours
CA
capsid
cART
Combination antiretroviral therapy
Cavg
average concentration
Cexpected-tau
expected concentration in a dosing interval
CD
Cluster designation (CD4; CD8)
CDC
Centers for Disease Control
CFC
corrected fold change
CFR
Code of Federal Regulations 
CI
confidence interval
CrCl
creatinine clearance
CLR
renal clearance
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CMV
cytomegalovirus
CNS
Central nervous system
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
Css,avg
average steady-state plasma concentration
CSR
Clinical study report
Ct
Expected concentration at a certain time, usually at the end of an 
expected future dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctau
Concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctrough
Trough observed plasma concentration
CT
Computed tomography
Revised Protocol No.: 01
Date: 19-Mar-2015
87
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
CTA
clinical trial agreement
CTX
Cross-linked C-telopeptide of Type 1 collagen
CYP
cytochrome p-450
D/C
discontinue
DDI
drug-drug interaction
DHHS
Department of Health and Human Services
dL
deciliter
DTG
dolutegravir
EC
Ethics committee
EC
effective concentration
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EFV
efavirenz
eg
exempli gratia (for example)
E-R
exposure-response
ESR
Expedited Safety Report
ET
Early termination or End of Treatment
EU
European Union
FAHI
Functional Assessment of HIV Infection
FDA
Food and Drug Administration
FDC
Fixed dose combination
FSH
follicle stimulating hormone
FTC
emtricitabine
g
gram
GFR
glomerular filtration rate
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
GSH
glutathione
Revised Protocol No.: 01
Date: 19-Mar-2015
88
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
h; hr
hour
HAART
Highly active antiretroviral therapy
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCG
Human chorionic gonadotropin
HCV
hepatitis C virus
HCO3-
bicarbonate
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HR
heart rate
HRT
hormone replacement therapy
HS
Human serum
HuSA
Human serum albumin
IAS
International AIDS Society
IB
Investigator brochure
IC
Inhibitory concentration
ICD
International Classification of Diseases
ICF
informed consent form
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
INI
Integrase inhibitor
IP
investigational product
IRB
Institutional Review Board
IU
International Unit
IUD
intrauterine device
IV
intravenous
IVRS
interactive voice response system
Revised Protocol No.: 01
Date: 19-Mar-2015
89
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
GALT
Gut associated lymphoid tissue
GI
gastrointestinal
kg
kilogram
L
liter
MAD
multiple ascending dose
MC
micronized crystalline
mg
milligram
MI
Maturation inhibitor
MIC
minimum inhibitory concentration
min
minute
mITT
Modified Intent to Treat
mL
milliliter
mmHg
millimeters of mercury
msec
millisecond
MOA
mechanism of action
g
microgram
M
micromolar
N
number of subjects or observations
N/A
not applicable
ng
nanogram
nM
nanomolar
NIMP
non-investigational medicinal products 
NNRTI
Non- nucleoside reverse transcriptase inhibitor
NOAEL
No observed adverse effect level
NOEL
No observed effect level
NRTI
nucleoside reverse transcriptase inhibitor
NSAID
nonsteroidal anti-inflammatory drug
pDILI
potential drug induced liver injury
PBMC
peripheral blood mononuclear cells
PCR
polymerase chain reaction
Revised Protocol No.: 01
Date: 19-Mar-2015
90
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
PD
pharmacodynamics
PI
protease inhibitor
PDVF
Protocol-defined virologic criteria
PK
pharmacokinetics
PPI
proton pump inhibitor
PR
atrial depolarization to ventricular depolarization
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
QD, qd
quaque die, once daily
QRS
interval representing the time for ventricular depolarization
QT
Duration of ventricular electrical activity
QTcF
QT corrected for heart rate using Frederica’s formula
RAL
raltegravir
RBC
red blood cell
RNA
ribonucleic acid
RTV
ritonavir
SAD
single ascending dose
SDD
spray-dried dispersion
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SDTM
Study Data Tabulation Model
SOP
Standard Operating Procedures
SP1
spacer peptide 1
Subj
subject
STR
single tablet regimen
t
temperature
T
time
TDF
tenofovir
Revised Protocol No.: 01
Date: 19-Mar-2015
91
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
TDF/FTC
Truvada (TDF 300 mg + FTC 200 mg)
TAO
Trial Access Online, the BMS implementation of an EDC capability
TAM
Thymidine analogue mutation
T-HALF
Half life
T-HALFeff_AUC
Effective elimination half life that explains the degree of AUC 
accumulation observed
Tmax, TMAX
time of maximum observed concentration
TR_AUC(0-T)
AUC(0-T) treatment ratio
TR_AUC(INF)
AUC(INF) treatment ratio
TR_Cmax
Cmax treatment ratio
UGT
UDP-glucuronosyltransferase
ULN
upper limit of normal
US
United States
VF
virologic failure
VK
Viral kinetics
VLP
Virus-like particles
WBC
white blood cell
WFD
Wallingford, Connecticut, USA
WHO
World Health Organization
Wk or WK
week
WOCBP
women of childbearing potential
Revised Protocol No.: 01
Date: 19-Mar-2015
92
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
REFERENCES
1
WHO HIV Department. Global Summary of the AIDS Epidemic 2013. Available at: 
http://www.who.int/hiv/data/epi_core_dec2014.png?ua=1 Accessed 12/29/14
2
European AIDS Clinical Society. European Guidelines for treatment of HIV-infected adults 
in Europe (Oct 2013). http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf. 
Accessed Nov 30, 2013.
3
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services.
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. 
Accessed 
Nov 30, 2013.
4
United States Department of Health and Human Services, Food and Drug Administration, 
Center for Drug Evaluation and Research. Guidance for Industry Human Immunodeficiency 
Virus-1 Infection: Developing Antiretroviral Drugs for Treatment. (June 2013). Revision 1.
5
Gupta S.K., Lombaard J., Echevarria J., et. al. HIV NRTI BMS-986001 in Antiretroviral-
Naive Subjects: Week 24/49 Analyses. ICAAC 2014 Oral Abstract: H-642
6
Study AI468001 Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple 
Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of 
BMS-955176 in Healthy Subjects. Document Control No. 930071044
7
Study AI468002 Randomized, Placebo-Controlled, Multiple-Dose Study to Evaluate the 
Pharmacodynamics, Safety and Pharmacokinetics of BMS-955176 (Double-Blinded) and 
BMS-955176 with Atazanavir +/- Ritonavir (Open-Labelled) in HIV-1 Infected Subjects. 
Draft Document Control No. 930087017
8
Min 
S., 
Sloan 
L., 
DeJesus 
E., 
et. 
al. 
Antiviral 
activity, 
safety, 
and 
pharmacokinetics/pharmacodynamics 
of 
dolutegravir 
as 
10-day 
monotherapy 
in 
HIV-1-infected adults. AIDS 2011. 25(14):1737-45.
9
Walmsley SL., Antela A., Clumeck N., et. al. Dolutegravir plus abacavir-lamivudine for the 
treatment of HIV-1 infection. NEJM 2013 369(19):1807-18.
10
Raffi F., Jaeger H., Quiros-Roland E., et. al. Once-daily dolutegravir versus twice-daily 
raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week 
results from a randomised, double-blind, non-inferiority trial. Lancet ID. 2013 13(11): 
927-35.
11
Cahn P., Pozniak AL., Mingrone H,. et. al. Dolutegravir versus raltegravir in antiretroviral-
experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, 
double-blind, non-inferiority SAILING study. Lancet 2013 382(9893):700-8.
Revised Protocol No.: 01
Date: 19-Mar-2015
93
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
Stellbrink HJ., Reynes J., Lazzarin A., Dolutegravir in antiretroviral-naive adults with 
HIV-1: 96-week results from a randomized dose-ranging study. AIDS 2013 27(11):1771-8.
13
Eron JJ., Clotet B., Durant J., Safety and efficacy of dolutegravir in treatment-experienced 
subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING 
Study. JID 2013 207(5): 740-748.
14
Sanne I, Piliero P, Squires K, Thiry A, Schnittman S. Results of a phase 2 clinical trial at 48 
weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at 
three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. 
J Acquir Immune Defic Syndr. Jan 1 2003;32(1):18-29.
15
Bertz RJ, Persson A, Chung E, et al. Pharmacokinetics and pharmacodynamics of atazanavir-
containing antiretroviral regimens, with or without ritonavir, in patients who are 
HIV-positive and treatment-naive. Pharmacotherapy. Mar 2013;33(3):284-294.
16
Molto J, Santos JR, Valle M, et al. Monitoring atazanavir concentrations with boosted or 
unboosted regimens in HIV-infected patients in routine clinical practice. Ther Drug Monit. 
Oct 2007;29(5):648-651.
17
Goutelle S, Baudry T, Gagnieu MC, et al. Pharmacokinetic-pharmacodynamic modeling of 
unboosted Atazanavir in a cohort of stable HIV-infected patients. Antimicrob Agents 
Chemother. Jan 2013;57(1):517-523.
18
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services. 
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed Nov 
30, 2013.
19
Malan DR, Krantz E, David N, Wirtz V, Hammond J, McGrath D. Efficacy and safety of 
atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy 
regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr. Feb 1 
2008;47(2):161-167.
20
Landman R, Diallo MB, Gueye NF, et al. Efficacy and safety of unboosted atazanavir in 
combination with lamivudine and didanosine in naive HIV type 1 patients in Senegal. AIDS 
Res Hum Retroviruses. May 2010;26(5):519-525.
21
Gianotti N, Seminari E, Guffanti M, et al. Evaluation of atazanavir Ctrough, atazanavir 
genotypic inhibitory quotient, and baseline HIV genotype as predictors of a 24-week 
virological response in highly drug-experienced, HIV-infected patients treated with 
unboosted atazanavir. New Microbiol. Apr 2005;28(2):119-125.
Revised Protocol No.: 01
Date: 19-Mar-2015
94
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
22
Giuntini R, Martinelli C, Ricci E, et al. Efficacy and safety of boosted and unboosted 
atazanavir-containing antiretroviral regimens in real life: results from a multicentre cohort 
study. HIV Med. Jan 2010;11(1):40-45.
23
Two Drug Combination Studies with BMS-955176 and HIV Antiviral Agents. Version 1.0. 
June 2013. DCN 930071469
24
Song I., Borland J., Chen S. Effect of atazanavir and atazanavir/ritonavir on the 
pharmacokinetics of the next-generation HIV integrase inhibitor, S/GSK1349572. Br. J. 
Pharm. 2011 72(1):103-108
25 BMS-955176 Investigator Brochure, Version 2.0, July 2013 DCN 930056146
26 BMS-955176 Investigator Brochure, Version 3.0, April 17, 2014 DCN 930056146
27 Partial response to FDA “May Proceed” Letter dated 27 Sep 2013 for IND 118,936. Bristol-
Myers Squibb Company; Jan 2014. Document Control No. 930076507 2.0. Insert this 
additional reference: “Evaluation of cross-resistance of HIV-1 Maturation Inhibitor 
BMS-955176 toward HIV-1 protease inhibitor resistant viruses. Bristol-Myers Squibb 
Company; 30-Sept-2014. Document Control No. 930083565.”
28 Evaluation of Cross Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. Document Control No. 930083565
29 Gilead 
Sciences. 
Prescribing 
Information 
for 
TDF. 
Available 
at: 
http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/viread/viread_pi.pdf.
Accessed Dec 31, 2014
30
ViiV 
Healthcare. 
Prescribing 
Information 
for 
DTG. 
Available 
at: 
https://www.viivhealthcare.com/media/58599/us_tivicay.pdf. Accessed Dec 31, 2014.
31 BMS. 
Prescribing 
Information 
for 
ATV. 
Available 
at: 
http://packageinserts.bms.com/pi/pi_reyataz.pdf. Accessed Dec 31, 2014
32 AbbVie. 
Prescribing 
Information 
for 
RTV. 
Available 
at: 
http://www.rxabbvie.com/pdf/norvirtab_pi.pdf. Accessed Dec 31, 2014
33 Evaluation of Cross-Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. DCN 930083565
34
Kestelman P. et. al., Efficacy of the Simultaneous Use of Condoms and Spermicides Family 
Planning Perspectives.Vol 23 (5); October 1991.
35
Gabbay MB, Thomas J, Gibbs A, Hold P. A Randomized Crossover Trial of The Impact of 
Additional Spermicide on Condom Failure Rates. Sex Transm Dis 2008; 35: 862-8.
Revised Protocol No.: 01
Date: 19-Mar-2015
95
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
36
Hasler WL Nausea, Vomiting, and Indigestion: Introduction. Chapter 39. Harrisons 
Principles of Internal Medicine 18th edition. 2012. McGraw Hill
37
Hasler WL and Owyang C Approach to the Patient with Gastrointestinal Disease. Chapter 
290. Harrisons Principles of Internal Medicine 18th edition. 2012. McGraw Hill
38
Soll AH and Graham DY. Peptic Ulcer Disease. Chapter 40. Textbook of Gastroenterology. 
5th edition. 2009. Blackwell Publishing
39
Rome Foundation. Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. 
Available: http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Accessed 
Dec 22 2014
Revised Protocol No.: 01
Date: 19-Mar-2015
96
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 1
LISTINGS OF PROHIBITED AND PRECAUTIONARY
THERAPIES
General Notes: 

Guidelines for the use of drugs with established or other potentially significant drug 
interactions listed in the Package Inserts of the marketed ARV agents used by subjects 
participating in this study (Reyataz, Norvir, Viread, Tivicay) should be followed. 

Medications listed in the Package Inserts as contra-indicated with the other marketed ARV 
agents used by subjects participating in this study are not permitted. 

Any immunizations deemed appropriate by the subject’s physician are permitted provided 
that the immunization is given > 4 weeks from any HIV-1 RNA measurement.

A subject may not be co-enrolled in a concomitant trial unless it is approved by the Medical 
Monitor prior to randomization.
Prohibited Therapies
Drugs that should not be administered throughout the duration of the study:
Anticonvulsants: Carbamazepine, 
Phenobarbital, Phenytoin
Use with ATV may result in decreased ATV concentrations. Use 
of Carbamazepine may result in decreased DTG concentrations.
Oral Antifungals: Itraconazole, 
Posaconazole, and Voriconazole
Use with ATV can result in increased ATV concentrations
Antimycobacterials: Rifampin, 
Rifapentine, Rifabutin
These antimycobacterials decrease ATV plasma concentrations
and may decrease BMS-955176 plasma concentrations.
St. John’s wort
Use with ATV or DTG may result in loss of antiviral therapeutic 
effect
GI motility agent: Cisapride
Potential for serious and/or life threatening reactions such as 
cardiac arrhythmias
Pimozide
Potential for serious and/or life threatening reactions such as 
cardiac arrhythmias
Zetia (ezetimibe)
Ezetimibe is a substrate of OATP1B1 (of which BMS-955176 is 
an inhibitor in vitro).
Dofetilide
Use with DTG may result in the potential for increased Dofetilide 
plasma concentrations and the risk for serious and/or life 
threatening events
Alfuzosin
ATV increases Alfuzosin concentrations which can result in 
hypotension
Benzodiazepines: Triazolam and 
Midazolam
ATV can increase the concentration of these Benzodiazepines 
with the potential to increase sedation or respiratory depression
Ergot derivatives: 
Dihydroergotamine, ergotamine, 
ergonovine, methylergonovine
ATV can increase potential for ergot toxicity (e.g. peripheral 
vasospasm)
Revised Protocol No.: 01
Date: 19-Mar-2015
97
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
HMG-CoA Reductase Inhibitors: 
Lovastatin, Simvastatin, 
Atorvastatin, Pitavastatin, 
Rosuvastatin, Pravastatin
Use with ATV may result in increased levels of HMG-CoA 
Reductase Inhibitors and potential for serious reactions such as 
myopathy
Antacids, H2 receptor angatonists, 
Proton Pump Inhibitors, Sucralfate
Use with ATV may result in decreased plasma concentrations of 
ATV. Use of Antacids containing Aluminium, Magnesium, or 
Calcium may result in decreased levels of DTG.
Macrolides: Clarithromycin
Use with ATV may result in increased Clarithromycin levels and 
QTc prolongation
Buprenorphine
Use with ATV may increase levels of Buprenorphine
Quetiapine
Use with ATV may increase levels of Quetiapine
Salmeterol
Use with ATV may result in increased levels of Salmeterol
Avanafil
Use with ATV may result in increased Avanafil levels
All drugs with antiretroviral 
activity other than those 
considered study therapy
Any drugs with antiretroviral activity not considered study 
therapy may interfere with the assessments of the study.
Precautionary Therapies
Drugs that should be administered with caution during the study:
Hormonal Contraceptives
Hormonal Contraceptives cannot be relied upon as a highly 
effective method of contraception. 
See Protocol Section 3.3.1, for more information on Highly 
Effective Methods of Contraception.
Antidepressants: Trazodone, 
Tricyclic Antidepressants (TCA)
Use with ATV/r may result in increased plasma concentrations of 
trazodone and TCA
Antimalarials: 
Atovaquone/Proguanil, Mefloquine
Use with ATV/r may result in decreased Atovaquone/Proguanil 
levels. The effect of Mefloquine on ATV/r is unknown.
Benzodiazepines: Alprazolam and 
Diazepam
ATV can increase the concentration of these Benzodiazepines 
Calcium Channel Blockers
Use with ATV may result in increased concentrations of CCB’s. 
Non-topical Corticosteroids: 
Budesonide, Fluticasone, 
Prednisone, Methylprednisolone, 
Prednisolone, Triamcinolone
Use with ATV/r may result in increased levels of glucocorticoids 
and adrenal insufficiency
Dexamethasone
Use with ATV may result in reduced levels of ATV.
Colchicine
Use with ATV may result in increased Colchicine levels
Metformin
Use with DTG may result in increased levels of metformin. 
A cation-containing (e.g. 
Magnesium) laxative
If used with DTG the laxative should be taken 2 hours before or 
6 hours after taking concomitant laxatives.
Revised Protocol No.: 01
Date: 19-Mar-2015
98
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 2
AIDS-DEFINING DIAGNOSES
I.
PARASITIC INFECTIONS
Pneumocystis carinii (PC)
1011
PC pneumonia histologically proven.
1012
PC pneumonia, clinical diagnosis by the following specifications and confirmed HIV 
infection:
A history of dyspnea on exertion or non-productive cough of recent onset (within the past 
3 months).
AND
Chest X-ray evidence of diffuse bilateral interstitial or gallium scan evidence of diffuse 
bilateral pulmonary disease;
AND
Arterial blood gas analysis showing an arterial pO2 of < 70 mmHg or a low respiratory 
diffusing capacity (< 80% of predicted values) or an increase in the alveolar-arterial 
oxygen tension gradient;
AND
Successful response to appropriate therapy and no evidence of pneumonias of other 
etiologies.
1013
Pneumocystis carinii, histologically proven, at a site other than lungs.
Toxoplasmosis (in patients > 1 month old)
1021
Toxoplasmosis, clinical diagnosis (of brain only) by the following specifications and 
confirmed HIV infection:
Recent onset of a neurologic disease consistent with toxoplasmosis;
AND
Brain imaging evidence of a mass lesion (on computed tomography, nuclear magnetic 
resonance of radiography enhanced by injection of contrast medium);
AND
Serum antibody to toxoplasmosis and successful response to therapy for toxoplasmosis.
1022
Toxoplasmosis, of brain or internal organs other than liver, spleen or lymph nodes. 
Proven by microscopy.
Isosporiasis
1031
Isosporiasis causing chronic diarrhea of > 1 month. Proven by microscopy.
Revised Protocol No.: 01
Date: 19-Mar-2015
99
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Cryptosporidiosis
1041
Cryptosporidiosis causing chronic diarrhea of > 1 month. Proven by microscopy.
II.
FUNGAL INFECTIONS
Candidiasis
2011
Candidiasis, Esophageal, definitive diagnosis by the following specifications:
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
2012
Candidiasis, Esophageal, presumptive diagnosis by the following specifications and 
confirmed HIV infection:
Recent onset of retrosternal pain on swallowing:
AND
Oral candidiasis diagnosed by the gross appearance of white patches or plaques on an 
erythematous base OR by the microscopic appearance of fungal mycelial filaments in an 
uncultured specimen scraped from the oral mucosa;
AND
Response to appropriate therapy.
2013
Candidiasis, Bronchial/Pulmonary, definitive diagnosis by the following specifications; 
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
Cryptococcosis
2022
Cryptococcosis, Extra-pulmonary, proven by microscopy (histology or cytology), culture 
or detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Histoplasmosis
2031
Histoplasmosis, Disseminated (at a site other than or in addition to lungs or cervical or 
hilar lymph nodes), proven by microscopy (histology or cytology), culture or detection of 
antigen in a specimen obtained directly from the tissues affected or a fluid from those 
tissues.
Coccidioidomycosis
2041
Coccidioidoidomycosis, Disseminated (at a site other than or in addition to lungs or 
cervical or hilar lymph nodes), proven by microscopy (histology or cytology), culture or 
detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Revised Protocol No.: 01
Date: 19-Mar-2015
100
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
2042
Coccidioidomycosis, clear reactivation of prior infection, proven by microscopy 
(histology or cytology), culture or detection of antigen in a specimen obtained directly 
from the tissues affected or a fluid from those tissues.
III.
BACTERIAL INFECTIONS
Mycobacterium
3001
Mycobacterium (unidentified species). Presumptive diagnosis, by the following 
specifications and confirmed HIV infection.
Acid fast bacilli (AFB) positive stain of specimen obtained from endoscopic biopsy or 
from a normal sterile site other than lungs, skin or cervical or hilar lymph nodes. Species 
NOT identified by culture.
Mycobacterium tuberculosis
3011
Mycobacterium tuberculosis, Pulmonary, definitive diagnosis proven by culture, without 
evidence of upper respiratory infection symptoms of Mycobacterium tuberculosis that 
could account for the positive culture.
3012
Mycobacterium tuberculosis, definitive diagnosis proven by culture, of at least one extra 
pulmonary site regardless of concurrent pulmonary involvement.
3013
Mycobacterium tuberculosis, Disseminated, definitive diagnosis proven by culture.
Mycobacterium avium intracellulare
3022
MAI in Blood, proven by culture.
3023
MAI Colitis, proven by histology and culture. (This does not include MAI of the stool 
alone).
3024
MAI, Disseminated, at a site other than or in addition to lungs or cervical or hilar lymph 
nodes, proven by culture.
Mycobacterium Kansasii, Mycobacterium Scrofulaceum and Other Atypical 
Mycobacterium
3032
M. Kansasii, in Blood, proven by culture.
3033
M. Kansasii Colitis, proven by histology and culture. (NOT including positive M. 
Kansasii of stool alone).
3034
M. Kansasii, Disseminated, at a site other than or in addition to lungs, or cervical or hilar 
lymph nodes, proven by culture.
3035
M. Scrofulaceum or other Atypical Mycobacterium, proven by culture.
Salmonella
3041
Salmonella, recurrent Bacteremia (non-typhoid), proven by culture.
Revised Protocol No.: 01
Date: 19-Mar-2015
101
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
IV.
VIRAL INFECTIONS
Cytomegalovirus
4011
CMV, Pneumonitis, pathologically or histologically confirmed. Serum antibody titer and 
culture alone is not sufficient for the diagnosis.
4012
CMV, Esophagitis, as diagnosed by histology, pathology or culture of an esophageal 
lesion. Serum antibody titer and culture of other than esophageal tissue is not sufficient 
for the diagnosis.
4013
CMV, Retinitis as evidenced by a characteristic appearance on serial ophthalmoscopic 
examinations (eg, discrete patches of retinal whitening with distinct borders, spreading in 
a centrifugal manner, following blood vessels, progressing over several months, 
frequently associated with retinal vasculitis, hemorrhage, and necrosis). Resolution of 
active disease leaves retinal scarring and atrophy with retinal pigment epithelial mottling.
4014
CMV, Colitis, as diagnosed by histology, pathology or culture of a colonic lesion. Serum 
antibody titer and culture of other than colonic tissue is not sufficient for the diagnosis.
4015
CMV, Encephalitis, as diagnosed by histology, pathology or culture of brain tissue or 
CSF. Serum antibody titer and culture of other than brain tissue or CSF is not sufficient 
for the diagnosis.
Herpes Simplex (in patients > 1 month old).
4021
HSV, Disseminated (but not encephalitis alone), proven by microscopy (histology or 
cytology), culture or detection of antigen in a specimen obtained directly from affected 
tissues.
4022
HSV, Esophagitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4023
HSV, Bronchitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4024
HSV, Pneumonitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for diagnosis.
4025
HSV, GI, other than mouth, throat, or peri-rectal, as diagnosed by microscopy (histology 
or cytology), culture or detection of antigen in a biopsy specimen obtained directly from 
affected tissue. Serological measurement and culture from other than the affected tissue is 
not sufficient for diagnosis.
Revised Protocol No.: 01
Date: 19-Mar-2015
102
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4026
HSV, Mucocutaneous, ulcers persisting for 1 month despite appropriate therapy, as 
diagnosed by microscopy (histology or cytology), culture or detection of antigen in a 
biopsy specimen obtained directly from affected tissue. Serological measurement and 
culture from other than the affected tissue is not sufficient for the diagnosis.
Progressive Multifocal Leukoencephalopathy
4041
Progressive Multifocal Leukoencephalopathy, proven by microscopy.
VI.
NEOPLASTIC DISEASES
Kaposi’s Sarcoma
6011
Kaposi’s sarcoma, Mucocutaneous, proven by microscopy.
6012
Kaposi’s sarcoma. Mucocutaneous, presumptive diagnosis with characteristic gross 
appearance and confirmed HIV infection.
6013
Kaposi’s sarcoma, Visceral.
6014
Kaposi’s sarcoma, other than above.
Lymphoma of the Brain
6021
Primary Lymphoma of the brain at any age, proven by microscopy.
Non-Hodgkins Lymphoma
6031
Small Non-cleaved lymphoma (either Burkitt or non-Burkitt type).
6032
Immunoblastic sarcoma, equivalent to any of the following, although not necessarily all 
in combination: Immunoblastic lymphoma, large-cell lymphoma, diffuse histocytic 
lymphoma.
Cervical Carcinoma
6041
Histologically proven invasive carcinoma of the cervix.
VII.
OTHER CONDITIONS
HIV Dementia/Motor Defects
7011
HIV Dementia, clinical findings of disabling cognitive and/or motor dysfunction 
interfering with occupation or activities of daily living progressing over weeks to months, 
in the absence of a concurrent illness or condition other than HIV infection that could 
explain the findings. Method to rule out such concurrent illnesses and conditions must 
include cerebrospinal fluid examination and either brain imaging (computed tomography 
or magnetic resonance) or autopsy.
Slim Disease or HIV Wasting Syndrome
7021
HIV Wasting Syndrome, findings of profound involuntary weight loss > 10% of baseline 
body weight plus either chronic diarrhea (at least two loose stools per day for 30 days) 
or chronic weakness and documented fever (for 30 days, intermittent to constant) in the 
Revised Protocol No.: 01
Date: 19-Mar-2015
103
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
absence of a concurrent illness or condition other than HIV infection that could explain 
the findings (eg, cancer, tuberculosis, cryptosporidiosis, or other specific enteritis).
7061
Recurrent pneumonia, acute onset within 12 months of most recent episode.
Revised Protocol No.: 01
Date: 19-Mar-2015
104
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 3
DAIDS TOXICITY GRADES
Revised Protocol No.: 01
Date: 19-Mar-2015
105
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
106
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
107
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
108
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
109
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
110
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
111
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
112
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
113
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
114
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
115
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
116
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
117
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
118
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
119
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
120
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
121
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
122
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
123
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
124
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 01
Date: 19-Mar-2015
125
2.0
Approved
2.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 4
COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE
Online calculator:
http://nephron.com/cgi-bin/CGSI.cgi
Manual calculation:
Male:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg)
72 x Serum Creatinine (mg/dL)
Female:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg) x 0.85
72 x Serum Creatinine (mg/dL)
1 pound = 0.4536 kilograms
Revised Protocol No.: 01
Date: 19-Mar-2015
126
2.0
Approved
2.0
v
930087072


PPD
PPD


Page:
1
Protocol Number:
AI468048
IND Number:
118,936
Ex-US
Non-IND
EUDRACT Number
N/A
Date:
28-Jan-2015
Revised Date:
03-Jun-2015
CLINICAL PROTOCOL AI468048
A Phase 2b Randomized, Active-Controlled, Staged, Open-Label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without 
Ritonavir) in Treatment-Experienced HIV-1 Infected Adults
Revised Protocol Number: 02
Incorporates Amendment(s): 05
Study Director/Central Medical Monitor
 DO, MPH
5 Research Parkway
Office 201D
Wallingford, CT  06492 USA
Telephone (office): 
Fax: 
24-hr Emergency Telephone Number
USA:
International: 
Bristol-Myers Squibb Research and Development
Virology Clinical Research and Development
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
5 Research Parkway
Wallingford, CT 06492
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
3.0
Approved
3.0
v
930087072
PPD
PPD
PPD
PPD
PPD


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 02
Date: 03-Jun-2015
2
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (eg, amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved. References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a 
copy of this revised protocol to all study personnel under your supervision, and archive the 
previous versions.
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 02
Date: 03-Jun-2015
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 02
03-Jun-2015
Incorporates Amendment 05
Amendment 05
03-Jun-2015
To mitigate the risk of randomizing subjects infected with HIV-1 with an 
unknown efficacy profile, exclusion criteria have been modified to now 
exclude subjects with Clade AE as well as those subjects who have failed a 
previous boosted PI- or Integrase strand transfer inhibitor (INSTI)-
containing regimen for which resistance analyses were not conducted at the 
time of failure. 
To remove “male condoms with spermicide” as a highly effective method 
of contraception (moved to the list of less effective methods) and require 
the use of a highly effective method of contraception as specified in the 
Clinical 
Trials 
Facilitation 
Group 
Recommendations 
Related 
to 
Contraception and Pregnancy Testing in Clinical Trials.  Most 
contraception methods were more clearly defined, including the removal of 
any text relative to hormonal methods used by female study subjects who 
are WOCBP, since they can’t be counted among the methods used at all.
Pregnancy was added as a reason to be discontinued from the study, and the 
practice of Rescreening was more clearly defined, an administrative change 
was made to clearly indicate that AIDS History will be taken at Screening,
In addition, at Week 24, a Time to Loss of Virologic Response analysis will 
be conducted as a sensitivity analysis that compliments the snapshot 
analysis, and a definition of virologic rebound was added.
A table of the laboratory assessments in detail was added as an appendix, 
and the appendix of the DAIDS Toxicity Table (updated 2009) was 
removed to include a link to the more current 2014 version of the table. In 
addition, and a table of laboratory assessment was added as a new appendix
Other changes, more administrative in nature, have been included.
Revised 
Protocol 01
19-Mar-2015
Incorporates Amendment 04
Amendment 04
19-Mar-2015
Incorporated information that more clarify the Week 24 data (consisting of 
efficacy, safety, and pharmacokinetic data) to be used to confirm the doses 
for Stage 2 and to trigger the start of Stage 2 of the study relative to other 
analyses conducted under the protocol for other purposes.
Removed the requirement that all Sparse PK samples need to be collected 
as pre-AM dose samplings.  Only one visit Weeks 4- 24 (as opposed to all 
visits Weeks 4 - 24) needs to be performed in the morning and to have the 
blood collected as a pre-AM dose sampling; (includes the deletion of 
Table 5.5.2-1).
Administrative changes.
Original 
Protocol
28-Jan-2015
Not applicable
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
SYNOPSIS
Clinical Protocol AI468048
Protocol Title: A Phase 2b Randomized, Active-Controlled, Staged, Open-label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without Ritonavir) in 
Treatment-Experienced HIV-1 Infected Adults
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): Subjects in each arm and per stage will begin QD dosing (in the morning, with a meal) with 
BMS-955176 in combination with atazanavir (ATV) [with or without ritonavir (RTV)] and dolutegravir (DTG), or 
tenofovir (TDF) in combination with atazanavir boosted with ritonavir (ATV/r) and DTG, for a duration of 
96 weeks.
Stage 1:

Arm 1: BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Study Phase: 2b
Research Hypothesis: This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with 
or without RTV) and DTG is efficacious, safe, and well-tolerated in HIV-1 infected treatment-experienced adults.
Objectives:
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg and a TDF 300 mg-containing arm, each when given in 
combination with ATV/r 300/100 and DTG 50 mg by determining the proportion of treatment-experienced 
subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when given in 
combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the antiviral efficacy of TDF 300 mg 
when given in combination with and ATV/r 300/100 mg and DTG 50 mg by determining the proportion of 
treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 Arms, and TDF-containing regimens (TDF + ATV/r + DTG), 
by determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 Arms, and TDF-containing regimens, by determining the 
proportion of treatment-experienced subjects with plasma HIV-1 RNA < 200 c/mL at Weeks 24, 48, 96
Revised Protocol No.: 02
Date: 03-Jun-2015
4
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess the emergence of HIV drug resistance in samples selected for drug resistance testing (according to 
criteria outlined in Protocol Section 5.4.1)

To assess efficacy of BMS-955176 Arms, and TDF-containing regimens, by using the mean changes from 
baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by measuring frequency 
of SAEs and AEs leading to discontinuation

To assess disease progression as measured by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV (with or without 
ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
Study Design: This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced subjects total will be randomized into the study. In Stage 1, approximately 80 subjects 
will be randomized 1:1 (approximately 40 per arm) to either of the treatment arms containing BMS-955176 or TDF 
in combination with boosted atazanavir (ATV/r) and DTG. In Stage 2, approximately 120 subjects will be 
randomized 1:1:1 (approximately 40 per arm) to either of the two BMS-955176 treatment arms containing 
unboosted ATV and DTG, or to the TDF-containing Arm containing ATV/r and DTG.
Stage 1:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
A Continuation Dose of BMS-955176 will be selected based on Week 24 data from Stage 1 and from study 
AI468038 (BMS-955176 in ARV treatment-naive HIV-1 infected subjects) with which subjects in Stage 1, Arm 1 
may transition to for the remainder of the study. The transition may occur on or after Week 48.
The data from the Week 24 analysis for AI468038 and Stage 1, including safety, efficacy and pharmacokinetics, will 
be examined to trigger the start of Stage 2 (utilizing unboosted ATV in the experimental arms) and confirm the two 
doses of BMS-955176 (in the experimental arms) for study in Stage 2.
After the Stage 2 Week 24 endpoint, a Continuation Dose of BMS-955176 will be selected based on data from 
Stages 1 and 2, and study AI468-038 with which subjects in Stage 2, Arms 3 and 4 will transition to for the 
remainder of the study. The switch in Stage 2 may occur sooner, between Week 24 and Week 48, or it may be after 
Week 48.
The assigned backbone for each arm, ATV and DTG, or ATV/r and DTG, will remain unaltered throughout the 
study.
All subjects in both stages are expected to receive study treatment for 96 weeks.
Revised Protocol No.: 02
Date: 03-Jun-2015
5
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Arm 2
TDF
300 mg QD
+ ATV/r + DTG
Day 1
Begin dosing
Arm 3
BMS-955176 
120 mg QD
+ ATV + DTG
1 Virologic Futility will be evaluated at Week 24 
(see Section 8.4.7).  
Results of Week 24 Stage 1 AI468-048 & AI468-038 
Confirm the Start of Stage 2   
Arm 4
BMS-955176 
180 mg QD
+ ATV + DTG
40
40
Week 2
Week 24
Week 24 Analysis1
Intensive PK subset
4 Based on totality of data from both studies the 
Continuation Dose for Arms 3 & 4 may be 
identified.  
Number
Randomized
STAGE 2
Week 96
Week 96 Analysis/End of Study
Week 48
Week 48 Analysis
The Switch to the Continuation Dose4,3     
is expected to occur on or after Week 48, 
but could occur sooner.
Arm 1
BMS-955176 
120 mg QD
+ ATV/r + DTG
Week 2
Number
Randomized
Week 24
Week 24 Analysis1
Day 1
Begin dosing
Intensive PK subset
40
40
Week 48
Week 96
Week 48 Analysis
Week 96 Analysis/End of Study
The Switch to             
the Continuation Dose2,3
may occur on or after 
Week 48 
STAGE 1
BMS-955176
Continuation Dose QD 
+ ATV/r + DTG
Arm 5
TDF
300 mg QD
+ ATV/r + DTG
40
3 The actual switch of subjects of BMS-955176 
subjects to that Continuation Dose may occur when 
all of the subjects have reached at least Week 48 
(though it could occur sooner in Stage 2).
BMS-955176
Continuation Dose QD
+ ATV + DTG
2 Based on Week 24 data from Arms 1 & 2 and 
from AI468-038, the Continuation Dose for 
Arm 1 may be identified.  
Revised Protocol No.: 02
Date: 03-Jun-2015
6
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Population:
Key Inclusion Criteria:

Men and non-pregnant women, at least 18 years of age (or minimum age as determined by local regulatory or as 
legal requirements dictate)

Antiretroviral treatment-experienced, defined as having documented evidence of having failed 1 or 2 regimens 
that include 2 or 3 classes of ARV (with or without documented resistance)

Confirmed Plasma HIV-1 RNA 400 copies/mL

CD4+ T-cell count > 50 cells/mm3

Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, FC < 2.2; DTG; TDF)
Key Exclusion Criteria:

Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens

Antiretroviral treatment-experienced adults infected with Clade AE

Subjects who have failed a previous boosted PI- or Integrase strand transfer inhibitor (INSTI)-containing 
regimen for which resistance analyses were not conducted at the time of failure

Resistance or partial resistance to any study drug

Three or more of the following PI mutations, historical or documented: M36I/V, M46I/L/T, G48M/V, 
I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M

Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S

Any major TDF mutation, historical or documented: K65R or T69ins

Three or more of the following non-accessory thymidine analogue mutations (TAMs): M41L, D67N, K70R, 
L210W, T215Y/F, K219Q/E

Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI resistance), historical or 
documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, Y143C/H/R, E157Q

Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV Ab and HCV RNA)

ALT or AST > 3 × ULN

Alkaline Phosphatase > 5 × ULN

Bilirubin 1.5 × ULN

History of decompensated cirrhosis or active decompensated cirrhosis

Hemoglobin < 8.0 g/dL

Platelets < 50,000 cells/mm3
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for AI468048
Medication 
Potency 
IMP/Non-IMP 
BMS-955176 
60 mg or 120 mga
IMP
Tenofovir (TDF)
300 mg
Non-IMP
Revised Protocol No.: 02
Date: 03-Jun-2015
7
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Drug for AI468048
Medication 
Potency 
IMP/Non-IMP 
Atazanavir (ATV)
200 mg and 300 mg
IMP
Ritonavir (RTV)
100 mg
Non-IMP
Dolutegravir (DTG)
50 mg
IMP and Non-IMP, based on 
country approval status
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Study Assessments: Efficacy assessments will include plasma HIV-1 RNA measurements. Safety Assessments will 
include blood chemistry and hematology, ECGs, Physical Exams and Vital Signs, and assessment of non-serious 
AEs, SAEs and AEs leading to discontinuation.
Statistical Considerations:
Sample Size:
This is an estimation study, without statistical testing, and hence there are no power considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere around 80%. With this 
response rate, and 40 subjects per arm, an exact 95% confidence interval would run from roughly 64% to 91%.
Endpoints:
Primary Endpoint(s) for Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24. This will be assessed with the FDA snapshot algorithm. This uses the last on-treatment plasma HIV-1 
RNA measurement, within an FDA-specified visit window, to determine response
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 RNA < 200 c/mL 
at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with positive response defined as HIV-1 
RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be assessed using the 
most recent version of the IAS-USA list of HIV-1 drug resistance mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the percentage of 
CD4+ T-cells will be assessed using on-treatment laboratory results, and pre-specified visit windows

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly from the case report 
forms (CRFs). The summary will count the number of subjects that have at least one event.

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from the CRFs. The 
summary will count the number of subjects that have at least one event.

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, collected at Week 2 
from a subset of subjects.
Revised Protocol No.: 02
Date: 03-Jun-2015
8
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Analyses:
There are two interim analyses scheduled before the start of Stage 2.
The first interim analysis will be conducted after approximately 50% of the randomized subjects have completed 
24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of SDTM (Study Data Tabulation Model) 
data (“level 1” data) to facilitate the development of models for: population pharmacokinetics; exposure-response 
relationships; and, as available, viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of therapy in Stage 1. 
This will be an analysis of the available efficacy, safety, resistance and pharmacokinetic data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well as the recruiting 
time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If Stage 2 is initiated, and recruiting 
follows projected timelines, then it is anticipated that analyses will be conducted when:

The last subject in Arms 3, 4 and 5 completes the Week 24 visit

At Week 24, a Time to Loss of Virologic Response (TLOVR) analysis will be conducted as a sensitivity 
analysis that compliments the snapshot analysis

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4 and 5 completes the Week 96 visit
Revised Protocol No.: 02
Date: 03-Jun-2015
9
3.0
Approved
3.0
v
930087072


TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Study Rationale ................................................................................................. 
1.1.1 Rationale to support study design ............................................................ 
1.1.2 Rationale to support the dose selection ................................................... 
1.1.3 Rationale to support drug combinations.................................................. 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objective .................................................................................... 
1.3.2 Secondary Objectives ............................................................................... 
1.3.3 Exploratory Objectives ............................................................................ 
1.4 Product Development Background ................................................................... 
1.4.1 Background Information BMS-955176 .................................................... 
1.4.1.1 Mechanism of Action....................................................................... 
1.4.1.2 Nonclinical studies .......................................................................... 
1.4.1.3 Clinical studies................................................................................ 
1.4.2 Background Information on TDF ............................................................ 
1.4.3 Background Information on DTG ............................................................ 
1.4.4 Background Information on ATV ............................................................. 
1.4.5 Background Information on RTV ............................................................. 
1.4.6 Drug-Drug Interactions ........................................................................... 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.1.1 Screening.................................................................................................. 
3.1.2 Day 1/Baseline Visit ................................................................................. 
3.1.2.1 Day 1/Baseline Visit for Arms 1 and 2 - Stage 1 ............................ 
3.1.2.2 Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2 ........................ 
3.1.3 Week 2 Intensive PK Visit ........................................................................ 
3.1.4 Visits Week 4 - 96 ..................................................................................... 
3.1.5 Selection of the Continuation Dose of BMS-955176 ............................... 
3.1.5.1 Selection of the Continuation Dose, and the Switch for Stage 1 .... 
3.1.5.2 Selection of the Continuation Dose, and the Switch for Stage 2 .... 
3.1.6 End of the study ........................................................................................ 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
1
3
4
10
14
14
14
16
19
21
21
21
21
22
22
22
22
23
28
31
31
31
32
32
32
35
35
35
36
37
37
38
38
38
38
38
39
39
39
40
40
42
42
42
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 02
Date: 03-Jun-2015
10
3.0
Approved
3.0
v
930087072


3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Other Restrictions and Precautions ......................................................... 
3.5 Discontinuation of Subjects following any Treatment with Study Drug .......... 
3.6 Post Study Drug Study Follow up .................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Instructions for Dose Administration ...................................................... 
4.5.1.1 General Instructions ....................................................................... 
4.5.1.2 Specific Dosing Instructions for Initial Treatment Arm Assignment
...............................................................................................................
4.5.2 Dose Modifications .................................................................................. 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Vital Signs and Physical Examinations ................................................... 
5.3.2 Adverse Events ......................................................................................... 
5.3.3 Concomitant Medication Assessment ...................................................... 
5.3.4 Electrocardiograms ................................................................................. 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.1.1 Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing .................................................................................. 
5.4.1.2 Protocol Defined Virologic Failure ................................................ 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.4.2.1 CD4+ and CD8+ T-Cells ............................................................... 
5.4.2.2 Drug Resistance Testing ................................................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.5.1 Intensive Pharmacokinetic Assessment .................................................... 
5.5.2 Sparse Pharmacokinetic Assessments ...................................................... 
5.6 Biomarker Assessments .................................................................................... 
5.7 Outcomes Research Assessments ..................................................................... 
44
46
46
46
46
46
47
48
48
48
50
50
50
50
51
51
51
51
52
52
52
52
53
54
54
60
60
61
61
61
61
61
61
61
62
63
63
63
63
63
63
64
65
65
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 02
Date: 03-Jun-2015
11
3.0
Approved
3.0
v
930087072


5.8 Other Assessments ............................................................................................ 
5.9 Results of Central Assessments ........................................................................ 
6 ADVERSE EVENTS ................................................................................................. 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) ..................................................... 
6.7 Other Safety Considerations ............................................................................. 
6.7.1 Toxicity Management ............................................................................... 
6.7.1.1 Management of Elevations in Liver Transaminases ....................... 
6.7.1.2 Management of Renal Toxicity ....................................................... 
6.7.1.3 Management of Hyperbilirubinemia ............................................... 
6.7.1.4 Gastrointestinal Toxicity Evaluation and Management Plan ......... 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s)Stage 1 and Stage 2 ................................................. 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Primary Efficacy Analyses .............................................................. 
8.4.2.2 Secondary Efficacy Analyses .......................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.4.1 Sparse Pharmacokinetic Analyses .................................................. 
8.4.4.2 PK/PD and PK/VK Analyses .......................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Other Analyses (including Virologic Futility) ......................................... 
8.5 Interim Analyses ............................................................................................... 
9 STUDY MANAGEMENT ........................................................................................ 
9.1 Compliance ....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
66
66
67
67
68
69
69
69
70
70
70
71
71
71
71
72
72
74
74
74
74
75
75
75
75
76
76
76
77
77
78
78
78
78
78
78
79
79
79
79
80
80
80
81
81
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 02
Date: 03-Jun-2015
12
3.0
Approved
3.0
v
930087072


9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10 GLOSSARY OF TERMS ........................................................................................ 
11 LIST OF ABBREVIATIONS .................................................................................. 
12 REFERENCES ........................................................................................................ 
APPENDIX 1 LISTINGS OF PROHIBITED AND PRECAUTIONARY 
THERAPIES ........................................................................................................... 
APPENDIX 2 AIDS-DEFINING DIAGNOSES.......................................................... 
APPENDIX 3 DAIDS TOXICITY GRADES .............................................................. 
APPENDIX 4 COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE .................................................................................... 
APPENDIX 5 LABORATORY ASSESSMENTS ....................................................... 
81
81
82
84
85
92
96
98
104
105
106
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 02
Date: 03-Jun-2015
13
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
1
INTRODUCTION AND STUDY RATIONALE
1.1
Study Rationale
Despite advances in prevention and care, HIV/AIDS remains a significant epidemic in both the 
US and worldwide. AIDS remains the 6th leading cause of death, internationally. Globally, 
approximately 35 million people were living with HIV infection in 2013.1 A number of these 
patients include those who are treatment-experienced. Note: the use of the term 
“treatment-experienced” herein refers to subjects who have failed at least one or two 
antiretroviral (ARV) regimens and who may be harboring drug resistant virus (current or 
archived) to at least one drug class.
In contrast to current HIV treatment guidelines for treatment-naïve patients, the recommended 
composition of combination
antiretroviral therapy (cART) is far less uniform for 
treatment-experienced subjects.2,3 The level of detail in the DHHS and EACS guidelines leads to 
a lack of uniformity in treatment for patients in later lines of therapy. Moreover, drug related 
toxicities (both short and longer term) in treatment-experienced subjects necessitate vigilance 
and continued monitoring. Thus, there is a need for new and efficacious agents with novel 
mechanisms of action (MOA) and favorable safety/tolerability profiles. Given the aging HIV-1 
infected population and overall fewer number of ARV options for treatment-experienced 
patients, there is a need for a more simplified regimen that may have a better long-term safety 
profile such as that of a nucleoside- and booster-sparing cART regimen. As discussed below, this 
study 
evaluates 
the 
merits 
of 
a 
nucleoside-sparing 
cART 
regimen 
and 
a 
nucleoside/booster-sparing cART regimen in Stage 1 and 2, respectively.
Given the aforementioned challenges with existing treatment in ARV treatment-experienced 
adults, the two primary objectives of this two stage, Phase 2b study are to: 1) To study the 
efficacy of one dose (120 mg) of BMS-955176 (a novel HIV-1 maturation inhibitor) when given 
in combination with atazanavir boosted with ritonavir (ATV/r) 300/100 mg and dolutegravir 
(DTG) 50 mg in Stage 1, and 2) to study the efficacy of two doses (120 and 180 mg) of 
BMS-955176 when given in combination with unboosted ATV 400 mg and dolutegravir (DTG) 
50 mg in Stage 2.
Ultimately this Phase 2b clinical trial will provide supportive data in the context of a therapeutic 
dose of BMS-955176 and the clinical safety/efficacy/resistance of the proposed component(s) of 
a single tablet regimen (STR, that is also a nucleoside/ritonavir sparing ARV strategy) for 
Phase 3 trial development in HIV-1 infected treatment-experienced subjects. Specifically, two 
arms in Stage 2 will contain the individual ARV components of a potential STR: BMS-955176, 
ATV, and DTG.
1.1.1
Rationale to support study design
This Phase 2b open-label clinical trial design is in general agreement with published Food and 
Drug 
Administration 
(FDA)
guidance.4
Initially,
in 
Stage 
1, 
approximately 
80 treatment-experienced HIV-1 infected subjects will be randomized 1:1 (approximately 40 per 
treatment group) to one experimental arm (Arm 1) and a TDF-containing arm (Arm 2). Stage 1
Revised Protocol No.: 02
Date: 03-Jun-2015
14
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
(see Figure 3.1.6-1) will study the efficacy of one dose (120 mg) of BMS-955176 when given in 
combination with ATV/r (300/100 mg) and DTG (50 mg). At the Week 24 primary endpoint of 
Stage 1, Bristol-Myers Squibb (BMS) will conduct an analysis of efficacy, safety, and 
pharmacokinetics. Combined with the Week 24 primary endpoint of AI468038 (see below), this 
analysis will be used to 1) select a continuation dose for BMS-955176 in Arm 1 of study 
AI468048, 2) trigger the start of Stage 2 (utilizing unboosted ATV in the experimental arms) of 
study in AI468048, and 3) confirm the two doses of BMS-955176 (in the experimental arms) for 
study in Stage 2 of study AI468048 (see below for further details).
AI468038 is a concurrent Phase 2b study in HIV-1 infected treatment naive adults; the primary 
objective is to evaluate three doses of BMS-955176 (60, 120, and 180 mg) and EFV when given 
in combination with TDF/FTC by determining the proportion of subjects with HIV-1 RNA < 40 
c/mL at Week 24.
To mitigate the clinical concerns of a potential subtherapeutic regimen and the subsequent 
development of virologic failure/resistance, the clinical trial design will contain a second stage. 
Specifically in Stage 2, approximately 120 additional treatment-experienced HIV-1 infected 
subjects will begin randomization 1:1:1 (approximately 40 per treatment group) to Arms 3, 4,
and 5 based upon the results of two concurrent analyses:

Results of the Week 24 analysis in Stage 1, including an analysis for virologic futility (see 
Section 8.4.7)

Results of the Week 24 analysis in AI468038 (treatment-naïve HIV-1 infected adults)
Thus, Stage 2 (Arms 3, 4, and 5) will not enroll if the likelihood of a subtherapeutic regimen 
(in Arms 3 and 4) is high based upon the results of the Week 24 analyses from either AI468038 
or Stage 1 of AI468048. Note, subjects in Arm 5 (Stage 2) will receive the same ARV regimen 
as subjects in Arm 2 (Stage 1); Arm 5 in Stage 2 exists to maintain similar baseline demographic 
and clinical characteristics among subjects who are randomized to the three Arms in Stage 2. 
This staged design allows Stage 2 (Arms 3, 4, and 5) to begin recruitment in a clinically 
de-risked fashion and accomplish this study’s Stage 2 primary study objective: to study the 
efficacy of two doses (120 mg and 180 mg) of BMS-955176 when given in combination with 
unboosted ATV 400 mg and DTG 50 mg. Ultimately, the totality of data from the Week 24 
primary endpoint of Stage 2 (Arms 3, 4, and 5), Stage 1 (Arms 1 and 2), and all arms in the 
AI468038 study will be used to select a continuation dose for BMS-955176 in Arms 3 and 4 of 
study AI468048. Across all five arms of this study, subjects will receive treatment with three 
fully-active ARVs (see Section 1.1.3, Rationale to support any drug combinations). Ultimately, 
subjects in experimental Arms 1, 3, and 4 will be given a continuation dose of BMS-955176 
which has acceptable efficacy, safety, and tolerability (see Figure 3.1.6-1) for subsequent 
development in HIV-1 treatment-experienced adults. 
Since the Phase 2a study AI468002 did not include any subjects infected with HIV-1 clade AE
(see Section 1.4.1.3), this multinational Phase 2b trial will not include Clade AE subjects. The 
Revised Protocol No.: 02
Date: 03-Jun-2015
15
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
study duration is expected to be 96 weeks in length to assess durability of response and longer 
term safety and tolerability.
1.1.2
Rationale to support the dose selection
Phase 1 and Phase 2a clinical trials (AI4680015 and AI4680026) investigating BMS-955176 
utilized a spray-dried dispersion (SDD) suspension. However, this Phase 2b study will utilize a 
micronized crystalline (MC) tablet.
In the concomitant dose-finding Phase 2b study in HIV-1 infected treatment naive adults for 
BMS-955176 (AI468038), doses of BMS-955176 of 60 mg, 120 mg, and 180 mg MC tablet are 
proposed for assessment. These doses are based upon modeling and simulation and formulation 
considerations. A population pharmacokinetic model was developed using single dose 
(10 mg - 120 mg SDD) and multiple dose (10 mg to 80 mg SDD) data in healthy subjects 
(AI468001) as well as multiple dose data in HIV-1 clade B-infected subjects (5 mg to 120 mg
SDD for 10 days, AI468002). An exposure-response analysis was conducted using data from 
Part A of the Phase 2a clinical trial where HIV-1 clade B infected subjects received 
BMS-955176 monotherapy (Dose range: 5 - 120 mg) for 10 days. The exposure-response 
relationship was assessed via an Emax model using observed BMS-955176 steady state Cmin. The 
primary endpoint was predicted maximum viral load decline from baseline.
Steady state BMS-955176 Cmin values in HIV-infected subjects administered MC tablet with 
food were projected according to the following data and assumptions:

Exposures in HIV-infected subjects are 35% less than normal healthy volunteers based on 
observations from AI468001 and AI468002 study

Single dose data projected to multiple dose using accumulation index from AI468001 study

BMS-955176 exposures from the MC tablet formulation with food were projected based on 
studies AI468001 and AI468034. The impact of food on the 60 mg MC tablet dose was 
assumed to be that observed for the 40 mg MC suspension formulation in AI468001. 
Exposures to BMS-955176 120 mg MC tablet with food were determined from observed data 
in Study AI468034, where BMS-955176 C24 increased approximately 70% when 120 mg 
MC tablet was given with a high fat meal, relative to fasted conditions. Finally, exposures to 
BMS-955176 180 mg MC tablet with food were assumed to be 1.5-times that of 120 mg MC 
tablet with food
Figure 1.1.2-1 depicts the simulated maximum viral load decline in HIV-infected subjects 
administered BMS-955176 MC tablet under fed conditions.
Revised Protocol No.: 02
Date: 03-Jun-2015
16
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 1.1.2-1:
Simulated Maximum Viral Load Decline from Baseline Under Fed 
Conditions1
1 Solid lines are 10th and 90th percentiles and the median of simulated data, shaded area is the 90% confidence 
interval of simulated data, vertical solid lines are the 25th to 75th percentile of the simulated steady state 
BMS-955176 Cmin for the 60 mg MC tablet dose, vertical dotted lines are the 25th to 75th percentile of the 
simulated steady state BMS-955176 Cmin for the 120 mg MC tablet dose, and vertical dashed and dotted lines 
are the 25th to 75th percentile of the simulated steady state BMS-955176 Cmin for the 180 mg MC tablet dose.
While baseline EC90 was not a covariate included in the model due to the lack of significance; 
this covariate, among others, was considered marginally significant and it is possible this 
covariate will become important with additional data.
Although data from AI468002 Part C (in HIV-1 clade C infected subjects) were not included in 
the exposure-response assessment described above, BMS-955176 doses 40 mg SDD once daily 
demonstrated median maximal reductions in HIV-1 RNA > 1 log10 in both clade B and clade C 
HIV-1-infected subjects (see Section 1.4.1.3); thus, doses of BMS-955176 60 mg, 120 mg, and 
180 mg are expected to yield a similar response in HIV-1 infected subjects of either clade.
Because the lowest dose assessed in AI468038 (BMS-955176 60 mg) has the potential for a 
suboptimal antiviral response and possible development of resistance, BMS-955176 120 mg in 
combination with ATV/r and DTG will be assessed in Stage 1 of this study. Based on previous 
data that demonstrated exposures to BMS-955176 increase approximately 50% when given in 
combination with RTV, exposures to BMS-955176 120 mg given in combination with ATV/r are 
expected to result in exposures similar to BMS-955176 180 mg given without RTV. Finally, 
BMS-955176 180 mg will not be used in Stage 1 because exposures (when administered with 
RTV) are expected to exceed those previously studied in clinical trials.
Revised Protocol No.: 02
Date: 03-Jun-2015
17
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.1.2-1 depicts the projected exposure multiples of BMS-955176 60 mg, 120 mg, and 
180 mg MC tablet with food at the NOAEL for pre-clinical findings of interest.
Table 1.1.2-1:
Exposure Multiples of BMS-955176 at NOAELa
Species/ Study 
NOAEL
Multiples
Dose 
(mg/kg/d)
Exposure
PK 
Parameter
60 mg
120 mg
180 mg
Rat/6-month (stomach 
histologic changes) 
No NOAEL
AUC
---
---
---
Dog/9-month (stomach 
histologic changes) 
1
AUC:
64.9 gh/mL
AUC 
3
2
1
Dog/1-month (heart rate)
20
Cmax:
17.8 g/mL 
Cmax
19
10
5
Dog/ Cardiovascular 
telemetry (heart rate) 
2
Cp:
1.93 g/mL 
Cmax
2
1
0.5
Mouse/EFD 
45
AUC:
197 gh/mL 
AUC
10
6
3
a Exposure multiple = animal value ÷ human value. Projected human Cmax values are 0.94, 1.79, and 3.61 g/mL 
and steady state AUC values are 19.3, 35.8, and 69.2 g•h/mL at 60, 120, and 180 mg in HIV-1 subjects 
receiving BMS-955176 MC tablets with high fat meal, respectively. High fat meal provides the highest exposure 
relative to other meal types or fasted state.
With regard to heart rate and the NOAEL of 1.93 g/mL observed in the cardiovascular 
telemetry study in dogs (N=2), it is noted that the projected exposure multiple is 1 at a dose of 
120 mg MC tablet in HIV-infected subjects. However, to date, there have been no clinically 
meaningful changes in heart rate observed in subjects treated with BMS-955176 up to 28 days
(in Part B of the Phase 2a study). With regard to stomach histologic changes, no NOAEL could 
be established based on the 6-month rat study and the projected exposure multiples from the 
9-month dog study are relatively low (eg, 2-fold at the 120 mg MC tablet dose). Despite these 
preclinical findings, a dose of BMS-955176 120mg MC tablet will provide exposures in this 
study which are expected to be generally safe and well tolerated based on existing clinical data 
(see Section 1.4.1).
Data from Study AI468034 demonstrated that BMS-955176 120 mg MC tablet AUC increased 
53% when given with a high fat meal, relative to fasted conditions. Furthermore, preliminary 
data from Study AI468049 demonstrated that a light meal, a standard meal, and a high fat meal 
increased BMS-955176 180 mg MC tablet AUC 1.8-, 2.1-, and 2.5-fold, respectively, relative to 
fasted conditions. Taken together, these data suggest that exposures to BMS-955176 MC tablet 
at doses up to 180 mg increase in a linear fashion when given with food and that similar 
exposures are observed regardless of meal type.
Revised Protocol No.: 02
Date: 03-Jun-2015
18
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In total, BMS-955176 120 mg is expected to be safe, well-tolerated, and efficacious in Stage 1 
and will inform the selection of a Stage 1 continuation dose and aspects of Stage 2 (as described 
in detail within Section 1.1.1).
The doses of BMS-955176 in Stage 2 will be confirmed based upon the Week 24 analyses
(efficacy, safety, and pharmacokinetics) of both Stage 1 and Study AI468038. As described in 
this protocol, the doses in Stage 2 are proposed to be BMS-955176 120 mg and 180 mg in Arms 
3 and 4, respectively.
1.1.3
Rationale to support drug combinations
This study co-administers BMS-955176, with unboosted ATV 400 mg QD or ATV/r 300/100 mg
QD, and DTG 50 mg. The drug combinations within this clinical trial design will provide 
supportive data in the context of a therapeutic dose of BMS-955176 and the clinical 
safety/efficacy/resistance of the proposed components (Stage 2, Arms 3 and 4) of a single tablet 
regimen (STR) for Phase 3 trial development. Ultimately, BMS will seek approval of 
BMS-955176 for use in treatment-experienced HIV-1 infected adults (including either a STR; 
FDC; and/or monoentity). 
The rationale for using a backbone of ATV and DTG in this treatment-experienced patient 
population is based upon established safety, efficacy, and tolerability of the individual 
components. DTG alone provides a 2.46 log10 c/mL reduction in HIV-1 RNA when administered 
as monotherapy for 10 days.7 Furthermore, DTG has been recently approved and is generally 
safe.8,9,10,11,12 Lastly, ATV/r is often used in treatment-experienced adults’ second-line therapies 
or beyond (for example, in individuals who may have failed an non-nucleoside reverse 
transcriptase inhibitor (NNRTI) and/or integrase inhibitor (INI) based regimen).2,4
This Phase 2b design allows treatment-experienced adults in the experimental arms to be 
exposed to three fully active ARVs (from three classes). Subjects will benefit from each ARV 
(except RTV) independently providing a > 1 log10
c/mL decrease in HIV-1 RNA
(see Section 1.4.1.3 for details on Phase 2a results [AI468002]). BMS expects the combination of 
two agents (unboosted ATV and DTG) with one investigational agent (BMS-955176) to provide 
a generally improved safety/tolerability profile relative to the respective arm containing ATV/r 
(Arms 3 and 4 relative to Arm 1, respectively) or TDF (Arms 3 and 4 relative to Arm 5, 
respectively).
There is a potential risk of a subtherapeutic regimen to treatment-experienced subjects enrolled 
in Arms 3 and 4 since unboosted ATV is only approved for use in treatment-naïve HIV infected 
adults (within the US) and the therapeutic dose of BMS-955176 has not been established.
Unboosted ATV (400 mg) in treatment-naïve adults results in a 1.41 log10 c/mL reduction in 
HIV-1 RNA after two weeks of monotherapy.13 Despite the monotherapy based reduction in 
HIV-1 RNA, pharmacokinetic data of unboosted ATV in prospective clinical trials,14
cross-sectional,15 and retrospective analyses16 generally supports the finding of DHHS defined 
subtherapeutic ATV levels (< 150 ng/mL) in patients.17
Revised Protocol No.: 02
Date: 03-Jun-2015
19
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In a randomized, open-label clinical trial, ATV/r has demonstrated non-inferiority to unboosted 
ATV (TLVOR: 75% vs 70% VR-OC: 87% vs 76%, respectively), similar declines in HIV-1 
RNA (approx -3.1 log10 c/mL), and increase in CD4 cell counts within treatment-naïve adults. 
However, the unboosted ATV arm had an increased number of subjects with emerging ATV and 
lamivudine (3TC) resistance. In particular, the difference in nucleoside/nucleotide reverse 
transcriptase inhibitor (NRTI) resistance was markedly greater in the unboosted ATV compared 
to RTV boosted ATV arm.18 Of note, in this clinical trial (AI468048) NRTIs are not used in the 
experimental Arms 1, 3, and 4. Similar single arm, prospective studies have replicated the viral 
efficacy and immunologic response using unboosted ATV in treatment-naïve HIV infected 
adults.19
Insights from limited data regarding the use of unboosted ATV in treatment-experienced adults 
have demonstrated a viral decay ranging from -1.4 to -2.7 log10 c/mL over 24 weeks of therapy 
in combination with NRTIs (such as TDF, 3TC, and didanosine).20 Also, observational data 
(mean: 24 months of follow-up) has shown similar percentages of subjects with their last HIV 
RNA being undetectable (80% vs 83%) after receiving unboosted and RTV boosted ATV, 
respectively.21
Taking the key findings from studies of ATV in both treatment-naïve and treatment-experienced 
HIV infected adults, Arms 3 and 4 containing unboosted ATV may have the potential for 
increased resistance (relative to Arm 1 containing RTV boosted ATV) and the development of 
virologic failure. However, several other factors must be taken into consideration. First, these 
Arms will use three potent (> 1 log10
c/mL) ARVs in combination. Moreover, 
treatment-experienced subjects who have failed one or two prior regimens are likely to be either 
naïve to ATV treatment (prior NNRTI- and/or INI-class failure) or will need to be fully 
susceptible to approved ARVs (including unboosted ATV, see Section 3.3.2). Second, both the 
combination of ATV and DTG with BMS-955176 independently have demonstrated additivity to 
synergy in-vitro22 (see Section 1.4.1.3 for clinical data on the combination of ATV and 
BMS-955176). Third, unboosted ATV increases the geometric mean ratio of Ctrough for DTG by 
a factor of 2.8.23 Fourth, in normal healthy volunteers, multiple dose administration of 
BMS-955176 40 mg (SDD suspension formulation) with ATV 400 mg for 14 days resulted in an 
approximate 25% increase in the AUC(TAU) of BMS-955176 administration alone24 and 
preliminary PK data from the Phase 2a (AI468002) demonstrated that BMS-955176 AUC(TAU) 
increased approximately 37% and 52% when ATV was combined with BMS-955176 40 and 
80 mg (SDD suspension formulation), respectively, relative to administration of BMS-955176 
alone. It is clinically unclear whether higher exposures of DTG and BMS-955176 would lead to 
a decreased incidence of unboosted ATV resistance in the context of Arms 3 and 4 
(BMS-955176 120 and 180 mg + ATV + DTG). Combined with these factors, BMS proposes to 
mitigate the potential risk of increased resistance by 1) studying two doses of BMS-955176 
(120 and 180 mg) in combination with unboosted ATV and DTG, and 2) using a two stage 
clinical trial design with Stage 2 (Arms 3, 4, and 5) enrolling after the Week 24 analysis
(efficacy, safety, and pharmacokinetics) of Stage 1 (Arms 1 and 2) and AI468038 are completed, 
and 3) only enrolling subjects who are susceptible to study medication (including unboosted 
Revised Protocol No.: 02
Date: 03-Jun-2015
20
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
ATV), (see Section 1.1.1, Rationale to support study design). This risk mitigation is employed to 
decrease the probability of exposure to a subtherapeutic regimen and increase the probability of 
establishing clinical efficacy (number of responders at the Week 24) in treatment-experienced 
HIV-1 infected adults.
BMS expects BMS-955176 120 and 180 mg given with unboosted atazanavir to be generally 
safe and well-tolerated. Subjects in Arms 3 and 4 treated with unboosted ATV would potentially 
benefit from a more favorable lipid profile, fewer gastrointestinal (GI) side effects, and 
decreased indirect hyperbilirubinemia. In total, the potential clinical risks for subjects 
randomized to Arms 3 and 4 in Stage 2 do not outweigh the potential benefits of a Nucleoside-
and Booster-sparing cART regimen that may offer both efficacy and long-term safety (including 
but not limited to improved bone mineral density, improved renal function, and improved lipid 
profile). Please see Section 1.5 for further details on the overall risk/benefit assessment.
1.2
Research Hypothesis 
This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with or 
without RTV)
and DTG
is efficacious, safe, and well-tolerated
in HIV-1 infected 
treatment-experienced adults.
1.3
Objectives(s)
1.3.1
Primary Objective
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg, and a TDF 300 mg-containing arm,
each when given in combination with ATV/r 300/100 mg and DTG 50 mg by determining 
the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when 
given in combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the 
antiviral efficacy of TDF 300 mg when given in combination with ATV/r 300/100 mg and 
DTG 50 mg by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
1.3.2
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 arms, and TDF-containing regimens (TDF + 
ATV/r + DTG), by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 arms, and TDF-containing regimens, by 
determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA 
< 200 c/mL at Weeks 24, 48, 96
Revised Protocol No.: 02
Date: 03-Jun-2015
21
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess the emergence of HIV drug resistance in samples selected for drug resistance 
testing (according to criteria outlined in Sections 5.4.1.1 and 5.4.1.2)

To assess efficacy of BMS-955176 arms, and TDF-containing regimens, by using the mean 
changes from baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ 
T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by 
measuring frequency of SAEs and AEs leading to discontinuation

To assess disease progression as measured by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV 
(with or without ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
1.3.3
Exploratory Objectives

To determine the effect of BMS-955176 arms, and TDF-containing regimens, on renal 
clinical parameters and biomarkers through Weeks 48 and 96

To determine the effect of BMS-955176 arms, and TDF-containing regimens, on bone 
biomarkers through Weeks 12 and 24

To assess the impact of baseline (pre-therapy) Gag polymorphisms on the efficacy of 
BMS-955176 by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL, HIV-1 RNA < 200 c/mL, and the changes from baseline in log10
HIV-1 RNA at Weeks 24, 48 and 96, by baseline polymorphisms

To characterize the steady-state plasma PK of DTG when co-administered with BMS-955176 
and ATV (with or without RTV) in treatment-experienced subjects. The effect of 
BMS-955176 on DTG PK in the presence of ATV (without RTV) may be assessed relative to 
historical data

To compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV

To characterize the PK of ATV when co-administered with DTG and BMS-955176, with or 
without RTV

To explore PK/PD and PK/viral kinetic (VK) relationships between BMS-955176, ATV, 
and/or DTG exposure and both efficacy and safety endpoints

To assess the impact of the study therapies on health-related quality of life measures
1.4
Product Development Background
1.4.1
Background Information BMS-955176
1.4.1.1
Mechanism of Action
BMS-955176 is an HIV-1 maturation inhibitor (MI), a novel class of anti-HIV-1 drugs that 
prevents the maturation of HIV-1 virions by binding near a key structural element within the Gag 
polyprotein that is required for virion maturation and assembly. Maturation inhibitors block the 
last protease cleavage event between Gag protein segments designated as capsid (CA) protein 
Revised Protocol No.: 02
Date: 03-Jun-2015
22
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
p24 (p24) and spacer peptide 1 (SP1), resulting in the release of immature noninfectious virus 
particles. BMS-955176 has excellent potency and broad spectrum activity, and mechanism of 
action studies indicate that BMS-955176 is a true MI, with a mechanism of action distinct from 
current antiretroviral agents.25 Development of BMS-955176 could potentially lead to novel 
HIV-1 treatment regimens in treatment-experienced HIV-1 patients.
1.4.1.2
Nonclinical studies
Nonclinical Pharmacology and Microbiology
BMS-955176 specifically inhibits HIV-1 protease cleavage at the CA(p24)/SP1 junction within 
the Gag protein in both HIV-1-infected cells and purified HIV-1 Gag virus-like particles (VLPs). 
Radiolabeled BMS-955176 specifically binds to purified HIV-1 Gag VLPs, and its binding is 
dose-dependently inhibited by related MIs and is reversible. BMS-955176 does not directly 
inhibit HIV-1 protease nor bind to a small HIV-1 protease peptide substrate. These results 
indicate that BMS-955176 inhibits late in the HIV-1 life cycle by specific binding to immature 
capsid structures at or near the CA(p24)/SP1 junction, thereby inhibiting cleavage at that 
particular site. In cell culture, the range of values for the concentration producing 50% effect 
(EC50) of BMS-955176 against 7 common laboratory strains of HIV-1 was 1.6 to 10.5 nM 
(mean = 6.0 3.5 nM). Using a reverse transcriptase readout, a phenotyping analysis of 
93 subtype B viruses whose genotypes are representative of 96% of the diversity (found in the 
Los Alamos National Laboratory [LANL] database) in Gag sequences indicates that the mean 
EC50 of this cohort was 2.7 1.9 nM, with a median value of 2.2 nM and a range between 0.6 to 
12 nM. A similar analysis of 23 isolates of subtype C viruses found a mean EC50 of 
6.1 3.1 nM, a median value of 5.6 nM, and a range from 2.5 to 16 nM. When evaluated against 
clinical isolates in peripheral blood mononuclear cells (PBMCs), BMS-955176 exhibited a mean 
EC50 of 24 24 nM against a cohort (N = 22) of subtype B viruses. Activity was also observed 
against viruses from subtypes A, C, D, F, and G, with average EC50 values for 96% of tested 
isolates (N = 41) between 5.9 and 87 nM. Clinical isolates from the CRF01_AE subtype were 
approximately 2- to 3-fold less susceptible to BMS-955176 (average EC50 77 nM, N = 7) 
viruses. BMS-955176 was active against 1 of 3 human immunodeficiency virus type-2 (HIV-2)
isolates (EC50 = 15 nM). BMS-955176 retains complete activity against reverse transcriptase 
(RT), protease, and integrase inhibitor-resistant viruses, with EC50 values similar to wild-type 
(wt) viruses, while the potency of currently approved nucleotide/nucleoside reverse transcriptase 
inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors 
(PIs), and integrase inhibitors (INIs) was undiminished when tested against viruses with reduced 
susceptibility to BMS-955176. BMS-955176 maintained activity against a panel of PI-resistant 
isolates from PI-treated subjects harboring a variety of major and minor PI-resistance
determinants in both protease and Gag.26,27 Protein binding to 100% human serum (HS) was 
86%, and in the presence of 40% HS supplemented with additional human serum albumin 
(HuSA) to match physiologic concentrations, BMS-955176 exhibited an approximately 4-fold 
reduction of antiviral activity. Selection for resistance to BMS-955176 in cell culture identified
changes that map to amino acids adjacent to the CA(p24)/SP1 cleavage site. These include an 
amino acid substitution of A364V or a combination of V362I with secondary changes (V370A, 
Revised Protocol No.: 02
Date: 03-Jun-2015
23
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
A374P or I376V). In vitro, virus with the A364V change exhibited a drastic loss of susceptibility 
to BMS-955176 (>100-fold), while the V362I plus secondary change-containing viruses were 
generally less sensitive to BMS-955176 (median EC50 25 nM, range 7.1 to 167 nM). In 2-drug 
combination studies with representative drugs from NRTI, NNRTI, PI, and INI classes, all 
combinations produced additive to synergistic effects, suggesting that BMS-955176 should be 
amenable for use in combination with any of these agents.
Bevirimat (BVM), a first-generation MI, demonstrated proof of concept and dose-dependent 
anti-HIV-1 potency in both Phase 1 and Phase 2 clinical studies. Patients infected with HIV-1 
sensitive to BVM demonstrated an approximate 1.2 log10 decline in HIV-1 RNA. However, 
approximately 50% of patients harboring naturally occurring polymorphisms located close to the 
CA(p24)/SP1 cleavage site showed a significantly reduced response to BVM treatment. In 
addition, BVM exhibited a large reduction in antiretroviral activity in the presence of human 
serum. BMS-955176 was developed to address the key flaws of BVM by providing improved 
coverage of BVM-resistant polymorphic variants and improved potency in serum. BMS-955176 
has been shown to be active against viruses with resistance from all marketed ARVs, and to 
possess a low serum effect. Development of BMS-955176 could potentially lead to novel HIV-1 
treatment regimens in treatment-experienced HIV-1 patients.
Nonclinical Pharmacokinetics
The absolute oral bioavailability of BMS-955176 was low (3.89% to 26.8%) in all preclinical 
species (mice, rats, dogs, and monkeys). In the dog, though there was a positive food effect and 
no pH dependent absorption, upon repeat dosing a less than dose-proportional increase in 
exposure was observed. BMS-955176 distributed preferentially into the duodenum, liver, and 
lymph nodes with little penetration into the brain. Protein binding was 86.1% in human serum 
and 78% to 94% in animal sera
In human in vitro systems, the metabolism of BMS-955176 was primarily mediated via 
cytochrome P450 (CYP)3A4. In vivo in rats, dogs, and monkeys, BMS-955176 was the 
predominant drug-related component in plasma following a single oral dose of BMS-955176. 
BMS-955176 was eliminated principally via metabolism followed by excretion in bile with little 
renal excretion. 
In vitro, BMS-955176 was an inhibitor of CYP2C8 (concentration at which 50% inhibition 
observed [IC50] = 28.5 M), CYP3A4 (IC50 = 32 M), and uridine diphosphate 
glucuronosyltransferase (UGT)1A1 (IC50 = 20 M) enzymes. No P-gp inhibition or 
time-dependent inhibition of CYPs was observed. BMS-955176 was not an inducer of CYP1A2, 
CYP2B6, or CYP3A4. The steady state Cmax of BMS-955176 180 mg tablet in HIV-infected 
patients with food is projected to be approximately 5.2 M. Thus, the potential exists for 
BMS-955176 to inhibit CYP2C8, CYP3A4, and/or UGT1A1 in vivo and increase exposures to 
co-administered drugs that are metabolized by these enzymes. Furthermore the potential exists 
for drug-drug interactions (DDI) if BMS-955176 is co-administered either with an inhibitor or 
inducer of CYP3A4 or P-gp.
Revised Protocol No.: 02
Date: 03-Jun-2015
24
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
BMS-955176 was a substrate of mouse P-glycoprotein (P-gp) based on higher bioavailability in 
P-gp knock-out mice when BMS-955176 was co-administered with elacridar, a potent inhibitor 
of P-gp and breast cancer resistance protein (BCRP). BMS-955176 could not be reliably assessed 
as a substrate for human P-gp due to nonspecific binding and low solubility. In vitro, 
BMS-955176 inhibited organic anion transporting polypeptide (OATP)1B1 and OATP1B3 
(IC50 5.3 and 4 M, respectively), but was not an inhibitor of P gp, sodium taurocholate 
cotransporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multiple 
drug-resistance protein (MRP)2, and bile salt export pump (BSEP). These findings suggest a 
potential for DDI between BMS-955176 (as the perpetrator) and substrates of OATP1B1 and 
OATP1B3, but not with those of P-gp, NTCP, OAT1, OAT3, MRP2, and BSEP. Furthermore, 
the potential exists for drug-drug interactions (DDI) if BMS-955176 is co-administered either 
with an inhibitor or inducer of CYP3A4 or P-gp. Preliminary data indicate that BMS-955176 
does not inhibit OCT2, a transporter that is inhibited by dolutegravir (DTG), a drug with which 
BMS-955176 is planned to be co-administered.
Nonclinical Toxicology
The toxicity profile of BMS-955176 was evaluated in single- and repeat-dose toxicity, 
genotoxicity, phototoxicity, safety pharmacology, sensitization, reproductive toxicity and 
embryo-fetal development studies. The scope of the toxicologic evaluation for BMS-955176
supports its proposed clinical use for HIV-1 infection. Unless otherwise mentioned, all animal 
studies were dosed by the oral route with an aqueous methylcellulose suspension of a 
BMS-955176 spray-dried dispersion (SDD). 
BMS-955176 was not phototoxic, mutagenic, or clastogenic in vitro and was not genotoxic in a 
rat micronucleus assay at 300 mg/kg/day (AUC 279 g·h/mL). BMS-955176 was not a skin 
sensitizer in the local lymph node assay in the mouse. BMS-955176 had a low potential (IC50 or 
EC50 > 5 M [> 3.45 µg/mL]) for in vitro off-target interactions on a broad range of enzymes, 
transporters, and receptors, including cardiac ion channels. 
In safety pharmacology evaluations in rats, there were no respiratory findings and no direct 
central nervous system (CNS) findings. Decreases in motor activity, arousal, and rearing were 
considered secondary to general toxicity (ie, body weight decreases).
Cardiovascular safety pharmacology evaluations were conducted in rabbits, rats, and dogs. In the 
definitive oral single-dose cardiovascular safety study in conscious telemeterized dogs, blood 
pressure and electrocardiogram were was unaffected at 20 mg/kg; however, increases in heart 
rate (mean 33% to 57% of pretest vehicle) were observed at 8 and 20 mg/kg. The increase in 
heart rate at these doses was primarily due to increases in 2 dogs at each dose that had higher 
plasma concentrations (12.83 g/mL) relative to the dogs without effects on heart rate 
(6.81 g/mL). The no-observed-effect level (NOEL) for cardiovascular effects in dogs was 
2 mg/kg (plasma concentration of 1.93 µg/mL). Importantly, there was no change in heart rate at 
20 mg/kg/day at higher plasma concentrations (Cmax 17.8 µg/mL) in the 1-month study in 
dogs (below). 
Revised Protocol No.: 02
Date: 03-Jun-2015
25
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Taken together, BMS-955176 has low potential for respiratory, CNS, and cardiovascular effects 
and no cardiovascular effects have been observed in humans to date.
Two-week, 1-month, and 6-month studies were conducted in rats. As the 2-week study was of 
limited scope, only the 1-month and 6-month studies are presented in this summary. 
BMS-955176 was administered for 1 month at doses of 30, 100, or 300 mg/kg/day. While there 
was no mortality at 100 mg/kg/day, the high dose of 300 mg/kg/day was associated with 
pronounced signs of clinical toxicity and early euthanasia of all the rats at that dose level on 
Days 8 to 9. The dose of 30 mg/kg/day was tolerated. The intermediate dose of 100 mg/kg/day 
(AUC 357 g·h/mL) resulted in dose-limiting toxicity including persistent reduction in food 
consumption and body weights. A number of minor hematology (including red cell parameter 
changes with no consistent effect on the erythron) and serum chemistry changes (including 
increased alkaline phosphatase and alanine aminotransferase) without correlating histologic liver 
findings) occurred at 30 and 100 mg/kg/day; these changes were considered not adverse due to 
small magnitude, occurrence only in 1 sex, and lack of microscopic correlates, and most were 
secondary to decreases in food consumption and body weight. Dose-related gastrointestinal 
toxicity was primarily characterized by morphologic changes in the stomach at 100 mg/kg/day 
and the stomach and small and large intestines at 300 mg/kg/day. At the end of the 2-week 
postdose recovery period, there was complete recovery of all BMS-955176-related findings at 
30 mg/kg/day. At 100 mg/kg/day, all findings recovered with the exception of increased red cell 
distribution width in females, minimally higher (1.94×) ALT activity in 1 male without any 
histologic correlates, and decreased mean prostate gland (with seminal vesicles) weights. The 
low dose of 30 mg/kg/day (AUC 113.5 g·h/mL) was considered the no-observed-adverse-effect 
level (NOAEL) because the body weight and food consumption changes were minimal and 
transient and there were no BMS-955176-related morphologic changes.
In a 6-month oral toxicity study in rats with 1-month recovery period, BMS-955176 was 
administered at doses of 10, 25, or 50 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month rat study and occurred at all doses (10 mg/kg/day; 
AUC 71 gh/mL). Findings included decreased body weight, food consumption, and in the 
stomach, minimal to marked atrophy involving both parietal and chief cells, minimal to mild 
single-cell necrosis and minimal regeneration in the glandular mucosa, which were partially 
reversible at the end of the 1-month recovery period. A NOAEL was not established in this 
study.
Five-day, 1-month, and 9-month repeat-dose studies were conducted in dogs. As the 5-day 
toxicokinetics and tolerability studies were of limited scope, only the 1-month and 9-month
studies are presented here. In the 1-month study, BMS-955176 was administered at doses of 2, 8, 
or 20 mg/kg/day. Increased incidences of sporadic vomiting and liquid, yellow, and/or mucoid 
feces occurred at all doses, but had no apparent effect on the overall health of these animals. 
At 20 mg/kg/day, additional findings included occasional decreases in food consumption in a 
few animals, loss of body weight (up to 8%) in 2 females, a minimal increase in serum ALT 
activity (2.10× pretest) in 1 female with no microscopic correlates, and minimal single-cell 
necrosis of stomach glandular epithelium. All BMS-955176-related changes were fully 
Revised Protocol No.: 02
Date: 03-Jun-2015
26
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
reversible by the end of the 2-week recovery period. The dose of 8 mg/kg/day was considered a 
NOAEL (AUC 219.5 g·h/mL) since the sporadic clinical observations had no adverse effects 
on the general health of the animals and there were no BMS-955176-related morphologic 
changes. 
In a 9-month oral toxicity study in dogs with 1-month recovery period, BMS-955176 was 
administered at 0 (vehicle), 1, 3, or 10 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month dog
study
and
occurred at doses 3 mg/kg/day 
(AUC 135 gh/mL). Findings included salivation (only males at 10 mg/kg/day), fur thinness 
(males), thin appearance, and abnormal feces (yellow, liquid, pale and/or mucoid) that occurred 
sporadically throughout the study; increases in mean food consumption; minimal to marked chief 
cell depletion in the glandular stomach. Additional findings at 10 mg/kg/day included thin 
appearance that correlated with decreases in body weight in food consumption; occasional 
vomitus in males; in the stomach, minimal to moderate mucous cell hyperplasia (often associated 
with glandular dilatation) correlating with increased thickness macroscopically (males only) and 
minimal to marked parietal cell depletion and single-cell necrosis of glandular epithelial cells; 
and increases in serum gastrin values (1.31 to 4.56× highest control value) for several dogs that
may have reflected the reductions in gastric parietal cells. The NOAEL was 1 mg/kg/day 
(AUC 64.9 gh/mL).
The embryo-fetal development (EFD) studies were conducted in 3 species (rabbits, rats, and 
mice) instead of the standard 2 species due to poor maternal tolerability and inability to achieve 
adequate systemic exposures in rabbits.
In a definitive EFD study in pregnant mice, BMS-955176 was administered at doses of 15, 45, or 
150 mg/kg/day from gestation day (GD) 6 through 15. BMS-955176 was a selective 
developmental toxicant in mice. Dose of 100 mg/kg/day was associated with an increase in 
embryo-fetal lethality (cumulative postimplantation losses of 11.5%, relative to 3.9% in control 
litters, attributed to increased incidences of dead fetuses, early resorptions and late resorptions). 
Cleft palate and exencephaly were observed in a few fetuses; additionally, marginal reductions in 
fetal body weight (5% relative to control values) were observed. There was no maternal toxicity 
at any dose tested. The developmental NOAEL was 45 mg/kg/day (AUC 213 g·h/mL).
In a definitive EFD study in pregnant rats, BMS-955176 was administered at doses of 10, 30, or 
100 mg/kg/day from GD 6 through 15. BMS-955176 was not a selective developmental toxicant. 
Developmental toxicity (reduced fetal body weights, increases in fetal alterations, and reduced 
fetal ossification) occurred only at 100 mg/kg/day; whereas, maternal toxicity (clinical 
observations, reduced body weights, and reduced food consumption) was observed at 
30 mg/kg/day. The developmental NOAEL was 30 mg/kg/day (AUC 114 gh/mL). 
In an EFD study in pregnant rabbits, BMS-955176 was administered at a dose of 80 mg/kg/day 
from GD 7 through 19. BMS-955176 was not a developmental toxicant in rabbits at 
80 mg/kg/day (AUC 3.26 gh/mL), at which reductions in maternal food consumption and 
weight gain were observed.
Revised Protocol No.: 02
Date: 03-Jun-2015
27
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In the fertility and early embryonic development study in rats, BMS-955176 was evaluated at 
doses of 10, 30, or 100/60 mg/kg/day in males and females. BMS-955176 did not affect 
reproduction or early embryonic development at doses 100 mg/kg/day that produced overt 
toxicity. The reproductive NOAEL was 100/60 mg/kg/day (AUC 210 g•h/mL) in male rats and
100 mg/kg/day (AUC 458 g•h/mL) in female rats.
Overall, results from the nonclinical toxicology studies demonstrate that BMS-955176 has a low 
potential for cardiovascular effects, is toxic to the gastrointestinal tract, and is a selective 
developmental toxicant. Clinical monitoring of vital signs (heart rate, systolic and diastolic blood 
pressure) and for gastrointestinal adverse events (AEs) (eg, nausea, vomiting, diarrhea, or fecal 
changes), along with screening for potential renal tubular injury, have not indicated any potential 
for these AEs in Phase 1 or proof of concept (POC) studies in humans. Clinical protocols will 
ensure that appropriate contraceptive measures will be followed to minimize the risk of 
pregnancy while enrolling women of child-bearing potential (WOCBP) males subjects who are 
sexually active with (see Section 3.3.1 Inclusion Criteria).
1.4.1.3
Clinical studies
Phase 1
The safety, tolerability, and PK of BMS-955176 were evaluated in a randomized, double-blind, 
placebo-controlled, sequential single ascending dose (SAD, 10-120 mg) and multiple ascending 
dose (MAD, 10-80 mg QD for 14-28 days) study in healthy subjects (AI468001). No SAEs, 
deaths, or discontinuations related to study drug occurred. No clinically meaningful trends were 
observed in vital signs, physical exam findings, laboratory values, or ECGs. Following 
single-dose and multiple-dose administration of BMS-955176, a slightly less than 
dose-proportional increase in Cmax and AUC(INF) was observed over the dose ranges studied. 
Steady state was reached in approximately 7 days following multiple-dose once daily 
administration of BMS-955176. The half life (T-HALF) of BMS-955176 is approximately 
35 hours. 
Study AI468034 assessed the relative bioavailability and dose proportionality of BMS-955176 
MC tablet - the formulation that will be used in the current study. Relative to 80 mg SDD 
suspension, the bioavailability of BMS-955176 120 mg MC tablet was approximately 23% 
lower. Furthermore, consistent with the low solubility of BMS-955176, considerable overlap in 
exposures was observed between 60 mg, 120 mg and 180 mg MC tablet, when given under 
fasted conditions. The impact of food on exposures to BMS-955176 120 mg MC tablet was 
assessed in Study AI468034 as well; a high fat meal increased BMS-955176 AUC approximately 
50% with negligible impact on BMS-955176 Cmax.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
Revised Protocol No.: 02
Date: 03-Jun-2015
28
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose. Preliminary safety 
results from AI468049 indicate that GI adverse events (eg, nausea, vomiting, loose stools) only 
occurred in the fed arms (where the BMS-955176 exposures were higher) relative to the fasted 
arms.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose.
Phase 2a
A randomized, double-blind, placebo-controlled proof of concept study in HIV subjects has 
completed enrollment and is undergoing analysis (AI468002). The three parts of this study were: 
1) Part A evaluated doses of 5, 10, 20, 40, 80, and 120 mg of BMS-955176 (SDD suspension) 
given for 10 days in HIV-1 clade B infected subjects, 2) Part B compared the antiviral activity of 
BMS-955176 (SDD suspension) administered with ATV (with or without RTV) against standard 
of care (TDF + FTC + ATV/r) for 28 days in HIV-1 clade B infected subjects, and 3) Part C 
evaluated BMS-955176 40 and 120 mg (SDD suspension) given for 10 days in HIV-1 clade C 
infected subjects. See Table 1.4.1.3-1 for baseline demographics. 
Preliminary results from the Phase 2a study (AI468002) in HIV-1 (clade B and C only) infected 
adults showed that at effective doses, a maximum median reduction in HIV-1 RNA ranging from 
1.3 to 1.7 log10 was observed. In the Phase 2b study BMS-955176 doses estimated to provide 
similar exposure to effective doses in the Phase 2a study will be used. Moreover, when 
BMS-955176 was combined with ATV RTV, these combinations resulted in maximum median 
declines in HIV-1 RNA ranging from 1.9 to 2.2 log10 (see Table 1.4.1.3-2). These results are 
generally similar to the antiviral effect demonstrated by other classes of ARVs in short-term
monotherapy trials, and thus BMS-955176 should contribute substantially with other ARVs to 
form an effective cART regimen. Lastly, preliminary safety data show acceptable safety and 
tolerability across all Phase 2a arms. Most AEs were Grade 1-2 and were most frequently due to 
an indirect hyperbilirubinemia; the levels seen with BMS-955176 and ATV/r were similar to 
those seen with ATV/r combined with TDF/FTC. The arms containing BMS-955176 and 
unboosted ATV had bilirubin levels that were approximately half of those observed in the arms
containing ATV/r. Last, arms containing BMS-955176 alone did not show elevated bilirubin
levels. Many of these events occurred in subjects who were randomized to an arm containing 
BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to headache and an 
increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia occurred in subjects also 
receiving ATV.
Revised Protocol No.: 02
Date: 03-Jun-2015
29
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.4.1.3-1:
Phase 2a Baseline Demographics and Characteristics of Subjects 
(Preliminary Results)
Treatment Arm
Subjects
(n)
Median 
age
Male
White
Median 
HIV 
RNA 
(log10
c/ml)
Median 
CD4 
(cells/mm3)
Part A (Clade B, 10 days 
monotherapy)
BMS-955176 5 mg
8
43.5
8 (100)
6 (75.0)
4.09
437
BMS-955176 10 mg
8
39
7 (87.5)
7 (87.5)
4.02
539
BMS-955176 20 mg
8
33
8 (100)
8 (100)
3.59
512
BMS-955176 40 mg
8
38
8 (100)
8 (100)
4.03
536
BMS-955176 80 mg
8
31.5
8 (100)
8 (100)
3.82
504
BMS-955176 120 mg
8
37.5
8 (100)
8 (100)
3.84
498
Placebo
12
36
12 
(100)
12 
(100)
3.98
458
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
8
32.5
8 (100)
6 (75)
4.04
581
BMS-955176 40 mg + ATV 300 mg + 
RTV 100 mg
8
34
8 (100)
8 (100)
4.45
480
BMS-955176 80 mg + ATV 400 mg
8
31.5
8 (100)
7 (87.5)
4.15
549
Truvada® + ATV 300 mg + RTV 
100 mg
4
32.5
4 (100)
4 (100)
4.12
427.5
Part C (Clade C, 10 days 
monotherapy)
BMS-955176 40 mg
7
35
4 (57.1)
2 (28.6)
4.53
554
Placebo
2
38.5
2 (100)
0 (0)
3.78
304
Table 1.4.1.3-2:
Maximum Decline Log10 HIV-1 RNA (Preliminary Results)
Treatment 
Mean 
S.D. 
Median 
Max
Min
Part A (Clade B, 10 days monotherapy)
BMS-955176 5 mg
-0.49
0.217
-0.498
-0.78
-0.22
BMS-955176 10 mg
-1.05
0.351
-0.976
-1.76
-0.64
BMS-955176 20 mg
-1.17
0.645
-1.115
-2.12
-0.13
BMS-955176 40 mg
-1.55
0.352
-1.701
-1.88
-0.93
BMS-955176 80 mg
-1.52
0.257
-1.555
-1.82
-1.04
Revised Protocol No.: 02
Date: 03-Jun-2015
30
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.4.1.3-2:
Maximum Decline Log10 HIV-1 RNA (Preliminary Results)
Treatment 
Mean 
S.D. 
Median 
Max
Min
BMS-955176 120 mg
-1.53
0.478
-1.654
-2.07
-0.83
Placebo
-0.48
0.581
-0.381
-1.46
0.56
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
-1.89
0.273
-1.858
-2.37
-1.49
BMS-955176 40 mg + ATV 300 mg + RTV 100 
mg
-2.22
0.676
-2.202
-3.52
-1.24
BMS-955176 80 mg + ATV 400 mg
-2.3
0.307
-2.228
-2.68
-1.87
Truvada® + ATV 300 mg + RTV 100 mg
-2.41
0.495
-2.39
-3.04
-1.83
Part C (Clade C, 10 days monotherapy)
BMS-955176 40 mg
-1.5
0.439
-1.285
-2.03
-1.04
Placebo
0.12
0.141
0.12
0.02
0.22
The pharmacokinetics of BMS-955176 were assessed in HIV-1 infected subjects in AI468002. 
Overall, exposures to BMS-955176 are approximately 30% to 35% lower in HIV-1-infected 
subjects compared to healthy subjects administered the same doses and formulation of 
BMS-955176. Furthermore, exposures to BMS-955176 increased in a generally linear fashion up 
to 40 mg, with a less than dose proportional increase in exposures between 40 mg and 80 mg, 
and considerable overlap in exposures between 80 mg and 120 mg.
1.4.2
Background Information on TDF
Tenofovir disoproxil fumarate (TDF) is an analog of the nucleotide adenosine 
5’-monophosphate. TDF inhibits HIV-1 reverse transcriptase and is indicated in combination 
with other ARVs for the treatment of HIV-1 infection. The most common adverse reactions 
include rash, diarrhea, headache, pain, depression, asthenia, and nausea. Clinicians are warned 
about new onset or worsening renal impairment, decreases in bone density, and immune 
reconstitution syndrome. For more information concerning TDF, please refer to the 
TDF/Viread® SmPC or TDF/Viread® USPI.28
1.4.3
Background Information on DTG
Dolutegravir (DTG) is a HIV-1 integrase strand transfer inhibitor indicated in combination with 
other ARVs for the treatment of HIV-1 infection. The most common adverse reactions of 
moderate to severe intensity include insomnia, fatigue, and headache. Clinicians are warned 
about immune reconstitution syndrome. For more information concerning DTG, please refer to 
the DTG/Tivicay SmPC or the DTG/Tivicay USPI.29
1.4.4
Background Information on ATV 
Atazanavir is a protease inhibitor indicated for use in combination with other ARVs for the 
treatment of HIV-1 infection. The most common adverse reactions include nausea, 
Revised Protocol No.: 02
Date: 03-Jun-2015
31
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
jaundice/scleral icterus, rash, headache, abdominal pain, vomiting, insomnia, peripheral 
neurologic symptoms, dizziness, myalgia, diarrhea, depression, and fever. Clinicians are warned 
about hyperbilirubinemia, nephrolithiasis, and cholelithiasis. For more information concerning 
ATV please refer to the ATV/Reyataz® SmPC or ATV/Reyataz® USPI.30
1.4.5
Background Information on RTV
Ritonavir is a protease inhibitor indicated in combination with other ARVs for the treatment of 
HIV-1 infection. The most frequently reported adverse drug reactions with RTV alone or in 
combination with other ARVs include diarrhea, nausea, vomiting, abdominal pain, paresthesia, 
rash, and fatigue/asthenia. Clinicians are warned about total cholesterol and triglyceride 
elevations. For more information concerning RTV please refer to the RTV/Norvir® SmPC or 
RTV/Norvir® USPI.31
1.4.6
Drug-Drug Interactions
In AI468001, coadministration of BMS-955176 as a single dose following two doses of 100 mg 
RTV resulted in an approximate 48% increase in BMS-955176 AUC(INF), consistent with
inhibition of CYP3A4 and/or P-gp. Multiple-dose administration of BMS-955176 with daily 
400 mg ATV and a standard meal for 14 days resulted in a modest (~25%) increase in the 
BMS-955176 AUC(TAU).
Study AI468005 assessed the two-way interaction between BMS-955176 40 mg (administered as 
an SDD suspension) and TDF at steady state in healthy subjects. Relative to administration of 
each drug alone, neither BMS-955176 nor TDF exposures were meaningfully impacted upon 
coadministration.
Study AI468041 assessed the impact of BMS-955176 80 mg (administered as an SDD 
suspension) on the pharmacokinetics of the components of a combined oral contraceptive 
containing ethinyl estradiol (EE) and norgestimate (NGM). Exposures to both EE and 
norelgestromin (NGMN), the active metabolite of NGM were reduced in the presence of 
BMS-955176. Furthermore, one subject had a serum progesterone level > 300 ng/dL while 
BMS-955176 and the oral contraceptive were concomitantly administered, indicative of 
ovulation and contraceptive failure.
Finally, in vitro data suggest that BMS-955176 may inhibit OATP1B1 and OATP1B3 and 
exposures to substrates of these transporters, such as HMG-CoA reductase inhibitors, may 
increase when co-administered with BMS-955176.
1.5
Overall Risk/Benefit Assessment
The preclinical and clinical safety data demonstrate that BMS-955176 administered at doses in 
this Phase 2b study (120, and 180 mg) should be well tolerated without a major clinically 
relevant impact on safety. Moreover, there have been no identified safety risks from 
completed/ongoing clinical studies to date.
Revised Protocol No.: 02
Date: 03-Jun-2015
32
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The preclinical toxicology studies demonstrate two potential risks to subjects:
First, BMS-955176 is a selective developmental toxicant. Developmental toxicity (skeletal 
alterations in rats; cleft palate and reduced fetal body weights in mice) were observed in 
embryofetal development studies. In order to address this concern, subjects will be required to 
use two methods of contraception (as described in Section 3.3.1 Inclusion Criteria) and undergo 
routine urine pregnancy testing (as described in the T&E Tables in Section 5.1). Furthermore, 
due to results from Study AI468041 that demonstrates reduced exposures to the components of a 
combination oral hormonal contraceptive containing ethinyl estradiol and norgestimate when 
given concomitantly with BMS-955176, oral hormonal contraceptives cannot be used as a 
method of contraception by WOCBP in this study.
Second, single or repeat oral doses of BMS-955176 were associated with sporadic vomiting in 
dogs and unformed and/or liquid feces in rats and dogs. In rats at 10 mg/kg/day there were 
decreases in body weight and food consumption; in the stomach there was atrophy involving 
both parietal and chief cells, single-cell necrosis and regeneration in the glandular mucosa, and 
modest increases in serum gastrin values. At higher doses (100 mg/kg/day) in rats there were 
additional findings in the intestines (distended jejunum, ileum, and cecum; hyperplasia of the 
crypt epithelium in the jejunum; ulcers and erosions in the cecum; and decreased mucosal cell 
extrusion and increased mucus in the colon). 
Similar gastric changes were seen in dogs. At 20 mg/kg/day there was single-cell necrosis of the 
stomach glandular epithelium. At 3 mg/kg/day gastric changes showed chief cell depletion. 
At 10 mg/kg/day changes in the stomach included: mucous cell hyperplasia correlating with 
increased thickness macroscopically, parietal cell depletion, single-cell necrosis of glandular 
epithelial cells, and modest increases in serum gastrin values. Unlike the rats, no changes were 
observed elsewhere in the alimentary canal including the gastroesophageal junction and the 
duodenum. There was no evidence of macrocytosis. Measurement of Total Protein and Albumin 
revealed no clinically relevant changes. The stomach histologic findings were BMS-955176 
dose- and duration dependent. In the 1-month studies, vomiting and fecal changes stopped soon 
after dosing cessation, and microscopic lesions in the stomach and/or intestines reversed 
completely within a 2-week treatment-free period. In the 6 month study in rats and the 9-month 
study in dogs, microscopic lesions in the stomach partially recovered after a 1 month treatment 
free period. The NOAEL was 1 mg/kg/day (AUC 64.9 mg•h/mL) in the 9-month study in dogs, 
and was not established in the 6-month study in rats. Investigative studies for gastric toxicity in 
rats and dogs indicated similar findings with both SDD and MC forms, and with no clear 
evidence that the gastric toxicity is a direct local effect of BMS-955176. The mechanism and 
clinical relevance of these gastrointestinal findings is unknown at present (see below).
A Phase 1 study (AI468001) in healthy volunteers evaluated single and multiple doses of 
BMS-955176 for 14-28 days both alone and in certain arms, in combination with ATV or RTV. 
Overall the safety data demonstrated that BMS-955176 was generally safe and well tolerated. 
A Phase 2a (AI468002) study in HIV-1 infected adults evaluated several doses of BMS-955176 
given alone or in combination with ATV RTV for 10-28 days. The preliminary results show 
Revised Protocol No.: 02
Date: 03-Jun-2015
33
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
acceptable safety and tolerability across all arms. There were no deaths, SAEs, or AEs leading to 
discontinuation. There were no clinically relevant changes in vital signs, lab parameters, or 
EKGs. Most of the AEs were Grade 1-2 and were most frequently due to hyperbilirubinemia 
(primarily observed in treatment arms with ATV). Of the GI AEs, most were attributable to 
diarrhea or loose/watery stools. Many of these events occurred in subjects who were randomized 
to an arm containing BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to 
headache and an increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia 
occurred in subjects also receiving ATV; moreover, the three arms with the highest average total 
bilirubin occurred in subjects receiving both BMS-955176 and ATV. Clinical changes/symptoms 
consistent with the GI findings from dogs and rats (described above) were not seen in the 
preliminary data set from short-term therapy with BMS-955176 in HIV-1 infected adults. 
In this treatment-experienced study population, we estimate GI safety multiples of 2× and 1×, 
(based on NOAEL in 9-month dog study), corresponding to projected human exposures at 
BMS-955176 doses of 120 and 180 mg.
While no clinically relevant GI safety signals have been observed in AI468001 or AI468002, in 
this clinical trial, subjects will undergo routine targeted and complete history/physical exams in 
addition to regular laboratory measurements (including CBC and chemistries). This will initially 
occur more frequently than in standard clinical practice and allow for increased vigilance for any 
potential GI toxicity. Guidance on the evaluation and management of potential GI toxicity is 
outlined in Section 6.7.1.4.
Subjects in this clinical study will benefit from receiving cART potentially containing 
BMS-955176. Preliminary data from the Phase 2a (Part A, B and C) study show a maximum 
median reduction in HIV-1 RNA (clades B and C) ranging from 1.3 to 1.7 log10 in the dose arms 
estimated to provide similar exposure to those in this current study. When BMS-955716 was 
combined with ATV RTV (Part B) this resulted in maximum median declines in HIV-1 RNA 
ranging from 1.9 to 2.2 log10. These results are generally similar to the antiviral effect 
demonstrated by other classes of ARVs. Thus, BMS-955176 should contribute with other ARVs 
substantially to form an effective cART regimen.
As with any antiretroviral study in HIV-1-infected subjects, there is a risk for the development of 
treatment failure and the development of drug resistance associated mutations to BMS-955176 
and/or other antiretrovirals. However, drug resistance to the maturation inhibitor would not be 
anticipated to result in cross-resistance to any other ARV class, including protease inhibitors.32
Ongoing analysis of preliminary data from the Phase 2a study is evaluating both emergent 
genotypic and phenotypic changes after short term monotherapy with BMS-955176. The use of 
three fully susceptible agents as a part of cART is expected to decrease the probability of 
virologic failure and drug resistance. Initially in this clinical trial, measurement of HIV-1 RNA 
will occur more frequently than in standard clinical practice which will allow for increased 
vigilance for the development of lack of efficacy/resistance. Finally, an analysis for virologic 
futility will occur at Week 24 (see Section 8.4.7).
Revised Protocol No.: 02
Date: 03-Jun-2015
34
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
As described earlier, treatment-experienced adults enrolled in Arms 3-4 may be exposed to a 
subtherapeutic regimen and may be at higher risk for virologic failure and the development of 
resistance. In order to decrease this probability, this clinical trial uses a two-stage design 
whereby enrollment in Arms 3-5 will be dependent upon the results of the Week 24 analyses
(efficacy, safety, and pharmacokinetics) in Stage 1 and Study AI468038. This will minimize the 
risk of virologic failure and resistance to subjects enrolled in Arms 3-4 because clinical data will 
already have been generated using BMS-955176 with ATV/r (Arm 1) in Stage 1.
Of note, the other ARVs used in this clinical trial have a known and acceptable risk benefit ratio 
and are frequently prescribed to HIV-1 infected adults as a part of standard of care.
Taken together, the clinical data to date show that BMS-955176 has potent antiretroviral activity 
and is generally safe and well tolerated in healthy volunteers and HIV-1 infected adults. These 
factors should allow subjects to benefit from achieving viral suppression whilst taking a 
generally safe and well-tolerated new antiretroviral; additionally subjects in Arms 1, 3, and 4 
may benefit from a cART regimen that is nucleoside and nucleoside/booster sparing, 
respectively. Specifically, these subjects may benefit from improved bone mineral density, renal 
function, and lipid profiles. The risks, including teratogenicity, GI toxicity, and drug resistance, 
will be appropriately managed by following guidance in the study protocol.
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
2.2
Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The 
Revised Protocol No.: 02
Date: 03-Jun-2015
35
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure 
or product labeling information to be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form which will include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
1) Provide a copy of the consent form and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language 
must be non-technical and easily understood. 
2) Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study.
3) Obtain an informed consent signed and personally dated by the subject or the subject's 
legally acceptable representative and by the person who conducted the informed consent 
discussion.
4) Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
5) If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his 
or her informed consent during the study, consent must additionally be obtained from the 
subject.
6) Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject's willingness to continue participation in the study. This communication should be 
documented.
Revised Protocol No.: 02
Date: 03-Jun-2015
36
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to 
refuse participation in, or to be withdrawn from, the clinical study at any time should be 
considered by the investigator.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced HIV-1 subjects will be randomized to one of five treatment arms
(approximately 40 per arm) in a staged fashion.
The data from the Week 24 analysis of Stage 1 and AI468038, including safety, efficacy and 
pharmacokinetics, will be examined to trigger the start of Stage 2 and confirm the two doses of 
BMS-955176 for study in Stage 2.
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with: 

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Revised Protocol No.: 02
Date: 03-Jun-2015
37
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.1.1
Screening
The screening period begins with the subject’s signature on the informed consent form (ICF).
The subject is then enrolled via the Interactive Voice Response System IVRS (or its web-based 
equivalent) See Section 4.4.
If the subject meets all eligibility criteria, the subject must be randomized within the 42 day 
screening period.
3.1.2
Day 1/Baseline Visit
3.1.2.1
Day 1/Baseline Visit for Arms 1 and 2 - Stage 1
In Stage 1, approximately 80 subjects will be randomized 1:1 (approximately 40 per arm) to 
either of the treatment arms containing boosted atazanavir (ATV/r).
On the Day 1 Visit, subjects in Arms 1 and 2 will begin QD dosing with BMS-955176 or TDF, 
each in combination with ATV/r and DTG (see Section 4.5 for additional details of Selection and 
Timing of Dose).

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
3.1.2.2
Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2
In Stage 2, approximately 120 subjects will be randomized 1:1:1 (approximately 40 per arm) to 
either of the two BMS-955176 treatment arms containing ATV, or to the TDF Arm.
On the Day 1 Visit, subjects will begin QD dosing with BMS-955176 in combination with ATV 
and DTG, or TDF in combination with ATV/r and DTG (see Section 4.5 for additional details of 
Selection and Timing of Dose).

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r QD 300/100 mg + DTG 50 mg QD
3.1.3
Week 2 Intensive PK Visit
Subjects with anemia, defined as Hemoglobin < 11.0 g/dL, should be excluded from 
participation in the Week 2 Intensive PK Substudy.
Subjects in all arms will have the opportunity to participate in an elective Intensive PK Substudy 
visit at Week 2 (window for visit: Day 12-16). Approximately 60 subjects, 12 subjects from each 
arm, are expected to participate in the substudy; BMS may allow the substudy to over-enroll in 
an effort to have a sufficient number of complete datasets.
The series of 12 blood draws begins with pre-dose (0-hour) blood samples to be collected
approximately 24 hours (20-28 hrs) after the morning doses of study drugs that were taken on the 
day before. Ten more samplings are drawn through the 12-hr time point, with one final sampling 
Revised Protocol No.: 02
Date: 03-Jun-2015
38
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
collected at the 24-hr time point, requiring the subject to either remain overnight in the clinic, or 
to return the next morning; the final 24-hr sample will be collected prior to administration of the 
morning doses of study drugs (See Section 5.5.1).
PK Tools/Job Aids will be provided to assist with the proper sequencing of dosing and blood 
sample collections, as well as the collection of required data.
3.1.4
Visits Week 4 - 96
Subjects are expected to be treated for the duration of 96 weeks. In each Stage, after Day 1 and 
the optional Intensive PK visit at Week 2, subjects will be required to attend 12 more in-clinic 
study visits over the 96-week treatment period, as follows:

Visits are conducted every 4 weeks from Week 4 through Week 16

Visits are conducted every 8 weeks from Week 24 through Week 48

Visits are conducted every 12 weeks from Week 60 through Week 96
Visits should be scheduled as an interval from the Day 1/Randomization date, and within a 
window of 5 days earlier or later.
One of the visits Week 4 - 24 should meet the very specific timing requirements as outlined in 
Section 5.5.2 for a pre-AM dose blood collection.
Telephonic visits will be conducted with each subject at visit Weeks 20, 28, 36, 44, 54, 66, 78,
and 90 to conduct an adherence assessment and to continue retention efforts
3.1.5
Selection of the Continuation Dose of BMS-955176
3.1.5.1
Selection of the Continuation Dose, and the Switch for Stage 1
Once all subjects in Stage 1 have reached Week 24*, BMS will conduct an interim analysis of 
efficacy, safety, resistance and pharmacokinetics.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If Arm 1 meets 
criteria for Virologic Futility at Week 24, the clinical trial will be terminated.
The Week 24 analysis of Arms 1 and 2, combined with the Week 24 analysis of all Arms in the 
AI468038 study, will be used to select a Continuation Dose of BMS-955176 for Arm 1 in this 
study. Subjects in the BMS-955176 Treatment Arm 1 may subsequently be transitioned to a
selected Continuation Dose.
Subjects in the Arm containing TDF will continue with the TDF treatment regimen.
The assigned backbone will not change.
The Week 24 efficacy, safety, and pharmacokinetic analyses from Stage 1 and study AI468038 
will also trigger the start of Stage 2.
* If the Continuation Dose cannot be clearly identified using the Week 24 data, the study 
will continue in original fashion until an analysis of the Week 48 data can be performed 
Revised Protocol No.: 02
Date: 03-Jun-2015
39
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
and the Continuation Dose is selected. If a Continuation Dose cannot be selected based 
upon the Week 24 data, this does not preclude the ability to start recruitment of Stage 2.
After the Continuation Dose is selected, and once all of the logistics (eg, distribution of clinical 
drug supplies, activation of the new portion of the IVRS) have been completed globally, the 
transition of the subjects in Arm 1 to the Continuation Dose will occur. It is anticipated that this 
transition will occur on or after all subjects have reached Week 48 (the earliest subjects to begin 
study treatment could be well beyond Week 48 when the switch to the Continuation Dose 
occurs).
3.1.5.2
Selection of the Continuation Dose, and the Switch for Stage 2
Once all subjects in Stage 2 have reached Week 24, BMS will conduct an analysis of efficacy, 
safety, resistance and pharmacokinetics.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If a BMS-955176 
dose arm meets criteria for Virologic Futility at Week 24, subjects in said arm will begin dosing 
with the next highest available remaining dose of BMS-955176.
The data from AI468038 and AI468048 (Stages 1 and 2) will be used to select a Continuation 
Dose of BMS-955176 for Arms 3 and 4. Subjects in the BMS-955176 Treatment Arms 3 and 4 
will subsequently be transitioned to a selected Continuation Dose. It is anticipated that this 
transition may occur on or after all subjects have reached Week 48, or it could occur sooner after 
Week 24.
The assigned backbone will not change.
Subjects in the arm containing TDF will continue with this assigned treatment regimen.
3.1.6
End of the study
The end of the study will occur when the last study visit has been completed, defined as the final 
subject completing their final study visit (expected to be a Week 96 or Early Termination visit).
The study design schematic is presented in Figure 3.1.6-1.
Revised Protocol No.: 02
Date: 03-Jun-2015
40
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 3.1.6-1:
Study Design Schematic
Arm 2
TDF
300 mg QD
+ ATV/r + DTG
Day 1
Begin dosing
Arm 3
BMS-955176 
120 mg QD
+ ATV + DTG
1 Virologic Futility will be evaluated at Week 24 
(see Section 8.4.7).  
Results of Week 24 Stage 1 AI468-048 & AI468-038 
Confirm the Start of Stage 2   
Arm 4
BMS-955176 
180 mg QD
+ ATV + DTG
40
40
Week 2
Week 24
Week 24 Analysis1
Intensive PK subset
4 Based on totality of data from both studies the 
Continuation Dose for Arms 3 & 4 may be 
identified.  
Number
Randomized
STAGE 2
Week 96
Week 96 Analysis/End of Study
Week 48
Week 48 Analysis
The Switch to the Continuation Dose4,3     
is expected to occur on or after Week 48, 
but could occur sooner.
Arm 1
BMS-955176 
120 mg QD
+ ATV/r + DTG
Week 2
Number
Randomized
Week 24
Week 24 Analysis1
Day 1
Begin dosing
Intensive PK subset
40
40
Week 48
Week 96
Week 48 Analysis
Week 96 Analysis/End of Study
The Switch to             
the Continuation Dose2,3
may occur on or after 
Week 48 
STAGE 1
BMS-955176
Continuation Dose QD 
+ ATV/r + DTG
Arm 5
TDF
300 mg QD
+ ATV/r + DTG
40
3 The actual switch of subjects of BMS-955176 
subjects to that Continuation Dose may occur when 
all of the subjects have reached at least Week 48 
(though it could occur sooner in Stage 2).
BMS-955176
Continuation Dose QD
+ ATV + DTG
2 Based on Week 24 data from Arms 1 & 2 and 
from AI468-038, the Continuation Dose for 
Arm 1 may be identified.  
Revised Protocol No.: 02
Date: 03-Jun-2015
41
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.2
Post Study Access to Therapy
At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be 
eligible to receive BMS supplied study drug. Study drug will be provided via an extension of the 
study, a rollover study requiring approval by responsible health authority and ethics committee 
or through another mechanism at the discretion of BMS. BMS reserves the right to terminate 
access to BMS supplied study drug if any of the following occur: a) the marketing application is 
rejected by responsible health authority; b) the study is terminated due to safety concerns; c) the 
subject can obtain medication from a government sponsored or private health program; or 
d) therapeutic alternatives become available in the local market.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Ability to understand and sign a written informed consent form
2. Target Population
a) Antiretroviral treatment-experienced, defined as having documented evidence of having
failed, 1 or 2 regimens that include 2 or 3 classes of ARV (with or without documented 
resistance)
b) Confirmed Plasma HIV-1 RNA 400 copies/mL (First value from investigator; second 
value from screening test)
c) CD4+ T-cell count > 50 cells/mm3
d) Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, 
FC < 2.2; DTG; TDF)
e) Estimated Life expectancy 1 year
Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued 
the study as a pre-treatment failure (ie, subject has not been randomized / has not been treated). 
If re-enrolled, the subject must be re-consented and assigned a new PID. (See Section 5.5.1 for 
additional details.)
3. Age and Reproductive Status
a) Males and non-pregnant females
b) At least 18 years of age, (or minimum age as determined by local regulatory or as legal 
requirements dictate)
c) Willingness to use approved highly effective methods of contraception (see below) to 
avoid pregnancy (female subjects who are WOCBP and male subjects who are sexually 
active with WOCBP)
Revised Protocol No.: 02
Date: 03-Jun-2015
42
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
d) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 
24 hours prior to the start of study drug.
e) Women must not be breastfeeding
f)
WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug BMS-955176 plus 12 weeks post-treatment completion.
g) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug BMS-955176
plus 5 half-lives of the study drug BMS-955176 (8 days) plus 90 days (duration of sperm 
turnover) for a total of 98 days post-treatment completion.
h) Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However WOCBP must still undergo 
pregnancy testing as described in this section.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception. 
All subjects must agree to the use of a highly effective method of contraception as listed below.
In addition male subjects should use condoms during treatment and for 98 days following the last 
treatment when relevant systemic exposure is no longer present.
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly effective methods of contraception have a failure rate of < 1% when used consistently 
and correctly. WOCBP and female partners of male subjects, who are WOCBP, are expected to 
use one of the highly effective methods of contraception listed below. 
Study subjects who are WOCBP cannot use hormonal methods of contraception as one of the 
highly effective methods of contraception because there are data to show a lack of effectiveness 
of systemic hormonal contraceptives in women taking BMS-955176. However, WOCBP can 
continue to use hormonal contraceptives, if necessary, in addition to one other non-hormonal 
highly effective methods of contraception.  
Male subjects must inform their female partners who are WOCBP of the contraceptive 
requirements of the protocol and are expected to adhere to using contraception with their partner. 
Relevant exposure of BMS-955176 in female partners of male participants in the study is 
expected to be negligible. Female partners of male subjects participating in the study may use 
hormone based contraceptives as one of the acceptable methods of contraception because 
exposure to the investigational product would be too small to alter exposure of hormonal 
contraceptives.
1.
Nonhormonal IUDs, such as ParaGard
2.
Bilateral tubal occlusion
3.
Vasectomised partner with documented azoospermia 90 days after procedure
Revised Protocol No.: 02
Date: 03-Jun-2015
43
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
o
Vasectomised partner is a highly effective birth control method provided that partner is 
the sole sexual partner of the WOCBP trial participant and that the vasectomised partner 
has received medical assessment of the surgical success.
4.
Complete abstinence
o
Complete abstinence is defined as the complete avoidance of heterosexual intercourse 
when this is the preferred lifestyle of the patient.
o
Complete abstinence is an acceptable form of contraception for all study drugs and must 
be used throughout the duration of study and for the duration of time as specified above.
o
It is not necessary to use any other method of contraception when complete abstinence is 
elected.
o
Subjects who choose complete abstinence must continue to have pregnancy tests. 
o
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the subject chooses to forego complete abstinence
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject.
At a minimum, subjects must agree to the use of two methods of contraception, with one method 
being highly effective and the other method being either highly effective or less effective as 
listed below:
LESS EFFECTIVE METHODS OF CONTRACEPTION

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal sponge with spermicide

Male or female condom with or without spermicide 

By male subject’s WOCBP partner only: Progestogen-only oral hormonal contraception, 
where inhibition of ovulation is not the primary mode of action.
* A male and female condom must not be used together
3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a) Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens
b) Resistance or partial resistance to any study drug
c) Three or more of the following PI mutations, historical or documented: M36I/V, 
M46I/L/T, G48M/V, I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M
d) Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S
e) Any major TDF mutation, historical or documented: K65R or T69ins
f)
Three or more of the following non-accessory thymidine analogue mutations (TAMs): 
M41L, D67N, K70R, L210W, T215Y/F, K219Q/E
Revised Protocol No.: 02
Date: 03-Jun-2015
44
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
g) Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI 
resistance), historical or documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, 
Y143C/H/R, E157Q
h) Antiretroviral treatment-experienced adults infected with Clade AE
i)
Patients who have failed a previous boosted PI- or Integrase strand transfer inhibitor 
(INSTI)-containing regimen for which resistance analyses were not conducted at the time 
of failure
2. Medical History and Concurrent Diseases
a) A new AIDS defining condition diagnosed within the 30 days prior to screening
(see Appendix 2)
b) Any other clinical condition (including but not limited to active substance use) or prior 
therapy that, in the opinion of the Investigator, would make the subject unsuitable for the 
study; unable to comply with dosing requirements; or unable to comply with study visits; 
or a condition that could affect the absorption, distribution, metabolism or excretion of 
the drug.
3. Physical and Laboratory Test Findings
a) Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV 
Ab and HCV RNA)
b) ALT or AST > 3 × ULN
c) Alkaline Phosphatase > 5 × ULN
d) Bilirubin ≥ 1.5 × ULN
e) History of decompensated cirrhosis or active decompensated cirrhosis
f)
Hemoglobin < 8.0 g/dL
g) Platelets < 50,000 cells/mm3
h) Estimated eGFR < 60 mL/min (CKD-EPI formula)
i)
Confirmed QT value > 500 msec at Screening or Day 1
j)
Confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or 
Day 1
k) Confirmed PR Interval > 260 msec (severe first degree AV block) at Screening or Day 1
l)
Confirmed second or third degree heart block at Screening or Day 1
4. Allergies and Adverse Drug Reaction
a) Medications contraindicated for use with investigational/non-investigational study drugs 
(ATV, RTV, DTG, TDF);
or subjects with any known allergies to the 
investigational/non-investigational study drugs (ATV, RTV, DTG, TDF)
b) Current or anticipated treatment with any of the medications listed in Appendix 1, in 
addition to any medications that are contraindicated with ATV, RTV, DTG or TDF
c) Participation in an experimental drug and/or HIV-1 vaccine trial(s) within 30 days prior 
to Screening
Revised Protocol No.: 02
Date: 03-Jun-2015
45
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
A woman of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 years in the absence of other biological or physiological causes. In 
addition, females under the age of 55 years must have a serum follicle stimulating hormone, 
(FSH) level > 40 mIU/mL to confirm menopause.
Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. If the serum FSH level is > 40 mIU/mL at any time 
during the washout period, the woman can be considered postmenopausal:

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Refer to Appendix 1 which details prohibited and precautionary therapies during the study, 
including specifics about the use of antacids and hormonal methods of contraception.
3.4.2
Other Restrictions and Precautions
None.
3.5
Discontinuation of Subjects following any Treatment with Study Drug 
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment
Revised Protocol No.: 02
Date: 03-Jun-2015
46
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject

Termination of the study by Bristol-Myers Squibb (BMS)

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Pregnancy (subjects should be discontinued in an appropriate manner)

Repeat non-adherence by the subject with the requirements of the protocol or treatment
(as determined by Investigator in consultation with the BMS Medical Monitor)

Evidence of Hepatitis B or C infection

Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8

Confirmed plasma HIV-1 RNA 1000 c/mL after Week 24

Confirmed plasma HIV-1 RNA 200 c/mL after Week 48

Emergence of genotypic and/or phenotypic resistance to any component of the study 
treatment regimen at any time after Screening

Subject requires switching to any other ARV

Development of pDILI (potential drug induced liver injury)

Confirmed QTcB or QTcF value > 500 msec

Confirmed second degree (Type II) or third degree AV block at any time during the study
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event. The study drug will be permanently discontinued in an 
appropriate manner.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Section 5 (ie, perform an Early Termination [ET] visit). The only 
exception to this requirement is when a subject withdraws consent for all study procedures 
including post-treatment study follow-up (no such period exists in this study) or loses the ability 
to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either a 
psychiatric or physical illness).
If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post Study Drug Study Follow up
Subjects who discontinue study drug may continue to be followed.
Subject’s contact information will be collected/confirmed throughout the study so that subjects 
who discontinue study drug may continue to be followed for resolution of a pregnancy or SAE.
Revised Protocol No.: 02
Date: 03-Jun-2015
47
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug will remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. In 
the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study. The site staff and representative will consult publicly available sources, such as public 
health registries and databases, in order to obtain updated contact information. If after all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
4
STUDY DRUG
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
Revised Protocol No.: 02
Date: 03-Jun-2015
48
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 4-1:
Study Drugs for AI468048:
Product Description / 
Class and Dosage Form
Potency
IMP/Non-IMP
Blinded or 
Open Label
Packaging/ Appearance
Storage Conditions
(per label)
BMS-955176 
60 mga
IMP
Open Label
Bottle/
A white to off-white, biconvex, 
oval shaped film coated tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
BMS-955176
120 mga
IMP 
Open Label
Bottle/
A white to off-white, biconvex, 
capsule shaped film coated tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
Tenofovir (TDF)
300 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Atazanavir (ATV)
200 mg
IMP
Open Label
Bottle/
Blue cap and blue body
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Atazanavir (ATV)
300 mg
IMP
Open Label
Bottle/
Red cap and blue body,
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Ritonavir (RTV)
100 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Dolutegravir (DTG)
50 mg
Non-IMP or 
IMP,
depending on 
country 
approval status.
Open Label
Various packaging configurations
Refer to label on
container or package insert.
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Revised Protocol No.: 02
Date: 03-Jun-2015
49
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, investigational product(s) is/are: BMS-955176, ATV, and DTG (in countries 
where DTG has not been approved for use). These products will be supplied.
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be 
considered as non-investigational products.
In this protocol, noninvestigational product(s) is/are: TDF, RTV, and DTG (in countries where 
DTG is approved for use). These products will be supplied.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be 
dispensed and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
that includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations.
4.4
Method of Assigning Subject Identification
At the start of the screening period, the investigative staff will call the Assignment Center via an 
Interactive Voice Response System ([IVRS], or its web-based equivalent) designated by the 
sponsor to enroll the subject and to obtain a subject patient identification number (PID).
For subjects who meet the protocol eligibility criteria, the investigative staff will call the IVRS 
and subjects will start treatment.
Revised Protocol No.: 02
Date: 03-Jun-2015
50
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Subjects will be randomly assigned in the staged fashion to one of the treatment arms, as
described in Section 3 and as outlined in the AI468048 Study Schematic Figure 3.1.6-1.
Note: All efforts should be made to limit the possibility of randomizing subjects that do not start 
treatment. If a subject is randomized but does not receive study medication, the BMS study team 
must be notified immediately.
4.5
Selection and Timing of Dose for Each Subject
Subjects will be randomized into the treatment arms in a staged fashion described in Section 3.1.
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
4.5.1
Instructions for Dose Administration
4.5.1.1
General Instructions

Subjects should administer doses of each drug from only one bottle at a time, until that bottle 
is empty, before another bottle may be opened. 

Subjects will be required to complete Dosing Diaries so that drug administration can be 
accurately accounted. It is important that sites provide instructions to subjects for completion 
and obtain their acknowledgment that doing so provides critical information for the clinical 
trial.

Dosing times (and study appointment times) must be carefully considered through Week 24 
due to the requirements of the PK collection outlined in Section 5.5.
4.5.1.2
Specific Dosing Instructions for Initial Treatment Arm Assignment
In the morning, with a meal, subjects will take the following:

Arm 1: One pill each from bottles BMS-955176 120 mg, ATV, RTV, and DTG

Arm 2: One pill each from bottles TDF, ATV, RTV and DTG
Revised Protocol No.: 02
Date: 03-Jun-2015
51
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Arm 3: One pill each from bottles BMS-955176 120 mg, DTG, and two pills from bottle
ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 4: One pill each from bottles BMS-955176 60 mg, BMS-955176 120 mg and DTG, and 
two pills from bottle ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 5: One pill each from bottles TDF, ATV, RTV and DTG
4.5.2
Dose Modifications
No dose adjustments or changes in intake frequency are allowed for any of the assigned study 
drugs in the protocol, except for the unique case of treatment-limiting renal toxicity which limits 
the use of the TDF. In the event of treatment-limiting renal toxicity, dose interval adjustments for 
TDF are permitted according to the local package insert/label, and only after the completion of 
the Week 2 Intensive PK optional Visit, if the subject is inclined to participate.
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Treatment Adherence to the treatment regimen will be critical to the conduct of this study. 
Adherence will be evaluated by the investigative staff at every treatment visit (including 
telephone contact visits) through interviews with the subjects and through examination of 
returned medication. It is expected that site staff attempt to have subjects maintain 90% 
treatment compliance or greater. Subjects should be instructed to bring all unused study 
medication back in the original container to each visit. Site staff are required to review Dosing 
Diaries completed by the subject, and to reinforce their use.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible Study Monitor unless study drug containers must be immediately destroyed as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:

On-site disposal practices must not expose humans to risks from the drug

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request
Revised Protocol No.: 02
Date: 03-Jun-2015
52
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor must be documented

Accountability and disposal records are complete, up-to-date, and available for the Monitor 
to review throughout the clinical trial period
If conditions for destruction cannot be met the responsible Study Monitor will make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible Study Monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
Revised Protocol No.: 02
Date: 03-Jun-2015
53
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)
Notes
Eligibility Assessments
Informed Consent
X
Call IVRS to Enroll the subject; PID assigned
X
Inclusion/Exclusion Criteria
X
Medical History
X
AIDS History
X
Non-Laboratory Safety Assessments
Full Physical Examination
X
See Section 5.3.1 for requirements
Vital Signs & Physical Measurements
X
See Section 5.3.1 for requirements
Pre-treatment events
X
Only CDC Class C events with onset during the Screening period
Serious Adverse Events Assessment
X
All SAEs that occur after the ICF has been signed should be reported
ECG
X
See Section 5.3.4 for requirements
Pregnancy Test
X
WOCBP
For females under age 55, an FSH level must be on record to confirm she 
is not a WOCBP if pregnancy testing is not being performed.
If positive urine, request serum hCG quant. on lab requisition.
Laboratory Assessments (See Appendix 5 for full details)
Fasting Chemistry and Lipid Panel
X
Fasting overnight
Hematology
X
Urinalysis
X
Revised Protocol No.: 02
Date: 03-Jun-2015
54
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)
Notes
Plasma HIV-1 RNA
X
This is the confirmatory HIV-1 RNA
(The first value is provided by the PI)
CD4+ and CD8+ T-cell count
X
HBV Surface Antigen
X
HCV Serology
X
Urine toxicology (drugs of abuse)
X
Could aid in the selection of appropriate study candidates.
Pharmacodiagnostic (PDx) samplea
X
Plasma collection to be banked for potential future use in development of 
novel predictive assay(s)
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
Complete set of test results may take up to 4 weeks.
PhenoSense Gag
X
Next Generation Seq. - Qs Gag
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
Molecular analysis at BMS WFD Discovery of baseline resistant samples 
and baseline sensitive controls in cases of subsequent on-treatment 
virologic failure
a By definition, a pharmacodiagnostic sample (PDx) is a pre-treatment test to determine whether or not a patient is likely to respond to a drug (ie, a predictive 
test). Based on the results of clinical studies with BMS-955176, BMS may have to develop a PDx assay. Thus, PDx samples obtained at Screening in this 
study would be used for that sole purpose.
Revised Protocol No.: 02
Date: 03-Jun-2015
55
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Eligibility Assessments
Inclusion/Exclusion Criteria
X
Non-Laboratory Safety Assessments
Full Physical Examination
WK 12, 24, 48, 96/ET
See Section 5.3.1 for requirements
Targeted Physical Examination
X
WK 4, 8, 16, 32, 40, 60, 72, 84
See Section 5.3.1 for requirements
Vital Signs & Physical 
Measurements
X
X
See Section 5.3.1 for requirements
Adherence Assessments
X
X
Including review of Dosing Diaries
Pre-treatment Events
X
See Table 5.1-1
Adverse Events Assessments
X
X
X
Serious and Non-serious AEs
Concomitant Medications
X
X
X
See Section 5.3.3
ECG
X
WK 4, 12, 24, 48, 96/ET
See Section 5.3.4 for requirements
Pregnancy Test
X
X
X
For females under age 55, an FSH 
level must be on record to confirm 
she is not a WOCBP if pregnancy
testing is not being performed.
If positive urine, request serum 
hCG quant. on lab requisition.
Revised Protocol No.: 02
Date: 03-Jun-2015
56
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Provide WOCBP with Home 
Pregnancy test kit(s) to be used 
during the in-clinic visit interval
WK 16, 24, 32, 40,
48, 60, 72, 84
Provide One Kit at Weeks 16 - 40
Provide Two Kits at Weeks 48 - 84
WOCBP subjects perform test Q4 
weeks at home and report results to 
site.
Laboratory Assessments for Safety and Efficacy and Other Endpoints (See Appendix 5 for full details)
Fasting Chemistry
X
X
Fasting overnight
Fasting Lipid Panel
X
WK 4, 12, 24, 48, 96/ET
Fasting overnight
Hematology
X
X
Urinalysis
X
X
Fractional Excretion of Phosphorous 
(FePO4)
(Urine creatinine and phosphorus, 
Serum creatinine and phosphorus)
X
WK 48 and 96/ET
Plasma HIV-1 RNA
X
X
X
If collecting an HIV-1 RNA at an 
UNSCHEDULED visit, also collect 
samples for Resistance and 
Exploratory Resistance Testing
CD4 and CD8 T-cell counts
X
X
HBV Surface Antigen
WK 48 and 96/ET
HCV Serology
WK 48 and 96/ET
Positive HCV Ab will reflex to 
HCV RNA
Revised Protocol No.: 02
Date: 03-Jun-2015
57
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
X
Samples stored and tested if needed
(ie, analyses of subjects if deemed 
clinically relevant)
See Section 5.4.2.2
PhenoSense Gag
X
X
Next Generation Seq. - Qs Gag
X
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
X
Samples stored and tested 
retrospectively if needed (ie,
exploratory analyses for subjects if 
deemed clinically relevant)
Intensive PK sample collection
X
Use of PK Tools for data collection 
recommended.
See Section 5.5.1 for requirements
Sparse PK sample collection
WK 4, 8, 12, 16, 24
See Section 5.5.2 for requirements
Bone Biomarkers
(P1NP and CTX)
X
WK 12 and 24/ET
Serum collection
Renal Biomarkers
(2-microglobulin and creatinine)
X
WK 48 and 96/ET
Urine collection
Backup Serum and Plasma Sample
X
X
Samples stored and tested if needed
Outcomes Measures
EQ-5D-3L Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Health Outcomes Questionnaire
Revised Protocol No.: 02
Date: 03-Jun-2015
58
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
FAHI Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Functional Assessment of HIV 
Infection
Clinical Drug Supply
Call IVRS to Randomize
X
Dispense Study Drug
X
X
There is no dispensation at Week 96 
or ET.
Revised Protocol No.: 02
Date: 03-Jun-2015
59
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory 
value). The Screening Period for this study is 42 days.
Any new result will override the previous result (ie, the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. Consultations 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant (eg, a previously failed inclusion criterion).
Rescreening is different than Retesting. Rescreening is the process of Re-enrollment and requires 
that all procedures be repeated in an entirely new screening period. A one-time Rescreening is 
permitted, if further rescreening is considered for reassessment of enrollment eligibility this 
should be discussed with the Medical Monitor.
The assigned patient identifier (PID) for the subject must be Screen Failed in the IVRS. A new 
call must be made to the IVRS for the assignment of a new PID for the subject, and all Screening 
parameters must be done again in reference to the new PID (See Section 3.3.1, Inclusion 
Criteria 2f). Subject must also be re-consented with the new PID.
5.2
Study Materials
The sponsor will provide each investigative site with the following:

BMS-955176 Investigator Brochure (IB) and any relevant safety addenda or updates

Protocol and any Amendments to the Protocol

Instructions for completing electronic Case Report Forms (eCRFs)

Laboratory Manual from the central laboratory

ECG Machines and manual

IVRS Worksheets to complete when calling the IVRS center to enroll, randomize, and 
discontinue subjects

Patient-reported Outcomes Questionnaires: EQ-5D-3L Health Outcome Questionnaire, FAHI 
(Functional Assessment of HIV Infection)

PK Tools/Job Aids that may be used for detailed instruction about the PK visits, and as a 
comprehensive source for documents of date/times of dosing and blood sampling

Dosing Diaries

Completion by subjects is required

Should include daily dose of study medications administered by subject, modified or 
missed

Site staff should review the diaries with the subject at each visit, and, in combination with 
detailed questioning, should be able to provide comprehensive information in the case 
Revised Protocol No.: 02
Date: 03-Jun-2015
60
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
report form, noting discrepancies in the subject’s file. Dosing Diaries should be 
maintained in the subject’s study file.
5.3
Safety Assessments
The investigative team should follow the protocol-specified scheduled of safety-related 
measurements. Only data for the procedures and assessments specified should be submitted to 
BMS on the case report form. Additional procedures and assessments may be performed as part 
of standard of care, however, data for these assessments should remain in the subject’s medical 
record and should not be submitted to BMS, unless specifically requested (ie, as part of an SAE).
5.3.1
Vital Signs and Physical Examinations
The schedule of vital signs, physical examinations, and targeted physical examinations is 
provided in Section 5.1 (Flow Chart/Time and Events Schedule). Vital signs include heart rate, 
blood pressure, respiration rate, and temperature and should be measured after the subject has 
been sitting/resting for at least 5 minutes. Physical measurements include height and weight. 
Targeted physical examinations will include examination of the heart, lungs, skin, abdomen, any 
symptomatic organ system, and general appearance.
5.3.2
Adverse Events
Subjects will be closely monitored throughout the study for any new or ongoing HIV-related 
diagnoses (Appendix 2) and/or adverse events. CDC Class C events that occur from the
Screening Visit through Day 1 (prior to dosing), will be recorded as Pre-treatment Events. All 
events that occur after dosing on Day 1 will be recorded on the appropriate Adverse Event eCRF. 
Additional information on Adverse Events is provided in Section 6.
5.3.3
Concomitant Medication Assessment
All medications taken from the Screening Visit throughout the duration of the study will be 
reported. In addition, any prior therapy with antiretroviral drugs will be reported
(See Appendix 1 for Prohibited and Precautionary Therapies).
5.3.4
Electrocardiograms
The schedule of electrocardiograms (ECGs) is provided in Section 5.1 (Flow Chart/Time and 
Events Schedule). ECG machines will be provided by a central vendor who will also perform the
read/interpretation of the output.
5.4
Efficacy Assessments
5.4.1
Primary Efficacy Assessment
The primary assessment for efficacy is HIV-1 RNA at Week 24.
Revised Protocol No.: 02
Date: 03-Jun-2015
61
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.1
Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing
A confirmatory HIV-1 RNA viral load should be obtained when:

HIV-1 RNA 40 c/mL if prior suppression 40 c/mL, or

> 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is 
40 c/mL
All efforts should be made to collect this sample within 2-4 weeks from the collection of the 
original sample.
When collecting a blood sample for HIV-1 RNA testing at an Unscheduled visit, samples should 
also be collected for the sets of Resistance and Exploratory Resistance Tests, so that the samples
are available should resistance testing be required or deemed necessary based on the result of the 
HIV-1 RNA test.  
Table 5.4.1.1-1:
Management of Detectable HIV-1 RNA, based on Confirmed 
(2-4 weeks from original sample) or Consecutive HIV-1 RNA 
Resulta
Day 1 through Week 24
40 - 399 c/mL
Reinforce Adherence
400 c/mL
Consider the need for resistance testing, in consultation with BMS Medical Monitor.
Consider possible discontinuation of subject, in consultation with BMS Medical Monitor, 
and/or reinforce adherence.
After Week 24 through Week 48
40 - 399 c/mL
Reinforce Adherence
400 - 999 c/mL
Resistance testing will be performed.
If resistance has developed, subject must be discontinued.
If resistance has not developed, consider possible discontinuation of subject, in consultation 
with BMS Medical Monitor, and/or reinforce adherence.
1000 c/mL
Resistance testing will be performed.
Regardless of result of resistance tests, subject must be discontinued (see Section 3.5).
After Week 48
40 to < 200 
c/mL
Reinforce Adherence
200 c/mL
Subject must be discontinued (see Section 3.5). 
If 400 c/mL, consider the need for resistance testing, in consultation with BMS Medical 
Monitor.
a When discontinuation is required or otherwise warranted and resistance results are needed, subject may continue 
on study medication/on study until resistance testing results are available.
Revised Protocol No.: 02
Date: 03-Jun-2015
62
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.2
Protocol Defined Virologic Failure
Protocol Defined Virologic Failure (PDVF) is defined by a subject meeting one of the following 
criteria:
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir 
is 40 c/mL
2) Confirmed HIV-1 RNA 400 c/mL after Week 24
3) Confirmed HIV-1 RNA 40 c/mL if prior suppression to < 40 c/mL
4) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 
week snapshot window
5) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8
In addition to the clinical management outlined in section 5.4.1.1, samples meeting criteria for 
PDVF will also be sent for resistance and exploratory resistance testing.
5.4.2
Secondary Efficacy Assessments
5.4.2.1
CD4+ and CD8+ T-Cells
CD4+ and CD8+ T-cells counts and percentages will be assessed using flow cytometry. The 
schedule of assessments is provided in Section 5.1 (Flow Chart/Time and Events Schedule). 
Procedures for samples collection and processing are provided in the central clinical laboratory 
manual.
5.4.2.2
Drug Resistance Testing
Plasma samples for viral drug resistance testing will be collected at Screening for all subjects and 
the HIV-1 drug resistance genotype will be analyzed to rule out resistance to any component of 
the study regimen or specific resistance mutations as outlined in Section 3.3.2, Exclusionary 
Criteria. At subsequent visits, samples for emergent drug resistance testing (both genotypic and 
phenotypic) will be collected and stored to be as outlined in Section 5.4.1.
5.5
Pharmacokinetic Assessments
It is extremely important to record the exact dose and time of the dose(s) taken the day prior to 
the visit/collection, and the exact date and time of the sample collection, even if drawn slightly 
off-schedule.
5.5.1
Intensive Pharmacokinetic Assessment
A subset of subjects (about 12 subjects per treatment group) will participate in an optional 
Intensive PK assessment at Week 2 (window Day 12-16).
Intensive PK samples collected in this study will provide for the assessment of BMS-955176, 
ATV, RTV, and DTG to support the secondary and exploratory objectives (to characterize the 
PK of BMS-955176, DTG, and ATV (with or without RTV) when given in combination, and to 
compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV).
Revised Protocol No.: 02
Date: 03-Jun-2015
63
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Intensive PK sampling begins with a morning pre-dose (0 hour) sampling, ie, prior to the 
administration of the morning doses of the study drugs on the day of the visit. The sampling 
should also begin 24 hours (between 20 and 28 hours) after the morning doses of the study drugs 
that were taken the day prior to the visit.
The subsequent 11 time points include samplings through Hour 12, with the last sample collected 
at Hour 24. The subject will either stay overnight or will return to the clinic so that the final 
sample can be collected at Hour 24.
It is critical to capture the exact date and time of each PK sample collection, even if drawn 
slightly off-schedule. There is no specified collection window end for which any one time point 
should be abandoned as the schedule progresses. If a sample collection time point is missed/late 
and the next collection time point has not yet been reached, collect the missed time point, and 
record the exact time of that collection, then get back on track for the next time point/on-time 
collection.
Table 5.5.1-1 lists the sampling schedule to be followed for the assessment of intensive 
pharmacokinetics. Further details of PK blood collection and sample processing will be provided 
in the central clinical laboratory manual.
Table 5.5.1-1:
AI468048 Intensive Pharmacokinetic Sampling Schedule at Week 2
Time 
(Event)
Time 
(Relative to Dosing)
Hour: Min
PK
Blood Sample
Study Week 2
(window Day 12-16)
0 (morning pre-dose)
00:00
X
1 Hr
01:00
X
2 Hr
02:00
X
2.5 Hr
02:30
X
3 Hr
03:00
X
4 Hr
04:00
X
4.5 Hr
04:30
X
5 Hr
05:00
X
6 Hr
06:00
X
8 Hr
08:00
X
12 Hr
12:00
X
24 hr (morning pre-dose)
24:00
X
5.5.2
Sparse Pharmacokinetic Assessments
All subjects will provide Sparse PK samples (as part of the regular blood collection) for the 
assessment of BMS-955176, ATV, RTV and DTG at visit Weeks 4- 24.
Revised Protocol No.: 02
Date: 03-Jun-2015
64
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Of the five visits (Week 4 - 24), it is requested that the following guidelines are followed:

At any one visit Week 4 through Week 24, the Sparse PK sample must be collected 
approximately 24 hours (between 20 and 28 hours) after the dose that was taken the morning 
before and before the morning dose is taken on the day of the visit

At the remaining four visits Week 4 through Week 24, the blood collections may be done 
without any specific consideration to timing of previous dose administration (taken either the 
day before the visit or on the day of the visit), though it is critical that the date and time of the 
most previous dose of study drug is recorded in the eCRF so that the exact interval between 
dose and blood sampling can be calculated for accurate PK analysis
PK Samples need to be tested on an ongoing basis prior to the Week 24 database lock and 
analysis.
5.6
Biomarker Assessments
In this study, BMS is confirming the safety of BMS-955176 demonstrated in the Phase 2a study 
to date. The proposed sample population of treatment-experienced adults in Arms 3, 4, and 5, 
will provide a representation of the potential benefits of BMS-955176 on nucleoside and RTV 
based toxicities of interest (ie, renal toxicity, bone mineral density, and dyslipidemia): Arms 3 
and 4 relative to Arms 1, 2, and 5.
Specifically, to evaluate for renal toxicity we will evaluate clinically relevant parameters and 
biomarkers for glomerular and tubular toxicity, which may include but are not limited to: 
fractional excretion of phosphorous and urinary β2-microglobulin/creatinine, in all available 
subjects. To evaluate for bone-related toxicity, clinically relevant bone biomarkers for both 
formation and resorption will be evaluated in all available subjects. These may include but are 
not limited to: N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked 
C-telopeptide of Type 1 collagen (CTX). The bone and renal biomarkers will be collected and 
measured at time points specified in Table 5.1-2 Additionally, back-up plasma and serum 
samples (at Baseline, Week 24, and Week 48) will be obtained for potential future evaluation of 
the safety of BMS-955176.
Samples will be collected at the screening visit for HIV-1 Gag sequencing, phenotypic 
susceptibility (PhenoSense Gag) and potential pharmacodiagnostic analysis as specified in Table 
5.1-1. These samples may be analyzed, if deemed clinically relevant, as a predictive marker of 
clinical response.
Any remaining blood and urine specimens that are available after completion of the designated 
analyses may be used in the future for identification of potentially predictive or 
pharmacodynamic markers of study drug activity or to enhance the understanding around disease 
biology, except where prohibited by local laws or regulations.
5.7
Outcomes Research Assessments
Increases in CD4 counts and avoidance of opportunistic infections and other AIDS-defining 
illnesses have been shown in many studies to improve health related quality of life (HRQoL). To 
Revised Protocol No.: 02
Date: 03-Jun-2015
65
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
help assess whether use of BMS-955176 will result in a better quality of life outcome, both a 
disease specific quality of life assessment and a generic quality of life assessment will be 
administered. Disease specific instruments are more sensitive to disease specific changes in 
quality of life and are more likely to show improvement with new interventions. The generic 
instruments are needed because Health Technology Authorities often require use of these 
instruments for cost-effectiveness modeling.
The Functional Assessment of HIV (FAHI) is the disease specific instrument that will be used. 
The FAHI evaluates physical well-being, functional and global well-being, emotional 
well-being/living with HIV, social well-being and cognitive functioning. It yields a total score 
and individual subscale scores.
The EQ-5D-3L is the generic instrument that will be used. The EQ-5D-3L includes two parts: the 
EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L 
descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some 
problems, extreme problems. The EQ VAS records the respondents’ self-rated health on a 
100 point, vertical, visual analogue scale where the endpoints are labeled ‘Best imaginable health 
state’ and ‘Worst imaginable health state.’
5.8
Other Assessments 
We will obtain back-up plasma and serum samples for current/future evaluation of the efficacy, 
safety and tolerability of BMS-955176. 
Should any new safety signal develop during the course of the ongoing analysis of the Phase 2a 
trial, appropriate measures for evaluation and management will be incorporated into the design 
of the Phase 2b trial via a protocol amendment.
5.9
Results of Central Assessments
The following describes the centrally assessed parameters and the timing with which they will be 
shared with investigators, if pertinent. Some parameters are relevant to ongoing subject 
management during the study and will be provided to the site for such purpose, while others are 
not relevant to subject management during the study and results may only be shared in a 
summarized way at the end of the study.

Samples sent to the central lab vendors for safety and efficacy assessments and that are tested 
real time will be provided to the sites as soon as results are available

The results of the read of each ECG will be sent to the site by the central ECG vendor as 
soon as results are available

Samples collected on-treatment for resistance testing will be tested if deemed clinically 
relevant (eg, if the development of resistance is suspected). If tested, results will be reported 
to the site

Other samples (including but not limited to biomarker assessments, exploratory resistance, 
pharmacodiagnostics) may not be tested immediately, and may only be tested if deemed 
clinically relevant. Results may be suppressed from laboratory reports and may not be 
provided to the sites
Revised Protocol No.: 02
Date: 03-Jun-2015
66
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Individual PK results will not be reported to the site; the overall PK assessments will be 
included in the CSR

Individual assessments of the Outcomes research will not be reported to the site; the overall 
Outcomes assessments will be included in the CSR
6
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE). The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term "reasonable causal relationship" means there is evidence to suggest a causal 
relationship.
Adverse events can be spontaneously reported or elicited during open-ended questioning,
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs).
6.1
Serious Adverse Events
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

results in death

is life-threatening (defined as an event in which the subject was at risk of death at the time of 
the event; it does not refer to an event which hypothetically might have caused death if it 
were more severe)

requires inpatient hospitalization or causes prolongation of existing hospitalization 
(see NOTE below)

results in persistent or significant disability/incapacity

is a congenital anomaly/birth defect

is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above).
Examples of such events include, but are not limited to, intensive treatment in an emergency 
Revised Protocol No.: 02
Date: 03-Jun-2015
67
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization). Potential drug induced liver injury (DILI) is also considered an 
important medical event. (See Section 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must
be handled as
SAEs. 
(See Section 6.1.1 for reporting pregnancies).
NOTE:
The following hospitalizations are not considered SAEs in BMS clinical studies:

a visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason)

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochure (IB) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
and within 30 days of discontinuation of dosing.
The investigator should report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure.
An SAE report should be completed for any event where doubt exists regarding its seriousness.
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship should be specified in the narrative section of the SAE Report Form.
Revised Protocol No.: 02
Date: 03-Jun-2015
68
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
SAEs, whether related or not related to study drug, and pregnancies, must be reported to BMS 
(or designee) within 24 hours. SAEs must be recorded on the SAE Report Form; pregnancies on 
a Pregnancy Surveillance Form (electronic or paper forms). The preferred method for SAE data 
reporting collection is through the eCRF. The paper SAE/pregnancy surveillance forms are only 
intended as a back-up option when the eCRF system is not functioning. In this case, the paper 
forms are to be transmitted via email or confirmed facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. The paper forms should be used and submitted immediately, only 
in the event the electronic system is unavailable for transmission. When paper forms are used, 
the original paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports should include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, a follow-up SAE report should be sent within 24 hours to the BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs should be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (paper or electronic) as appropriate:
Revised Protocol No.: 02
Date: 03-Jun-2015
69
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Any laboratory test result that is clinically significant or meets the definition of an SAE

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance 
Form to BMS Designee within 24 hours and in accordance with SAE reporting procedures 
described in Section 6.1.1.
The study drug will be permanently discontinued in an appropriate manner (eg, dose tapering if 
necessary for subject safety).
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important.
All occurrences of overdose must be reported as an SAE (see Section 6.1.1 for reporting details).
6.6
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
Potential drug induced liver injury in HIV-1 mono-infected subjects is defined as:
1. AT (ALT or AST) elevation > 3 times upper limit of normal (ULN)
AND
Revised Protocol No.: 02
Date: 03-Jun-2015
70
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3. No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic
6.7
Other Safety Considerations
Any 
significant 
worsening
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
6.7.1
Toxicity Management
The link to the current grading system for specific AEs and laboratory abnormalities is located in 
Appendix 3 (DAIDS; See Appendix 3).
6.7.1.1
Management of Elevations in Liver Transaminases
The following Table 6.7.1.1-1 summarizes the management of elevations in liver transaminases:
Table 6.7.1.1-1:
Management of Elevations in Liver Transaminases Grade Level of 
AST or ALT Recommendationsa
Grade
Recommendation
Grade1
None
Grade 2
none
Grade 3
Confirm elevation, evaluate for potential causes (including but not limited to alcohol or other 
substance abuse, concomitant medications, reactivation of existing or de novo infection with 
hepatitis viruses) consult with BMS Medical Monitor or designate as soon as possible.
Grade 4
Interrupt all study medications, evaluate for potential causes (including but not limited to alcohol 
or other substance abuse, concomitant medications, reactivation of existing or de novo infection 
with hepatitis viruses), monitor values frequently and consult with BMS Medical Monitor or 
designate as soon as possible. If Grade 4 is deemed related to study medication the subject must 
be discontinued from the study. Otherwise, if reinstitution of study therapy is considered, please 
obtain approval from the BMS Medical Monitor or designate.
a If persisting (> Grade 1/2), evaluate for alternative etiologies, including alcohol use and viral hepatitis
6.7.1.2
Management of Renal Toxicity
Serum phosphate levels and creatinine clearance (CrCl; CCL: as calculated by the Cockcroft 
Gault Equation [see Appendix 4] or eGFR) should be monitored and managed as described in the 
Viread local package insert/label.28 Dose interval adjustments of TDF (Viread) are permitted, as 
described in Section 4.5.2.
Revised Protocol No.: 02
Date: 03-Jun-2015
71
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
6.7.1.3
Management of Hyperbilirubinemia
Most patients taking ATV experience asymptomatic elevations in indirect (unconjugated) 
bilirubin related to inhibition of UDP-glucuronosyl transferase (UGT). Hepatic transaminase 
elevations that occur with hyperbilirubinemia should be evaluated for alternative etiologies. Dose 
modification of ATV is not permitted. Subjects who experience unacceptable jaundice/scleral 
icterus should be discussed with the BMS Medical Monitor or designate to determine if subjects 
are to be discontinued from study. The investigator must contact the BMS Medical Monitor or 
designate prior to discontinuing any subject due to hyperbilirubinemia.
6.7.1.4
Gastrointestinal Toxicity Evaluation and Management Plan
Pre-clinical toxicology studies in rats and dogs (see Section 1.4.1.2) have suggested a potential 
for GI related toxicity with BMS-955176. This section provides general guidance to the 
Investigator on the evaluation and management of primarily upper gastrointestinal symptoms. 
The Investigator may contact the Medical Monitor to discuss evaluation and management 
(including interruption of ARVs or discontinuation of a subject) of any GI symptoms throughout 
the trial.
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical 
trial. 
Nausea and Vomiting
The investigator should attempt to identify the etiology of these symptoms (and whether 
it is intraperitoneal, extraperitoneal, medication related, infection related, or due to a 
metabolic disorder).33 Medications can cause nausea and vomiting acutely. 
Dyspepsia
The Investigator should identify the presence of red flags (odynophagia, unexplained 
weight loss, recurrent vomiting, GI bleeding, jaundice, palpable mass or adenopathy, or 
family history of GI malignancy). Symptoms of dyspepsia could include early satiety, 
bloating, or belching. Additionally, atypical symptoms of dyspepsia could include: 
pharyngitis, asthma, bronchitis, hoarseness, chest pain, or abdominal pain. 
Ulcerative Disease
Symptoms suggestive of ulceration often are intermittent over a period of weeks to 
months and may be relieved by eating or antacid use;34 penetrating ulcers become more 
acute with localized pain and may not improve with food.35 The development of 
perforation may be indicated by severe diffuse abdominal pain. 
Other Clinical 
Syndromes
Additional diagnostic criteria for other GI disorders potentially encountered in the 
clinical trial are available elsewhere.36
PHYSICAL 
EXAMINATION
Physical examination should complement elements obtained from the history34
Acutely, the investigator may assess for signs of intravascular volume depletion 
(eg, orthostasis) and/or aspiration of vomitus as appropriate. Abdominal 
tenderness and guarding may indicate inflammation. The presence of fecal blood 
can indicate mucosal damage (eg, from an ulcer). Complete evaluation of dyspepsia 
should include an oral examination (poor dentition or pharyngeal erythema) and 
lungs for wheezing. 
Revised Protocol No.: 02
Date: 03-Jun-2015
72
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical 
trial. 
DIAGNOSTIC 
EVALUATION 
AND 
MANAGEMENT
A major goal in the diagnostic evaluation of a subject with upper GI symptoms is 
to quickly arrive at a final diagnosis without exposing the subject to unnecessary 
(invasive) testing; Investigators should exercise good clinical judgment35 in this 
regard. A major goal of therapy is directed at correcting the underlying 
identifiable medical or surgical abnormalities. Consultation (eg, gastroenterologist) 
is recommended as clinically indicated.
Grade 1 symptoms
Subjects may be treated symptomatically. If subjects develop dyspepsia alone, generally 
only limited and direct diagnostic testing should be performed.34 If the subject has 
dyspepsia they should limit alcohol, caffeine, chocolate, tobacco, other contributing 
concomitant medications (eg, NSAIDs) and eating directly before bedtime. A variety of 
OTC medications are available to address constipation and diarrhea as indicated. Please 
refer to Appendix 1 for Prohibited and Precautionary Therapies.
Grade 2 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

Serum chemistries and assessment of hemoglobin if not recently performed. 

Testing for Helicobacter pylori

Serologies (eg, celiac disease) 

PCR for viruses (eg, CMV)

Iron panel or Vitamin B12 level
For subjects who develop dyspepsia or are infected with H. pylori the use of H2 
antagonists, PPIs, Sucralfate, and antacids are prohibited (see Appendix 1 Prohibited 
Medications). If such therapy is required, discontinuation from the trial is necessary. 
The use of antiemetic’s (eg, Prochlorperazine) can be utilized as indicated. Management 
should be targeted at addressing the underlying pathology.
Grade 3 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

The testing outlined above in Grade 2

A fasting serum gastrin level can be obtained in cases of known ulcers refractory to 
therapy, a family history of the disease, or when surgery is required; of note, H. 
pylori can increase gastrin levels.35

A barium swallow to detect ulcers 

CT to identify gastrointestinal inflammation and a penetrating or perforated ulcer. 

Upper endoscopy with biopsy as indicated in order to evaluate dyspepsia further 
(eg, mucosal injury, new onset unexplained dyspepsia in subjects > 55 y/o, or the 
presence of red flags).
Management should be targeted at addressing the underlying pathology.
Grade 4 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):
Revised Protocol No.: 02
Date: 03-Jun-2015
73
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical 
trial. 

The testing outlined above in Grade 2 and Grade 3

An acute abdominal series

If a perforated ulcer is clinically suspected, surgical consultation may be necessary
Initial management can include correction of hemodynamic and electrolyte 
abnormalities as clinically indicated. After stabilization, management should be targeted 
at addressing the underlying pathology.
a For Grade 2-4 symptoms if any ARV is thought to have a direct causal relationship to the patient’s 
gastrointestinal symptoms, the Investigator should consider discontinuing the subject from the study and 
performing an evaluation/management plan incorporating elements above. The Investigator can consider 
interruption of the potential offending ARV(s) but must balance this with the increased probability of 
development of viral resistance/lack of efficacy. As stated above, prior to discontinuing the subject from the 
study, attempts should be made to discuss with the BMS Medical Monitor unless the safety of the subject is 
acutely at risk.
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
This is an estimation study, without statistical testing, and hence there are no power 
considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere 
around 80%. With this response rate, and 40 subjects per arm, an exact 95% confidence interval 
would run from roughly 64% to 91%.
8.2
Populations for Analyses
The following definitions are used in this document:

Enrolled subjects: Subject who signed an informed consent form and were assigned a 
Patient Identification number (PID);

Randomized subjects: Enrolled subjects who received a treatment assignment from the 
IVRS;

Treated subjects: Randomized subjects who received at least 1 dose of BMS-955176 or 
TDF. (Also referred to as the mITT analysis set)
Revised Protocol No.: 02
Date: 03-Jun-2015
74
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
8.3
Endpoints
8.3.1
Primary Endpoint(s)Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Week 24. This will be assessed with the FDA snapshot algorithm. This uses 
the last on-treatment plasma HIV-1 RNA measurement, within an FDA-specified visit window, 
to determine response. 
8.3.2
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 
RNA < 200 c/mL at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with 
positive response defined as HIV-1 RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be 
assessed using the most recent version of the IAS-USA list of HIV-1 drug resistance 
mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells will be assessed using on-treatment laboratory results, and 
pre-specified visit windows

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly 
from the case report forms (CRFs). The summary will count the number of subjects that have 
at least one event

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from 
the CRFs. The summary will count the number of subjects that have at least one event

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, 
collected at Week 2 from a subset of subjects
8.4
Analyses
In general, categorical variables are tabulated with counts and percents. Continuous variables are 
summarized with univariate statistics (eg, mean, median, standard error).
Longitudinal analyses use pre-defined visit week windows. Unless otherwise specified, windows 
around planned measurement times are constructed based on the midpoint between planned 
study visits (ie, half the duration of time between study visits), and data are summarized at each 
scheduled visit. 
For the calculation of descriptive statistics of observed data, subjects must have a baseline 
measurement to be evaluable for longitudinal tabulations of parameter values and changes from 
baseline. 
Tabulations of the following endpoints present the number of unique subjects with an event: 
protocol deviations; interruptions of study therapy; non-study medications; adverse events; and 
Revised Protocol No.: 02
Date: 03-Jun-2015
75
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
laboratory abnormalities. Thus, multiple occurrences of the same event are counted only once 
per subject.
8.4.1
Demographics and Baseline Characteristics
The following demographic and baseline characteristics will be summarized by treatment arm
and overall using the treated subjects:

Demographics: age, race, ethnicity, gender, geographic region;

Disease characteristics at baseline: plasma HIV-1 RNA level, CD4+ T-cell counts and 
percentages, CD8+ T-cell counts, HIV-1 subtype;

Laboratory tests at baseline;

Pre-treatment CDC Class C AIDS events;

Prior medications
8.4.2
Efficacy Analyses
The efficacy analyses will be based on the treated subjects.
8.4.2.1
Primary Efficacy Analyses
The primary efficacy endpoint is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL 
at the Week 24 snapshot within each stage. This endpoint is assessed with the FDA snapshot 
algorithm. The primary analysis will be based on a modified ITT (mITT) approach. A sensitivity 
analysis will be conducted using an observed values approach. The two approaches will be 
implemented as follows:

Modified ITT: The numerator will be based on subjects with plasma HIV-1 RNA < 40 c/mL 
at Week 24. The denominator will be based on all treated subjects

Observed values: Similar to the mITT approach, the numerator will be based on subjects with 
plasma HIV-1 RNA < 40 c/mL at Week 24. However, the denominator will be based on the 
treated subjects with plasma HIV-1 RNA at Week 24
Response rates will be tabulated by treatment arm (within the stage) with exact binomial 95% 
confidence intervals.
Subgroup summaries will be provided to examine the impact of baseline viral load. Subgroup
summaries may be provided to examine the impact of other important covariates such as CD4+ 
count, sex, geographic region, etc.
At Week 24, a Time to Loss of Virologic Response (TLOVR) analysis will be conducted as a
sensitivity analysis that compliments the snapshot analysis. The following definition for 
virologic rebound will be used:
“For subjects that have been confirmed as having reached virologic suppression, by 
having two consecutive HIV-1 RNA readings below the assay limit of detection 
(40 copies/mL), virologic rebound is defined as confirmed HIV-1 RNA levels above the 
Revised Protocol No.: 02
Date: 03-Jun-2015
76
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
limit of detection. For levels above the limit of detection, confirmation consists of either 
two consecutive readings, or a single reading followed by loss to follow-up.”
8.4.2.2
Secondary Efficacy Analyses
The following secondary endpoints will be summarized by treatment arm:

Proportion of subjects with HIV-1 RNA < 40 c/mL at Week 48 and Week 96 using mITT 
and observed values

Proportion of subjects with HIV-1 RNA < 200 c/mL at Week 24, 48 and 96 using mITT and 
observed values

Change from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells over time

Newly emergent genotypic substitutions (using all on-treatment isolates) will be tabulated by 
treatment arm

The newly emergent phenotypic resistance profile (using all on-treatment isolates) will be 
tabulated by treatment arm
8.4.3
Safety Analyses
The investigators will determine the intensity of adverse events (AEs) and the relationship of 
AEs to study therapy. The investigators’ terms will be coded and grouped by system organ class 
using the latest version of the Medical Dictionary for Regulatory Activities (MedDRA) in 
production at BMS. AEs will be presented by system organ class and preferred term. 
Presentations will include both non-serious and serious adverse events, unless specified 
otherwise. If a subject had an adverse event with different intensities over time, then only the 
greatest intensity will be reported.
Deaths will be listed for enrolled subjects without regard to onset.
In analyses of fasting lipids over time, values will be excluded after the start of serum lipid 
reducing agents.
The frequency of the following safety events will be summarized by treatment arm for treated 
subjects:

SAEs

AEs leading to discontinuation of study therapy

AEs by intensity

CDC Class C AIDS events

Laboratory abnormalities by toxicity grade
Revised Protocol No.: 02
Date: 03-Jun-2015
77
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
8.4.4
Pharmacokinetic Analyses
The following PK parameters will be summarized by treatment arm:

Cmax: maximum observed plasma concentration

Tmax: time of maximum observed plasma concentration

Ctau: observed plasma concentration at the end of a dosing interval (eg, concentration at 
24 hours)

C0: observed pre-dose plasma concentration

AUC(TAU) : area under the concentration-time curve in one dosing interval
8.4.4.1
Sparse Pharmacokinetic Analyses
Sparse pharmacokinetic data will be used in population PK, PK/PD and, as available, PK/VK 
analyses.
8.4.4.2
PK/PD and PK/VK Analyses
PK data obtained from this study will be pooled with data from other studies to perform an 
integrated population PK analysis, exposure-response analyses for selected safety and efficacy 
endpoints, and, as available, viral kinetic modeling of BMS-955176 in combination with other 
ARVs to support the on-going development of BMS-955176. These analyses will facilitate 
optimal dose selection for future Phase 3 studies. 
The population PK, exposure-response, and, as available, viral kinetic analyses, will be reported 
separately.
8.4.5
Biomarker Analyses
Details about the biomarker analyses will be provided in the Statistical Analysis Plan (SAP).
8.4.6
Outcomes Research Analyses
Details about the outcomes research analyses will be provided in the SAP.
8.4.7
Other Analyses (including Virologic Futility)
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 1 completes their Week 24 visit. This analysis will be conducted to evaluate whether the 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 1 (containing 
BMS-955176) to Arm 2 (containing TDF) will be made with one-sided, Fisher’s exact tests, 
conducted at the 0.01 probability level.
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 2 completes their Week 24 visit. This analysis will be conducted to evaluate whether a 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 3-4
Revised Protocol No.: 02
Date: 03-Jun-2015
78
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
(containing BMS-955176) to Arm 5 (containing TDF) will be made with one-sided, Fisher’s 
exact tests, conducted at the 0.01 probability level.
8.5
Interim Analyses
There are two interim analyses scheduled before the start of Stage 2.
The first interim analysis will be conducted after approximately 50% of the randomized subjects
have completed 24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of 
SDTM (Study Data Tabulation Model) data (“level 1” data) to facilitate the development of 
models for: population pharmacokinetics; exposure-response relationships; and, as available,
viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of 
therapy in Stage 1. This will be an analysis of the available efficacy, safety, resistance and 
pharmacokinetic data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well 
as the recruiting time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If 
Stage 2 is initiated, and recruiting follows projected timelines, then it is anticipated that analyses 
will be conducted when:

The last subject in Arms 3, 4, and 5 completes the Week 24 visit

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4, and 5 completes the Week 96 visit
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
deviation or change to the protocol without prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change 
will be submitted to:

IRB/IEC for review and approval/favorable opinion

BMS

Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
Revised Protocol No.: 02
Date: 03-Jun-2015
79
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
If an amendment substantially alters the study design or increases the potential risk to the 
subject: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a 
schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the 
source documents:
In addition, the study may be evaluated by BMS internal auditors and government inspectors 
who must be allowed access to CRFs, source documents, other study files, and study facilities. 
BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to BMS.
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records 
(EMRs/EHRs), adverse event tracking/reporting, protocol required assessments, and/or drug 
accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
Revised Protocol No.: 02
Date: 03-Jun-2015
80
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
9.2
Records
9.2.1
Records Retention
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS.
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include the investigational product 
and the non-investigational product(s). Records or logs must comply with applicable regulations 
and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each subject, including unique subject identifiers

amount transferred to another area/site for dispensing or storage

nonstudy disposition (eg, lost, wasted)

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for bioavailability/bioequivalence, if applicable

dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
Revised Protocol No.: 02
Date: 03-Jun-2015
81
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
For sites using the BMS electronic data capture tool, electronic CRFs will be prepared for all 
data collection fields except for fields specific to SAEs and pregnancy, which will be reported on 
the paper or electronic SAE form and Pregnancy Surveillance form, respectively. Spaces may be 
left blank only in those circumstances permitted by study-specific CRF completion guidelines 
provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated by the investigator or qualified physician who is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form. For electronic CRFs, review 
and approval/signature is completed electronically through the BMS electronic data capture tool.
The investigator must retain a copy of the CRFs including records of the changes and 
corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements 
and must only access the BMS electronic data capture tool using the unique user account 
provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the 
following criteria:

External Principal Investigator designated at protocol development

National Coordinating Investigator 

Study Steering Committee chair or their designee

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region or 
country)

Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study require approval by BMS prior to publication or presentation 
and must adhere to BMS’s publication requirements as set forth in the approved clinical trial 
agreement (CTA). All draft publications, including abstracts or detailed summaries of any 
proposed presentations, must be submitted to BMS at the earliest practicable time for review, but 
at any event not less than 30 days before submission or presentation unless otherwise set forth in 
the CTA. BMS shall have the right to delete any confidential or proprietary information 
Revised Protocol No.: 02
Date: 03-Jun-2015
82
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
contained in any proposed presentation or abstract and may delay publication for up to 60 days 
for purposes of filing a patent application.
Revised Protocol No.: 02
Date: 03-Jun-2015
83
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete Abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Female subjects must continue 
to have pregnancy tests. Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject chooses to 
forego complete abstinence.
If two forms of contraception is required, Complete abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Subjects who choose complete 
abstinence are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. Acceptable 
alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as complete 
avoidance of heterosexual intercourse is an acceptable form of 
contraception for all study drugs. This also means that abstinence is the 
preferred and usual lifestyle of the patient. This does not mean periodic 
abstinence (eg, calendar, ovulation, symptothermal, profession of 
abstinence for entry into a clinical trial, post-ovulation methods) and 
withdrawal, which are not acceptable methods of contraception. Subjects 
who choose complete abstinence are not required to use a second method 
of contraception, but female subjects must continue to have pregnancy 
tests. Acceptable alternate methods of highly effective contraception must 
be discussed in the event that the subject chooses to forego complete 
abstinence
Revised Protocol No.: 02
Date: 03-Jun-2015
84
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
11
LIST OF ABBREVIATIONS
Term
Definition
3TC
Lamivudine
AE
adverse event
AI
accumulation index
AIDS
Acquired Immunodeficiency Syndrome
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after the 
first dose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALT
alanine aminotransferase
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir
ATV/r
atazanavir boosted with ritonavir
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the time of 
the last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
A-V
atrioventricular
-HCG
beta-human chorionic gonadotrophin
BA/BE
bioavailability/bioequivalence
BID, bid
bis in die, twice daily
BCRP
Breast cancer reactive protein
BDC
Bile duct-cannulated
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
BVM
bevirimat
Revised Protocol No.: 02
Date: 03-Jun-2015
85
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
c
copies
c/mL
copies per milliliter
C
Celsius
C12
concentration at 12 hours
C24
concentration at 24 hours
CA
capsid
cART
Combination antiretroviral therapy
Cavg
average concentration
Cexpected-tau
expected concentration in a dosing interval
CD
Cluster designation (CD4; CD8)
CDC
Centers for Disease Control
CFC
corrected fold change
CFR
Code of Federal Regulations 
CI
confidence interval
CrCl; CCL
creatinine clearance
CLR
renal clearance
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CMV
cytomegalovirus
CNS
Central nervous system
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
Css,avg
average steady-state plasma concentration
CSR
Clinical study report
Ct
Expected concentration at a certain time, usually at the end of an 
expected future dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctau
Concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctrough
Trough observed plasma concentration
CT
Computed tomography
Revised Protocol No.: 02
Date: 03-Jun-2015
86
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
CTA
clinical trial agreement
CTX
Cross-linked C-telopeptide of Type 1 collagen
CYP
cytochrome p-450
D/C
discontinue
DDI
drug-drug interaction
DHHS
Department of Health and Human Services
dL
deciliter
DTG
dolutegravir
EC
Ethics committee
EC
effective concentration
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EFV
efavirenz
eg
exempli gratia (for example)
E-R
exposure-response
ESR
Expedited Safety Report
ET
Early termination or End of Treatment
EU
European Union
FAHI
Functional Assessment of HIV Infection
FDA
Food and Drug Administration
FDC
Fixed dose combination
FSH
follicle stimulating hormone
FTC
emtricitabine
g
gram
GFR
glomerular filtration rate
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
GSH
glutathione
Revised Protocol No.: 02
Date: 03-Jun-2015
87
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
h; hr
hour
HAART
Highly active antiretroviral therapy
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCG
Human chorionic gonadotropin
HCV
hepatitis C virus
HCO3-
bicarbonate
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HR
heart rate
HRT
hormone replacement therapy
HS
Human serum
HuSA
Human serum albumin
IAS
International AIDS Society
IB
Investigator brochure
IC
Inhibitory concentration
ICD
International Classification of Diseases
ICF
informed consent form
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
INI
Integrase inhibitor
IP
investigational product
IRB
Institutional Review Board
IU
International Unit
IUD
intrauterine device
IV
intravenous
IVRS
interactive voice response system
Revised Protocol No.: 02
Date: 03-Jun-2015
88
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
GALT
Gut associated lymphoid tissue
GI
gastrointestinal
kg
kilogram
L
liter
MAD
multiple ascending dose
MC
micronized crystalline
mg
milligram
MI
Maturation inhibitor
MIC
minimum inhibitory concentration
min
minute
mITT
Modified Intent to Treat
mL
milliliter
mmHg
millimeters of mercury
msec
millisecond
MOA
mechanism of action
g
microgram
M
micromolar
N
number of subjects or observations
N/A
not applicable
ng
nanogram
nM
nanomolar
NIMP
non-investigational medicinal products 
NNRTI
Non- nucleoside reverse transcriptase inhibitor
NOAEL
No observed adverse effect level
NOEL
No observed effect level
NRTI
nucleoside reverse transcriptase inhibitor
NSAID
nonsteroidal anti-inflammatory drug
pDILI
potential drug induced liver injury
PBMC
peripheral blood mononuclear cells
PCR
polymerase chain reaction
Revised Protocol No.: 02
Date: 03-Jun-2015
89
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
PD
pharmacodynamics
PI
protease inhibitor
PDVF
Protocol-defined virologic criteria
PK
pharmacokinetics
PPI
proton pump inhibitor
PR
atrial depolarization to ventricular depolarization
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
QD, qd
quaque die, once daily
QRS
interval representing the time for ventricular depolarization
QT
Duration of ventricular electrical activity
QTcF
QT corrected for heart rate using Frederica’s formula
RAL
raltegravir
RBC
red blood cell
RNA
ribonucleic acid
RTV
ritonavir
SAD
single ascending dose
SDD
spray-dried dispersion
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SDTM
Study Data Tabulation Model
SOP
Standard Operating Procedures
SP1
spacer peptide 1
Subj
subject
STR
single tablet regimen
t
temperature
T
time
TDF
tenofovir
Revised Protocol No.: 02
Date: 03-Jun-2015
90
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
TDF/FTC
Truvada (TDF 300 mg + FTC 200 mg)
TAO
Trial Access Online, the BMS implementation of an EDC capability
TAM
Thymidine analogue mutation
T-HALF
Half life
T-HALFeff_AUC
Effective elimination half life that explains the degree of AUC 
accumulation observed
Tmax, TMAX
time of maximum observed concentration
TR_AUC(0-T)
AUC(0-T) treatment ratio
TR_AUC(INF)
AUC(INF) treatment ratio
TR_Cmax
Cmax treatment ratio
UGT
UDP-glucuronosyltransferase
ULN
upper limit of normal
US
United States
VF
virologic failure
VK
Viral kinetics
VLP
Virus-like particles
WBC
white blood cell
WFD
Wallingford, Connecticut, USA
WHO
World Health Organization
Wk or WK
week
WOCBP
women of childbearing potential
Revised Protocol No.: 02
Date: 03-Jun-2015
91
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
REFERENCES
1
WHO HIV Department. Global Summary of the AIDS Epidemic 2013. Available at: 
http://www.who.int/hiv/data/epi_core_dec2014.png?ua=1 Accessed 12/29/14
2
European AIDS Clinical Society. European Guidelines for treatment of HIV-infected adults 
in Europe (Oct 2013). http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf. 
Accessed Nov 30, 2013.
3
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services.
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. 
Accessed 
Nov 30, 2013.
4
United States Department of Health and Human Services, Food and Drug Administration, 
Center for Drug Evaluation and Research. Guidance for Industry Human Immunodeficiency 
Virus-1 Infection: Developing Antiretroviral Drugs for Treatment. (June 2013). Revision 1.
5
Study AI468001 Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple 
Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of 
BMS-955176 in Healthy Subjects. Document Control No. 930071044
6
Study AI468002 Randomized, Placebo-Controlled, Multiple-Dose Study to Evaluate the 
Pharmacodynamics, Safety and Pharmacokinetics of BMS-955176 (Double-Blinded) and 
BMS-955176 with Atazanavir +/- Ritonavir (Open-Labelled) in HIV-1 Infected Subjects. 
Draft Document Control No. 930087017
7
Min 
S., 
Sloan 
L., 
DeJesus 
E., 
et. 
al. 
Antiviral 
activity, 
safety, 
and 
pharmacokinetics/pharmacodynamics 
of 
dolutegravir 
as 
10-day 
monotherapy 
in 
HIV-1-infected adults. AIDS 2011. 25(14):1737-45.
8
Walmsley SL., Antela A., Clumeck N., et. al. Dolutegravir plus abacavir-lamivudine for the 
treatment of HIV-1 infection. NEJM 2013 369(19):1807-18.
9
Raffi F., Jaeger H., Quiros-Roland E., et. al. Once-daily dolutegravir versus twice-daily 
raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week 
results from a randomised, double-blind, non-inferiority trial. Lancet ID. 2013 13(11): 
927-35.
10
Cahn P., Pozniak AL., Mingrone H,. et. al. Dolutegravir versus raltegravir in antiretroviral-
experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, 
double-blind, non-inferiority SAILING study. Lancet 2013 382(9893):700-8.
11
Stellbrink HJ., Reynes J., Lazzarin A., Dolutegravir in antiretroviral-naive adults with 
HIV-1: 96-week results from a randomized dose-ranging study. AIDS 2013 27(11):1771-8.
Revised Protocol No.: 02
Date: 03-Jun-2015
92
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
Eron JJ., Clotet B., Durant J., Safety and efficacy of dolutegravir in treatment-experienced 
subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING 
Study. JID 2013 207(5): 740-748.
13
Sanne I, Piliero P, Squires K, Thiry A, Schnittman S. Results of a phase 2 clinical trial at 48 
weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at 
three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. 
J Acquir Immune Defic Syndr. Jan 1 2003;32(1):18-29.
14
Bertz RJ, Persson A, Chung E, et al. Pharmacokinetics and pharmacodynamics of atazanavir-
containing antiretroviral regimens, with or without ritonavir, in patients who are 
HIV-positive and treatment-naive. Pharmacotherapy. Mar 2013;33(3):284-294.
15
Molto J, Santos JR, Valle M, et al. Monitoring atazanavir concentrations with boosted or 
unboosted regimens in HIV-infected patients in routine clinical practice. Ther Drug Monit. 
Oct 2007;29(5):648-651.
16
Goutelle S, Baudry T, Gagnieu MC, et al. Pharmacokinetic-pharmacodynamic modeling of 
unboosted Atazanavir in a cohort of stable HIV-infected patients. Antimicrob Agents 
Chemother. Jan 2013;57(1):517-523.
17
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services. 
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed Nov 
30, 2013.
18
Malan DR, Krantz E, David N, Wirtz V, Hammond J, McGrath D. Efficacy and safety of 
atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy 
regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr. Feb 1 
2008;47(2):161-167.
19
Landman R, Diallo MB, Gueye NF, et al. Efficacy and safety of unboosted atazanavir in 
combination with lamivudine and didanosine in naive HIV type 1 patients in Senegal. AIDS 
Res Hum Retroviruses. May 2010;26(5):519-525.
20
Gianotti N, Seminari E, Guffanti M, et al. Evaluation of atazanavir Ctrough, atazanavir 
genotypic inhibitory quotient, and baseline HIV genotype as predictors of a 24-week 
virological response in highly drug-experienced, HIV-infected patients treated with 
unboosted atazanavir. New Microbiol. Apr 2005;28(2):119-125.
21
Giuntini R, Martinelli C, Ricci E, et al. Efficacy and safety of boosted and unboosted 
atazanavir-containing antiretroviral regimens in real life: results from a multicentre cohort 
study. HIV Med. Jan 2010;11(1):40-45.
Revised Protocol No.: 02
Date: 03-Jun-2015
93
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
22
Two Drug Combination Studies with BMS-955176 and HIV Antiviral Agents. Version 1.0. 
June 2013. DCN 930071469
23
Song I., Borland J., Chen S. Effect of atazanavir and atazanavir/ritonavir on the 
pharmacokinetics of the next-generation HIV integrase inhibitor, S/GSK1349572. Br. J. 
Pharm. 2011 72(1):103-108
24 BMS-955176 Investigator Brochure, Version 2.0, July 2013 DCN 930056146
25 BMS-955176 Investigator Brochure, Version 3.0, April 17, 2014 DCN 930056146
26 Partial response to FDA “May Proceed” Letter dated 27 Sep 2013 for IND 118,936. Bristol-
Myers Squibb Company; Jan 2014. Document Control No. 930076507 2.0. Insert this 
additional reference: “Evaluation of cross-resistance of HIV-1 Maturation Inhibitor 
BMS-955176 toward HIV-1 protease inhibitor resistant viruses. Bristol-Myers Squibb 
Company; 30-Sept-2014. Document Control No. 930083565.”
27 Evaluation of Cross Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. Document Control No. 930083565
28 Gilead 
Sciences. 
Prescribing 
Information 
for 
TDF. 
Available 
at: 
http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/viread/viread_pi.pdf.
Accessed Dec 31, 2014
29
ViiV 
Healthcare. 
Prescribing 
Information 
for 
DTG. 
Available 
at: 
https://www.viivhealthcare.com/media/58599/us_tivicay.pdf. Accessed Dec 31, 2014.
30 BMS. 
Prescribing 
Information 
for 
ATV. 
Available 
at: 
http://packageinserts.bms.com/pi/pi_reyataz.pdf. Accessed Dec 31, 2014
31 AbbVie. 
Prescribing 
Information 
for 
RTV. 
Available 
at: 
http://www.rxabbvie.com/pdf/norvirtab_pi.pdf. Accessed Dec 31, 2014
32 Evaluation of Cross-Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. DCN 930083565
33
Hasler WL Nausea, Vomiting, and Indigestion: Introduction. Chapter 39. Harrisons 
Principles of Internal Medicine 18th edition. 2012. McGraw Hill
34
Hasler WL and Owyang C Approach to the Patient with Gastrointestinal Disease. Chapter 
290. Harrisons Principles of Internal Medicine 18th edition. 2012. McGraw Hill
35
Soll AH and Graham DY. Peptic Ulcer Disease. Chapter 40. Textbook of Gastroenterology. 
5th edition. 2009. Blackwell Publishing
Revised Protocol No.: 02
Date: 03-Jun-2015
94
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
36
Rome Foundation. Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. 
Available: http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Accessed 
Dec 22 2014
Revised Protocol No.: 02
Date: 03-Jun-2015
95
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 1
LISTINGS OF PROHIBITED AND PRECAUTIONARY
THERAPIES
General Notes: 

Guidelines for the use of drugs with established or other potentially significant drug 
interactions listed in the Package Inserts of the marketed ARV agents used by subjects 
participating in this study (Reyataz, Norvir, Viread, Tivicay) should be followed. 

Medications listed in the Package Inserts as contra-indicated with the other marketed ARV 
agents used by subjects participating in this study are not permitted. 

Any immunizations deemed appropriate by the subject’s physician are permitted provided 
that the immunization is given > 4 weeks from any HIV-1 RNA measurement.

A subject may not be co-enrolled in a concomitant trial unless it is approved by the Medical 
Monitor prior to randomization.
Prohibited Therapies
Drugs that should not be administered throughout the duration of the study:
Anticonvulsants: Carbamazepine, 
Phenobarbital, Phenytoin
Use with ATV may result in decreased ATV concentrations. Use of 
Carbamazepine may result in decreased DTG concentrations.
Oral Antifungals: Itraconazole, 
Posaconazole, and Voriconazole
Use with ATV can result in increased ATV concentrations
Antimycobacterials: Rifampin, 
Rifapentine, Rifabutin
These antimycobacterials decrease ATV plasma concentrations and 
may decrease BMS-955176 plasma concentrations.
St. John’s wort
Use with ATV or DTG may result in loss of antiviral therapeutic effect
GI motility agent: Cisapride
Potential for serious and/or life threatening reactions such as cardiac 
arrhythmias
Pimozide
Potential for serious and/or life threatening reactions such as cardiac 
arrhythmias
Zetia (ezetimibe)
Ezetimibe is a substrate of OATP1B1 (of which BMS-955176 is an 
inhibitor in vitro).
Dofetilide
Use with DTG may result in the potential for increased Dofetilide 
plasma concentrations and the risk for serious and/or life threatening 
events
Alfuzosin
ATV increases Alfuzosin concentrations which can result in 
hypotension
Benzodiazepines: Triazolam and 
Midazolam
ATV can increase the concentration of these Benzodiazepines with the 
potential to increase sedation or respiratory depression
Ergot derivatives: 
Dihydroergotamine, ergotamine, 
ergonovine, methylergonovine
ATV can increase potential for ergot toxicity (e.g. peripheral 
vasospasm)
Revised Protocol No.: 02
Date: 03-Jun-2015
96
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
HMG-CoA Reductase Inhibitors: 
Lovastatin, Simvastatin, Atorvastatin, 
Pitavastatin, Rosuvastatin, Pravastatin
Use with ATV may result in increased levels of HMG-CoA Reductase 
Inhibitors and potential for serious reactions such as myopathy
Antacids, H2 receptor angatonists, 
Proton Pump Inhibitors, Sucralfate
Use with ATV may result in decreased plasma concentrations of ATV. 
Use of Antacids containing Aluminium, Magnesium, or Calcium may 
result in decreased levels of DTG.
Macrolides: Clarithromycin
Use with ATV may result in increased Clarithromycin levels and QTc 
prolongation
Buprenorphine
Use with ATV may increase levels of Buprenorphine
Quetiapine
Use with ATV may increase levels of Quetiapine
Salmeterol
Use with ATV may result in increased levels of Salmeterol
Avanafil
Use with ATV may result in increased Avanafil levels
All drugs with antiretroviral activity 
other than those considered study 
therapy
Any drugs with antiretroviral activity not considered study therapy 
may interfere with the assessments of the study.
Precautionary Therapies
Drugs that should be administered with caution during the study:
Hormonal Contraceptives
Hormonal Contraceptives cannot be relied upon as a highly effective 
method of contraception. 
See Protocol Section 3.3.1, for more information on Highly Effective 
Methods of Contraception.
Antidepressants: Trazodone, Tricyclic 
Antidepressants (TCA)
Use with ATV/r may result in increased plasma concentrations of 
trazodone and TCA
Antimalarials: Atovaquone/Proguanil, 
Mefloquine
Use with ATV/r may result in decreased Atovaquone/Proguanil levels. 
The effect of Mefloquine on ATV/r is unknown.
Benzodiazepines: Alprazolam and 
Diazepam
ATV can increase the concentration of these Benzodiazepines 
Calcium Channel Blockers
Use with ATV may result in increased concentrations of CCB’s. 
Non-topical Corticosteroids: 
Budesonide, Fluticasone, Prednisone, 
Methylprednisolone, Prednisolone, 
Triamcinolone
Use with ATV/r may result in increased levels of glucocorticoids and 
adrenal insufficiency
Dexamethasone
Use with ATV may result in reduced levels of ATV.
Colchicine
Use with ATV may result in increased Colchicine levels
Metformin
Use with DTG may result in increased levels of metformin. 
A cation-containing (e.g. Magnesium) 
laxative
If used with DTG the laxative should be taken 2 hours before or 6 
hours after taking concomitant laxatives.
Revised Protocol No.: 02
Date: 03-Jun-2015
97
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 2
AIDS-DEFINING DIAGNOSES
I.
PARASITIC INFECTIONS
Pneumocystis carinii (PC)
1011
PC pneumonia histologically proven.
1012
PC pneumonia, clinical diagnosis by the following specifications and confirmed HIV 
infection:
A history of dyspnea on exertion or non-productive cough of recent onset (within the past 
3 months).
AND
Chest X-ray evidence of diffuse bilateral interstitial or gallium scan evidence of diffuse 
bilateral pulmonary disease;
AND
Arterial blood gas analysis showing an arterial pO2 of < 70 mmHg or a low respiratory 
diffusing capacity (< 80% of predicted values) or an increase in the alveolar-arterial 
oxygen tension gradient;
AND
Successful response to appropriate therapy and no evidence of pneumonias of other 
etiologies.
1013
Pneumocystis carinii, histologically proven, at a site other than lungs.
Toxoplasmosis (in patients > 1 month old)
1021
Toxoplasmosis, clinical diagnosis (of brain only) by the following specifications and 
confirmed HIV infection:
Recent onset of a neurologic disease consistent with toxoplasmosis;
AND
Brain imaging evidence of a mass lesion (on computed tomography, nuclear magnetic 
resonance of radiography enhanced by injection of contrast medium);
AND
Serum antibody to toxoplasmosis and successful response to therapy for toxoplasmosis.
1022
Toxoplasmosis, of brain or internal organs other than liver, spleen or lymph nodes. 
Proven by microscopy.
Isosporiasis
1031
Isosporiasis causing chronic diarrhea of > 1 month. Proven by microscopy.
Revised Protocol No.: 02
Date: 03-Jun-2015
98
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Cryptosporidiosis
1041
Cryptosporidiosis causing chronic diarrhea of > 1 month. Proven by microscopy.
II.
FUNGAL INFECTIONS
Candidiasis
2011
Candidiasis, Esophageal, definitive diagnosis by the following specifications:
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
2012
Candidiasis, Esophageal, presumptive diagnosis by the following specifications and 
confirmed HIV infection:
Recent onset of retrosternal pain on swallowing:
AND
Oral candidiasis diagnosed by the gross appearance of white patches or plaques on an 
erythematous base OR by the microscopic appearance of fungal mycelial filaments in an 
uncultured specimen scraped from the oral mucosa;
AND
Response to appropriate therapy.
2013
Candidiasis, Bronchial/Pulmonary, definitive diagnosis by the following specifications; 
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
Cryptococcosis
2022
Cryptococcosis, Extra-pulmonary, proven by microscopy (histology or cytology), culture 
or detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Histoplasmosis
2031
Histoplasmosis, Disseminated (at a site other than or in addition to lungs or cervical or 
hilar lymph nodes), proven by microscopy (histology or cytology), culture or detection of 
antigen in a specimen obtained directly from the tissues affected or a fluid from those 
tissues.
Coccidioidomycosis
2041
Coccidioidoidomycosis, Disseminated (at a site other than or in addition to lungs or 
cervical or hilar lymph nodes), proven by microscopy (histology or cytology), culture or 
detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Revised Protocol No.: 02
Date: 03-Jun-2015
99
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
2042
Coccidioidomycosis, clear reactivation of prior infection, proven by microscopy 
(histology or cytology), culture or detection of antigen in a specimen obtained directly 
from the tissues affected or a fluid from those tissues.
III.
BACTERIAL INFECTIONS
Mycobacterium
3001
Mycobacterium (unidentified species). Presumptive diagnosis, by the following 
specifications and confirmed HIV infection.
Acid fast bacilli (AFB) positive stain of specimen obtained from endoscopic biopsy or 
from a normal sterile site other than lungs, skin or cervical or hilar lymph nodes. Species 
NOT identified by culture.
Mycobacterium tuberculosis
3011
Mycobacterium tuberculosis, Pulmonary, definitive diagnosis proven by culture, without 
evidence of upper respiratory infection symptoms of Mycobacterium tuberculosis that 
could account for the positive culture.
3012
Mycobacterium tuberculosis, definitive diagnosis proven by culture, of at least one extra 
pulmonary site regardless of concurrent pulmonary involvement.
3013
Mycobacterium tuberculosis, Disseminated, definitive diagnosis proven by culture.
Mycobacterium avium intracellulare
3022
MAI in Blood, proven by culture.
3023
MAI Colitis, proven by histology and culture. (This does not include MAI of the stool 
alone).
3024
MAI, Disseminated, at a site other than or in addition to lungs or cervical or hilar lymph 
nodes, proven by culture.
Mycobacterium Kansasii, Mycobacterium Scrofulaceum and Other Atypical 
Mycobacterium
3032
M. Kansasii, in Blood, proven by culture.
3033
M. Kansasii Colitis, proven by histology and culture. (NOT including positive M. 
Kansasii of stool alone).
3034
M. Kansasii, Disseminated, at a site other than or in addition to lungs, or cervical or hilar 
lymph nodes, proven by culture.
3035
M. Scrofulaceum or other Atypical Mycobacterium, proven by culture.
Salmonella
3041
Salmonella, recurrent Bacteremia (non-typhoid), proven by culture.
Revised Protocol No.: 02
Date: 03-Jun-2015
100
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
IV.
VIRAL INFECTIONS
Cytomegalovirus
4011
CMV, Pneumonitis, pathologically or histologically confirmed. Serum antibody titer and 
culture alone is not sufficient for the diagnosis.
4012
CMV, Esophagitis, as diagnosed by histology, pathology or culture of an esophageal 
lesion. Serum antibody titer and culture of other than esophageal tissue is not sufficient 
for the diagnosis.
4013
CMV, Retinitis as evidenced by a characteristic appearance on serial ophthalmoscopic 
examinations (eg, discrete patches of retinal whitening with distinct borders, spreading in 
a centrifugal manner, following blood vessels, progressing over several months, 
frequently associated with retinal vasculitis, hemorrhage, and necrosis). Resolution of 
active disease leaves retinal scarring and atrophy with retinal pigment epithelial mottling.
4014
CMV, Colitis, as diagnosed by histology, pathology or culture of a colonic lesion. Serum 
antibody titer and culture of other than colonic tissue is not sufficient for the diagnosis.
4015
CMV, Encephalitis, as diagnosed by histology, pathology or culture of brain tissue or 
CSF. Serum antibody titer and culture of other than brain tissue or CSF is not sufficient 
for the diagnosis.
Herpes Simplex (in patients > 1 month old).
4021
HSV, Disseminated (but not encephalitis alone), proven by microscopy (histology or 
cytology), culture or detection of antigen in a specimen obtained directly from affected 
tissues.
4022
HSV, Esophagitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4023
HSV, Bronchitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4024
HSV, Pneumonitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for diagnosis.
4025
HSV, GI, other than mouth, throat, or peri-rectal, as diagnosed by microscopy (histology 
or cytology), culture or detection of antigen in a biopsy specimen obtained directly from 
affected tissue. Serological measurement and culture from other than the affected tissue is 
not sufficient for diagnosis.
Revised Protocol No.: 02
Date: 03-Jun-2015
101
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4026
HSV, Mucocutaneous, ulcers persisting for 1 month despite appropriate therapy, as 
diagnosed by microscopy (histology or cytology), culture or detection of antigen in a 
biopsy specimen obtained directly from affected tissue. Serological measurement and 
culture from other than the affected tissue is not sufficient for the diagnosis.
Progressive Multifocal Leukoencephalopathy
4041
Progressive Multifocal Leukoencephalopathy, proven by microscopy.
VI.
NEOPLASTIC DISEASES
Kaposi’s Sarcoma
6011
Kaposi’s sarcoma, Mucocutaneous, proven by microscopy.
6012
Kaposi’s sarcoma. Mucocutaneous, presumptive diagnosis with characteristic gross 
appearance and confirmed HIV infection.
6013
Kaposi’s sarcoma, Visceral.
6014
Kaposi’s sarcoma, other than above.
Lymphoma of the Brain
6021
Primary Lymphoma of the brain at any age, proven by microscopy.
Non-Hodgkins Lymphoma
6031
Small Non-cleaved lymphoma (either Burkitt or non-Burkitt type).
6032
Immunoblastic sarcoma, equivalent to any of the following, although not necessarily all 
in combination: Immunoblastic lymphoma, large-cell lymphoma, diffuse histocytic 
lymphoma.
Cervical Carcinoma
6041
Histologically proven invasive carcinoma of the cervix.
VII.
OTHER CONDITIONS
HIV Dementia/Motor Defects
7011
HIV Dementia, clinical findings of disabling cognitive and/or motor dysfunction 
interfering with occupation or activities of daily living progressing over weeks to months, 
in the absence of a concurrent illness or condition other than HIV infection that could 
explain the findings. Method to rule out such concurrent illnesses and conditions must 
include cerebrospinal fluid examination and either brain imaging (computed tomography 
or magnetic resonance) or autopsy.
Slim Disease or HIV Wasting Syndrome
7021
HIV Wasting Syndrome, findings of profound involuntary weight loss > 10% of baseline 
body weight plus either chronic diarrhea (at least two loose stools per day for 30 days) 
or chronic weakness and documented fever (for 30 days, intermittent to constant) in the 
Revised Protocol No.: 02
Date: 03-Jun-2015
102
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
absence of a concurrent illness or condition other than HIV infection that could explain 
the findings (eg, cancer, tuberculosis, cryptosporidiosis, or other specific enteritis).
7061
Recurrent pneumonia, acute onset within 12 months of most recent episode.
Revised Protocol No.: 02
Date: 03-Jun-2015
103
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 3
DAIDS TOXICITY GRADES
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events
Version 2.0 - November 2014
http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx
Revised Protocol No.: 02
Date: 03-Jun-2015
104
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 4
COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE
Online calculator:
http://nephron.com/cgi-bin/CGSI.cgi
Manual calculation:
Male:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg)
72 x Serum Creatinine (mg/dL)
Female:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg) x 0.85
72 x Serum Creatinine (mg/dL)
1 pound = 0.4536 kilograms
Revised Protocol No.: 02
Date: 03-Jun-2015
105
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 5
LABORATORY ASSESSMENTS
HEMATOLOGY
WBC
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
RBC
Hemoglobin
Hematocrit
Platelets
Absolute Differential
CHEMISTRY
Glucose
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
Total Protein
Albumin
CK
Total Bilirubin
Direct Bilirubin
Indirect Bilirubin
AST
ALT
Alkaline Phosphatase
LDH 
Amylase
Lipase
Electrolytes (Sodium, 
Potassium, Chloride, 
Bicarbonate)
Calcium
Phosphorous
Creatinine + eGFR
Uric Acid
BUN
Revised Protocol No.: 02
Date: 03-Jun-2015
106
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
LIPIDS
Cholesterol
Screening
Day 1, Week 4, Week 12, Week 24
HDL
LDL Calculated
Triglycerides
OTHER SERUM TESTS
FSH
Screening
Optional; upon request
HCG
Optional; upon 
request
Optional; upon request
P1NP
Day 1, Week 12, Week 24, Early Term
CTX
Day 1, Week 12, Week 24, Early Term
URINE
Urine Pregnancy test (if 
positive, request serum HCG)
Screening
Every 4 weeks (either done at in-clinic 
visits, or at home)
Urine Toxicology (drugs of 
abuse)
Screening
Urine Creatinine
Day 1, Week 48, Week 96, Early Term
Urine Phosphorous
2 microglobulin
Macroscopic Urinalysis (no 
microscopic)
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
SEROLOGY
HIV-1 RNA
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
HbSAg
Screening
Week 48, Week 96, Early Term
HCV Ab (if positive, reflex to 
HCV RNA)
Screening
Week 48, Week 96, Early Term
Revised Protocol No.: 02
Date: 03-Jun-2015
107
3.0
Approved
3.0
v
930087072


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
RESISTANCE
Specimens for HIV 
Resistance testing at 
Monogram
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
Specimens for HIV 
Exploratory Resistance 
testing at BMS
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
PHARMACOKINETICS
Intensive PK
Week 2 (optional)
Sparse PK
Week 4, Week 8, Week 12, Week 16, 
Week 24
IMMUNE PANEL
%CD3+/CD4+
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
%CD3+/CD8+
Absolute CD3/CD4
Absolute CD3/CD8
OTHER
Pharmacodiagnostic (PDx)
Screening
Plasma & Serum Back-ups 
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
Revised Protocol No.: 02
Date: 03-Jun-2015
108
3.0
Approved
3.0
v
930087072


PPD


Page:
1
Protocol Number:
AI468048
IND Number:
118,936
Ex-US
Non-IND
EUDRACT Number
N/A
Date:
28-Jan-2015
Revised Date:
17-Mar-2016
CLINICAL PROTOCOL AI468048
A Phase 2b Randomized, Active-Controlled, Staged, Open-Label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without 
Ritonavir) in Treatment-Experienced HIV-1 Infected Adults
Revised Protocol Number: 03
Incorporates Amendment(s): 07
Study Director/Central Medical Monitor
 DO, MPH
5 Research Parkway
Office 201D
Wallingford, CT  06492 USA
Telephone (office): 
Fax: 
24-hr Emergency Telephone Number
USA:
International: 
Bristol-Myers Squibb Research and Development
Virology Clinical Research and Development
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
5 Research Parkway
Wallingford, CT 06492
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, 
PPD
PPD
PPD
PPD
PPD


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 03
Date: 17-Mar-2016
2
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (eg, amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved. References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a 
copy of this revised protocol to all study personnel under your supervision, and archive the 
previous versions.


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 03
Date: 17-Mar-2016
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 03
17-Mar-2016
Incorporates Amendment 07
Amendment 07
17-Mar-2016
The primary purpose of this amendment is to broaden the study population 
to reflect the general, treatment experienced HIV-1 infected adults based 
upon feedback from global Principal Investigator participation in 
AI468048. Thus, the study population for AI468048 will now include HIV-
1 infected adults who have documented evidenced of having failed at least 
1 ARV treatment regimen (with or without documented resistance). This 
definition remains consistent with the current overall clinical understanding 
of treatment experienced adults.
In addition, corrections, and modifications have been made to the 
Reproductive Status relative to Inclusion. Previously, two methods of 
contraception were required: one chosen from a list of highly effective 
methods, and a second method that could be highly effective or chosen 
from a list of methods identified as less effective. It is now required that 
male study subjects and WOCBP (females who are either a study subject or 
the sexual partner of a male study subject) must use one highly effective 
method of contraception. Male study subjects must use a condom, not for 
contraceptive purposes, but to prevent potential secondary exposure to 
BMS-955176 from seminal fluid to a WOCBP during any stage of 
pregnancy, even in the very earliest stages of a pregnancy that has not yet 
been positively confirmed. These changes are consistent with the European 
Union 
Clinical 
Trials 
Facilitation 
Group 
(CTFG) 
Guidance, 
“Recommendations related to contraception and pregnancy testing in 
clinical trials.” The contraceptive requirements have also been corrected to 
reduce the length of time during which contraceptive requirements should 
be followed, and to allow the use of IUDs that are either hormonal or 
nonhormonal.
The screening window has been modified to allow for an extension up to 60 
days, but only if awaiting the report of the PhenoSenseGT + Integrase 
resistance results. All other results should be on file by Day 42.
Prior exposure to BMS-955176 has been added to the list of exclusion 
criteria.
Revised 
Protocol 02
03-Jun-2015
Incorporates Amendment 05
Amendment 05
03-Jun-2015
To mitigate the risk of randomizing subjects infected with HIV-1 with an 
unknown efficacy profile, exclusion criteria have been modified to now 
exclude subjects with Clade AE as well as those subjects who have failed a 
previous boosted PI- or Integrase strand transfer inhibitor (INSTI)-
containing regimen for which resistance analyses were not conducted at the 
time of failure. 
To remove “male condoms with spermicide” as a highly effective method 
of contraception (moved to the list of less effective methods) and require 
the use of a highly effective method of contraception as specified in the 
Clinical 
Trials 
Facilitation 
Group 
Recommendations 
Related 
to 


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Revised Protocol No.: 03
Date: 17-Mar-2016
4
Document
Date of Issue
Summary of Change
Contraception and Pregnancy Testing in Clinical Trials.  Most 
contraception methods were more clearly defined, including the removal of 
any text relative to hormonal methods used by female study subjects who 
are WOCBP, since they can’t be counted among the methods used at all.
Pregnancy was added as a reason to be discontinued from the study, and the 
practice of Rescreening was more clearly defined, an administrative change 
was made to clearly indicate that AIDS History will be taken at Screening,
In addition, at Week 24, a Time to Loss of Virologic Response analysis will 
be conducted as a sensitivity analysis that compliments the snapshot 
analysis, and a definition of virologic rebound was added.
A table of the laboratory assessments in detail was added as an appendix, 
and the appendix of the DAIDS Toxicity Table (updated 2009) was 
removed to include a link to the more current 2014 version of the table. In 
addition, and a table of laboratory assessment was added as a new appendix
Other changes, more administrative in nature, have been included.
Revised 
Protocol 01
19-Mar-2015
Incorporates Amendment 04
Amendment 04
19-Mar-2015
Incorporated information that more clarify the Week 24 data (consisting of 
efficacy, safety, and pharmacokinetic data) to be used to confirm the doses 
for Stage 2 and to trigger the start of Stage 2 of the study relative to other 
analyses conducted under the protocol for other purposes.
Removed the requirement that all Sparse PK samples need to be collected 
as pre-AM dose samplings.  Only one visit Weeks 4- 24 (as opposed to all 
visits Weeks 4 - 24) needs to be performed in the morning and to have the 
blood collected as a pre-AM dose sampling; (includes the deletion of 
Table 5.5.2-1).
Administrative changes.
Original 
Protocol
28-Jan-2015
Not applicable


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
SYNOPSIS
Clinical Protocol AI468048
Protocol Title: A Phase 2b Randomized, Active-Controlled, Staged, Open-label Trial to Investigate Safety and 
Efficacy of BMS-955176 in Combination with Dolutegravir and Atazanavir (with or without Ritonavir) in 
Treatment-Experienced HIV-1 Infected Adults
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): Subjects in each arm and per stage will begin QD dosing (in the morning, with a meal) with 
BMS-955176 in combination with atazanavir (ATV) [with or without ritonavir (RTV)] and dolutegravir (DTG), or 
tenofovir (TDF) in combination with atazanavir boosted with ritonavir (ATV/r) and DTG, for a duration of 
96 weeks.
Stage 1:

Arm 1: BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Study Phase: 2b
Research Hypothesis: This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with 
or without RTV) and DTG is efficacious, safe, and well-tolerated in HIV-1 infected treatment-experienced adults.
Objectives:
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg and a TDF 300 mg-containing arm, each when given in 
combination with ATV/r 300/100 and DTG 50 mg by determining the proportion of treatment-experienced 
subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when given in 
combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the antiviral efficacy of TDF 300 mg 
when given in combination with and ATV/r 300/100 mg and DTG 50 mg by determining the proportion of 
treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 Arms, and TDF-containing regimens (TDF + ATV/r + DTG), 
by determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 Arms, and TDF-containing regimens, by determining the 
proportion of treatment-experienced subjects with plasma HIV-1 RNA < 200 c/mL at Weeks 24, 48, 96

To assess the emergence of HIV drug resistance in samples selected for drug resistance testing (according to 
criteria outlined in Protocol Section 5.4.1)
Revised Protocol No.: 03
Date: 17-Mar-2016
5


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess efficacy of BMS-955176 Arms, and TDF-containing regimens, by using the mean changes from 
baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by measuring frequency 
of SAEs and AEs leading to discontinuation

To assess disease progression as measured
by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV (with or without 
ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
Study Design: This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced subjects total will be randomized into the study. In Stage 1, approximately 80 subjects 
will be randomized 1:1 (approximately 40 per arm) to either of the treatment arms containing BMS-955176 or TDF 
in combination with boosted atazanavir (ATV/r) and DTG. In Stage 2, approximately 120 subjects will be 
randomized 1:1:1 (approximately 40 per arm) to either of the two BMS-955176 treatment arms containing
unboosted ATV and DTG, or to the TDF-containing Arm containing ATV/r and DTG.
Stage 1:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, OR

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, OR

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
A Continuation Dose of BMS-955176 will be selected based on Week 24 data from Stage 1 and from study 
AI468038 (BMS-955176 in ARV treatment-naive HIV-1 infected subjects) with which subjects in Stage 1, Arm 1 
may transition to for the remainder of the study. The transition may occur on or after Week 48.
The data from the Week 24 analysis for AI468038 and Stage 1, including safety, efficacy and pharmacokinetics, will 
be examined to trigger the start of Stage 2 (utilizing unboosted ATV in the experimental arms) and confirm the two 
doses of BMS-955176 (in the experimental arms) for study in Stage 2.
After the Stage 2 Week 24 endpoint, a Continuation Dose of BMS-955176 will be selected based on data from 
Stages 1 and 2, and study AI468-038 with which subjects in Stage 2, Arms 3 and 4 will transition to for the 
remainder of the study. The switch in Stage 2 may occur sooner, between Week 24 and Week 48, or it may be after 
Week 48.
The assigned backbone for each arm, ATV and DTG, or ATV/r and DTG, will remain unaltered throughout the 
study.
All subjects in both stages are expected to receive study treatment for 96 weeks.
Revised Protocol No.: 03
Date: 17-Mar-2016
6


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Arm 2
TDF
300 mg QD
+ ATV/r + DTG
Day 1
Begin dosing
Arm 3
BMS-955176 
120 mg QD
+ ATV + DTG
1 Virologic Futility will be evaluated at Week 24 
(see Section 8.4.7).  
Results of Week 24 Stage 1 AI468-048 & AI468-038 
Confirm the Start of Stage 2   
Arm 4
BMS-955176 
180 mg QD
+ ATV + DTG
40
40
Week 2
Week 24
Week 24 Analysis1
Intensive PK subset
4 Based on totality of data from both studies the 
Continuation Dose for Arms 3 & 4 may be 
identified.  
Number
Randomized
STAGE 2
Week 96
Week 96 Analysis/End of Study
Week 48
Week 48 Analysis
The Switch to the Continuation Dose4,3     
is expected to occur on or after Week 48, 
but could occur sooner.
Arm 1
BMS-955176 
120 mg QD
+ ATV/r + DTG
Week 2
Number
Randomized
Week 24
Week 24 Analysis1
Day 1
Begin dosing
Intensive PK subset
40
40
Week 48
Week 96
Week 48 Analysis
Week 96 Analysis/End of Study
The Switch to             
the Continuation Dose2,3
may occur on or after 
Week 48 
STAGE 1
BMS-955176
Continuation Dose QD 
+ ATV/r + DTG
Arm 5
TDF
300 mg QD
+ ATV/r + DTG
40
3 The actual switch of subjects of BMS-955176 
subjects to that Continuation Dose may occur when 
all of the subjects have reached at least Week 48 
(though it could occur sooner in Stage 2).
BMS-955176
Continuation Dose QD
+ ATV + DTG
2 Based on Week 24 data from Arms 1 & 2 and 
from AI468-038, the Continuation Dose for 
Arm 1 may be identified.  
Revised Protocol No.: 03
Date: 17-Mar-2016
7


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Population:
Key Inclusion Criteria:

Men and non-pregnant women, at least 18 years of age (or minimum age as determined by local regulatory or as 
legal requirements dictate)

Antiretroviral treatment-experienced, defined as having documented evidence of having failed at least 1 
treatment regimen (with or without documented resistance)

Failure could be due (but is not limited) to cART intolerance, sub-optimal adherence, or an adverse 
event

Screening Plasma HIV-1 RNA 400 copies/mL (An initial, pre-screening value from Investigator must 
demonstrate HIV-1 RNA > 40 c/mL)

CD4+ T-cell count > 50 cells/mm3

Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, FC < 2.2; DTG; TDF)
Key Exclusion Criteria:

Antiretroviral treatment-experienced adults who have failed < 1 ARV regimen

Antiretroviral treatment-experienced adults infected with Clade AE

Subjects who have failed a previous boosted PI- or Integrase strand transfer inhibitor (INSTI)-containing 
regimen for which resistance analyses were not conducted at the time of failure

Resistance or partial resistance to any study drug

Three or more of the following PI mutations, historical or documented: M36I/V, M46I/L/T, G48M/V, 
I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M

Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S

Any major TDF mutation, historical or documented: K65R or T69ins

Three or more of the following non-accessory thymidine analogue mutations (TAMs): M41L, D67N, K70R, 
L210W, T215Y/F, K219Q/E

Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI resistance), historical or 
documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, Y143C/H/R, E157Q

Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV Ab and HCV RNA)

ALT or AST > 3 × ULN

Alkaline Phosphatase > 5 × ULN

Bilirubin 1.5 × ULN

History of decompensated cirrhosis or active decompensated cirrhosis

Hemoglobin < 8.0 g/dL

Platelets < 50,000 cells/mm3

Prior exposure to BMS-955176
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for AI468048
Medication 
Potency 
IMP/Non-IMP 
BMS-955176 
60 mg or 120 mga
IMP
Revised Protocol No.: 03
Date: 17-Mar-2016
8


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Study Drug for AI468048
Medication 
Potency 
IMP/Non-IMP 
Tenofovir (TDF)
300 mg
Non-IMP
Atazanavir (ATV)
200 mg and 300 mg
IMP
Ritonavir (RTV)
100 mg
Non-IMP
Dolutegravir (DTG)
50 mg
IMP and Non-IMP, based on country
approval status
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Study Assessments: Efficacy assessments will include plasma HIV-1 RNA measurements. Safety Assessments will 
include blood chemistry and hematology, ECGs, Physical Exams and Vital Signs, and assessment of non-serious 
AEs, SAEs and AEs leading to discontinuation.
Statistical Considerations:
Sample Size:
This is an estimation study, without statistical testing, and hence there are no power considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere around 80%. With this 
response rate, and 40 subjects per arm, an exact 95% confidence interval would run from roughly 64% to 91%.
Endpoints:
Primary Endpoint(s) for Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24. This will be assessed with the FDA snapshot algorithm. This uses the last on-treatment plasma HIV-1 
RNA measurement, within an FDA-specified visit window, to determine response
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at 
Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 RNA < 200 c/mL 
at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with positive response defined as HIV-1 
RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be assessed using the 
most recent version of the IAS-USA list of HIV-1 drug resistance mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the percentage of 
CD4+ T-cells will be assessed using on-treatment laboratory results, and pre-specified visit windows

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly from the case report 
forms (CRFs). The summary will count the number of subjects that have at least one event.

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from the CRFs. The 
summary will count the number of subjects that have at least one event.

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, collected at Week 2 
from a subset of subjects.
Revised Protocol No.: 03
Date: 17-Mar-2016
9


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Analyses:
There are two interim analyses scheduled before the start of Stage 2.
The first interim analysis will be conducted after approximately 50% of the randomized subjects have completed 
24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of SDTM (Study Data Tabulation Model) 
data (“level 1” data) to facilitate the development of models for: population pharmacokinetics; exposure-response 
relationships; and, as available, viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of therapy in Stage 1. 
This will be an analysis of the available efficacy, safety, resistance and pharmacokinetic data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well as the recruiting 
time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If Stage 2 is initiated, and recruiting 
follows projected timelines, then it is anticipated that analyses will be conducted when:

The last subject in Arms 3, 4 and 5 completes the Week 24 visit

At Week 24, a Time to Loss of Virologic Response (TLOVR) analysis will be conducted as a sensitivity 
analysis that compliments the snapshot analysis

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4 and 5 completes the Week 96 visit
Revised Protocol No.: 03
Date: 17-Mar-2016
10


TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Study Rationale ................................................................................................. 
1.1.1 Rationale to support study design ............................................................ 
1.1.2 Rationale to support the dose selection ................................................... 
1.1.3 Rationale to support drug combinations.................................................. 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objective .................................................................................... 
1.3.2 Secondary Objectives ............................................................................... 
1.3.3 Exploratory Objectives ............................................................................ 
1.4 Product Development Background ................................................................... 
1.4.1 Background Information BMS-955176 .................................................... 
1.4.1.1 Mechanism of Action....................................................................... 
1.4.1.2 Nonclinical studies .......................................................................... 
1.4.1.3 Clinical studies................................................................................ 
1.4.2 Background Information on TDF ............................................................ 
1.4.3 Background Information on DTG ............................................................ 
1.4.4 Background Information on ATV ............................................................. 
1.4.5 Background Information on RTV ............................................................. 
1.4.6 Drug-Drug Interactions ........................................................................... 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.1.1 Screening.................................................................................................. 
3.1.2 Day 1/Baseline Visit ................................................................................. 
3.1.2.1 Day 1/Baseline Visit for Arms 1 and 2 - Stage 1 ............................ 
3.1.2.2 Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2 ........................ 
3.1.3 Week 2 Intensive PK Visit ........................................................................ 
3.1.4 Visits Week 4 - 96 ..................................................................................... 
3.1.5 Selection of the Continuation Dose of BMS-955176 ............................... 
3.1.5.1 Selection of the Continuation Dose, and the Switch for Stage 1 .... 
3.1.5.2 Selection of the Continuation Dose, and the Switch for Stage 2 .... 
3.1.6 End of the study ........................................................................................ 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
1
3
5
11
15
15
15
17
20
22
22
22
22
23
23
23
23
24
29
32
32
32
33
33
33
36
36
36
37
38
38
39
39
39
39
39
40
40
40
41
41
43
43
43
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 03
Date: 17-Mar-2016
11


3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Other Restrictions and Precautions ......................................................... 
3.5 Discontinuation of Subjects following any Treatment with Study Drug .......... 
3.6 Post Study Drug Study Follow up .................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Instructions for Dose Administration ...................................................... 
4.5.1.1 General Instructions ....................................................................... 
4.5.1.2 Specific Dosing Instructions for Initial Treatment Arm Assignment
...............................................................................................................
4.5.2 Dose Modifications .................................................................................. 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Vital Signs and Physical Examinations ................................................... 
5.3.2 Adverse Events ......................................................................................... 
5.3.3 Concomitant Medication Assessment ...................................................... 
5.3.4 Electrocardiograms ................................................................................. 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.1.1 Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing .................................................................................. 
5.4.1.2 Protocol Defined Virologic Failure ................................................ 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.4.2.1 CD4+ and CD8+ T-Cells ............................................................... 
5.4.2.2 Drug Resistance Testing ................................................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.5.1 Intensive Pharmacokinetic Assessment .................................................... 
5.5.2 Sparse Pharmacokinetic Assessments ...................................................... 
5.6 Biomarker Assessments .................................................................................... 
5.7 Outcomes Research Assessments ..................................................................... 
45
46
47
47
47
47
48
48
48
49
51
51
51
51
52
52
52
52
53
53
53
53
54
55
55
61
61
62
62
62
62
62
62
62
63
64
64
64
64
64
64
65
66
66
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 03
Date: 17-Mar-2016
12


5.8 Other Assessments ............................................................................................ 
5.9 Results of Central Assessments ........................................................................ 
6 ADVERSE EVENTS ................................................................................................. 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) ..................................................... 
6.7 Other Safety Considerations ............................................................................. 
6.7.1 Toxicity Management ............................................................................... 
6.7.1.1 Management of Elevations in Liver Transaminases ....................... 
6.7.1.2 Management of Renal Toxicity ....................................................... 
6.7.1.3 Management of Hyperbilirubinemia ............................................... 
6.7.1.4 Gastrointestinal Toxicity Evaluation and Management Plan ......... 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s)Stage 1 and Stage 2 ................................................. 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Primary Efficacy Analyses .............................................................. 
8.4.2.2 Secondary Efficacy Analyses .......................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.4.1 Sparse Pharmacokinetic Analyses .................................................. 
8.4.4.2 PK/PD and PK/VK Analyses .......................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Other Analyses (including Virologic Futility) ......................................... 
8.5 Interim Analyses ............................................................................................... 
9 STUDY MANAGEMENT ........................................................................................ 
9.1 Compliance ....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
67
67
68
68
69
70
70
70
71
71
71
72
72
72
72
73
73
75
75
75
75
75
75
76
76
76
77
77
77
78
78
79
79
79
79
79
79
80
80
80
80
81
81
81
81
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 03
Date: 17-Mar-2016
13


9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10 GLOSSARY OF TERMS ........................................................................................ 
11 LIST OF ABBREVIATIONS .................................................................................. 
12 REFERENCES ........................................................................................................ 
APPENDIX 1 LISTINGS OF PROHIBITED AND PRECAUTIONARY 
THERAPIES ........................................................................................................... 
APPENDIX 2 AIDS-DEFINING DIAGNOSES.......................................................... 
APPENDIX 3 DAIDS TOXICITY GRADES .............................................................. 
APPENDIX 4 COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE .................................................................................... 
APPENDIX 5 LABORATORY ASSESSMENTS ....................................................... 
82
82
83
84
85
92
96
98
104
105
106
Clinical Protocol
BMS-955176
AI468048
HIV Maturation Inhibitor
Revised Protocol No.: 03
Date: 17-Mar-2016
14


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
1
INTRODUCTION AND STUDY RATIONALE
1.1
Study Rationale
Despite advances in prevention and care, HIV/AIDS remains a significant epidemic in both the 
US and worldwide. AIDS remains the 6th leading cause of death, internationally. Globally, 
approximately 35 million people were living with HIV infection in 2013.1 A number of these 
patients include those who are treatment-experienced. Note: the use of the term 
“treatment-experienced” herein refers to subjects who have failed at least one or two 
antiretroviral (ARV) regimens and who may be harboring drug resistant virus (current or 
archived) to at least one drug class.
In contrast to current HIV treatment guidelines for treatment-naïve patients, the recommended 
composition of combination
antiretroviral therapy (cART) is far less uniform for 
treatment-experienced subjects.2,3 The level of detail in the DHHS and EACS guidelines leads to 
a lack of uniformity in treatment for patients in later lines of therapy. Moreover, drug related 
toxicities (both short and longer term) in treatment-experienced subjects necessitate vigilance 
and continued monitoring. Thus, there is a need for new and efficacious agents with novel 
mechanisms of action (MOA) and favorable safety/tolerability profiles. Given the aging HIV-1 
infected population and overall fewer number of ARV options for treatment-experienced 
patients, there is a need for a more simplified regimen that may have a better long-term safety 
profile such as that of a nucleoside- and booster-sparing cART regimen. As discussed below, this 
study 
evaluates 
the 
merits 
of 
a 
nucleoside-sparing 
cART 
regimen 
and 
a 
nucleoside/booster-sparing cART regimen in Stage 1 and 2, respectively.
Given the aforementioned challenges with existing treatment in ARV treatment-experienced 
adults, the two primary objectives of this two stage, Phase 2b study are to: 1) To study the 
efficacy of one dose (120 mg) of BMS-955176 (a novel HIV-1 maturation inhibitor) when given 
in combination with atazanavir boosted with ritonavir (ATV/r) 300/100 mg and dolutegravir 
(DTG) 50 mg in Stage 1, and 2) to study the efficacy of two doses (120 and 180 mg) of 
BMS-955176 when given in combination with unboosted ATV 400 mg and dolutegravir (DTG) 
50 mg in Stage 2.
Ultimately this Phase 2b clinical trial will provide supportive data in the context of a therapeutic 
dose of BMS-955176 and the clinical safety/efficacy/resistance of the proposed component(s) of 
a single tablet regimen (STR, that is also a nucleoside/ritonavir sparing ARV strategy) for 
Phase 3 trial development in HIV-1 infected treatment-experienced subjects. Specifically, two 
arms in Stage 2 will contain the individual ARV components of a potential STR: BMS-955176, 
ATV, and DTG.
1.1.1
Rationale to support study design
This Phase 2b open-label clinical trial design is in general agreement with published Food and 
Drug 
Administration 
(FDA)
guidance.4
Initially,
in 
Stage 
1, 
approximately 
80 treatment-experienced HIV-1 infected subjects will be randomized 1:1 (approximately 40 per 
treatment group) to one experimental arm (Arm 1) and a TDF-containing arm (Arm 2). Stage 1
Revised Protocol No.: 03
Date: 17-Mar-2016
15


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
(see Figure 3.1.6-1) will study the efficacy of one dose (120 mg) of BMS-955176 when given in 
combination with ATV/r (300/100 mg) and DTG (50 mg). At the Week 24 primary endpoint of 
Stage 1, Bristol-Myers Squibb (BMS) will conduct an analysis of efficacy, safety, and 
pharmacokinetics. Combined with the Week 24 primary endpoint of AI468038 (see below), this 
analysis will be used to 1) select a continuation dose for BMS-955176 in Arm 1 of study 
AI468048, 2) trigger the start of Stage 2 (utilizing unboosted ATV in the experimental arms) of 
study in AI468048, and 3) confirm the two doses of BMS-955176 (in the experimental arms) for 
study in Stage 2 of study AI468048 (see below for further details).
AI468038 is a concurrent Phase 2b study in HIV-1 infected treatment naive adults; the primary 
objective is to evaluate three doses of BMS-955176 (60, 120, and 180 mg) and EFV when given 
in combination with TDF/FTC by determining the proportion of subjects with HIV-1 RNA < 40 
c/mL at Week 24.
To mitigate the clinical concerns of a potential subtherapeutic regimen and the subsequent 
development of virologic failure/resistance, the clinical trial design will contain a second stage. 
Specifically in Stage 2, approximately 120 additional treatment-experienced HIV-1 infected 
subjects will begin randomization 1:1:1 (approximately 40 per treatment group) to Arms 3, 4,
and 5 based upon the results of two concurrent analyses:

Results of the Week 24 analysis in Stage 1, including an analysis for virologic futility (see 
Section 8.4.7)

Results of the Week 24 analysis in AI468038 (treatment-naïve HIV-1 infected adults)
Thus, Stage 2 (Arms 3, 4, and 5) will not enroll if the likelihood of a subtherapeutic regimen 
(in Arms 3 and 4) is high based upon the results of the Week 24 analyses from either AI468038 
or Stage 1 of AI468048. Note, subjects in Arm 5 (Stage 2) will receive the same ARV regimen 
as subjects in Arm 2 (Stage 1); Arm 5 in Stage 2 exists to maintain similar baseline demographic 
and clinical characteristics among subjects who are randomized to the three Arms in Stage 2. 
This staged design allows Stage 2 (Arms 3, 4, and 5) to begin recruitment in a clinically 
de-risked fashion and accomplish this study’s Stage 2 primary study objective: to study the 
efficacy of two doses (120 mg and 180 mg) of BMS-955176 when given in combination with 
unboosted ATV 400 mg and DTG 50 mg. Ultimately, the totality of data from the Week 24 
primary endpoint of Stage 2 (Arms 3, 4, and 5), Stage 1 (Arms 1 and 2), and all arms in the 
AI468038 study will be used to select a continuation dose for BMS-955176 in Arms 3 and 4 of 
study AI468048. Across all five arms of this study, subjects will receive treatment with three 
fully-active ARVs (see Section 1.1.3, Rationale to support any drug combinations). Ultimately, 
subjects in experimental Arms 1, 3, and 4 will be given a continuation dose of BMS-955176 
which has acceptable efficacy, safety, and tolerability (see Figure 3.1.6-1) for subsequent 
development in HIV-1 treatment-experienced adults. 
Since the Phase 2a study AI468002 did not include any subjects infected with HIV-1 clade AE
(see Section 1.4.1.3), this multinational Phase 2b trial will not include Clade AE subjects. The 
Revised Protocol No.: 03
Date: 17-Mar-2016
16


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
study duration is expected to be 96 weeks in length to assess durability of response and longer 
term safety and tolerability.
1.1.2
Rationale to support the dose selection
Phase 1 and Phase 2a clinical trials (AI4680015 and AI4680026) investigating BMS-955176 
utilized a spray-dried dispersion (SDD) suspension. However, this Phase 2b study will utilize a 
micronized crystalline (MC) tablet.
In the concomitant dose-finding Phase 2b study in HIV-1 infected treatment naive adults for 
BMS-955176 (AI468038), doses of BMS-955176 of 60 mg, 120 mg, and 180 mg MC tablet are 
proposed for assessment. These doses are based upon modeling and simulation and formulation 
considerations. A population pharmacokinetic model was developed using single dose 
(10 mg - 120 mg SDD) and multiple dose (10 mg to 80 mg SDD) data in healthy subjects 
(AI468001) as well as multiple dose data in HIV-1 clade B-infected subjects (5 mg to 120 mg
SDD for 10 days, AI468002). An exposure-response analysis was conducted using data from 
Part A of the Phase 2a clinical trial where HIV-1 clade B infected subjects received 
BMS-955176 monotherapy (Dose range: 5 - 120 mg) for 10 days. The exposure-response 
relationship was assessed via an Emax model using observed BMS-955176 steady state Cmin. The 
primary endpoint was predicted maximum viral load decline from baseline.
Steady state BMS-955176 Cmin values in HIV-infected subjects administered MC tablet with 
food were projected according to the following data and assumptions:

Exposures in HIV-infected subjects are 35% less than normal healthy volunteers based on 
observations from AI468001 and AI468002 study

Single dose data projected to multiple dose using accumulation index from AI468001 study

BMS-955176 exposures from the MC tablet formulation with food were projected based on 
studies AI468001 and AI468034. The impact of food on the 60 mg MC tablet dose was 
assumed to be that observed for the 40 mg MC suspension formulation in AI468001. 
Exposures to BMS-955176 120 mg MC tablet with food were determined from observed data 
in Study AI468034, where BMS-955176 C24 increased approximately 70% when 120 mg 
MC tablet was given with a high fat meal, relative to fasted conditions. Finally, exposures to 
BMS-955176 180 mg MC tablet with food were assumed to be 1.5-times that of 120 mg MC 
tablet with food
Figure 1.1.2-1 depicts the simulated maximum viral load decline in HIV-infected subjects 
administered BMS-955176 MC tablet under fed conditions.
Revised Protocol No.: 03
Date: 17-Mar-2016
17


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 1.1.2-1:
Simulated Maximum Viral Load Decline from Baseline Under Fed 
Conditions1
1 Solid lines are 10th and 90th percentiles and the median of simulated data, shaded area is the 90% confidence 
interval of simulated data, vertical solid lines are the 25th to 75th percentile of the simulated steady state 
BMS-955176 Cmin for the 60 mg MC tablet dose, vertical dotted lines are the 25th to 75th percentile of the 
simulated steady state BMS-955176 Cmin for the 120 mg MC tablet dose, and vertical dashed and dotted lines 
are the 25th to 75th percentile of the simulated steady state BMS-955176 Cmin for the 180 mg MC tablet dose.
While baseline EC90 was not a covariate included in the model due to the lack of significance; 
this covariate, among others, was considered marginally significant and it is possible this 
covariate will become important with additional data.
Although data from AI468002 Part C (in HIV-1 clade C infected subjects) were not included in 
the exposure-response assessment described above, BMS-955176 doses 40 mg SDD once daily 
demonstrated median maximal reductions in HIV-1 RNA > 1 log10 in both clade B and clade C 
HIV-1-infected subjects (see Section 1.4.1.3); thus, doses of BMS-955176 60 mg, 120 mg, and 
180 mg are expected to yield a similar response in HIV-1 infected subjects of either clade.
Because the lowest dose assessed in AI468038 (BMS-955176 60 mg) has the potential for a 
suboptimal antiviral response and possible development of resistance, BMS-955176 120 mg in 
combination with ATV/r and DTG will be assessed in Stage 1 of this study. Based on previous 
data that demonstrated exposures to BMS-955176 increase approximately 50% when given in 
combination with RTV, exposures to BMS-955176 120 mg given in combination with ATV/r are 
expected to result in exposures similar to BMS-955176 180 mg given without RTV. Finally, 
BMS-955176 180 mg will not be used in Stage 1 because exposures (when administered with 
RTV) are expected to exceed those previously studied in clinical trials.
Revised Protocol No.: 03
Date: 17-Mar-2016
18


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.1.2-1 depicts the projected exposure multiples of BMS-955176 60 mg, 120 mg, and 
180 mg MC tablet with food at the NOAEL for pre-clinical findings of interest.
Table 1.1.2-1:
Exposure Multiples of BMS-955176 at NOAELa
Species/ Study 
NOAEL
Multiples
Dose 
(mg/kg/d)
Exposure
PK 
Parameter
60 mg
120 mg
180 mg
Rat/6-month (stomach 
histologic changes) 
No NOAEL
AUC
---
---
---
Dog/9-month (stomach 
histologic changes) 
1
AUC:
64.9 gh/mL
AUC 
3
2
1
Dog/1-month (heart rate)
20
Cmax:
17.8 g/mL 
Cmax
19
10
5
Dog/ Cardiovascular 
telemetry (heart rate) 
2
Cp:
1.93 g/mL 
Cmax
2
1
0.5
Mouse/EFD 
45
AUC:
197 gh/mL 
AUC
10
6
3
a Exposure multiple = animal value ÷ human value. Projected human Cmax values are 0.94, 1.79, and 3.61 g/mL 
and steady state AUC values are 19.3, 35.8, and 69.2 g•h/mL at 60, 120, and 180 mg in HIV-1 subjects 
receiving BMS-955176 MC tablets with high fat meal, respectively. High fat meal provides the highest exposure 
relative to other meal types or fasted state.
With regard to heart rate and the NOAEL of 1.93 g/mL observed in the cardiovascular 
telemetry study in dogs (N = 2), it is noted that the projected exposure multiple is 1 at a dose of 
120 mg MC tablet in HIV-infected subjects. However, to date, there have been no clinically 
meaningful changes in heart rate observed in subjects treated with BMS-955176 up to 28 days
(in Part B of the Phase 2a study). With regard to stomach histologic changes, no NOAEL could 
be established based on the 6-month rat study and the projected exposure multiples from the 
9-month dog study are relatively low (eg, 2-fold at the 120 mg MC tablet dose). Despite these 
preclinical findings, a dose of BMS-955176 120mg MC tablet will provide exposures in this 
study which are expected to be generally safe and well tolerated based on existing clinical data 
(see Section 1.4.1).
Data from Study AI468034 demonstrated that BMS-955176 120 mg MC tablet AUC increased 
53% when given with a high fat meal, relative to fasted conditions. Furthermore, preliminary 
data from Study AI468049 demonstrated that a light meal, a standard meal, and a high fat meal 
increased BMS-955176 180 mg MC tablet AUC 1.8-, 2.1-, and 2.5-fold, respectively, relative to 
fasted conditions. Taken together, these data suggest that exposures to BMS-955176 MC tablet 
at doses up to 180 mg increase in a linear fashion when given with food and that similar 
exposures are observed regardless of meal type.
Revised Protocol No.: 03
Date: 17-Mar-2016
19


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In total, BMS-955176 120 mg is expected to be safe, well-tolerated, and efficacious in Stage 1 
and will inform the selection of a Stage 1 continuation dose and aspects of Stage 2 (as described 
in detail within Section 1.1.1).
The doses of BMS-955176 in Stage 2 will be confirmed based upon the Week 24 analyses
(efficacy, safety, and pharmacokinetics) of both Stage 1 and Study AI468038. As described in 
this protocol, the doses in Stage 2 are proposed to be BMS-955176 120 mg and 180 mg in Arms 
3 and 4, respectively.
1.1.3
Rationale to support drug combinations
This study co-administers BMS-955176, with unboosted ATV 400 mg QD or ATV/r 300/100 mg
QD, and DTG 50 mg. The drug combinations within this clinical trial design will provide 
supportive data in the context of a therapeutic dose of BMS-955176 and the clinical 
safety/efficacy/resistance of the proposed components (Stage 2, Arms 3 and 4) of a single tablet 
regimen (STR) for Phase 3 trial development. Ultimately, BMS will seek approval of 
BMS-955176 for use in treatment-experienced HIV-1 infected adults (including either a STR; 
FDC; and/or monoentity). 
The rationale for using a backbone of ATV and DTG in this treatment-experienced patient 
population is based upon established safety, efficacy, and tolerability of the individual 
components. DTG alone provides a 2.46 log10 c/mL reduction in HIV-1 RNA when administered 
as monotherapy for 10 days.7 Furthermore, DTG has been recently approved and is generally 
safe.8,9,10,11,12 Lastly, ATV/r is often used in treatment-experienced adults’ second-line therapies 
or beyond (for example, in individuals who may have failed an non-nucleoside reverse 
transcriptase inhibitor (NNRTI) and/or integrase inhibitor (INI) based regimen).2,4
This Phase 2b design allows treatment-experienced adults in the experimental arms to be 
exposed to three fully active ARVs (from three classes). Subjects will benefit from each ARV 
(except RTV) independently providing a > 1 log10
c/mL decrease in HIV-1 RNA
(see Section 1.4.1.3 for details on Phase 2a results [AI468002]). BMS expects the combination of 
two agents (unboosted ATV and DTG) with one investigational agent (BMS-955176) to provide 
a generally improved safety/tolerability profile relative to the respective arm containing ATV/r 
(Arms 3 and 4 relative to Arm 1, respectively) or TDF (Arms 3 and 4 relative to Arm 5, 
respectively).
There is a potential risk of a subtherapeutic regimen to treatment-experienced subjects enrolled 
in Arms 3 and 4 since unboosted ATV is only approved for use in treatment-naïve HIV infected 
adults (within the US) and the therapeutic dose of BMS-955176 has not been established.
Unboosted ATV (400 mg) in treatment-naïve adults results in a 1.41 log10 c/mL reduction in 
HIV-1 RNA after two weeks of monotherapy.13 Despite the monotherapy based reduction in 
HIV-1 RNA, pharmacokinetic data of unboosted ATV in prospective clinical trials,14
cross-sectional,15 and retrospective analyses16 generally supports the finding of DHHS defined 
subtherapeutic ATV levels (< 150 ng/mL) in patients.17
Revised Protocol No.: 03
Date: 17-Mar-2016
20


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In a randomized, open-label clinical trial, ATV/r has demonstrated non-inferiority to unboosted 
ATV (TLVOR: 75% vs 70% VR-OC: 87% vs 76%, respectively), similar declines in HIV-1 
RNA (approx -3.1 log10 c/mL), and increase in CD4 cell counts within treatment-naïve adults. 
However, the unboosted ATV arm had an increased number of subjects with emerging ATV and 
lamivudine (3TC) resistance. In particular, the difference in nucleoside/nucleotide reverse 
transcriptase inhibitor (NRTI) resistance was markedly greater in the unboosted ATV compared 
to RTV boosted ATV arm.18 Of note, in this clinical trial (AI468048) NRTIs are not used in the 
experimental Arms 1, 3, and 4. Similar single arm, prospective studies have replicated the viral 
efficacy and immunologic response using unboosted ATV in treatment-naïve HIV infected 
adults.19
Insights from limited data regarding the use of unboosted ATV in treatment-experienced adults 
have demonstrated a viral decay ranging from -1.4 to -2.7 log10 c/mL over 24 weeks of therapy 
in combination with NRTIs (such as TDF, 3TC, and didanosine).20 Also, observational data 
(mean: 24 months of follow-up) has shown similar percentages of subjects with their last HIV 
RNA being undetectable (80% vs 83%) after receiving unboosted and RTV boosted ATV, 
respectively.21
Taking the key findings from studies of ATV in both treatment-naïve and treatment-experienced 
HIV infected adults, Arms 3 and 4 containing unboosted ATV may have the potential for 
increased resistance (relative to Arm 1 containing RTV boosted ATV) and the development of 
virologic failure. However, several other factors must be taken into consideration. First, these 
Arms will use three potent (> 1 log10
c/mL) ARVs in combination. Moreover, 
treatment-experienced subjects who have failed one or two prior regimens are likely to be either 
naïve to ATV treatment (prior NNRTI- and/or INI-class failure) or will need to be fully 
susceptible to approved ARVs (including unboosted ATV, see Section 3.3.2). Second, both the 
combination of ATV and DTG with BMS-955176 independently have demonstrated additivity to 
synergy in-vitro22 (see Section 1.4.1.3 for clinical data on the combination of ATV and 
BMS-955176). Third, unboosted ATV increases the geometric mean ratio of Ctrough for DTG by 
a factor of 2.8.23 Fourth, in normal healthy volunteers, multiple dose administration of 
BMS-955176 40 mg (SDD suspension formulation) with ATV 400 mg for 14 days resulted in an 
approximate 25% increase in the AUC(TAU) of BMS-955176 administration alone24 and 
preliminary PK data from the Phase 2a (AI468002) demonstrated that BMS-955176 AUC(TAU) 
increased approximately 37% and 52% when ATV was combined with BMS-955176 40 and 
80 mg (SDD suspension formulation), respectively, relative to administration of BMS-955176 
alone. It is clinically unclear whether higher exposures of DTG and BMS-955176 would lead to 
a decreased incidence of unboosted ATV resistance in the context of Arms 3 and 4 
(BMS-955176 120 and 180 mg + ATV + DTG). Combined with these factors, BMS proposes to 
mitigate the potential risk of increased resistance by 1) studying two doses of BMS-955176 
(120 and 180 mg) in combination with unboosted ATV and DTG, and 2) using a two stage 
clinical trial design with Stage 2 (Arms 3, 4, and 5) enrolling after the Week 24 analysis
(efficacy, safety, and pharmacokinetics) of Stage 1 (Arms 1 and 2) and AI468038 are completed, 
and 3) only enrolling subjects who are susceptible to study medication (including unboosted 
Revised Protocol No.: 03
Date: 17-Mar-2016
21


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
ATV), (see Section 1.1.1, Rationale to support study design). This risk mitigation is employed to 
decrease the probability of exposure to a subtherapeutic regimen and increase the probability of 
establishing clinical efficacy (number of responders at the Week 24) in treatment-experienced 
HIV-1 infected adults.
BMS expects BMS-955176 120 and 180 mg given with unboosted atazanavir to be generally 
safe and well-tolerated. Subjects in Arms 3 and 4 treated with unboosted ATV would potentially 
benefit from a more favorable lipid profile, fewer gastrointestinal (GI) side effects, and 
decreased indirect hyperbilirubinemia. In total, the potential clinical risks for subjects 
randomized to Arms 3 and 4 in Stage 2 do not outweigh the potential benefits of a Nucleoside-
and Booster-sparing cART regimen that may offer both efficacy and long-term safety (including 
but not limited to improved bone mineral density, improved renal function, and improved lipid 
profile). Please see Section 1.5 for further details on the overall risk/benefit assessment.
1.2
Research Hypothesis 
This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with or 
without RTV)
and DTG
is efficacious, safe, and well-tolerated
in HIV-1 infected 
treatment-experienced adults.
1.3
Objectives(s)
1.3.1
Primary Objective
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120 mg, and a TDF 300 mg-containing arm,
each when given in combination with ATV/r 300/100 mg and DTG 50 mg by determining 
the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40 c/mL at 
Week 24 in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180 mg) of BMS-955176, each when 
given in combination with unboosted ATV 400 mg and DTG 50 mg, and to assess the 
antiviral efficacy of TDF 300 mg when given in combination with ATV/r 300/100 mg and 
DTG 50 mg by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Week 24 in Stage 2. 
1.3.2
Secondary Objectives

To assess the antiviral efficacy of BMS-955176 arms, and TDF-containing regimens (TDF + 
ATV/r + DTG), by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL at Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 arms, and TDF-containing regimens, by 
determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA 
< 200 c/mL at Weeks 24, 48, 96
Revised Protocol No.: 03
Date: 17-Mar-2016
22


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

To assess the emergence of HIV drug resistance in samples selected for drug resistance 
testing (according to criteria outlined in Sections 5.4.1.1 and 5.4.1.2)

To assess efficacy of BMS-955176 arms, and TDF-containing regimens, by using the mean 
changes from baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ 
T-cells

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by 
measuring frequency of SAEs and AEs leading to discontinuation

To assess disease progression as measured by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV 
(with or without ritonavir) and DTG in treatment-experienced HIV-1 infected subjects
1.3.3
Exploratory Objectives

To determine the effect of BMS-955176 arms, and TDF-containing regimens, on renal 
clinical parameters and biomarkers through Weeks 48 and 96

To determine the effect of BMS-955176 arms, and TDF-containing regimens, on bone 
biomarkers through Weeks 12 and 24

To assess the impact of baseline (pre-therapy) Gag polymorphisms on the efficacy of 
BMS-955176 by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40 c/mL, HIV-1 RNA < 200 c/mL, and the changes from baseline in log10
HIV-1 RNA at Weeks 24, 48 and 96, by baseline polymorphisms

To characterize the steady-state plasma PK of DTG when co-administered with BMS-955176 
and ATV (with or without RTV) in treatment-experienced subjects. The effect of 
BMS-955176 on DTG PK in the presence of ATV (without RTV) may be assessed relative to 
historical data

To compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV

To characterize the PK of ATV when co-administered with DTG and BMS-955176, with or 
without RTV

To explore PK/PD and PK/viral kinetic (VK) relationships between BMS-955176, ATV, 
and/or DTG exposure and both efficacy and safety endpoints

To assess the impact of the study therapies on health-related quality of life measures
1.4
Product Development Background
1.4.1
Background Information BMS-955176
1.4.1.1
Mechanism of Action
BMS-955176 is an HIV-1 maturation inhibitor (MI), a novel class of anti-HIV-1 drugs that 
prevents the maturation of HIV-1 virions by binding near a key structural element within the Gag 
polyprotein that is required for virion maturation and assembly. Maturation inhibitors block the 
last protease cleavage event between Gag protein segments designated as capsid (CA) protein 
Revised Protocol No.: 03
Date: 17-Mar-2016
23


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
p24 (p24) and spacer peptide 1 (SP1), resulting in the release of immature noninfectious virus 
particles. BMS-955176 has excellent potency and broad spectrum activity, and mechanism of 
action studies indicate that BMS-955176 is a true MI, with a mechanism of action distinct from 
current antiretroviral agents.25 Development of BMS-955176 could potentially lead to novel 
HIV-1 treatment regimens in treatment-experienced HIV-1 patients.
1.4.1.2
Nonclinical studies
Nonclinical Pharmacology and Microbiology
BMS-955176 specifically inhibits HIV-1 protease cleavage at the CA(p24)/SP1 junction within 
the Gag protein in both HIV-1-infected cells and purified HIV-1 Gag virus-like particles (VLPs). 
Radiolabeled BMS-955176 specifically binds to purified HIV-1 Gag VLPs, and its binding is 
dose-dependently inhibited by related MIs and is reversible. BMS-955176 does not directly 
inhibit HIV-1 protease nor bind to a small HIV-1 protease peptide substrate. These results 
indicate that BMS-955176 inhibits late in the HIV-1 life cycle by specific binding to immature 
capsid structures at or near the CA(p24)/SP1 junction, thereby inhibiting cleavage at that 
particular site. In cell culture, the range of values for the concentration producing 50% effect 
(EC50) of BMS-955176 against 7 common laboratory strains of HIV-1 was 1.6 to 10.5 nM 
(mean = 6.0 3.5 nM). Using a reverse transcriptase readout, a phenotyping analysis of 
93 subtype B viruses whose genotypes are representative of 96% of the diversity (found in the 
Los Alamos National Laboratory [LANL] database) in Gag sequences indicates that the mean 
EC50 of this cohort was 2.7 1.9 nM, with a median value of 2.2 nM and a range between 0.6 to 
12 nM. A similar analysis of 23 isolates of subtype C viruses found a mean EC50 of 
6.1 3.1 nM, a median value of 5.6 nM, and a range from 2.5 to 16 nM. When evaluated against 
clinical isolates in peripheral blood mononuclear cells (PBMCs), BMS-955176 exhibited a mean 
EC50 of 24 24 nM against a cohort (N = 22) of subtype B viruses. Activity was also observed 
against viruses from subtypes A, C, D, F, and G, with average EC50 values for 96% of tested 
isolates (N = 41) between 5.9 and 87 nM. Clinical isolates from the CRF01_AE subtype were 
approximately 2- to 3-fold less susceptible to BMS-955176 (average EC50 77 nM, N = 7) 
viruses. BMS-955176 was active against 1 of 3 human immunodeficiency virus type-2 (HIV-2)
isolates (EC50 = 15 nM). BMS-955176 retains complete activity against reverse transcriptase 
(RT), protease, and integrase inhibitor-resistant viruses, with EC50 values similar to wild-type 
(wt) viruses, while the potency of currently approved nucleotide/nucleoside reverse transcriptase 
inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors 
(PIs), and integrase inhibitors (INIs) was undiminished when tested against viruses with reduced 
susceptibility to BMS-955176. BMS-955176 maintained activity against a panel of PI-resistant 
isolates from PI-treated subjects harboring a variety of major and minor PI-resistance
determinants in both protease and Gag.26,27 Protein binding to 100% human serum (HS) was 
86%, and in the presence of 40% HS supplemented with additional human serum albumin 
(HuSA) to match physiologic concentrations, BMS-955176 exhibited an approximately 4-fold 
reduction of antiviral activity. Selection for resistance to BMS-955176 in cell culture identified
changes that map to amino acids adjacent to the CA(p24)/SP1 cleavage site. These include an 
amino acid substitution of A364V or a combination of V362I with secondary changes (V370A, 
Revised Protocol No.: 03
Date: 17-Mar-2016
24


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
A374P or I376V). In vitro, virus with the A364V change exhibited a drastic loss of susceptibility 
to BMS-955176 (>100-fold), while the V362I plus secondary change-containing viruses were 
generally less sensitive to BMS-955176 (median EC50 25 nM, range 7.1 to 167 nM). In 2-drug 
combination studies with representative drugs from NRTI, NNRTI, PI, and INI classes, all 
combinations produced additive to synergistic effects, suggesting that BMS-955176 should be 
amenable for use in combination with any of these agents.
Bevirimat (BVM), a first-generation MI, demonstrated proof of concept and dose-dependent 
anti-HIV-1 potency in both Phase 1 and Phase 2 clinical studies. Patients infected with HIV-1 
sensitive to BVM demonstrated an approximate 1.2 log10 decline in HIV-1 RNA. However, 
approximately 50% of patients harboring naturally occurring polymorphisms located close to the 
CA(p24)/SP1 cleavage site showed a significantly reduced response to BVM treatment. In 
addition, BVM exhibited a large reduction in antiretroviral activity in the presence of human 
serum. BMS-955176 was developed to address the key flaws of BVM by providing improved 
coverage of BVM-resistant polymorphic variants and improved potency in serum. BMS-955176 
has been shown to be active against viruses with resistance from all marketed ARVs, and to 
possess a low serum effect. Development of BMS-955176 could potentially lead to novel HIV-1 
treatment regimens in treatment-experienced HIV-1 patients.
Nonclinical Pharmacokinetics
The absolute oral bioavailability of BMS-955176 was low (3.89% to 26.8%) in all preclinical 
species (mice, rats, dogs, and monkeys). In the dog, though there was a positive food effect and 
no pH dependent absorption, upon repeat dosing a less than dose-proportional increase in 
exposure was observed. BMS-955176 distributed preferentially into the duodenum, liver, and 
lymph nodes with little penetration into the brain. Protein binding was 86.1% in human serum 
and 78% to 94% in animal sera
In human in vitro systems, the metabolism of BMS-955176 was primarily mediated via 
cytochrome P450 (CYP)3A4. In vivo in rats, dogs, and monkeys, BMS-955176 was the 
predominant drug-related component in plasma following a single oral dose of BMS-955176. 
BMS-955176 was eliminated principally via metabolism followed by excretion in bile with little 
renal excretion. 
In vitro, BMS-955176 was an inhibitor of CYP2C8 (concentration at which 50% inhibition 
observed [IC50] = 28.5 M), CYP3A4 (IC50 = 32 M), and uridine diphosphate 
glucuronosyltransferase (UGT)1A1 (IC50 = 20 M) enzymes. No P-gp inhibition or 
time-dependent inhibition of CYPs was observed. BMS-955176 was not an inducer of CYP1A2, 
CYP2B6, or CYP3A4. The steady state Cmax of BMS-955176 180 mg tablet in HIV-infected 
patients with food is projected to be approximately 5.2 M. Thus, the potential exists for 
BMS-955176 to inhibit CYP2C8, CYP3A4, and/or UGT1A1 in vivo and increase exposures to 
co-administered drugs that are metabolized by these enzymes. Furthermore the potential exists 
for drug-drug interactions (DDI) if BMS-955176 is co-administered either with an inhibitor or 
inducer of CYP3A4 or P-gp.
Revised Protocol No.: 03
Date: 17-Mar-2016
25


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
BMS-955176 was a substrate of mouse P-glycoprotein (P-gp) based on higher bioavailability in 
P-gp knock-out mice when BMS-955176 was co-administered with elacridar, a potent inhibitor 
of P-gp and breast cancer resistance protein (BCRP). BMS-955176 could not be reliably assessed 
as a substrate for human P-gp due to nonspecific binding and low solubility. In vitro, 
BMS-955176 inhibited organic anion transporting polypeptide (OATP)1B1 and OATP1B3 
(IC50 5.3 and 4 M, respectively), but was not an inhibitor of P gp, sodium taurocholate 
cotransporting polypeptide (NTCP), organic anion transporter (OAT)1, OAT3, multiple 
drug-resistance protein (MRP)2, and bile salt export pump (BSEP). These findings suggest a 
potential for DDI between BMS-955176 (as the perpetrator) and substrates of OATP1B1 and 
OATP1B3, but not with those of P-gp, NTCP, OAT1, OAT3, MRP2, and BSEP. Furthermore, 
the potential exists for drug-drug interactions (DDI) if BMS-955176 is co-administered either 
with an inhibitor or inducer of CYP3A4 or P-gp. Preliminary data indicate that BMS-955176 
does not inhibit OCT2, a transporter that is inhibited by dolutegravir (DTG), a drug with which
BMS-955176 is planned to be co-administered.
Nonclinical Toxicology
The toxicity profile of BMS-955176 was evaluated in single- and repeat-dose toxicity, 
genotoxicity, phototoxicity, safety pharmacology, sensitization, reproductive toxicity and 
embryo-fetal development studies. The scope of the toxicologic evaluation for BMS-955176
supports its proposed clinical use for HIV-1 infection. Unless otherwise mentioned, all animal 
studies were dosed by the oral route with an aqueous methylcellulose suspension of a 
BMS-955176 spray-dried dispersion (SDD). 
BMS-955176 was not phototoxic, mutagenic, or clastogenic in vitro and was not genotoxic in a 
rat micronucleus assay at 300 mg/kg/day (AUC 279 g·h/mL). BMS-955176 was not a skin 
sensitizer in the local lymph node assay in the mouse. BMS-955176 had a low potential (IC50 or 
EC50 > 5 M [> 3.45 µg/mL]) for in vitro off-target interactions on a broad range of enzymes, 
transporters, and receptors, including cardiac ion channels. 
In safety pharmacology evaluations in rats, there were no respiratory findings and no direct 
central nervous system (CNS) findings. Decreases in motor activity, arousal, and rearing were 
considered secondary to general toxicity (ie, body weight decreases).
Cardiovascular safety pharmacology evaluations were conducted in rabbits, rats, and dogs. In the 
definitive oral single-dose cardiovascular safety study in conscious telemeterized dogs, blood 
pressure and electrocardiogram were was unaffected at 20 mg/kg; however, increases in heart 
rate (mean 33% to 57% of pretest vehicle) were observed at 8 and 20 mg/kg. The increase in 
heart rate at these doses was primarily due to increases in 2 dogs at each dose that had higher 
plasma concentrations (12.83 g/mL) relative to the dogs without effects on heart rate 
(6.81 g/mL). The no-observed-effect level (NOEL) for cardiovascular effects in dogs was 
2 mg/kg (plasma concentration of 1.93 µg/mL). Importantly, there was no change in heart rate at 
20 mg/kg/day at higher plasma concentrations (Cmax 17.8 µg/mL) in the 1-month study in 
dogs (below). 
Revised Protocol No.: 03
Date: 17-Mar-2016
26


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Taken together, BMS-955176 has low potential for respiratory, CNS, and cardiovascular effects 
and no cardiovascular effects have been observed in humans to date.
Two-week, 1-month, and 6-month studies were conducted in rats. As the 2-week study was of 
limited scope, only the 1-month and 6-month studies are presented in this summary. 
BMS-955176 was administered for 1 month at doses of 30, 100, or 300 mg/kg/day. While there 
was no mortality at 100 mg/kg/day, the high dose of 300 mg/kg/day was associated with 
pronounced signs of clinical toxicity and early euthanasia of all the rats at that dose level on 
Days 8 to 9. The dose of 30 mg/kg/day was tolerated. The intermediate dose of 100 mg/kg/day 
(AUC 357 g·h/mL) resulted in dose-limiting toxicity including persistent reduction in food 
consumption and body weights. A number of minor hematology (including red cell parameter 
changes with no consistent effect on the erythron) and serum chemistry changes (including 
increased alkaline phosphatase and alanine aminotransferase) without correlating histologic liver 
findings) occurred at 30 and 100 mg/kg/day; these changes were considered not adverse due to 
small magnitude, occurrence only in 1 sex, and lack of microscopic correlates, and most were 
secondary to decreases in food consumption and body weight. Dose-related gastrointestinal 
toxicity was primarily characterized by morphologic changes in the stomach at 100 mg/kg/day 
and the stomach and small and large intestines at 300 mg/kg/day. At the end of the 2-week 
postdose recovery period, there was complete recovery of all BMS-955176-related findings at 
30 mg/kg/day. At 100 mg/kg/day, all findings recovered with the exception of increased red cell 
distribution width in females, minimally higher (1.94×) ALT activity in 1 male without any 
histologic correlates, and decreased mean prostate gland (with seminal vesicles) weights. The 
low dose of 30 mg/kg/day (AUC 113.5 g·h/mL) was considered the no-observed-adverse-effect 
level (NOAEL) because the body weight and food consumption changes were minimal and 
transient and there were no BMS-955176-related morphologic changes.
In a 6-month oral toxicity study in rats with 1-month recovery period, BMS-955176 was 
administered at doses of 10, 25, or 50 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month rat study and occurred at all doses (10 mg/kg/day; 
AUC 71 gh/mL). Findings included decreased body weight, food consumption, and in the 
stomach, minimal to marked atrophy involving both parietal and chief cells, minimal to mild 
single-cell necrosis and minimal regeneration in the glandular mucosa, which were partially 
reversible at the end of the 1-month recovery period. A NOAEL was not established in this 
study.
Five-day, 1-month, and 9-month repeat-dose studies were conducted in dogs. As the 5-day 
toxicokinetics and tolerability studies were of limited scope, only the 1-month and 9-month
studies are presented here. In the 1-month study, BMS-955176 was administered at doses of 2, 8, 
or 20 mg/kg/day. Increased incidences of sporadic vomiting and liquid, yellow, and/or mucoid 
feces occurred at all doses, but had no apparent effect on the overall health of these animals. 
At 20 mg/kg/day, additional findings included occasional decreases in food consumption in a 
few animals, loss of body weight (up to 8%) in 2 females, a minimal increase in serum ALT 
activity (2.10× pretest) in 1 female with no microscopic correlates, and minimal single-cell 
necrosis of stomach glandular epithelium. All BMS-955176-related changes were fully 
Revised Protocol No.: 03
Date: 17-Mar-2016
27


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
reversible by the end of the 2-week recovery period. The dose of 8 mg/kg/day was considered a 
NOAEL (AUC 219.5 g·h/mL) since the sporadic clinical observations had no adverse effects 
on the general health of the animals and there were no BMS-955176-related morphologic 
changes. 
In a 9-month oral toxicity study in dogs with 1-month recovery period, BMS-955176 was 
administered at 0 (vehicle), 1, 3, or 10 mg/kg/day. BMS-955176-related effects were similar to 
those observed in the 1-month dog
study
and
occurred at doses 3 mg/kg/day 
(AUC 135 gh/mL). Findings included salivation (only males at 10 mg/kg/day), fur thinness 
(males), thin appearance, and abnormal feces (yellow, liquid, pale and/or mucoid) that occurred 
sporadically throughout the study; increases in mean food consumption; minimal to marked chief 
cell depletion in the glandular stomach. Additional findings at 10 mg/kg/day included thin 
appearance that correlated with decreases in body weight in food consumption; occasional 
vomitus in males; in the stomach, minimal to moderate mucous cell hyperplasia (often associated 
with glandular dilatation) correlating with increased thickness macroscopically (males only) and 
minimal to marked parietal cell depletion and single-cell necrosis of glandular epithelial cells; 
and increases in serum gastrin values (1.31 to 4.56× highest control value) for several dogs that
may have reflected the reductions in gastric parietal cells. The NOAEL was 1 mg/kg/day 
(AUC 64.9 gh/mL).
The embryo-fetal development (EFD) studies were conducted in 3 species (rabbits, rats, and 
mice) instead of the standard 2 species due to poor maternal tolerability and inability to achieve 
adequate systemic exposures in rabbits.
In a definitive EFD study in pregnant mice, BMS-955176 was administered at doses of 15, 45, or 
150 mg/kg/day from gestation day (GD) 6 through 15. BMS-955176 was a selective 
developmental toxicant in mice. Dose of 100 mg/kg/day was associated with an increase in 
embryo-fetal lethality (cumulative postimplantation losses of 11.5%, relative to 3.9% in control 
litters, attributed to increased incidences of dead fetuses, early resorptions and late resorptions). 
Cleft palate and exencephaly were observed in a few fetuses; additionally, marginal reductions in 
fetal body weight (5% relative to control values) were observed. There was no maternal toxicity 
at any dose tested. The developmental NOAEL was 45 mg/kg/day (AUC 213 g·h/mL).
In a definitive EFD study in pregnant rats, BMS-955176 was administered at doses of 10, 30, or 
100 mg/kg/day from GD 6 through 15. BMS-955176 was not a selective developmental toxicant. 
Developmental toxicity (reduced fetal body weights, increases in fetal alterations, and reduced 
fetal ossification) occurred only at 100 mg/kg/day; whereas, maternal toxicity (clinical 
observations, reduced body weights, and reduced food consumption) was observed at 
30 mg/kg/day. The developmental NOAEL was 30 mg/kg/day (AUC 114 gh/mL). 
In an EFD study in pregnant rabbits, BMS-955176 was administered at a dose of 80 mg/kg/day 
from GD 7 through 19. BMS-955176 was not a developmental toxicant in rabbits at 
80 mg/kg/day (AUC 3.26 gh/mL), at which reductions in maternal food consumption and 
weight gain were observed.
Revised Protocol No.: 03
Date: 17-Mar-2016
28


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
In the fertility and early embryonic development study in rats, BMS-955176 was evaluated at 
doses of 10, 30, or 100/60 mg/kg/day in males and females. BMS-955176 did not affect 
reproduction or early embryonic development at doses 100 mg/kg/day that produced overt 
toxicity. The reproductive NOAEL was 100/60 mg/kg/day (AUC 210 g•h/mL) in male rats and
100 mg/kg/day (AUC 458 g•h/mL) in female rats.
Overall, results from the nonclinical toxicology studies demonstrate that BMS-955176 has a low 
potential for cardiovascular effects, is toxic to the gastrointestinal tract, and is a selective 
developmental toxicant. Clinical monitoring of vital signs (heart rate, systolic and diastolic blood 
pressure) and for gastrointestinal adverse events (AEs) (eg, nausea, vomiting, diarrhea, or fecal 
changes), along with screening for potential renal tubular injury, have not indicated any potential 
for these AEs in Phase 1 or proof of concept (POC) studies in humans. Clinical protocols will 
ensure that appropriate contraceptive measures will be followed to minimize the risk of 
pregnancy while enrolling women of child-bearing potential (WOCBP) males subjects who are 
sexually active with (see Section 3.3.1 Inclusion Criteria).
1.4.1.3
Clinical studies
Phase 1
The safety, tolerability, and PK of BMS-955176 were evaluated in a randomized, double-blind, 
placebo-controlled, sequential single ascending dose (SAD, 10-120 mg) and multiple ascending 
dose (MAD, 10-80 mg QD for 14-28 days) study in healthy subjects (AI468001). No SAEs, 
deaths, or discontinuations related to study drug occurred. No clinically meaningful trends were 
observed in vital signs, physical exam findings, laboratory values, or ECGs. Following 
single-dose and multiple-dose administration of BMS-955176, a slightly less than 
dose-proportional increase in Cmax and AUC(INF) was observed over the dose ranges studied. 
Steady state was reached in approximately 7 days following multiple-dose once daily 
administration of BMS-955176. The half life (T-HALF) of BMS-955176 is approximately 
35 hours. 
Study AI468034 assessed the relative bioavailability and dose proportionality of BMS-955176 
MC tablet - the formulation that will be used in the current study. Relative to 80 mg SDD 
suspension, the bioavailability of BMS-955176 120 mg MC tablet was approximately 23% 
lower. Furthermore, consistent with the low solubility of BMS-955176, considerable overlap in 
exposures was observed between 60 mg, 120 mg and 180 mg MC tablet, when given under 
fasted conditions. The impact of food on exposures to BMS-955176 120 mg MC tablet was 
assessed in Study AI468034 as well; a high fat meal increased BMS-955176 AUC approximately 
50% with negligible impact on BMS-955176 Cmax.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
Revised Protocol No.: 03
Date: 17-Mar-2016
29


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose. Preliminary safety 
results from AI468049 indicate that GI adverse events (eg, nausea, vomiting, loose stools) only
occurred in the fed arms (where the BMS-955176 exposures were higher) relative to the fasted 
arms.
Study AI468049 assessed the impact of a light meal, a standard meal, and a high fat meal on the 
PK of BMS-955176 180 mg MC tablet. Preliminary results demonstrate that, relative to fasted 
conditions, BMS-955176 Cmax is increased approximately 2-fold with all three meal types, while 
BMS-955176 AUC increased approximately 1.8-, 2.1-, and 2.5-fold with a light meal, a standard 
meal, and a high fat meal, respectively. These results, taken together with those from AI468034 
described above, demonstrate that the impact of food on exposures to BMS-955176 is 
dose-dependent with the degree of impact increasing with increasing dose.
Phase 2a
A randomized, double-blind, placebo-controlled proof of concept study in HIV subjects has 
completed enrollment and is undergoing analysis (AI468002). The three parts of this study were: 
1) Part A evaluated doses of 5, 10, 20, 40, 80, and 120 mg of BMS-955176 (SDD suspension) 
given for 10 days in HIV-1 clade B infected subjects, 2) Part B compared the antiviral activity of 
BMS-955176 (SDD suspension) administered with ATV (with or without RTV) against standard 
of care (TDF + FTC + ATV/r) for 28 days in HIV-1 clade B infected subjects, and 3) Part C 
evaluated BMS-955176 40 and 120 mg (SDD suspension) given for 10 days in HIV-1 clade C 
infected subjects. See Table 1.4.1.3-1 for baseline demographics. 
Preliminary results from the Phase 2a study (AI468002) in HIV-1 (clade B and C only) infected 
adults showed that at effective doses, a maximum median reduction in HIV-1 RNA ranging from 
1.3 to 1.7 log10 was observed. In the Phase 2b study BMS-955176 doses estimated to provide 
similar exposure to effective doses in the Phase 2a study will be used. Moreover, when 
BMS-955176 was combined with ATV RTV, these combinations resulted in maximum median 
declines in HIV-1 RNA ranging from 1.9 to 2.2 log10 (see Table 1.4.1.3-2). These results are 
generally similar to the antiviral effect demonstrated by other classes of ARVs in short-term
monotherapy trials, and thus BMS-955176 should contribute substantially with other ARVs to 
form an effective cART regimen. Lastly, preliminary safety data show acceptable safety and 
tolerability across all Phase 2a arms. Most AEs were Grade 1-2 and were most frequently due to 
an indirect hyperbilirubinemia; the levels seen with BMS-955176 and ATV/r were similar to 
those seen with ATV/r combined with TDF/FTC. The arms containing BMS-955176 and 
unboosted ATV had bilirubin levels that were approximately half of those observed in the arms
containing ATV/r. Last, arms containing BMS-955176 alone did not show elevated bilirubin
levels. Many of these events occurred in subjects who were randomized to an arm containing 
BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to headache and an 
increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia occurred in subjects also 
receiving ATV.
Revised Protocol No.: 03
Date: 17-Mar-2016
30


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.4.1.3-1:
Phase 2a Baseline Demographics and Characteristics of Subjects 
(Preliminary Results)
Treatment Arm
Subjects
(n)
Median 
age
Male
White
Median 
HIV 
RNA 
(log10
c/ml)
Median 
CD4 
(cells/mm3)
Part A (Clade B, 10 days 
monotherapy)
BMS-955176 5 mg
8
43.5
8 (100)
6 (75.0)
4.09
437
BMS-955176 10 mg
8
39
7 (87.5)
7 (87.5)
4.02
539
BMS-955176 20 mg
8
33
8 (100)
8 (100)
3.59
512
BMS-955176 40 mg
8
38
8 (100)
8 (100)
4.03
536
BMS-955176 80 mg
8
31.5
8 (100)
8 (100)
3.82
504
BMS-955176 120 mg
8
37.5
8 (100)
8 (100)
3.84
498
Placebo
12
36
12 
(100)
12 
(100)
3.98
458
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
8
32.5
8 (100)
6 (75)
4.04
581
BMS-955176 40 mg + ATV 300 mg + 
RTV 100 mg
8
34
8 (100)
8 (100)
4.45
480
BMS-955176 80 mg + ATV 400 mg
8
31.5
8 (100)
7 (87.5)
4.15
549
Truvada® + ATV 300 mg + RTV 
100 mg
4
32.5
4 (100)
4 (100)
4.12
427.5
Part C (Clade C, 10 days 
monotherapy)
BMS-955176 40 mg
7
35
4 (57.1)
2 (28.6)
4.53
554
Placebo
2
38.5
2 (100)
0 (0)
3.78
304
Table 1.4.1.3-2:
Maximum Decline Log10 HIV-1 RNA (Preliminary Results)
Treatment 
Mean 
S.D. 
Median 
Max
Min
Part A (Clade B, 10 days monotherapy)
BMS-955176 5 mg
-0.49
0.217
-0.498
-0.78
-0.22
BMS-955176 10 mg
-1.05
0.351
-0.976
-1.76
-0.64
BMS-955176 20 mg
-1.17
0.645
-1.115
-2.12
-0.13
BMS-955176 40 mg
-1.55
0.352
-1.701
-1.88
-0.93
BMS-955176 80 mg
-1.52
0.257
-1.555
-1.82
-1.04
Revised Protocol No.: 03
Date: 17-Mar-2016
31


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 1.4.1.3-2:
Maximum Decline Log10 HIV-1 RNA (Preliminary Results)
Treatment 
Mean 
S.D. 
Median 
Max
Min
BMS-955176 120 mg
-1.53
0.478
-1.654
-2.07
-0.83
Placebo
-0.48
0.581
-0.381
-1.46
0.56
Part B (Clade B, 28 days therapy)
BMS-955176 40 mg + ATV 400 mg
-1.89
0.273
-1.858
-2.37
-1.49
BMS-955176 40 mg + ATV 300 mg + RTV 100 
mg
-2.22
0.676
-2.202
-3.52
-1.24
BMS-955176 80 mg + ATV 400 mg
-2.3
0.307
-2.228
-2.68
-1.87
Truvada® + ATV 300 mg + RTV 100 mg
-2.41
0.495
-2.39
-3.04
-1.83
Part C (Clade C, 10 days monotherapy)
BMS-955176 40 mg
-1.5
0.439
-1.285
-2.03
-1.04
Placebo
0.12
0.141
0.12
0.02
0.22
The pharmacokinetics of BMS-955176 were assessed in HIV-1 infected subjects in AI468002. 
Overall, exposures to BMS-955176 are approximately 30% to 35% lower in HIV-1-infected 
subjects compared to healthy subjects administered the same doses and formulation of 
BMS-955176. Furthermore, exposures to BMS-955176 increased in a generally linear fashion up 
to 40 mg, with a less than dose proportional increase in exposures between 40 mg and 80 mg, 
and considerable overlap in exposures between 80 mg and 120 mg.
1.4.2
Background Information on TDF
Tenofovir disoproxil fumarate (TDF) is an analog of the nucleotide adenosine 
5’-monophosphate. TDF inhibits HIV-1 reverse transcriptase and is indicated in combination 
with other ARVs for the treatment of HIV-1 infection. The most common adverse reactions 
include rash, diarrhea, headache, pain, depression, asthenia, and nausea. Clinicians are warned 
about new onset or worsening renal impairment, decreases in bone density, and immune 
reconstitution syndrome. For more information concerning TDF, please refer to the 
TDF/Viread® SmPC or TDF/Viread® USPI.28
1.4.3
Background Information on DTG
Dolutegravir (DTG) is a HIV-1 integrase strand transfer inhibitor indicated in combination with 
other ARVs for the treatment of HIV-1 infection. The most common adverse reactions of 
moderate to severe intensity include insomnia, fatigue, and headache. Clinicians are warned 
about immune reconstitution syndrome. For more information concerning DTG, please refer to 
the DTG/Tivicay SmPC or the DTG/Tivicay USPI.29
1.4.4
Background Information on ATV 
Atazanavir is a protease inhibitor indicated for use in combination with other ARVs for the 
treatment of HIV-1 infection. The most common adverse reactions include nausea, 
Revised Protocol No.: 03
Date: 17-Mar-2016
32


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
jaundice/scleral icterus, rash, headache, abdominal pain, vomiting, insomnia, peripheral 
neurologic symptoms, dizziness, myalgia, diarrhea, depression, and fever. Clinicians are warned 
about hyperbilirubinemia, nephrolithiasis, and cholelithiasis. For more information concerning 
ATV please refer to the ATV/Reyataz® SmPC or ATV/Reyataz® USPI.30
1.4.5
Background Information on RTV
Ritonavir is a protease inhibitor indicated in combination with other ARVs for the treatment of 
HIV-1 infection. The most frequently reported adverse drug reactions with RTV alone or in 
combination with other ARVs include diarrhea, nausea, vomiting, abdominal pain, paresthesia, 
rash, and fatigue/asthenia. Clinicians are warned about total cholesterol and triglyceride 
elevations. For more information concerning RTV please refer to the RTV/Norvir® SmPC or 
RTV/Norvir® USPI.31
1.4.6
Drug-Drug Interactions
In AI468001, coadministration of BMS-955176 as a single dose following two doses of 100 mg 
RTV resulted in an approximate 48% increase in BMS-955176 AUC(INF), consistent with 
inhibition of CYP3A4 and/or P-gp. Multiple-dose administration of BMS-955176 with daily 
400 mg ATV and a standard meal for 14 days resulted in a modest (~25%) increase in the 
BMS-955176 AUC(TAU).
Study AI468005 assessed the two-way interaction between BMS-955176 40 mg (administered as 
an SDD suspension) and TDF at steady state in healthy subjects. Relative to administration of 
each drug alone, neither BMS-955176 nor TDF exposures were meaningfully impacted upon 
coadministration.
Study AI468041 assessed the impact of BMS-955176 80 mg (administered as an SDD 
suspension) on the pharmacokinetics of the components of a combined oral contraceptive 
containing ethinyl estradiol (EE) and norgestimate (NGM). Exposures to both EE and 
norelgestromin (NGMN), the active metabolite of NGM were reduced in the presence of 
BMS-955176. Furthermore, one subject had a serum progesterone level > 300 ng/dL while 
BMS-955176 and the oral contraceptive were concomitantly administered, indicative of 
ovulation and contraceptive failure.
Finally, in vitro data suggest that BMS-955176 may inhibit OATP1B1 and OATP1B3 and 
exposures to substrates of these transporters, such as HMG-CoA reductase inhibitors, may 
increase when co-administered with BMS-955176.
1.5
Overall Risk/Benefit Assessment
The preclinical and clinical safety data demonstrate that BMS-955176 administered at doses in 
this Phase 2b study (120, and 180 mg) should be well tolerated without a major clinically 
relevant impact on safety. Moreover, there have been no identified safety risks from 
completed/ongoing clinical studies to date.
Revised Protocol No.: 03
Date: 17-Mar-2016
33


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The preclinical toxicology studies demonstrate two potential risks to subjects:
First, BMS-955176 is a selective developmental toxicant. Developmental toxicity (skeletal 
alterations in rats; cleft palate and reduced fetal body weights in mice) were observed in 
embryofetal development studies. In order to address this concern, subjects will be required to 
use two methods of contraception (as described in Section 3.3.1 Inclusion Criteria) and undergo 
routine urine pregnancy testing (as described in the T&E Tables in Section 5.1). Furthermore, 
due to results from Study AI468041 that demonstrates reduced exposures to the components of a 
combination oral hormonal contraceptive containing ethinyl estradiol and norgestimate when 
given concomitantly with BMS-955176, oral hormonal contraceptives cannot be used as a 
method of contraception by WOCBP in this study.
Second, single or repeat oral doses of BMS-955176 were associated with sporadic vomiting in 
dogs and unformed and/or liquid feces in rats and dogs. In rats at 10 mg/kg/day there were 
decreases in body weight and food consumption; in the stomach there was atrophy involving 
both parietal and chief cells, single-cell necrosis and regeneration in the glandular mucosa, and 
modest increases in serum gastrin values. At higher doses (100 mg/kg/day) in rats there were 
additional findings in the intestines (distended jejunum, ileum, and cecum; hyperplasia of the 
crypt epithelium in the jejunum; ulcers and erosions in the cecum; and decreased mucosal cell 
extrusion and increased mucus in the colon). 
Similar gastric changes were seen in dogs. At 20 mg/kg/day there was single-cell necrosis of the 
stomach glandular epithelium. At 3 mg/kg/day gastric changes showed chief cell depletion. 
At 10 mg/kg/day changes in the stomach included: mucous cell hyperplasia correlating with 
increased thickness macroscopically, parietal cell depletion, single-cell necrosis of glandular 
epithelial cells, and modest increases in serum gastrin values. Unlike the rats, no changes were 
observed elsewhere in the alimentary canal including the gastroesophageal junction and the 
duodenum. There was no evidence of macrocytosis. Measurement of Total Protein and Albumin 
revealed no clinically relevant changes. The stomach histologic findings were BMS-955176 
dose- and duration dependent. In the 1-month studies, vomiting and fecal changes stopped soon 
after dosing cessation, and microscopic lesions in the stomach and/or intestines reversed 
completely within a 2-week treatment-free period. In the 6 month study in rats and the 9-month 
study in dogs, microscopic lesions in the stomach partially recovered after a 1 month treatment 
free period. The NOAEL was 1 mg/kg/day (AUC 64.9 mg•h/mL) in the 9-month study in dogs, 
and was not established in the 6-month study in rats. Investigative studies for gastric toxicity in 
rats and dogs indicated similar findings with both SDD and MC forms, and with no clear 
evidence that the gastric toxicity is a direct local effect of BMS-955176. The mechanism and 
clinical relevance of these gastrointestinal findings is unknown at present (see below).
A Phase 1 study (AI468001) in healthy volunteers evaluated single and multiple doses of 
BMS-955176 for 14-28 days both alone and in certain arms, in combination with ATV or RTV. 
Overall the safety data demonstrated that BMS-955176 was generally safe and well tolerated. 
A Phase 2a (AI468002) study in HIV-1 infected adults evaluated several doses of BMS-955176 
given alone or in combination with ATV RTV for 10-28 days. The preliminary results show 
Revised Protocol No.: 03
Date: 17-Mar-2016
34


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
acceptable safety and tolerability across all arms. There were no deaths, SAEs, or AEs leading to 
discontinuation. There were no clinically relevant changes in vital signs, lab parameters, or 
EKGs. Most of the AEs were Grade 1-2 and were most frequently due to hyperbilirubinemia 
(primarily observed in treatment arms with ATV). Of the GI AEs, most were attributable to 
diarrhea or loose/watery stools. Many of these events occurred in subjects who were randomized 
to an arm containing BMS-955176 and ATV. Of the Grade 2-4 related AEs, many were due to 
headache and an increase in hyperbilirubinemia. Many of the AEs of hyperbilirubinemia 
occurred in subjects also receiving ATV; moreover, the three arms with the highest average total 
bilirubin occurred in subjects receiving both BMS-955176 and ATV. Clinical changes/symptoms 
consistent with the GI findings from dogs and rats (described above) were not seen in the 
preliminary data set from short-term therapy with BMS-955176 in HIV-1 infected adults. 
In this treatment-experienced study population, we estimate GI safety multiples of 2× and 1×, 
(based on NOAEL in 9-month dog study), corresponding to projected human exposures at 
BMS-955176 doses of 120 and 180 mg.
While no clinically relevant GI safety signals have been observed in AI468001 or AI468002, in 
this clinical trial, subjects will undergo routine targeted and complete history/physical exams in 
addition to regular laboratory measurements (including CBC and chemistries). This will initially 
occur more frequently than in standard clinical practice and allow for increased vigilance for any 
potential GI toxicity. Guidance on the evaluation and management of potential GI toxicity is 
outlined in Section 6.7.1.4.
Subjects in this clinical study will benefit from receiving cART potentially containing 
BMS-955176. Preliminary data from the Phase 2a (Part A, B and C) study show a maximum 
median reduction in HIV-1 RNA (clades B and C) ranging from 1.3 to 1.7 log10 in the dose arms 
estimated to provide similar exposure to those in this current study. When BMS-955716 was 
combined with ATV RTV (Part B) this resulted in maximum median declines in HIV-1 RNA 
ranging from 1.9 to 2.2 log10. These results are generally similar to the antiviral effect 
demonstrated by other classes of ARVs. Thus, BMS-955176 should contribute with other ARVs 
substantially to form an effective cART regimen.
As with any antiretroviral study in HIV-1-infected subjects, there is a risk for the development of 
treatment failure and the development of drug resistance associated mutations to BMS-955176 
and/or other antiretrovirals. However, drug resistance to the maturation inhibitor would not be 
anticipated to result in cross-resistance to any other ARV class, including protease inhibitors.32
Ongoing analysis of preliminary data from the Phase 2a study is evaluating both emergent 
genotypic and phenotypic changes after short term monotherapy with BMS-955176. The use of 
three fully susceptible agents as a part of cART is expected to decrease the probability of 
virologic failure and drug resistance. Initially in this clinical trial, measurement of HIV-1 RNA 
will occur more frequently than in standard clinical practice which will allow for increased 
vigilance for the development of lack of efficacy/resistance. Finally, an analysis for virologic 
futility will occur at Week 24 (see Section 8.4.7).
Revised Protocol No.: 03
Date: 17-Mar-2016
35


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
As described earlier, treatment-experienced adults enrolled in Arms 3-4 may be exposed to a 
subtherapeutic regimen and may be at higher risk for virologic failure and the development of 
resistance. In order to decrease this probability, this clinical trial uses a two-stage design 
whereby enrollment in Arms 3-5 will be dependent upon the results of the Week 24 analyses
(efficacy, safety, and pharmacokinetics) in Stage 1 and Study AI468038. This will minimize the 
risk of virologic failure and resistance to subjects enrolled in Arms 3-4 because clinical data will 
already have been generated using BMS-955176 with ATV/r (Arm 1) in Stage 1.
Of note, the other ARVs used in this clinical trial have a known and acceptable risk benefit ratio 
and are frequently prescribed to HIV-1 infected adults as a part of standard of care.
Taken together, the clinical data to date show that BMS-955176 has potent antiretroviral activity 
and is generally safe and well tolerated in healthy volunteers and HIV-1 infected adults. These 
factors should allow subjects to benefit from achieving viral suppression whilst taking a 
generally safe and well-tolerated new antiretroviral; additionally subjects in Arms 1, 3, and 4 
may benefit from a cART regimen that is nucleoside and nucleoside/booster sparing, 
respectively. Specifically, these subjects may benefit from improved bone mineral density, renal 
function, and lipid profiles. The risks, including teratogenicity, GI toxicity, and drug resistance, 
will be appropriately managed by following guidance in the study protocol.
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
2.2
Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The 
Revised Protocol No.: 03
Date: 17-Mar-2016
36


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure 
or product labeling information to be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form which will include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
1) Provide a copy of the consent form and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language 
must be non-technical and easily understood. 
2) Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study.
3) Obtain an informed consent signed and personally dated by the subject or the subject's 
legally acceptable representative and by the person who conducted the informed consent 
discussion.
4) Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
5) If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his 
or her informed consent during the study, consent must additionally be obtained from the 
subject.
6) Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject's willingness to continue participation in the study. This communication should be 
documented.
Revised Protocol No.: 03
Date: 17-Mar-2016
37


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to 
refuse participation in, or to be withdrawn from, the clinical study at any time should be 
considered by the investigator.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a randomized, active-controlled, staged, open-label clinical trial. Approximately 
200 treatment-experienced HIV-1 subjects will be randomized to one of five treatment arms
(approximately 40 per arm) in a staged fashion.
The data from the Week 24 analysis of Stage 1 and AI468038, including safety, efficacy and 
pharmacokinetics, will be examined to trigger the start of Stage 2 and confirm the two doses of 
BMS-955176 for study in Stage 2.
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with: 

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Revised Protocol No.: 03
Date: 17-Mar-2016
38


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.1.1
Screening
The screening period begins with the subject’s signature on the informed consent form (ICF).
The subject is then enrolled via the Interactive Voice Response System IVRS (or its web-based 
equivalent) See Section 4.4.
If the subject meets all eligibility criteria, the subject must be randomized within the 42 day 
screening period.*
* If, within the 42-day screening window, the resistance results have not yet been reported, the 
screening window may be extended up to 60 days for only these results.
3.1.2
Day 1/Baseline Visit
3.1.2.1
Day 1/Baseline Visit for Arms 1 and 2 - Stage 1
In Stage 1, approximately 80 subjects will be randomized 1:1 (approximately 40 per arm) to 
either of the treatment arms containing boosted atazanavir (ATV/r).
On the Day 1 Visit, subjects in Arms 1 and 2 will begin QD dosing with BMS-955176 or TDF, 
each in combination with ATV/r and DTG (see Section 4.5 for additional details of Selection and 
Timing of Dose).

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
3.1.2.2
Day 1/Baseline Visit for Arms 3, 4 and 5 - Stage 2
In Stage 2, approximately 120 subjects will be randomized 1:1:1 (approximately 40 per arm) to 
either of the two BMS-955176 treatment arms containing ATV, or to the TDF Arm.
On the Day 1 Visit, subjects will begin QD dosing with BMS-955176 in combination with ATV 
and DTG, or TDF in combination with ATV/r and DTG (see Section 4.5 for additional details of 
Selection and Timing of Dose).

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r QD 300/100 mg + DTG 50 mg QD
3.1.3
Week 2 Intensive PK Visit
Subjects with anemia, defined as Hemoglobin < 11.0 g/dL, should be excluded from 
participation in the Week 2 Intensive PK Substudy.
Subjects in all arms will have the opportunity to participate in an elective Intensive PK Substudy 
visit at Week 2 (window for visit: Day 12-16). Approximately 60 subjects, 12 subjects from each 
arm, are expected to participate in the substudy; BMS may allow the substudy to over-enroll in 
an effort to have a sufficient number of complete datasets.
Revised Protocol No.: 03
Date: 17-Mar-2016
39


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The series of 12 blood draws begins with pre-dose (0-hour) blood samples to be collected
approximately 24 hours (20-28 hrs) after the morning doses of study drugs that were taken on the 
day before. Ten more samplings are drawn through the 12-hr time point, with one final sampling 
collected at the 24-hr time point, requiring the subject to either remain overnight in the clinic, or 
to return the next morning; the final 24-hr sample will be collected prior to administration of the 
morning doses of study drugs (See Section 5.5.1).
PK Tools/Job Aids will be provided to assist with the proper sequencing of dosing and blood 
sample collections, as well as the collection of required data.
3.1.4
Visits Week 4 - 96
Subjects are expected to be treated for the duration of 96 weeks. In each Stage, after Day 1 and 
the optional Intensive PK visit at Week 2, subjects will be required to attend 12 more in-clinic 
study visits over the 96-week treatment period, as follows:

Visits are conducted every 4 weeks from Week 4 through Week 16

Visits are conducted every 8 weeks from Week 24 through Week 48

Visits are conducted every 12 weeks from Week 60 through Week 96
Visits should be scheduled as an interval from the Day 1/Randomization date, and within a 
window of 5 days earlier or later.
One of the visits Week 4 - 24 should meet the very specific timing requirements as outlined in 
Section 5.5.2 for a pre-AM dose blood collection.
Telephonic visits will be conducted with each subject at visit Weeks 20, 28, 36, 44, 54, 66, 78,
and 90 to conduct an adherence assessment and to continue retention efforts
3.1.5
Selection of the Continuation Dose of BMS-955176
3.1.5.1
Selection of the Continuation Dose, and the Switch for Stage 1
Once all subjects in Stage 1 have reached Week 24*, BMS will conduct an interim analysis of 
efficacy, safety, resistance and pharmacokinetics.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If Arm 1 meets 
criteria for Virologic Futility at Week 24, the clinical trial will be terminated.
The Week 24 analysis of Arms 1 and 2, combined with the Week 24 analysis of all Arms in the 
AI468038 study, will be used to select a Continuation Dose of BMS-955176 for Arm 1 in this 
study. Subjects in the BMS-955176 Treatment Arm 1 may subsequently be transitioned to a
selected Continuation Dose.
Subjects in the Arm containing TDF will continue with the TDF treatment regimen.
The assigned backbone will not change.
The Week 24 efficacy, safety, and pharmacokinetic analyses from Stage 1 and study AI468038 
will also trigger the start of Stage 2.
Revised Protocol No.: 03
Date: 17-Mar-2016
40


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
* If the Continuation Dose cannot be clearly identified using the Week 24 data, the study 
will continue in original fashion until an analysis of the Week 48 data can be performed 
and the Continuation Dose is selected. If a Continuation Dose cannot be selected based 
upon the Week 24 data, this does not preclude the ability to start recruitment of Stage 2.
After the Continuation Dose is selected, and once all of the logistics (eg, distribution of clinical 
drug supplies, activation of the new portion of the IVRS) have been completed globally, the 
transition of the subjects in Arm 1 to the Continuation Dose will occur. It is anticipated that this 
transition will occur on or after all subjects have reached Week 48 (the earliest subjects to begin 
study treatment could be well beyond Week 48 when the switch to the Continuation Dose 
occurs).
3.1.5.2
Selection of the Continuation Dose, and the Switch for Stage 2
Once all subjects in Stage 2 have reached Week 24, BMS will conduct an analysis of efficacy, 
safety, resistance and pharmacokinetics.
As described in Section 8.4.7, an analysis of Virologic Futility will also occur. If a BMS-955176 
dose arm meets criteria for Virologic Futility at Week 24, subjects in said arm will begin dosing 
with the next highest available remaining dose of BMS-955176.
The data from AI468038 and AI468048 (Stages 1 and 2) will be used to select a Continuation 
Dose of BMS-955176 for Arms 3 and 4. Subjects in the BMS-955176 Treatment Arms 3 and 4 
will subsequently be transitioned to a selected Continuation Dose. It is anticipated that this 
transition may occur on or after all subjects have reached Week 48, or it could occur sooner after 
Week 24.
The assigned backbone will not change.
Subjects in the arm containing TDF will continue with this assigned treatment regimen.
3.1.6
End of the study
The end of the study will occur when the last study visit has been completed, defined as the final 
subject completing their final study visit (expected to be a Week 96 or Early Termination visit).
The study design schematic is presented in Figure 3.1.6-1.
Revised Protocol No.: 03
Date: 17-Mar-2016
41


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Figure 3.1.6-1:
Study Design Schematic
Arm 2
TDF
300 mg QD
+ ATV/r + DTG
Day 1
Begin dosing
Arm 3
BMS-955176 
120 mg QD
+ ATV + DTG
1 Virologic Futility will be evaluated at Week 24 
(see Section 8.4.7).  
Results of Week 24 Stage 1 AI468-048 & AI468-038 
Confirm the Start of Stage 2   
Arm 4
BMS-955176 
180 mg QD
+ ATV + DTG
40
40
Week 2
Week 24
Week 24 Analysis1
Intensive PK subset
4 Based on totality of data from both studies the 
Continuation Dose for Arms 3 & 4 may be 
identified.  
Number
Randomized
STAGE 2
Week 96
Week 96 Analysis/End of Study
Week 48
Week 48 Analysis
The Switch to the Continuation Dose4,3     
is expected to occur on or after Week 48, 
but could occur sooner.
Arm 1
BMS-955176 
120 mg QD
+ ATV/r + DTG
Week 2
Number
Randomized
Week 24
Week 24 Analysis1
Day 1
Begin dosing
Intensive PK subset
40
40
Week 48
Week 96
Week 48 Analysis
Week 96 Analysis/End of Study
The Switch to             
the Continuation Dose2,3
may occur on or after 
Week 48 
STAGE 1
BMS-955176
Continuation Dose QD 
+ ATV/r + DTG
Arm 5
TDF
300 mg QD
+ ATV/r + DTG
40
3 The actual switch of subjects of BMS-955176 
subjects to that Continuation Dose may occur when 
all of the subjects have reached at least Week 48 
(though it could occur sooner in Stage 2).
BMS-955176
Continuation Dose QD
+ ATV + DTG
2 Based on Week 24 data from Arms 1 & 2 and 
from AI468-038, the Continuation Dose for 
Arm 1 may be identified.  
Revised Protocol No.: 03
Date: 17-Mar-2016
42


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3.2
Post Study Access to Therapy
At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be 
eligible to receive BMS supplied study drug. Study drug will be provided via an extension of the 
study, a rollover study requiring approval by responsible health authority and ethics committee 
or through another mechanism at the discretion of BMS. BMS reserves the right to terminate 
access to BMS supplied study drug if any of the following occur: a) the marketing application is 
rejected by responsible health authority; b) the study is terminated due to safety concerns; c) the 
subject can obtain medication from a government sponsored or private health program; or 
d) therapeutic alternatives become available in the local market.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Ability to understand and sign a written informed consent form
2. Target Population
a) Antiretroviral treatment-experienced, defined as having documented evidence of having
failed at least 1 ARV regimen (with or without documented resistance)
i)
Failure could be due (but is not limited) to cART intolerance, sub-optimal adherence, 
or an adverse event
b) Screening Plasma HIV-1 RNA 400 copies/mL (An initial, pre-screening value from 
Investigator must demonstrate HIV-1 RNA > 40 c/mL)
c) CD4+ T-cell count > 50 cells/mm3
d) Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, 
FC < 2.2; DTG; TDF)
e) Estimated Life expectancy 1 year
Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued 
the study as a pre-treatment failure (ie, subject has not been randomized / has not been treated). 
If re-enrolled, the subject must be re-consented and assigned a new PID. (See Section 5.5.1 for 
additional details.)
3. Age and Reproductive Status
a) Males and non-pregnant females
b) At least 18 years of age, (or minimum age as determined by local regulatory or as legal 
requirements dictate)
c) Willingness to use approved highly effective methods of contraception (see below) to 
avoid pregnancy (female subjects who are WOCBP or female partners of male subjects 
who are sexually active with WOCBP)
Revised Protocol No.: 03
Date: 17-Mar-2016
43


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
d) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 
24 hours prior to the start of study drug.
e) Women must not be breastfeeding
f)
WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug BMS-955176 plus 5 half-lives of the study drug 
BMS-955176 (8 days) plus 30 days (38 days) post-treatment completion.
g) Males who are sexually active with WOCBP must agree to use a condom for the duration 
of treatment with study drug BMS-955176 plus 5 half-lives of the study drug 
BMS-955176 (8 days) post-treatment completion.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception. 
All subjects must agree to the use of a highly effective method of contraception as listed below.
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION FOR FEMALE SUBJECTS 
WHO ARE WOCBP, MALE SUBJECTS AND THEIR FEMALE PARTNERS (WHO 
ARE WOCBP)
Highly effective methods of contraception have a failure rate of < 1% when used consistently 
and correctly. WOCBP and female partners of male subjects, who are WOCBP, are expected to 
use one of the highly effective methods of contraception listed below. 
Study subjects who are WOCBP cannot use hormonal methods of contraception as one of the 
highly effective methods of contraception because there are data to show a lack of effectiveness 
of systemic hormonal contraceptives in women taking BMS-955176. However, WOCBP can 
continue to use hormonal contraceptives, if necessary, in addition to one other non-hormonal 
highly effective methods of contraception.  
Male subjects must inform their female partners who are WOCBP of the contraceptive 
requirements of the protocol and are expected to adhere to using contraception with their partner. 
Relevant exposure of BMS-955176 in female partners of male participants in the study is 
expected to be negligible. Female partners of male subjects participating in the study may use 
hormone based contraceptives as one of the acceptable methods of contraception because 
exposure to the investigational product would be too small to alter exposure of hormonal 
contraceptives.
1. IUDs
2. Bilateral tubal occlusion
3. Vasectomised partner with documented azoospermia 90 days after procedure
o
Vasectomised partner is a highly effective birth control method provided that partner is 
the sole sexual partner of the WOCBP trial participant and that the vasectomised partner 
has received medical assessment of the surgical success.
Revised Protocol No.: 03
Date: 17-Mar-2016
44


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4. Complete abstinence
o
Complete abstinence is defined as the complete avoidance of heterosexual intercourse 
when this is the preferred lifestyle of the patient.
o
Complete abstinence is an acceptable form of contraception for all study drugs and must 
be used throughout the duration of study and for the duration of time as specified above.
o
It is not necessary to use any other method of contraception when complete abstinence is 
elected.
o
Subjects who choose complete abstinence must continue to have pregnancy tests. 
o
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the subject chooses to forego complete abstinence
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject.
3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a) Antiretroviral treatment-experienced adults who have failed < 1 ARV regimen
b) Resistance or partial resistance to any study drug
c) Three or more of the following PI mutations, historical or documented: M36I/V, 
M46I/L/T, G48M/V, I54V/L/T/M/A, G73S/A/C/T, V82A/F/T/S/I, or L90M
d) Any major ATV mutations, historical or documented: I50L, I84V/A, N88D/S
e) Any major TDF mutation, historical or documented: K65R or T69ins
f)
Three or more of the following non-accessory thymidine analogue mutations (TAMs): 
M41L, D67N, K70R, L210W, T215Y/F, K219Q/E
g) Any major mutations for raltegravir (RAL), elvitegravir (or clinically suspected INI 
resistance), historical or documented: T66IAK, E92Q, S147G, N155H, Q148H/K/R, 
Y143C/H/R, E157Q
h) Antiretroviral treatment-experienced adults infected with Clade AE
i)
Patients who have failed a previous boosted PI- or Integrase strand transfer inhibitor 
(INSTI)-containing regimen for which resistance analyses were not conducted at the time 
of failure
j)
Prior exposure to BMS-955176
2. Medical History and Concurrent Diseases
a) A new AIDS defining condition diagnosed within the 30 days prior to screening
(see Appendix 2)
b) Any other clinical condition (including but not limited to active substance use) or prior 
therapy that, in the opinion of the Investigator, would make the subject unsuitable for the 
study; unable to comply with dosing requirements; or unable to comply with study visits; 
or a condition that could affect the absorption, distribution, metabolism or excretion of 
the drug.
Revised Protocol No.: 03
Date: 17-Mar-2016
45


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
3. Physical and Laboratory Test Findings
a) Chronic HBV/HCV (Positive blood screen for HBsAg; Positive blood screen for HCV 
Ab and HCV RNA)
b) ALT or AST > 3 × ULN
c) Alkaline Phosphatase > 5 × ULN
d) Bilirubin 1.5 × ULN
e) History of decompensated cirrhosis or active decompensated cirrhosis
f)
Hemoglobin < 8.0 g/dL
g) Platelets < 50,000 cells/mm3
h) Estimated eGFR < 60 mL/min (CKD-EPI formula)
i)
Confirmed QT value > 500 msec at Screening or Day 1
j)
Confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or 
Day 1
k) Confirmed PR Interval > 260 msec (severe first degree AV block) at Screening or Day 1
l)
Confirmed second or third degree heart block at Screening or Day 1
4. Allergies and Adverse Drug Reaction
a) Medications contraindicated for use with investigational/non-investigational study drugs 
(ATV, RTV, DTG, TDF);
or subjects with any known allergies to the 
investigational/non-investigational study drugs (ATV, RTV, DTG, TDF)
b) Current or anticipated treatment with any of the medications listed in Appendix 1, in 
addition to any medications that are contraindicated with ATV, RTV, DTG or TDF
c) Participation in an experimental drug and/or HIV-1 vaccine trial(s) within 30 days prior 
to Screening
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
A woman of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 years in the absence of other biological or physiological causes. In 
addition, females under the age of 55 years must have a serum follicle stimulating hormone, 
(FSH) level > 40 mIU/mL to confirm menopause.
Revised Protocol No.: 03
Date: 17-Mar-2016
46


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. If the serum FSH level is > 40 mIU/mL at any time 
during the washout period, the woman can be considered postmenopausal:

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Refer to Appendix 1 which details prohibited and precautionary therapies during the study, 
including specifics about the use of antacids and hormonal methods of contraception.
3.4.2
Other Restrictions and Precautions
None.
3.5
Discontinuation of Subjects following any Treatment with Study Drug 
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject

Termination of the study by Bristol-Myers Squibb (BMS)

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Pregnancy (subjects should be discontinued in an appropriate manner)

Repeat non-adherence by the subject with the requirements of the protocol or treatment
(as determined by Investigator in consultation with the BMS Medical Monitor)

Evidence of Hepatitis B or C infection

Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8

Confirmed plasma HIV-1 RNA 1000 c/mL after Week 24

Confirmed plasma HIV-1 RNA 200 c/mL after Week 48

Emergence of genotypic and/or phenotypic resistance to any component of the study 
treatment regimen at any time after Screening

Subject requires switching to any other ARV
Revised Protocol No.: 03
Date: 17-Mar-2016
47


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Development of pDILI (potential drug induced liver injury)

Confirmed QTcB or QTcF value > 500 msec

Confirmed second degree (Type II) or third degree AV block at any time during the study
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event. The study drug will be permanently discontinued in an 
appropriate manner.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Section 5 (ie, perform an Early Termination [ET] visit). The only 
exception to this requirement is when a subject withdraws consent for all study procedures 
including post-treatment study follow-up (no such period exists in this study) or loses the ability 
to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either a 
psychiatric or physical illness).
If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post Study Drug Study Follow up
Subjects who discontinue study drug may continue to be followed.
Subject’s contact information will be collected/confirmed throughout the study so that subjects 
who discontinue study drug may continue to be followed for resolution of a pregnancy or SAE.
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug will remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. In 
the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
Revised Protocol No.: 03
Date: 17-Mar-2016
48


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study. The site staff and representative will consult publicly available sources, such as public 
health registries and databases, in order to obtain updated contact information. If after all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
4
STUDY DRUG
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
Revised Protocol No.: 03
Date: 17-Mar-2016
49


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 4-1:
Study Drugs for AI468048:
Product Description / 
Class and Dosage Form
Potency
IMP/Non-IMP
Blinded or 
Open Label
Packaging/ Appearance
Storage Conditions
(per label)
BMS-955176 
60 mga
IMP
Open Label
Bottle/
A white to off-white, biconvex, 
oval shaped film coated tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
BMS-955176
120 mga
IMP 
Open Label
Bottle/
A white to off-white, biconvex, 
capsule shaped film coated tablet
Store at 2 - 30°C
Protect from light.
Store in a tightly closed container.
Tenofovir (TDF)
300 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Atazanavir (ATV)
200 mg
IMP
Open Label
Bottle/
Blue cap and blue body
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Atazanavir (ATV)
300 mg
IMP
Open Label
Bottle/
Red cap and blue body,
printed with white ink
Store at 15 - 30°C
Store in a tightly closed container.
Ritonavir (RTV)
100 mg
Non-IMP
Open Label
Various packaging configurations
Refer to label on
container or package insert.
Dolutegravir (DTG)
50 mg
Non-IMP or 
IMP,
depending on 
country 
approval status.
Open Label
Various packaging configurations
Refer to label on
container or package insert.
a The 180 mg dose of BMS-955176 will be constructed with BMS-955176 60 mg + BMS-955176 120 mg
Revised Protocol No.: 03
Date: 17-Mar-2016
50


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, investigational product(s) is/are: BMS-955176, ATV, and DTG (in countries 
where DTG has not been approved for use). These products will be supplied.
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be 
considered as non-investigational products.
In this protocol, noninvestigational product(s) is/are: TDF, RTV, and DTG (in countries where 
DTG is approved for use). These products will be supplied.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be 
dispensed and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
that includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations.
4.4
Method of Assigning Subject Identification
At the start of the screening period, the investigative staff will call the Assignment Center via an 
Interactive Voice Response System ([IVRS], or its web-based equivalent) designated by the 
sponsor to enroll the subject and to obtain a subject patient identification number (PID).
For subjects who meet the protocol eligibility criteria, the investigative staff will call the IVRS 
and subjects will start treatment.
Revised Protocol No.: 03
Date: 17-Mar-2016
51


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Subjects will be randomly assigned in the staged fashion to one of the treatment arms, as
described in Section 3 and as outlined in the AI468048 Study Schematic Figure 3.1.6-1.
Note: All efforts should be made to limit the possibility of randomizing subjects that do not start 
treatment. If a subject is randomized but does not receive study medication, the BMS study team 
must be notified immediately.
4.5
Selection and Timing of Dose for Each Subject
Subjects will be randomized into the treatment arms in a staged fashion described in Section 3.1.
Stage 1:
In Stage 1, subjects will be randomly assigned 1:1 to one of two treatment arms and on Day 1 
will begin dosing with:

Arm 1 : BMS-955176 120 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD, or

Arm 2: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
Stage 2:
In Stage 2, subjects will be randomly assigned 1:1:1 to one of three treatment arms and on Day 1 
will begin dosing with:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD
4.5.1
Instructions for Dose Administration
4.5.1.1
General Instructions

Subjects should administer doses of each drug from only one bottle at a time, until that bottle 
is empty, before another bottle may be opened. 

Subjects will be required to complete Dosing Diaries so that drug administration can be 
accurately accounted. It is important that sites provide instructions to subjects for completion 
and obtain their acknowledgment that doing so provides critical information for the clinical 
trial.

Dosing times (and study appointment times) must be carefully considered through Week 24 
due to the requirements of the PK collection outlined in Section 5.5.
4.5.1.2
Specific Dosing Instructions for Initial Treatment Arm Assignment
In the morning, with a meal, subjects will take the following:

Arm 1: One pill each from bottles BMS-955176 120 mg, ATV, RTV, and DTG

Arm 2: One pill each from bottles TDF, ATV, RTV and DTG
Revised Protocol No.: 03
Date: 17-Mar-2016
52


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Arm 3: One pill each from bottles BMS-955176 120 mg, DTG, and two pills from bottle
ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 4: One pill each from bottles BMS-955176 60 mg, BMS-955176 120 mg and DTG, and 
two pills from bottle ATV (the unboosted dose of ATV is 400 mg, achieved by 200 mg x 2)

Arm 5: One pill each from bottles TDF, ATV, RTV and DTG
4.5.2
Dose Modifications
No dose adjustments or changes in intake frequency are allowed for any of the assigned study 
drugs in the protocol, except for the unique case of treatment-limiting renal toxicity which limits 
the use of the TDF. In the event of treatment-limiting renal toxicity, dose interval adjustments for 
TDF are permitted according to the local package insert/label, and only after the completion of 
the Week 2 Intensive PK optional Visit, if the subject is inclined to participate.
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Treatment Adherence to the treatment regimen will be critical to the conduct of this study. 
Adherence will be evaluated by the investigative staff at every treatment visit (including 
telephone contact visits) through interviews with the subjects and through examination of 
returned medication. It is expected that site staff attempt to have subjects maintain 90% 
treatment compliance or greater. Subjects should be instructed to bring all unused study 
medication back in the original container to each visit. Site staff are required to review Dosing 
Diaries completed by the subject, and to reinforce their use.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible Study Monitor unless study drug containers must be immediately destroyed as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:

On-site disposal practices must not expose humans to risks from the drug

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request
Revised Protocol No.: 03
Date: 17-Mar-2016
53


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor must be documented

Accountability and disposal records are complete, up-to-date, and available for the Monitor 
to review throughout the clinical trial period
If conditions for destruction cannot be met the responsible Study Monitor will make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible Study Monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
Revised Protocol No.: 03
Date: 17-Mar-2016
54


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)a
Notes
Eligibility Assessments
Informed Consent
X
Call IVRS to Enroll the subject; PID assigned
X
Inclusion/Exclusion Criteria
X
Medical History
X
AIDS History
X
Non-Laboratory Safety Assessments
Full Physical Examination
X
See Section 5.3.1 for requirements
Vital Signs & Physical Measurements
X
See Section 5.3.1 for requirements
Pre-treatment events
X
Only CDC Class C events with onset during the Screening period
Serious Adverse Events Assessment
X
All SAEs that occur after the ICF has been signed should be reported
ECG
X
See Section 5.3.4 for requirements
Pregnancy Test
X
WOCBP
For females under age 55, an FSH level must be on record to confirm she 
is not a WOCBP if pregnancy testing is not being performed.
If positive urine, request serum hCG quant. on lab requisition.
Laboratory Assessments (See Appendix 5 for full details)
Fasting Chemistry and Lipid Panel
X
Fasting overnight
Hematology
X
Urinalysis
X
Revised Protocol No.: 03
Date: 17-Mar-2016
55


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-1:
Screening Procedural Outline (AI468048)
Procedure
Screening Visit
(42-day screening period)a
Notes
Plasma HIV-1 RNA
X
This is the confirmatory HIV-1 RNA
(The first value is provided by the PI)
CD4+ and CD8+ T-cell count
X
HBV Surface Antigen
X
HCV Serology
X
Urine toxicology (drugs of abuse)
X
Could aid in the selection of appropriate study candidates.
Pharmacodiagnostic (PDx) sampleb
X
Plasma collection to be banked for potential future use in development of 
novel predictive assay(s)
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
Proper collection of the full volume of plasma outlined in the lab manual 
will allow for repeat testing of the sample if assay steps fail during 
testing.a
Gag assays are not performed in real-time, and Gag results are not used to 
assess eligibility
PhenoSense Gag
X
Next Generation Seq. - Qs Gag
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
Molecular analysis at BMS WFD Discovery of baseline resistant samples 
and baseline sensitive controls in cases of subsequent on-treatment 
virologic failure
a If the PSGT + Integrase resistance assay cannot be resulted within 42 days, the Screening window can be extended up to 60 days, and solely for this procedure 
to allow time for Monogram to complete the testing.  
b By definition, a pharmacodiagnostic sample (PDx) is a pre-treatment test to determine whether or not a patient is likely to respond to a drug (ie, a predictive 
test). Based on the results of clinical studies with BMS-955176, BMS may have to develop a PDx assay. Thus, PDx samples obtained at Screening in this 
study would be used for that sole purpose.
Revised Protocol No.: 03
Date: 17-Mar-2016
56


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Eligibility Assessments
Inclusion/Exclusion Criteria
X
Non-Laboratory Safety Assessments
Full Physical Examination
WK 12, 24, 48, 96/ET
See Section 5.3.1 for requirements
Targeted Physical Examination
X
WK 4, 8, 16, 32, 40, 60, 72, 84
See Section 5.3.1 for requirements
Vital Signs & Physical 
Measurements
X
X
See Section 5.3.1 for requirements
Adherence Assessments
X
X
Including review of Dosing Diaries
Pre-treatment Events
X
See Table 5.1-1
Adverse Events Assessments
X
X
X
Serious and Non-serious AEs
Concomitant Medications
X
X
X
See Section 5.3.3
ECG
X
WK 4, 12, 24, 48, 96/ET
See Section 5.3.4 for requirements
Pregnancy Test
X
X
X
For females under age 55, an FSH 
level must be on record to confirm 
she is not a WOCBP if pregnancy 
testing is not being performed.
If positive urine, request serum 
hCG quant. on lab requisition.
Revised Protocol No.: 03
Date: 17-Mar-2016
57


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Provide WOCBP with Home 
Pregnancy test kit(s) to be used 
during the in-clinic visit interval
WK 16, 24, 32, 40,
48, 60, 72, 84
Provide One Kit at Weeks 16 - 40
Provide Two Kits at Weeks 48 - 84
WOCBP subjects perform test Q4 
weeks at home and report results to 
site.
Laboratory Assessments for Safety and Efficacy and Other Endpoints (See Appendix 5 for full details)
Fasting Chemistry
X
X
Fasting overnight
Fasting Lipid Panel
X
WK 4, 12, 24, 48, 96/ET
Fasting overnight
Hematology
X
X
Urinalysis
X
X
Fractional Excretion of Phosphorous 
(FePO4)
(Urine creatinine and phosphorus, 
Serum creatinine and phosphorus)
X
WK 48 and 96/ET
Plasma HIV-1 RNA
X
X
X
If collecting an HIV-1 RNA at an 
UNSCHEDULED visit, also collect 
samples for Resistance and 
Exploratory Resistance Testing
CD4 and CD8 T-cell counts
X
X
HBV Surface Antigen
WK 48 and 96/ET
HCV Serology
WK 48 and 96/ET
Positive HCV Ab will reflex to 
HCV RNA
Revised Protocol No.: 03
Date: 17-Mar-2016
58


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
Resistance Testing
(HIV-1 Drug Resistance)
PhenoSense GT Plus Integrase
X
X
Samples stored and tested if needed
(ie, analyses of subjects if deemed 
clinically relevant)
See Section 5.4.2.2
PhenoSense Gag
X
X
Next Generation Seq. - Qs Gag
X
X
Exploratory Resistance
(HIV-1 Drug Resistance)
X
X
Samples stored and tested 
retrospectively if needed (ie,
exploratory analyses for subjects if 
deemed clinically relevant)
Intensive PK sample collection
X
Use of PK Tools for data collection 
recommended.
See Section 5.5.1 for requirements
Sparse PK sample collection
WK 4, 8, 12, 16, 24
See Section 5.5.2 for requirements
Bone Biomarkers
(P1NP and CTX)
X
WK 12 and 24/ET
Serum collection
Renal Biomarkers
(2-microglobulin and creatinine)
X
WK 48 and 96/ET
Urine collection
Backup Serum and Plasma Sample
X
X
Samples stored and tested if needed
Outcomes Measures
EQ-5D-3L Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Health Outcomes Questionnaire
Revised Protocol No.: 03
Date: 17-Mar-2016
59


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 5.1-2:
Short-term Procedural Outline (AI468048)
Procedure
In-clinic 
Visit
Day 1
In-Clinic Visit 
Optional 
Week 2 for 
Intensive PK
(Day 12-16)
In-Clinic Visits
Weeks 4, 8, 12, 16, 24, 32, 40, 
48, 60, 72, 84, 96, and/or 
Early Termination (ET)
(5 days)
Phone Visits
Weeks 20, 
28, 36, 44, 
54, 66, 78, 90
(5 days)
Notes
FAHI Form
X
WK 12, 24, 32, 40, 48,
60, 72, 84, 96
Functional Assessment of HIV 
Infection
Clinical Drug Supply
Call IVRS to Randomize
X
Dispense Study Drug
X
X
There is no dispensation at Week 96 
or ET.
Revised Protocol No.: 03
Date: 17-Mar-2016
60


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory 
value). The Screening Period for this study is 42 days (see Table 5.1-1, Table Note a, for the 
single parameter for which the screening period may be extended).
Any new result will override the previous result (ie, the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. Consultations 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant (eg, a previously failed inclusion criterion).
Rescreening is different than Retesting. Rescreening is the process of Re-enrollment and requires 
that all procedures be repeated in an entirely new screening period. A one-time Rescreening is 
permitted, if further rescreening is considered for reassessment of enrollment eligibility this 
should be discussed with the Medical Monitor.
The assigned patient identifier (PID) for the subject must be Screen Failed in the IVRS. A new 
call must be made to the IVRS for the assignment of a new PID for the subject, and all Screening 
parameters must be done again in reference to the new PID (See Section 3.3.1, Inclusion 
Criteria 2f). Subject must also be re-consented with the new PID.
5.2
Study Materials
The sponsor will provide each investigative site with the following:

BMS-955176 Investigator Brochure (IB) and any relevant safety addenda or updates

Protocol and any Amendments to the Protocol

Instructions for completing electronic Case Report Forms (eCRFs)

Laboratory Manual from the central laboratory

ECG Machines and manual

IVRS Worksheets to complete when calling the IVRS center to enroll, randomize, and 
discontinue subjects

Patient-reported Outcomes Questionnaires: EQ-5D-3L Health Outcome Questionnaire, FAHI 
(Functional Assessment of HIV Infection)

PK Tools/Job Aids that may be used for detailed instruction about the PK visits, and as a 
comprehensive source for documents of date/times of dosing and blood sampling

Dosing Diaries

Completion by subjects is required

Should include daily dose of study medications administered by subject, modified or 
missed
Revised Protocol No.: 03
Date: 17-Mar-2016
61


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Site staff should review the diaries with the subject at each visit, and, in combination with 
detailed questioning, should be able to provide comprehensive information in the case 
report form, noting discrepancies in the subject’s file. Dosing Diaries should be 
maintained in the subject’s study file.
5.3
Safety Assessments
The investigative team should follow the protocol-specified scheduled of safety-related 
measurements. Only data for the procedures and assessments specified should be submitted to 
BMS on the case report form. Additional procedures and assessments may be performed as part 
of standard of care, however, data for these assessments should remain in the subject’s medical 
record and should not be submitted to BMS, unless specifically requested (ie, as part of an SAE).
5.3.1
Vital Signs and Physical Examinations
The schedule of vital signs, physical examinations, and targeted physical examinations is 
provided in Section 5.1 (Flow Chart/Time and Events Schedule). Vital signs include heart rate, 
blood pressure, respiration rate, and temperature and should be measured after the subject has 
been sitting/resting for at least 5 minutes. Physical measurements include height and weight. 
Targeted physical examinations will include examination of the heart, lungs, skin, abdomen, any 
symptomatic organ system, and general appearance.
5.3.2
Adverse Events
Subjects will be closely monitored throughout the study for any new or ongoing HIV-related 
diagnoses (Appendix 2) and/or adverse events. CDC Class C events that occur from the 
Screening Visit through Day 1 (prior to dosing), will be recorded as Pre-treatment Events. All 
events that occur after dosing on Day 1 will be recorded on the appropriate Adverse Event eCRF. 
Additional information on Adverse Events is provided in Section 6.
5.3.3
Concomitant Medication Assessment
All medications taken from the Screening Visit throughout the duration of the study will be 
reported. In addition, any prior therapy with antiretroviral drugs will be reported
(See Appendix 1 for Prohibited and Precautionary Therapies).
5.3.4
Electrocardiograms
The schedule of electrocardiograms (ECGs) is provided in Section 5.1 (Flow Chart/Time and 
Events Schedule). ECG machines will be provided by a central vendor who will also perform the
read/interpretation of the output.
5.4
Efficacy Assessments
5.4.1
Primary Efficacy Assessment
The primary assessment for efficacy is HIV-1 RNA at Week 24.
Revised Protocol No.: 03
Date: 17-Mar-2016
62


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.1
Guidelines for Confirmatory Testing of Plasma HIV-1 RNA and 
Resistance testing
A confirmatory HIV-1 RNA viral load should be obtained when:

HIV-1 RNA 40 c/mL if prior suppression 40 c/mL, or

> 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is 
40 c/mL
All efforts should be made to collect this sample within 2-4 weeks from the collection of the 
original sample.
When collecting a blood sample for HIV-1 RNA testing at an Unscheduled visit, samples should 
also be collected for the sets of Resistance and Exploratory Resistance Tests, so that the samples
are available should resistance testing be required or deemed necessary based on the result of the 
HIV-1 RNA test.  
Table 5.4.1.1-1:
Management of Detectable HIV-1 RNA, based on Confirmed 
(2-4 weeks from original sample) or Consecutive HIV-1 RNA 
Resulta
Day 1 through Week 24
40 - 399 c/mL
Reinforce Adherence
400 c/mL
Consider the need for resistance testing, in consultation with BMS Medical Monitor.
Consider possible discontinuation of subject, in consultation with BMS Medical Monitor, 
and/or reinforce adherence.
After Week 24 through Week 48
40 - 399 c/mL
Reinforce Adherence
400 - 999 c/mL
Resistance testing will be performed.
If resistance has developed, subject must be discontinued.
If resistance has not developed, consider possible discontinuation of subject, in consultation 
with BMS Medical Monitor, and/or reinforce adherence.
1000 c/mL
Resistance testing will be performed.
Regardless of result of resistance tests, subject must be discontinued (see Section 3.5).
After Week 48
40 to < 200 
c/mL
Reinforce Adherence
200 c/mL
Subject must be discontinued (see Section 3.5). 
If 400 c/mL, consider the need for resistance testing, in consultation with BMS Medical 
Monitor.
a When discontinuation is required or otherwise warranted and resistance results are needed, subject may continue 
on study medication/on study until resistance testing results are available.
Revised Protocol No.: 03
Date: 17-Mar-2016
63


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
5.4.1.2
Protocol Defined Virologic Failure
Protocol Defined Virologic Failure (PDVF) is defined by a subject meeting one of the following 
criteria:
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir 
is 40 c/mL
2) Confirmed HIV-1 RNA 400 c/mL after Week 24
3) Confirmed HIV-1 RNA 40 c/mL if prior suppression to < 40 c/mL
4) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 
week snapshot window
5) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8
In addition to the clinical management outlined in section 5.4.1.1, samples meeting criteria for 
PDVF will also be sent for resistance and exploratory resistance testing.
5.4.2
Secondary Efficacy Assessments
5.4.2.1
CD4+ and CD8+ T-Cells
CD4+ and CD8+ T-cells counts and percentages will be assessed using flow cytometry. The 
schedule of assessments is provided in Section 5.1 (Flow Chart/Time and Events Schedule). 
Procedures for samples collection and processing are provided in the central clinical laboratory 
manual.
5.4.2.2
Drug Resistance Testing
Plasma samples for viral drug resistance testing will be collected at Screening for all subjects and 
the HIV-1 drug resistance genotype will be analyzed to rule out resistance to any component of 
the study regimen or specific resistance mutations as outlined in Section 3.3.2, Exclusionary 
Criteria. At subsequent visits, samples for emergent drug resistance testing (both genotypic and 
phenotypic) will be collected and stored to be as outlined in Section 5.4.1.
5.5
Pharmacokinetic Assessments
It is extremely important to record the exact dose and time of the dose(s) taken the day prior to 
the visit/collection, and the exact date and time of the sample collection, even if drawn slightly 
off-schedule.
5.5.1
Intensive Pharmacokinetic Assessment
A subset of subjects (about 12 subjects per treatment group) will participate in an optional 
Intensive PK assessment at Week 2 (window Day 12-16).
Intensive PK samples collected in this study will provide for the assessment of BMS-955176, 
ATV, RTV, and DTG to support the secondary and exploratory objectives (to characterize the 
PK of BMS-955176, DTG, and ATV (with or without RTV) when given in combination, and to 
compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV).
Revised Protocol No.: 03
Date: 17-Mar-2016
64


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Intensive PK sampling begins with a morning pre-dose (0 hour) sampling, ie, prior to the 
administration of the morning doses of the study drugs on the day of the visit. The sampling 
should also begin 24 hours (between 20 and 28 hours) after the morning doses of the study drugs 
that were taken the day prior to the visit.
The subsequent 11 time points include samplings through Hour 12, with the last sample collected 
at Hour 24. The subject will either stay overnight or will return to the clinic so that the final 
sample can be collected at Hour 24.
It is critical to capture the exact date and time of each PK sample collection, even if drawn 
slightly off-schedule. There is no specified collection window end for which any one time point 
should be abandoned as the schedule progresses. If a sample collection time point is missed/late 
and the next collection time point has not yet been reached, collect the missed time point, and 
record the exact time of that collection, then get back on track for the next time point/on-time 
collection.
Table 5.5.1-1 lists the sampling schedule to be followed for the assessment of intensive 
pharmacokinetics. Further details of PK blood collection and sample processing will be provided 
in the central clinical laboratory manual.
Table 5.5.1-1:
AI468048 Intensive Pharmacokinetic Sampling Schedule at Week 2
Time 
(Event)
Time 
(Relative to Dosing)
Hour: Min
PK
Blood Sample
Study Week 2
(window Day 12-16)
0 (morning pre-dose)
00:00
X
1 Hr
01:00
X
2 Hr
02:00
X
2.5 Hr
02:30
X
3 Hr
03:00
X
4 Hr
04:00
X
4.5 Hr
04:30
X
5 Hr
05:00
X
6 Hr
06:00
X
8 Hr
08:00
X
12 Hr
12:00
X
24 hr (morning pre-dose)
24:00
X
5.5.2
Sparse Pharmacokinetic Assessments
All subjects will provide Sparse PK samples (as part of the regular blood collection) for the 
assessment of BMS-955176, ATV, RTV and DTG at visit Weeks 4- 24.
Revised Protocol No.: 03
Date: 17-Mar-2016
65


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Of the five visits (Week 4 - 24), it is requested that the following guidelines are followed:

At any one visit Week 4 through Week 24, the Sparse PK sample must be collected 
approximately 24 hours (between 20 and 28 hours) after the dose that was taken the morning 
before and before the morning dose is taken on the day of the visit

At the remaining four visits Week 4 through Week 24, the blood collections may be done 
without any specific consideration to timing of previous dose administration (taken either the 
day before the visit or on the day of the visit), though it is critical that the date and time of the 
most previous dose of study drug is recorded in the eCRF so that the exact interval between 
dose and blood sampling can be calculated for accurate PK analysis
PK Samples need to be tested on an ongoing basis prior to the Week 24 database lock and 
analysis.
5.6
Biomarker Assessments
In this study, BMS is confirming the safety of BMS-955176 demonstrated in the Phase 2a study 
to date. The proposed sample population of treatment-experienced adults in Arms 3, 4, and 5, 
will provide a representation of the potential benefits of BMS-955176 on nucleoside and RTV 
based toxicities of interest (ie, renal toxicity, bone mineral density, and dyslipidemia): Arms 3 
and 4 relative to Arms 1, 2, and 5.
Specifically, to evaluate for renal toxicity we will evaluate clinically relevant parameters and 
biomarkers for glomerular and tubular toxicity, which may include but are not limited to: 
fractional excretion of phosphorous and urinary β2-microglobulin/creatinine, in all available 
subjects. To evaluate for bone-related toxicity, clinically relevant bone biomarkers for both 
formation and resorption will be evaluated in all available subjects. These may include but are 
not limited to: N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked 
C-telopeptide of Type 1 collagen (CTX). The bone and renal biomarkers will be collected and 
measured at time points specified in Table 5.1-2 Additionally, back-up plasma and serum 
samples (at Baseline, Week 24, and Week 48) will be obtained for potential future evaluation of 
the safety of BMS-955176.
Samples will be collected at the screening visit for HIV-1 Gag sequencing, phenotypic 
susceptibility (PhenoSense Gag) and potential pharmacodiagnostic analysis as specified in Table 
5.1-1. These samples may be analyzed, if deemed clinically relevant, as a predictive marker of 
clinical response.
Any remaining blood and urine specimens that are available after completion of the designated 
analyses may be used in the future for identification of potentially predictive or 
pharmacodynamic markers of study drug activity or to enhance the understanding around disease 
biology, except where prohibited by local laws or regulations.
5.7
Outcomes Research Assessments
Increases in CD4 counts and avoidance of opportunistic infections and other AIDS-defining 
illnesses have been shown in many studies to improve health related quality of life (HRQoL). To 
Revised Protocol No.: 03
Date: 17-Mar-2016
66


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
help assess whether use of BMS-955176 will result in a better quality of life outcome, both a 
disease specific quality of life assessment and a generic quality of life assessment will be 
administered. Disease specific instruments are more sensitive to disease specific changes in 
quality of life and are more likely to show improvement with new interventions. The generic 
instruments are needed because Health Technology Authorities often require use of these 
instruments for cost-effectiveness modeling.
The Functional Assessment of HIV (FAHI) is the disease specific instrument that will be used. 
The FAHI evaluates physical well-being, functional and global well-being, emotional 
well-being/living with HIV, social well-being and cognitive functioning. It yields a total score 
and individual subscale scores.
The EQ-5D-3L is the generic instrument that will be used. The EQ-5D-3L includes two parts: the 
EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L 
descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some 
problems, extreme problems. The EQ VAS records the respondents’ self-rated health on a 
100 point, vertical, visual analogue scale where the endpoints are labeled ‘Best imaginable health 
state’ and ‘Worst imaginable health state.’
5.8
Other Assessments 
We will obtain back-up plasma and serum samples for current/future evaluation of the efficacy, 
safety and tolerability of BMS-955176. 
Should any new safety signal develop during the course of the ongoing analysis of the Phase 2a 
trial, appropriate measures for evaluation and management will be incorporated into the design 
of the Phase 2b trial via a protocol amendment.
5.9
Results of Central Assessments
The following describes the centrally assessed parameters and the timing with which they will be 
shared with investigators, if pertinent. Some parameters are relevant to ongoing subject 
management during the study and will be provided to the site for such purpose, while others are 
not relevant to subject management during the study and results may only be shared in a 
summarized way at the end of the study.

Samples sent to the central lab vendors for safety and efficacy assessments and that are tested 
real time will be provided to the sites as soon as results are available

The results of the read of each ECG will be sent to the site by the central ECG vendor as 
soon as results are available

Samples collected on-treatment for resistance testing will be tested if deemed clinically 
relevant (eg, if the development of resistance is suspected). If tested, results will be reported 
to the site

Other samples (including but not limited to biomarker assessments, exploratory resistance, 
pharmacodiagnostics) may not be tested immediately, and may only be tested if deemed 
clinically relevant. Results may be suppressed from laboratory reports and may not be 
provided to the sites
Revised Protocol No.: 03
Date: 17-Mar-2016
67


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Individual PK results will not be reported to the site; the overall PK assessments will be 
included in the CSR

Individual assessments of the Outcomes research will not be reported to the site; the overall 
Outcomes assessments will be included in the CSR
6
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE). The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term "reasonable causal relationship" means there is evidence to suggest a causal 
relationship.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs).
6.1
Serious Adverse Events
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

results in death

is life-threatening (defined as an event in which the subject was at risk of death at the time of 
the event; it does not refer to an event which hypothetically might have caused death if it 
were more severe)

requires inpatient hospitalization or causes prolongation of existing hospitalization 
(see NOTE below)

results in persistent or significant disability/incapacity

is a congenital anomaly/birth defect

is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above).
Examples of such events include, but are not limited to, intensive treatment in an emergency 
Revised Protocol No.: 03
Date: 17-Mar-2016
68


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization). Potential drug induced liver injury (DILI) is also considered an 
important medical event. (See Section 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must
be handled as
SAEs. 
(See Section 6.1.1 for reporting pregnancies).
NOTE:
The following hospitalizations are not considered SAEs in BMS clinical studies:

a visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason)

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochure (IB) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
and within 30 days of discontinuation of dosing.
The investigator should report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure.
An SAE report should be completed for any event where doubt exists regarding its seriousness.
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship should be specified in the narrative section of the SAE Report Form.
Revised Protocol No.: 03
Date: 17-Mar-2016
69


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
SAEs, whether related or not related to study drug, and pregnancies, must be reported to BMS 
(or designee) within 24 hours. SAEs must be recorded on the SAE Report Form; pregnancies on 
a Pregnancy Surveillance Form (electronic or paper forms). The preferred method for SAE data 
reporting collection is through the eCRF. The paper SAE/pregnancy surveillance forms are only 
intended as a back-up option when the eCRF system is not functioning. In this case, the paper 
forms are to be transmitted via email or confirmed facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. The paper forms should be used and submitted immediately, only 
in the event the electronic system is unavailable for transmission. When paper forms are used, 
the original paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports should include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, a follow-up SAE report should be sent within 24 hours to the BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs should be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (paper or electronic) as appropriate:
Revised Protocol No.: 03
Date: 17-Mar-2016
70


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Any laboratory test result that is clinically significant or meets the definition of an SAE

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance 
Form to BMS Designee within 24 hours and in accordance with SAE reporting procedures 
described in Section 6.1.1.
The study drug will be permanently discontinued in an appropriate manner (eg, dose tapering if 
necessary for subject safety).
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important.
All occurrences of overdose must be reported as an SAE (see Section 6.1.1 for reporting details).
6.6
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
Potential drug induced liver injury in HIV-1 mono-infected subjects is defined as:
1. AT (ALT or AST) elevation > 3 times upper limit of normal (ULN)
AND
Revised Protocol No.: 03
Date: 17-Mar-2016
71


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3. No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic
6.7
Other Safety Considerations
Any 
significant 
worsening
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
6.7.1
Toxicity Management
The link to the current grading system for specific AEs and laboratory abnormalities is located in 
Appendix 3 (DAIDS; See Appendix 3).
6.7.1.1
Management of Elevations in Liver Transaminases
The following Table 6.7.1.1-1 summarizes the management of elevations in liver transaminases:
Table 6.7.1.1-1:
Management of Elevations in Liver Transaminases Grade Level of 
AST or ALT Recommendationsa
Grade
Recommendation
Grade1
None
Grade 2
none
Grade 3
Confirm elevation, evaluate for potential causes (including but not limited to alcohol or other 
substance abuse, concomitant medications, reactivation of existing or de novo infection with 
hepatitis viruses) consult with BMS Medical Monitor or designate as soon as possible.
Grade 4
Interrupt all study medications, evaluate for potential causes (including but not limited to alcohol 
or other substance abuse, concomitant medications, reactivation of existing or de novo infection 
with hepatitis viruses), monitor values frequently and consult with BMS Medical Monitor or 
designate as soon as possible. If Grade 4 is deemed related to study medication the subject must 
be discontinued from the study. Otherwise, if reinstitution of study therapy is considered, please 
obtain approval from the BMS Medical Monitor or designate.
a If persisting (> Grade 1/2), evaluate for alternative etiologies, including alcohol use and viral hepatitis
6.7.1.2
Management of Renal Toxicity
Serum phosphate levels and creatinine clearance (CrCl; CCL: as calculated by the Cockcroft 
Gault Equation [see Appendix 4] or eGFR) should be monitored and managed as described in the 
Viread local package insert/label.28 Dose interval adjustments of TDF (Viread) are permitted, as 
described in Section 4.5.2.
Revised Protocol No.: 03
Date: 17-Mar-2016
72


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
6.7.1.3
Management of Hyperbilirubinemia
Most patients taking ATV experience asymptomatic elevations in indirect (unconjugated) 
bilirubin related to inhibition of UDP-glucuronosyl transferase (UGT). Hepatic transaminase 
elevations that occur with hyperbilirubinemia should be evaluated for alternative etiologies. Dose 
modification of ATV is not permitted. Subjects who experience unacceptable jaundice/scleral 
icterus should be discussed with the BMS Medical Monitor or designate to determine if subjects 
are to be discontinued from study. The investigator must contact the BMS Medical Monitor or 
designate prior to discontinuing any subject due to hyperbilirubinemia.
6.7.1.4
Gastrointestinal Toxicity Evaluation and Management Plan
Pre-clinical toxicology studies in rats and dogs (see Section 1.4.1.2) have suggested a potential 
for GI related toxicity with BMS-955176. This section provides general guidance to the 
Investigator on the evaluation and management of primarily upper gastrointestinal symptoms. 
The Investigator may contact the Medical Monitor to discuss evaluation and management 
(including interruption of ARVs or discontinuation of a subject) of any GI symptoms throughout 
the trial.
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
HISTORY
For symptoms of all grades, a thorough history forms the foundation of proper 
evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical 
trial. 
Nausea and Vomiting
The investigator should attempt to identify the etiology of these symptoms (and whether 
it is intraperitoneal, extraperitoneal, medication related, infection related, or due to a 
metabolic disorder).33 Medications can cause nausea and vomiting acutely. 
Dyspepsia
The Investigator should identify the presence of red flags (odynophagia, unexplained 
weight loss, recurrent vomiting, GI bleeding, jaundice, palpable mass or adenopathy, or 
family history of GI malignancy). Symptoms of dyspepsia could include early satiety, 
bloating, or belching. Additionally, atypical symptoms of dyspepsia could include: 
pharyngitis, asthma, bronchitis, hoarseness, chest pain, or abdominal pain. 
Ulcerative Disease
Symptoms suggestive of ulceration often are intermittent over a period of weeks to 
months and may be relieved by eating or antacid use;34 penetrating ulcers become more 
acute with localized pain and may not improve with food.35 The development of 
perforation may be indicated by severe diffuse abdominal pain. 
Other Clinical 
Syndromes
Additional diagnostic criteria for other GI disorders potentially encountered in the 
clinical trial are available elsewhere.36
PHYSICAL 
EXAMINATION
Physical examination should complement elements obtained from the history34
Acutely, the investigator may assess for signs of intravascular volume depletion 
(eg, orthostasis) and/or aspiration of vomitus as appropriate. Abdominal 
tenderness and guarding may indicate inflammation. The presence of fecal blood 
can indicate mucosal damage (eg, from an ulcer). Complete evaluation of dyspepsia 
should include an oral examination (poor dentition or pharyngeal erythema) and 
lungs for wheezing. 
Revised Protocol No.: 03
Date: 17-Mar-2016
73


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
DIAGNOSTIC 
EVALUATION 
AND 
MANAGEMENT
A major goal in the diagnostic evaluation of a subject with upper GI symptoms is 
to quickly arrive at a final diagnosis without exposing the subject to unnecessary 
(invasive) testing; Investigators should exercise good clinical judgment35 in this 
regard. A major goal of therapy is directed at correcting the underlying 
identifiable medical or surgical abnormalities. Consultation (eg, gastroenterologist) 
is recommended as clinically indicated.
Grade 1 symptoms
Subjects may be treated symptomatically. If subjects develop dyspepsia alone, generally 
only limited and direct diagnostic testing should be performed.34 If the subject has 
dyspepsia they should limit alcohol, caffeine, chocolate, tobacco, other contributing 
concomitant medications (eg, NSAIDs) and eating directly before bedtime. A variety of 
OTC medications are available to address constipation and diarrhea as indicated. Please 
refer to Appendix 1 for Prohibited and Precautionary Therapies.
Grade 2 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

Serum chemistries and assessment of hemoglobin if not recently performed. 

Testing for Helicobacter pylori

Serologies (eg, celiac disease) 

PCR for viruses (eg, CMV)

Iron panel or Vitamin B12 level
For subjects who develop dyspepsia or are infected with H. pylori the use of H2 
antagonists, PPIs, Sucralfate, and antacids are prohibited (see Appendix 1 Prohibited 
Medications). If such therapy is required, discontinuation from the trial is necessary. 
The use of antiemetic’s (eg, Prochlorperazine) can be utilized as indicated. Management 
should be targeted at addressing the underlying pathology.
Grade 3 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

The testing outlined above in Grade 2

A fasting serum gastrin level can be obtained in cases of known ulcers refractory to 
therapy, a family history of the disease, or when surgery is required; of note, H. 
pylori can increase gastrin levels.35

A barium swallow to detect ulcers 

CT to identify gastrointestinal inflammation and a penetrating or perforated ulcer. 

Upper endoscopy with biopsy as indicated in order to evaluate dyspepsia further 
(eg, mucosal injury, new onset unexplained dyspepsia in subjects > 55 y/o, or the 
presence of red flags).
Management should be targeted at addressing the underlying pathology.
Grade 4 symptomsa
Diagnostic testing may include but is not limited to the following (as clinically 
indicated):

The testing outlined above in Grade 2 and Grade 3

An acute abdominal series

If a perforated ulcer is clinically suspected, surgical consultation may be necessary
Revised Protocol No.: 03
Date: 17-Mar-2016
74


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Table 6.7.1.4-1:
GI Toxicity Evaluation and Management
Initial management can include correction of hemodynamic and electrolyte 
abnormalities as clinically indicated. After stabilization, management should be targeted 
at addressing the underlying pathology.
a For Grade 2-4 symptoms if any ARV is thought to have a direct causal relationship to the patient’s 
gastrointestinal symptoms, the Investigator should consider discontinuing the subject from the study and 
performing an evaluation/management plan incorporating elements above. The Investigator can consider 
interruption of the potential offending ARV(s) but must balance this with the increased probability of 
development of viral resistance/lack of efficacy. As stated above, prior to discontinuing the subject from the 
study, attempts should be made to discuss with the BMS Medical Monitor unless the safety of the subject is 
acutely at risk.
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
This is an estimation study, without statistical testing, and hence there are no power 
considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere 
around 80%. With this response rate, and 40 subjects per arm, an exact 95% confidence interval 
would run from roughly 64% to 91%.
8.2
Populations for Analyses
The following definitions are used in this document:

Enrolled subjects: Subject who signed an informed consent form and were assigned a 
Patient Identification number (PID);

Randomized subjects: Enrolled subjects who received a treatment assignment from the 
IVRS;

Treated subjects: Randomized subjects who received at least 1 dose of BMS-955176 or 
TDF. (Also referred to as the mITT analysis set)
8.3
Endpoints
8.3.1
Primary Endpoint(s)Stage 1 and Stage 2
The primary endpoint for Stage 1 and Stage 2 is the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Week 24. This will be assessed with the FDA snapshot algorithm. This uses 
the last on-treatment plasma HIV-1 RNA measurement, within an FDA-specified visit window, 
to determine response. 
Revised Protocol No.: 03
Date: 17-Mar-2016
75


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
8.3.2
Secondary Endpoint(s)

The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 
RNA < 40 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm

The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 
RNA < 200 c/mL at Weeks 24, 48 and 96 using the FDA snapshot algorithm approach with 
positive response defined as HIV-1 RNA < 200 c/mL

The emergence of HIV drug resistance among samples sent for drug resistance testing will be 
assessed using the most recent version of the IAS-USA list of HIV-1 drug resistance 
mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells will be assessed using on-treatment laboratory results, and 
pre-specified visit windows

The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly 
from the case report forms (CRFs). The summary will count the number of subjects that have 
at least one event

The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from 
the CRFs. The summary will count the number of subjects that have at least one event

The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, 
collected at Week 2 from a subset of subjects
8.4
Analyses
In general, categorical variables are tabulated with counts and percents. Continuous variables are 
summarized with univariate statistics (eg, mean, median, standard error).
Longitudinal analyses use pre-defined visit week windows. Unless otherwise specified, windows 
around planned measurement times are constructed based on the midpoint between planned 
study visits (ie, half the duration of time between study visits), and data are summarized at each 
scheduled visit. 
For the calculation of descriptive statistics of observed data, subjects must have a baseline 
measurement to be evaluable for longitudinal tabulations of parameter values and changes from 
baseline. 
Tabulations of the following endpoints present the number of unique subjects with an event: 
protocol deviations; interruptions of study therapy; non-study medications; adverse events; and 
laboratory abnormalities. Thus, multiple occurrences of the same event are counted only once 
per subject.
8.4.1
Demographics and Baseline Characteristics
The following demographic and baseline characteristics will be summarized by treatment arm
and overall using the treated subjects:

Demographics: age, race, ethnicity, gender, geographic region;
Revised Protocol No.: 03
Date: 17-Mar-2016
76


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Disease characteristics at baseline: plasma HIV-1 RNA level, CD4+ T-cell counts and 
percentages, CD8+ T-cell counts, HIV-1 subtype;

Laboratory tests at baseline;

Pre-treatment CDC Class C AIDS events;

Prior medications
8.4.2
Efficacy Analyses
The efficacy analyses will be based on the treated subjects.
8.4.2.1
Primary Efficacy Analyses
The primary efficacy endpoint is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL 
at the Week 24 snapshot within each stage. This endpoint is assessed with the FDA snapshot 
algorithm. The primary analysis will be based on a modified ITT (mITT) approach. A sensitivity 
analysis will be conducted using an observed values approach. The two approaches will be 
implemented as follows:

Modified ITT: The numerator will be based on subjects with plasma HIV-1 RNA < 40 c/mL 
at Week 24. The denominator will be based on all treated subjects

Observed values: Similar to the mITT approach, the numerator will be based on subjects with 
plasma HIV-1 RNA < 40 c/mL at Week 24. However, the denominator will be based on the 
treated subjects with plasma HIV-1 RNA at Week 24
Response rates will be tabulated by treatment arm (within the stage) with exact binomial 95% 
confidence intervals.
Subgroup summaries will be provided to examine the impact of baseline viral load. Subgroup
summaries may be provided to examine the impact of other important covariates such as CD4+ 
count, sex, geographic region, etc.
At Week 24, a Time to Loss of Virologic Response (TLOVR) analysis will be conducted as a 
sensitivity analysis that compliments the snapshot analysis. The following definition for 
virologic rebound will be used:
“For subjects that have been confirmed as having reached virologic suppression, by 
having two consecutive HIV-1 RNA readings below the assay limit of detection 
(40 copies/mL), virologic rebound is defined as confirmed HIV-1 RNA levels above the 
limit of detection. For levels above the limit of detection, confirmation consists of either 
two consecutive readings, or a single reading followed by loss to follow-up.”
8.4.2.2
Secondary Efficacy Analyses
The following secondary endpoints will be summarized by treatment arm:

Proportion of subjects with HIV-1 RNA < 40 c/mL at Week 48 and Week 96 using mITT 
and observed values
Revised Protocol No.: 03
Date: 17-Mar-2016
77


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor

Proportion of subjects with HIV-1 RNA < 200 c/mL at Week 24, 48 and 96 using mITT and 
observed values

Change from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells over time

Newly emergent genotypic substitutions (using all on-treatment isolates) will be tabulated by 
treatment arm

The newly emergent phenotypic resistance profile (using all on-treatment isolates) will be 
tabulated by treatment arm
8.4.3
Safety Analyses
The investigators will determine the intensity of adverse events (AEs) and the relationship of 
AEs to study therapy. The investigators’ terms will be coded and grouped by system organ class 
using the latest version of the Medical Dictionary for Regulatory Activities (MedDRA) in 
production at BMS. AEs will be presented by system organ class and preferred term. 
Presentations will include both non-serious and serious adverse events, unless specified 
otherwise. If a subject had an adverse event with different intensities over time, then only the 
greatest intensity will be reported.
Deaths will be listed for enrolled subjects without regard to onset.
In analyses of fasting lipids over time, values will be excluded after the start of serum lipid 
reducing agents.
The frequency of the following safety events will be summarized by treatment arm for treated 
subjects:

SAEs

AEs leading to discontinuation of study therapy

AEs by intensity

CDC Class C AIDS events

Laboratory abnormalities by toxicity grade
8.4.4
Pharmacokinetic Analyses
The following PK parameters will be summarized by treatment arm:

Cmax: maximum observed plasma concentration

Tmax: time of maximum observed plasma concentration

Ctau: observed plasma concentration at the end of a dosing interval (eg, concentration at 
24 hours)

C0: observed pre-dose plasma concentration

AUC(TAU) : area under the concentration-time curve in one dosing interval
Revised Protocol No.: 03
Date: 17-Mar-2016
78


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
8.4.4.1
Sparse Pharmacokinetic Analyses
Sparse pharmacokinetic data will be used in population PK, PK/PD and, as available, PK/VK 
analyses.
8.4.4.2
PK/PD and PK/VK Analyses
PK data obtained from this study will be pooled with data from other studies to perform an 
integrated population PK analysis, exposure-response analyses for selected safety and efficacy 
endpoints, and, as available, viral kinetic modeling of BMS-955176 in combination with other 
ARVs to support the on-going development of BMS-955176. These analyses will facilitate 
optimal dose selection for future Phase 3 studies. 
The population PK, exposure-response, and, as available, viral kinetic analyses, will be reported 
separately.
8.4.5
Biomarker Analyses
Details about the biomarker analyses will be provided in the Statistical Analysis Plan (SAP).
8.4.6
Outcomes Research Analyses
Details about the outcomes research analyses will be provided in the SAP.
8.4.7
Other Analyses (including Virologic Futility)
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 1 completes their Week 24 visit. This analysis will be conducted to evaluate whether the 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 1 (containing 
BMS-955176) to Arm 2 (containing TDF) will be made with one-sided, Fisher’s exact tests, 
conducted at the 0.01 probability level.
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 2 completes their Week 24 visit. This analysis will be conducted to evaluate whether a 
BMS-955176 arm shows significantly worse antiviral efficacy (HIV-1 RNA < 40 c/mL using the 
FDA snapshot algorithm) than the TDF-containing arm. The comparison of Arms 3-4
(containing BMS-955176) to Arm 5 (containing TDF) will be made with one-sided, Fisher’s 
exact tests, conducted at the 0.01 probability level.
8.5
Interim Analyses
There are two interim analyses scheduled before the start of Stage 2.
The first interim analysis will be conducted after approximately 50% of the randomized subjects
have completed 24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of 
SDTM (Study Data Tabulation Model) data (“level 1” data) to facilitate the development of 
models for: population pharmacokinetics; exposure-response relationships; and, as available,
viral kinetics.
Revised Protocol No.: 03
Date: 17-Mar-2016
79


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
A second interim analysis will be conducted after the last subject has completed 24 weeks of 
therapy in Stage 1. This will be an analysis of the available efficacy, safety, resistance and 
pharmacokinetic data.
The schedule for additional analyses will depend upon the decision to initiate the Stage 2, as well 
as the recruiting time frame of Arms 1 & 2 relative to the time frame for Arms 3, 4, and 5. If 
Stage 2 is initiated, and recruiting follows projected timelines, then it is anticipated that analyses 
will be conducted when:

The last subject in Arms 3, 4, and 5 completes the Week 24 visit

The last subject in Arms 1 and 2 completes the Week 96 visit

The last subject in Arms 3, 4, and 5 completes the Week 96 visit
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
deviation or change to the protocol without prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change 
will be submitted to:

IRB/IEC for review and approval/favorable opinion

BMS

Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
subject: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a 
schedule of on-site visits for targeted review of study records.
Revised Protocol No.: 03
Date: 17-Mar-2016
80


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the 
source documents:
In addition, the study may be evaluated by BMS internal auditors and government inspectors 
who must be allowed access to CRFs, source documents, other study files, and study facilities. 
BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to BMS.
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records 
(EMRs/EHRs), adverse event tracking/reporting, protocol required assessments, and/or drug 
accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS.
Revised Protocol No.: 03
Date: 17-Mar-2016
81


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include the investigational product 
and the non-investigational product(s). Records or logs must comply with applicable regulations 
and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each subject, including unique subject identifiers

amount transferred to another area/site for dispensing or storage

nonstudy disposition (eg, lost, wasted)

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for bioavailability/bioequivalence, if applicable

dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS electronic data capture tool, electronic CRFs will be prepared for all 
data collection fields except for fields specific to SAEs and pregnancy, which will be reported on 
the paper or electronic SAE form and Pregnancy Surveillance form, respectively. Spaces may be 
left blank only in those circumstances permitted by study-specific CRF completion guidelines 
provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
Revised Protocol No.: 03
Date: 17-Mar-2016
82


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated by the investigator or qualified physician who is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form. For electronic CRFs, review 
and approval/signature is completed electronically through the BMS electronic data capture tool.
The investigator must retain a copy of the CRFs including records of the changes and 
corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements 
and must only access the BMS electronic data capture tool using the unique user account 
provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the 
following criteria:

External Principal Investigator designated at protocol development

National Coordinating Investigator 

Study Steering Committee chair or their designee

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region or 
country)

Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study require approval by BMS prior to publication or presentation 
and must adhere to BMS’s publication requirements as set forth in the approved clinical trial 
agreement (CTA). All draft publications, including abstracts or detailed summaries of any 
proposed presentations, must be submitted to BMS at the earliest practicable time for review, but 
at any event not less than 30 days before submission or presentation unless otherwise set forth in 
the CTA. BMS shall have the right to delete any confidential or proprietary information 
contained in any proposed presentation or abstract and may delay publication for up to 60 days 
for purposes of filing a patent application.
Revised Protocol No.: 03
Date: 17-Mar-2016
83


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete Abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Female subjects must continue 
to have pregnancy tests. Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject chooses to 
forego complete abstinence.
If two forms of contraception is required, Complete abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Subjects who choose complete 
abstinence are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. Acceptable 
alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as complete 
avoidance of heterosexual intercourse is an acceptable form of 
contraception for all study drugs. This also means that abstinence is the 
preferred and usual lifestyle of the patient. This does not mean periodic 
abstinence (eg, calendar, ovulation, symptothermal, profession of 
abstinence for entry into a clinical trial, post-ovulation methods) and 
withdrawal, which are not acceptable methods of contraception. Subjects 
who choose complete abstinence are not required to use a second method 
of contraception, but female subjects must continue to have pregnancy 
tests. Acceptable alternate methods of highly effective contraception must 
be discussed in the event that the subject chooses to forego complete 
abstinence
Revised Protocol No.: 03
Date: 17-Mar-2016
84


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
11
LIST OF ABBREVIATIONS
Term
Definition
3TC
Lamivudine
AE
adverse event
AI
accumulation index
AIDS
Acquired Immunodeficiency Syndrome
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after the 
first dose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALT
alanine aminotransferase
ARV
antiretroviral
AST
aspartate aminotransferase
ATV
atazanavir
ATV/r
atazanavir boosted with ritonavir
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the time of 
the last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
A-V
atrioventricular
-HCG
beta-human chorionic gonadotrophin
BA/BE
bioavailability/bioequivalence
BID, bid
bis in die, twice daily
BCRP
Breast cancer reactive protein
BDC
Bile duct-cannulated
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
BVM
bevirimat
Revised Protocol No.: 03
Date: 17-Mar-2016
85


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
c
copies
c/mL
copies per milliliter
C
Celsius
C12
concentration at 12 hours
C24
concentration at 24 hours
CA
capsid
cART
Combination antiretroviral therapy
Cavg
average concentration
Cexpected-tau
expected concentration in a dosing interval
CD
Cluster designation (CD4; CD8)
CDC
Centers for Disease Control
CFC
corrected fold change
CFR
Code of Federal Regulations 
CI
confidence interval
CrCl; CCL
creatinine clearance
CLR
renal clearance
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CMV
cytomegalovirus
CNS
Central nervous system
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
Css,avg
average steady-state plasma concentration
CSR
Clinical study report
Ct
Expected concentration at a certain time, usually at the end of an 
expected future dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctau
Concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctrough
Trough observed plasma concentration
CT
Computed tomography
Revised Protocol No.: 03
Date: 17-Mar-2016
86


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
CTA
clinical trial agreement
CTX
Cross-linked C-telopeptide of Type 1 collagen
CYP
cytochrome p-450
D/C
discontinue
DDI
drug-drug interaction
DHHS
Department of Health and Human Services
dL
deciliter
DTG
dolutegravir
EC
Ethics committee
EC
effective concentration
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EFV
efavirenz
eg
exempli gratia (for example)
E-R
exposure-response
ESR
Expedited Safety Report
ET
Early termination or End of Treatment
EU
European Union
FAHI
Functional Assessment of HIV Infection
FDA
Food and Drug Administration
FDC
Fixed dose combination
FSH
follicle stimulating hormone
FTC
emtricitabine
g
gram
GFR
glomerular filtration rate
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
GSH
glutathione
Revised Protocol No.: 03
Date: 17-Mar-2016
87


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
h; hr
hour
HAART
Highly active antiretroviral therapy
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCG
Human chorionic gonadotropin
HCV
hepatitis C virus
HCO3-
bicarbonate
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HR
heart rate
HRT
hormone replacement therapy
HS
Human serum
HuSA
Human serum albumin
IAS
International AIDS Society
IB
Investigator brochure
IC
Inhibitory concentration
ICD
International Classification of Diseases
ICF
informed consent form
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
INI
Integrase inhibitor
IP
investigational product
IRB
Institutional Review Board
IU
International Unit
IUD
intrauterine device
IV
intravenous
IVRS
interactive voice response system
Revised Protocol No.: 03
Date: 17-Mar-2016
88


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
GALT
Gut associated lymphoid tissue
GI
gastrointestinal
kg
kilogram
L
liter
MAD
multiple ascending dose
MC
micronized crystalline
mg
milligram
MI
Maturation inhibitor
MIC
minimum inhibitory concentration
min
minute
mITT
Modified Intent to Treat
mL
milliliter
mmHg
millimeters of mercury
msec
millisecond
MOA
mechanism of action
g
microgram
M
micromolar
N
number of subjects or observations
N/A
not applicable
ng
nanogram
nM
nanomolar
NIMP
non-investigational medicinal products 
NNRTI
Non- nucleoside reverse transcriptase inhibitor
NOAEL
No observed adverse effect level
NOEL
No observed effect level
NRTI
nucleoside reverse transcriptase inhibitor
NSAID
nonsteroidal anti-inflammatory drug
pDILI
potential drug induced liver injury
PBMC
peripheral blood mononuclear cells
PCR
polymerase chain reaction
Revised Protocol No.: 03
Date: 17-Mar-2016
89


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
PD
pharmacodynamics
PI
protease inhibitor
PDVF
Protocol-defined virologic criteria
PK
pharmacokinetics
PPI
proton pump inhibitor
PR
atrial depolarization to ventricular depolarization
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
QD, qd
quaque die, once daily
QRS
interval representing the time for ventricular depolarization
QT
Duration of ventricular electrical activity
QTcF
QT corrected for heart rate using Frederica’s formula
RAL
raltegravir
RBC
red blood cell
RNA
ribonucleic acid
RTV
ritonavir
SAD
single ascending dose
SDD
spray-dried dispersion
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SDTM
Study Data Tabulation Model
SOP
Standard Operating Procedures
SP1
spacer peptide 1
Subj
subject
STR
single tablet regimen
t
temperature
T
time
TDF
tenofovir
Revised Protocol No.: 03
Date: 17-Mar-2016
90


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Term
Definition
TDF/FTC
Truvada (TDF 300 mg + FTC 200 mg)
TAO
Trial Access Online, the BMS implementation of an EDC capability
TAM
Thymidine analogue mutation
T-HALF
Half life
T-HALFeff_AUC
Effective elimination half life that explains the degree of AUC 
accumulation observed
Tmax, TMAX
time of maximum observed concentration
TR_AUC(0-T)
AUC(0-T) treatment ratio
TR_AUC(INF)
AUC(INF) treatment ratio
TR_Cmax
Cmax treatment ratio
UGT
UDP-glucuronosyltransferase
ULN
upper limit of normal
US
United States
VF
virologic failure
VK
Viral kinetics
VLP
Virus-like particles
WBC
white blood cell
WFD
Wallingford, Connecticut, USA
WHO
World Health Organization
Wk or WK
week
WOCBP
women of childbearing potential
Revised Protocol No.: 03
Date: 17-Mar-2016
91


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
REFERENCES
1
WHO HIV Department. Global Summary of the AIDS Epidemic 2013. Available at: 
http://www.who.int/hiv/data/epi_core_dec2014.png?ua=1 Accessed 12/29/14
2
European AIDS Clinical Society. European Guidelines for treatment of HIV-infected adults 
in Europe (Oct 2013). http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf. 
Accessed Nov 30, 2013.
3
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services.
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. 
Accessed 
Nov 30, 2013.
4
United States Department of Health and Human Services, Food and Drug Administration, 
Center for Drug Evaluation and Research. Guidance for Industry Human Immunodeficiency 
Virus-1 Infection: Developing Antiretroviral Drugs for Treatment. (June 2013). Revision 1.
5
Study AI468001 Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple 
Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of 
BMS-955176 in Healthy Subjects. Document Control No. 930071044
6
Study AI468002 Randomized, Placebo-Controlled, Multiple-Dose Study to Evaluate the 
Pharmacodynamics, Safety and Pharmacokinetics of BMS-955176 (Double-Blinded) and 
BMS-955176 with Atazanavir +/- Ritonavir (Open-Labelled) in HIV-1 Infected Subjects. 
Draft Document Control No. 930087017
7
Min 
S., 
Sloan 
L., 
DeJesus 
E., 
et. 
al. 
Antiviral 
activity, 
safety, 
and 
pharmacokinetics/pharmacodynamics 
of 
dolutegravir 
as 
10-day 
monotherapy 
in 
HIV-1-infected adults. AIDS 2011. 25(14):1737-45.
8
Walmsley SL., Antela A., Clumeck N., et. al. Dolutegravir plus abacavir-lamivudine for the 
treatment of HIV-1 infection. NEJM 2013 369(19):1807-18.
9
Raffi F., Jaeger H., Quiros-Roland E., et. al. Once-daily dolutegravir versus twice-daily 
raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week 
results from a randomised, double-blind, non-inferiority trial. Lancet ID. 2013 13(11): 
927-35.
10
Cahn P., Pozniak AL., Mingrone H,. et. al. Dolutegravir versus raltegravir in antiretroviral-
experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, 
double-blind, non-inferiority SAILING study. Lancet 2013 382(9893):700-8.
11
Stellbrink HJ., Reynes J., Lazzarin A., Dolutegravir in antiretroviral-naive adults with 
HIV-1: 96-week results from a randomized dose-ranging study. AIDS 2013 27(11):1771-8.
Revised Protocol No.: 03
Date: 17-Mar-2016
92


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
12
Eron JJ., Clotet B., Durant J., Safety and efficacy of dolutegravir in treatment-experienced 
subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING 
Study. JID 2013 207(5): 740-748.
13
Sanne I, Piliero P, Squires K, Thiry A, Schnittman S. Results of a phase 2 clinical trial at 48 
weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at 
three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. 
J Acquir Immune Defic Syndr. Jan 1 2003;32(1):18-29.
14
Bertz RJ, Persson A, Chung E, et al. Pharmacokinetics and pharmacodynamics of atazanavir-
containing antiretroviral regimens, with or without ritonavir, in patients who are 
HIV-positive and treatment-naive. Pharmacotherapy. Mar 2013;33(3):284-294.
15
Molto J, Santos JR, Valle M, et al. Monitoring atazanavir concentrations with boosted or 
unboosted regimens in HIV-infected patients in routine clinical practice. Ther Drug Monit. 
Oct 2007;29(5):648-651.
16
Goutelle S, Baudry T, Gagnieu MC, et al. Pharmacokinetic-pharmacodynamic modeling of 
unboosted Atazanavir in a cohort of stable HIV-infected patients. Antimicrob Agents 
Chemother. Jan 2013;57(1):517-523.
17
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services. 
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed Nov 
30, 2013.
18
Malan DR, Krantz E, David N, Wirtz V, Hammond J, McGrath D. Efficacy and safety of 
atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy 
regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr. Feb 1 
2008;47(2):161-167.
19
Landman R, Diallo MB, Gueye NF, et al. Efficacy and safety of unboosted atazanavir in 
combination with lamivudine and didanosine in naive HIV type 1 patients in Senegal. AIDS 
Res Hum Retroviruses. May 2010;26(5):519-525.
20
Gianotti N, Seminari E, Guffanti M, et al. Evaluation of atazanavir Ctrough, atazanavir 
genotypic inhibitory quotient, and baseline HIV genotype as predictors of a 24-week 
virological response in highly drug-experienced, HIV-infected patients treated with 
unboosted atazanavir. New Microbiol. Apr 2005;28(2):119-125.
21
Giuntini R, Martinelli C, Ricci E, et al. Efficacy and safety of boosted and unboosted 
atazanavir-containing antiretroviral regimens in real life: results from a multicentre cohort 
study. HIV Med. Jan 2010;11(1):40-45.
Revised Protocol No.: 03
Date: 17-Mar-2016
93


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
22
Two Drug Combination Studies with BMS-955176 and HIV Antiviral Agents. Version 1.0. 
June 2013. DCN 930071469
23
Song I., Borland J., Chen S. Effect of atazanavir and atazanavir/ritonavir on the 
pharmacokinetics of the next-generation HIV integrase inhibitor, S/GSK1349572. Br. J. 
Pharm. 2011 72(1):103-108
24 BMS-955176 Investigator Brochure, Version 2.0, July 2013 DCN 930056146
25 BMS-955176 Investigator Brochure, Version 3.0, April 17, 2014 DCN 930056146
26 Partial response to FDA “May Proceed” Letter dated 27 Sep 2013 for IND 118,936. Bristol-
Myers Squibb Company; Jan 2014. Document Control No. 930076507 2.0. Insert this 
additional reference: “Evaluation of cross-resistance of HIV-1 Maturation Inhibitor 
BMS-955176 toward HIV-1 protease inhibitor resistant viruses. Bristol-Myers Squibb 
Company; 30-Sept-2014. Document Control No. 930083565.”
27 Evaluation of Cross Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. Document Control No. 930083565
28 Gilead 
Sciences. 
Prescribing 
Information 
for 
TDF. 
Available 
at: 
http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/viread/viread_pi.pdf.
Accessed Dec 31, 2014
29
ViiV 
Healthcare. 
Prescribing 
Information 
for 
DTG. 
Available 
at: 
https://www.viivhealthcare.com/media/58599/us_tivicay.pdf. Accessed Dec 31, 2014.
30 BMS. 
Prescribing 
Information 
for 
ATV. 
Available 
at: 
http://packageinserts.bms.com/pi/pi_reyataz.pdf. Accessed Dec 31, 2014
31 AbbVie. 
Prescribing 
Information 
for 
RTV. 
Available 
at: 
http://www.rxabbvie.com/pdf/norvirtab_pi.pdf. Accessed Dec 31, 2014
32 Evaluation of Cross-Resistance of HIV-1 Maturation Inhibitor BMS-955176 Toward HIV-1 
Protease Inhibitor Resistant Viruses. DCN 930083565
33
Hasler WL Nausea, Vomiting, and Indigestion: Introduction. Chapter 39. Harrisons 
Principles of Internal Medicine 18th edition. 2012. McGraw Hill
34
Hasler WL and Owyang C Approach to the Patient with Gastrointestinal Disease. Chapter 
290. Harrisons Principles of Internal Medicine 18th edition. 2012. McGraw Hill
35
Soll AH and Graham DY. Peptic Ulcer Disease. Chapter 40. Textbook of Gastroenterology. 
5th edition. 2009. Blackwell Publishing
Revised Protocol No.: 03
Date: 17-Mar-2016
94


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
36
Rome Foundation. Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. 
Available: http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Accessed 
Dec 22 2014
Revised Protocol No.: 03
Date: 17-Mar-2016
95


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 1
LISTINGS OF PROHIBITED AND PRECAUTIONARY
THERAPIES
General Notes: 

Guidelines for the use of drugs with established or other potentially significant drug 
interactions listed in the Package Inserts of the marketed ARV agents used by subjects 
participating in this study (Reyataz, Norvir, Viread, Tivicay) should be followed. 

Medications listed in the Package Inserts as contra-indicated with the other marketed ARV 
agents used by subjects participating in this study are not permitted. 

Any immunizations deemed appropriate by the subject’s physician are permitted provided 
that the immunization is given > 4 weeks from any HIV-1 RNA measurement.

A subject may not be co-enrolled in a concomitant trial unless it is approved by the Medical 
Monitor prior to randomization.
Prohibited Therapies
Drugs that should not be administered throughout the duration of the study:
Anticonvulsants: Carbamazepine, 
Phenobarbital, Phenytoin
Use with ATV may result in decreased ATV concentrations. Use of 
Carbamazepine may result in decreased DTG concentrations.
Oral Antifungals: Itraconazole, 
Posaconazole, and Voriconazole
Use with ATV can result in increased ATV concentrations
Antimycobacterials: Rifampin, 
Rifapentine, Rifabutin
These antimycobacterials decrease ATV plasma concentrations and 
may decrease BMS-955176 plasma concentrations.
St. John’s wort
Use with ATV or DTG may result in loss of antiviral therapeutic effect
GI motility agent: Cisapride
Potential for serious and/or life threatening reactions such as cardiac 
arrhythmias
Pimozide
Potential for serious and/or life threatening reactions such as cardiac 
arrhythmias
Zetia (ezetimibe)
Ezetimibe is a substrate of OATP1B1 (of which BMS-955176 is an 
inhibitor in vitro).
Dofetilide
Use with DTG may result in the potential for increased Dofetilide 
plasma concentrations and the risk for serious and/or life threatening 
events
Alfuzosin
ATV increases Alfuzosin concentrations which can result in 
hypotension
Benzodiazepines: Triazolam and 
Midazolam
ATV can increase the concentration of these Benzodiazepines with the 
potential to increase sedation or respiratory depression
Ergot derivatives: 
Dihydroergotamine, ergotamine, 
ergonovine, methylergonovine
ATV can increase potential for ergot toxicity (e.g. peripheral 
vasospasm)
Revised Protocol No.: 03
Date: 17-Mar-2016
96


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
HMG-CoA Reductase Inhibitors: 
Lovastatin, Simvastatin, Atorvastatin, 
Pitavastatin, Rosuvastatin, Pravastatin
Use with ATV may result in increased levels of HMG-CoA Reductase 
Inhibitors and potential for serious reactions such as myopathy
Antacids, H2 receptor angatonists, 
Proton Pump Inhibitors, Sucralfate
Use with ATV may result in decreased plasma concentrations of ATV. 
Use of Antacids containing Aluminium, Magnesium, or Calcium may 
result in decreased levels of DTG.
Macrolides: Clarithromycin
Use with ATV may result in increased Clarithromycin levels and QTc 
prolongation
Buprenorphine
Use with ATV may increase levels of Buprenorphine
Quetiapine
Use with ATV may increase levels of Quetiapine
Salmeterol
Use with ATV may result in increased levels of Salmeterol
Avanafil
Use with ATV may result in increased Avanafil levels
All drugs with antiretroviral activity 
other than those considered study 
therapy
Any drugs with antiretroviral activity not considered study therapy 
may interfere with the assessments of the study.
Precautionary Therapies
Drugs that should be administered with caution during the study:
Hormonal Contraceptives
Hormonal Contraceptives cannot be relied upon as a highly effective 
method of contraception. 
See Protocol Section 3.3.1, for more information on Highly Effective 
Methods of Contraception.
Antidepressants: Trazodone, Tricyclic 
Antidepressants (TCA)
Use with ATV/r may result in increased plasma concentrations of 
trazodone and TCA
Antimalarials: Atovaquone/Proguanil, 
Mefloquine
Use with ATV/r may result in decreased Atovaquone/Proguanil levels. 
The effect of Mefloquine on ATV/r is unknown.
Benzodiazepines: Alprazolam and 
Diazepam
ATV can increase the concentration of these Benzodiazepines 
Calcium Channel Blockers
Use with ATV may result in increased concentrations of CCB’s. 
Non-topical Corticosteroids: 
Budesonide, Fluticasone, Prednisone, 
Methylprednisolone, Prednisolone, 
Triamcinolone
Use with ATV/r may result in increased levels of glucocorticoids and 
adrenal insufficiency
Dexamethasone
Use with ATV may result in reduced levels of ATV.
Colchicine
Use with ATV may result in increased Colchicine levels
Metformin
Use with DTG may result in increased levels of metformin. 
A cation-containing (e.g. Magnesium) 
laxative
If used with DTG the laxative should be taken 2 hours before or 6 
hours after taking concomitant laxatives.
Revised Protocol No.: 03
Date: 17-Mar-2016
97


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 2
AIDS-DEFINING DIAGNOSES
I.
PARASITIC INFECTIONS
Pneumocystis carinii (PC)
1011
PC pneumonia histologically proven.
1012
PC pneumonia, clinical diagnosis by the following specifications and confirmed HIV 
infection:
A history of dyspnea on exertion or non-productive cough of recent onset (within the past 
3 months).
AND
Chest X-ray evidence of diffuse bilateral interstitial or gallium scan evidence of diffuse 
bilateral pulmonary disease;
AND
Arterial blood gas analysis showing an arterial pO2 of < 70 mmHg or a low respiratory 
diffusing capacity (< 80% of predicted values) or an increase in the alveolar-arterial 
oxygen tension gradient;
AND
Successful response to appropriate therapy and no evidence of pneumonias of other 
etiologies.
1013
Pneumocystis carinii, histologically proven, at a site other than lungs.
Toxoplasmosis (in patients > 1 month old)
1021
Toxoplasmosis, clinical diagnosis (of brain only) by the following specifications and 
confirmed HIV infection:
Recent onset of a neurologic disease consistent with toxoplasmosis;
AND
Brain imaging evidence of a mass lesion (on computed tomography, nuclear magnetic 
resonance of radiography enhanced by injection of contrast medium);
AND
Serum antibody to toxoplasmosis and successful response to therapy for toxoplasmosis.
1022
Toxoplasmosis, of brain or internal organs other than liver, spleen or lymph nodes. 
Proven by microscopy.
Isosporiasis
1031
Isosporiasis causing chronic diarrhea of > 1 month. Proven by microscopy.
Revised Protocol No.: 03
Date: 17-Mar-2016
98


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
Cryptosporidiosis
1041
Cryptosporidiosis causing chronic diarrhea of > 1 month. Proven by microscopy.
II.
FUNGAL INFECTIONS
Candidiasis
2011
Candidiasis, Esophageal, definitive diagnosis by the following specifications:
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
2012
Candidiasis, Esophageal, presumptive diagnosis by the following specifications and 
confirmed HIV infection:
Recent onset of retrosternal pain on swallowing:
AND
Oral candidiasis diagnosed by the gross appearance of white patches or plaques on an 
erythematous base OR by the microscopic appearance of fungal mycelial filaments in an 
uncultured specimen scraped from the oral mucosa;
AND
Response to appropriate therapy.
2013
Candidiasis, Bronchial/Pulmonary, definitive diagnosis by the following specifications; 
Gross inspection by endoscopy or autopsy or by microscopy (histology or cytology) on a 
specimen obtained directly from the tissues affected (including scrapings from the 
mucosal surface), not from a culture.
Cryptococcosis
2022
Cryptococcosis, Extra-pulmonary, proven by microscopy (histology or cytology), culture 
or detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Histoplasmosis
2031
Histoplasmosis, Disseminated (at a site other than or in addition to lungs or cervical or 
hilar lymph nodes), proven by microscopy (histology or cytology), culture or detection of 
antigen in a specimen obtained directly from the tissues affected or a fluid from those 
tissues.
Coccidioidomycosis
2041
Coccidioidoidomycosis, Disseminated (at a site other than or in addition to lungs or 
cervical or hilar lymph nodes), proven by microscopy (histology or cytology), culture or 
detection of antigen in a specimen obtained directly from the tissues affected or a fluid 
from those tissues.
Revised Protocol No.: 03
Date: 17-Mar-2016
99


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
2042
Coccidioidomycosis, clear reactivation of prior infection, proven by microscopy 
(histology or cytology), culture or detection of antigen in a specimen obtained directly 
from the tissues affected or a fluid from those tissues.
III.
BACTERIAL INFECTIONS
Mycobacterium
3001
Mycobacterium (unidentified species). Presumptive diagnosis, by the following 
specifications and confirmed HIV infection.
Acid fast bacilli (AFB) positive stain of specimen obtained from endoscopic biopsy or 
from a normal sterile site other than lungs, skin or cervical or hilar lymph nodes. Species 
NOT identified by culture.
Mycobacterium tuberculosis
3011
Mycobacterium tuberculosis, Pulmonary, definitive diagnosis proven by culture, without 
evidence of upper respiratory infection symptoms of Mycobacterium tuberculosis that 
could account for the positive culture.
3012
Mycobacterium tuberculosis, definitive diagnosis proven by culture, of at least one extra 
pulmonary site regardless of concurrent pulmonary involvement.
3013
Mycobacterium tuberculosis, Disseminated, definitive diagnosis proven by culture.
Mycobacterium avium intracellulare
3022
MAI in Blood, proven by culture.
3023
MAI Colitis, proven by histology and culture. (This does not include MAI of the stool 
alone).
3024
MAI, Disseminated, at a site other than or in addition to lungs or cervical or hilar lymph 
nodes, proven by culture.
Mycobacterium Kansasii, Mycobacterium Scrofulaceum and Other Atypical 
Mycobacterium
3032
M. Kansasii, in Blood, proven by culture.
3033
M. Kansasii Colitis, proven by histology and culture. (NOT including positive M. 
Kansasii of stool alone).
3034
M. Kansasii, Disseminated, at a site other than or in addition to lungs, or cervical or hilar 
lymph nodes, proven by culture.
3035
M. Scrofulaceum or other Atypical Mycobacterium, proven by culture.
Salmonella
3041
Salmonella, recurrent Bacteremia (non-typhoid), proven by culture.
Revised Protocol No.: 03
Date: 17-Mar-2016
100


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
IV.
VIRAL INFECTIONS
Cytomegalovirus
4011
CMV, Pneumonitis, pathologically or histologically confirmed. Serum antibody titer and 
culture alone is not sufficient for the diagnosis.
4012
CMV, Esophagitis, as diagnosed by histology, pathology or culture of an esophageal 
lesion. Serum antibody titer and culture of other than esophageal tissue is not sufficient 
for the diagnosis.
4013
CMV, Retinitis as evidenced by a characteristic appearance on serial ophthalmoscopic 
examinations (eg, discrete patches of retinal whitening with distinct borders, spreading in 
a centrifugal manner, following blood vessels, progressing over several months, 
frequently associated with retinal vasculitis, hemorrhage, and necrosis). Resolution of 
active disease leaves retinal scarring and atrophy with retinal pigment epithelial mottling.
4014
CMV, Colitis, as diagnosed by histology, pathology or culture of a colonic lesion. Serum 
antibody titer and culture of other than colonic tissue is not sufficient for the diagnosis.
4015
CMV, Encephalitis, as diagnosed by histology, pathology or culture of brain tissue or 
CSF. Serum antibody titer and culture of other than brain tissue or CSF is not sufficient 
for the diagnosis.
Herpes Simplex (in patients > 1 month old).
4021
HSV, Disseminated (but not encephalitis alone), proven by microscopy (histology or 
cytology), culture or detection of antigen in a specimen obtained directly from affected 
tissues.
4022
HSV, Esophagitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4023
HSV, Bronchitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for the diagnosis.
4024
HSV, Pneumonitis, as diagnosed by microscopy (histology or cytology), culture or 
detection of antigen in a biopsy specimen obtained directly from affected tissue. 
Serological measurement and culture from other than the affected tissue is not sufficient 
for diagnosis.
4025
HSV, GI, other than mouth, throat, or peri-rectal, as diagnosed by microscopy (histology 
or cytology), culture or detection of antigen in a biopsy specimen obtained directly from 
affected tissue. Serological measurement and culture from other than the affected tissue is 
not sufficient for diagnosis.
Revised Protocol No.: 03
Date: 17-Mar-2016
101


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
4026
HSV, Mucocutaneous, ulcers persisting for 1 month despite appropriate therapy, as 
diagnosed by microscopy (histology or cytology), culture or detection of antigen in a 
biopsy specimen obtained directly from affected tissue. Serological measurement and 
culture from other than the affected tissue is not sufficient for the diagnosis.
Progressive Multifocal Leukoencephalopathy
4041
Progressive Multifocal Leukoencephalopathy, proven by microscopy.
VI.
NEOPLASTIC DISEASES
Kaposi’s Sarcoma
6011
Kaposi’s sarcoma, Mucocutaneous, proven by microscopy.
6012
Kaposi’s sarcoma. Mucocutaneous, presumptive diagnosis with characteristic gross 
appearance and confirmed HIV infection.
6013
Kaposi’s sarcoma, Visceral.
6014
Kaposi’s sarcoma, other than above.
Lymphoma of the Brain
6021
Primary Lymphoma of the brain at any age, proven by microscopy.
Non-Hodgkins Lymphoma
6031
Small Non-cleaved lymphoma (either Burkitt or non-Burkitt type).
6032
Immunoblastic sarcoma, equivalent to any of the following, although not necessarily all 
in combination: Immunoblastic lymphoma, large-cell lymphoma, diffuse histocytic 
lymphoma.
Cervical Carcinoma
6041
Histologically proven invasive carcinoma of the cervix.
VII.
OTHER CONDITIONS
HIV Dementia/Motor Defects
7011
HIV Dementia, clinical findings of disabling cognitive and/or motor dysfunction 
interfering with occupation or activities of daily living progressing over weeks to months, 
in the absence of a concurrent illness or condition other than HIV infection that could 
explain the findings. Method to rule out such concurrent illnesses and conditions must 
include cerebrospinal fluid examination and either brain imaging (computed tomography 
or magnetic resonance) or autopsy.
Slim Disease or HIV Wasting Syndrome
7021
HIV Wasting Syndrome, findings of profound involuntary weight loss > 10% of baseline 
body weight plus either chronic diarrhea (at least two loose stools per day for 30 days) 
or chronic weakness and documented fever (for 30 days, intermittent to constant) in the 
Revised Protocol No.: 03
Date: 17-Mar-2016
102


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
absence of a concurrent illness or condition other than HIV infection that could explain 
the findings (eg, cancer, tuberculosis, cryptosporidiosis, or other specific enteritis).
7061
Recurrent pneumonia, acute onset within 12 months of most recent episode.
Revised Protocol No.: 03
Date: 17-Mar-2016
103


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 3
DAIDS TOXICITY GRADES
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events
Version 2.0 - November 2014
http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx
Revised Protocol No.: 03
Date: 17-Mar-2016
104


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 4
COCKCROFT-GAULT EQUATION TO CALCULATE SERUM 
CREATINE CLEARANCE
Online calculator:
http://nephron.com/cgi-bin/CGSI.cgi
Manual calculation:
Male:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg)
72 x Serum Creatinine (mg/dL)
Female:
Estimated Creatinine Clearance =
(140-age in years) x Body Weight (kg) x 0.85
72 x Serum Creatinine (mg/dL)
1 pound = 0.4536 kilograms
Revised Protocol No.: 03
Date: 17-Mar-2016
105


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
APPENDIX 5
LABORATORY ASSESSMENTS
HEMATOLOGY
WBC
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
RBC
Hemoglobin
Hematocrit
Platelets
Absolute Differential
CHEMISTRY
Glucose
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
Total Protein
Albumin
CK
Total Bilirubin
Direct Bilirubin
Indirect Bilirubin
AST
ALT
Alkaline Phosphatase
LDH 
Amylase
Lipase
Electrolytes (Sodium, 
Potassium, Chloride, 
Bicarbonate)
Calcium
Phosphorous
Creatinine + eGFR
Uric Acid
BUN
Revised Protocol No.: 03
Date: 17-Mar-2016
106


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
LIPIDS
Cholesterol
Screening
Day 1, Week 4, Week 12, Week 24
HDL
LDL Calculated
Triglycerides
OTHER SERUM TESTS
FSH
Screening
Optional; upon request
HCG
Optional; upon 
request
Optional; upon request
P1NP
Day 1, Week 12, Week 24, Early Term
CTX
Day 1, Week 12, Week 24, Early Term
URINE
Urine Pregnancy test (if 
positive, request serum HCG)
Screening
Every 4 weeks (either done at in-clinic 
visits, or at home)
Urine Toxicology (drugs of 
abuse)
Screening
Urine Creatinine
Day 1, Week 48, Week 96, Early Term
Urine Phosphorous
2 microglobulin
Macroscopic Urinalysis (no 
microscopic)
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
SEROLOGY
HIV-1 RNA
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
HbSAg
Screening
Week 48, Week 96, Early Term
HCV Ab (if positive, reflex to 
HCV RNA)
Screening
Week 48, Week 96, Early Term
Revised Protocol No.: 03
Date: 17-Mar-2016
107


Clinical Protocol
AI468048
BMS-955176
HIV Maturation Inhibitor
RESISTANCE
Specimens for HIV 
Resistance testing at 
Monogram
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
Specimens for HIV 
Exploratory Resistance 
testing at BMS
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
PHARMACOKINETICS
Intensive PK
Week 2 (optional)
Sparse PK
Week 4, Week 8, Week 12, Week 16, 
Week 24
IMMUNE PANEL
%CD3+/CD4+
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
%CD3+/CD8+
Absolute CD3/CD4
Absolute CD3/CD8
OTHER
Pharmacodiagnostic (PDx)
Screening
Plasma & Serum Back-ups 
Screening
Day 1, Week 4, Week 8, Week 12, Week 
16, Week 24, Week 32, Week 40, Week 
48, Week 60, Week 72, Week 84, Week 
96, Early Term
Revised Protocol No.: 03
Date: 17-Mar-2016
108

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
FOR CLINICAL STUDY REPORT 
A PHASE 2B RANDOMIZED, ACTIVE-CONTROLLED, STAGED, OPEN-LABEL 
TRIAL TO INVESTIGATE SAFETY AND EFFICACY OF BMS-955176 IN 
COMBINATION WITH DOLUTEGRAVIR AND ATAZANAVIR (WITH OR WITHOUT 
RITONAVIR) IN TREATMENT-EXPERIENCED HIV-1 INFECTED ADULTS 
PROTOCOL AI468048 
VERSION # 2.0 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
2
TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN FOR CLINICAL STUDY REPORT.....................................1
TABLE OF CONTENTS.................................................................................................................2
LIST OF TABLES...........................................................................................................................5
1
BACKGROUND AND RATIONALE.........................................................................6
2
OBJECTIVES...............................................................................................................7
2.1
Study Design.................................................................................................................7
2.2
Treatment Assignment..................................................................................................9
2.3
Blinding and Unblinding ..............................................................................................9
2.4
Protocol Amendments ..................................................................................................9
3
ENDPOINTS ..............................................................................................................10
3.1
Primary .......................................................................................................................10
3.2
Secondary ...................................................................................................................11
3.3
Exploratory .................................................................................................................11
4
ENDPOINTS ..............................................................................................................12
4.1
Primary Endpoints ......................................................................................................12
4.2
Secondary Endpoints ..................................................................................................12
4.3
Exploratory Endpoints................................................................................................12
5
SAMPLE SIZE AND POWER ..................................................................................13
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS 
FOR ANALYSES.......................................................................................................13
6.1
Study Periods..............................................................................................................13
6.2
Treatment Regimens...................................................................................................13
6.3
Populations for Analyses ............................................................................................14
7
STATISTICAL ANALYSIS ......................................................................................14
7.1
General Methods.........................................................................................................14
7.2
Study Conduct ............................................................................................................15
7.3
Study Population.........................................................................................................15
7.3.1
Subject Disposition.....................................................................................................15
7.3.2
Demographics and Other Characteristics..................................................................16
7.3.2.1
Demographics and Other Baseline Characteristics...................................................16
7.3.2.2
Pre-treatment CDC Class C AIDS Events..................................................................19
7.3.2.3
Previous Medication...................................................................................................19
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
3
7.3.2.4
Baseline Resistance ....................................................................................................19
7.4
Extent of Exposure .....................................................................................................20
7.4.1
Study Therapy.............................................................................................................20
7.4.2
Discontinuation of Study Therapy ..............................................................................21
7.4.3
Interruption or Delay of Study Therapy .....................................................................21
7.4.4
Concomitant Therapy .................................................................................................21
7.5
Efficacy.......................................................................................................................21
7.5.1
Primary Efficacy Endpoint: Proportion of Subjects with Plasma HIV-1 RNA 
< 40c/mL at the Week 24 Snapshot ............................................................................21
7.5.1.1
Summaries of Primary Efficacy Endpoint Within Subgroups.....................................22
7.5.2
Secondary Efficacy Endpoints....................................................................................23
7.5.2.1
Proportion of Subjects with Plasma HIV-1 RNA < 40c/mL at Weeks 48 and 
96 ................................................................................................................................23
7.5.2.2
Proportion of Subjects with Plasma HIV-1 RNA < 200c/mL at the Week 24, 
48 and 96 Snapshot.....................................................................................................23
7.5.2.3
Change from Baseline in Plasma HIV-1 RNA (log10) over Time ...............................23
7.5.2.4
Changes from Baseline in CD4+ and CD8+ T-cell Count over Time .......................23
7.5.2.5
Newly-emergent Genotypic Substitutions, IC50 Fold Changes from Baseline 
and Newly-emergent Gag Polymorphisms .................................................................24
7.5.3
Exploratory Efficacy Endpoints..................................................................................25
7.5.3.1
Proportion of Subjects with Plasma HIV-1 RNA within Certain Range over 
Time ............................................................................................................................25
7.5.3.2
Efficacy Summaries by Baseline Gag Polymorphisms...............................................25
7.5.4
Futility Analysis..........................................................................................................25
7.6
Safety..........................................................................................................................26
7.6.1
Overall Adverse Events...............................................................................................26
7.6.2
Deaths.........................................................................................................................27
7.6.3
Serious Adverse Events...............................................................................................27
7.6.4
Serious Adverse Events Emerging After Switch to Continuation Therapy.................27
7.6.5
Non-Serious Adverse Events.......................................................................................27
7.6.6
Adverse Events Leading to Discontinuation of Therapy ............................................28
7.6.7
Adverse  Events Leading to Discontinuation of Therapy After Switch to 
Continuation Therapy.................................................................................................28
7.6.8
Adverse Events by Relationship..................................................................................28
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
4
7.6.9
Adverse Events by Intensity ........................................................................................28
7.6.10
CDC Class C AIDS Events .........................................................................................28
7.6.11
Adverse Events of Special Interest..............................................................................28
7.6.12
Multiple Adverse Events .............................................................................................28
7.6.13
Clinical Laboratory Evaluations................................................................................29
7.6.13.1
Laboratory Abnormalities ..........................................................................................29
7.6.13.2
Laboratory Tests over Time........................................................................................29
7.6.14
Electrocardiograms ....................................................................................................30
7.6.15
Vital Signs...................................................................................................................30
7.7
Clinical Biomarker Assessments................................................................................31
7.8
Integrated Summaries .................................................................................................31
7.9
Outcomes Research ....................................................................................................32
7.9.1
EQ-5D-3L ...................................................................................................................32
7.9.2
FAHI ...........................................................................................................................33
7.10
Pharmacokinetics........................................................................................................34
8
CONVENTIONS........................................................................................................35
8.1
Derivation of Baseline and On-Treatment Parameters Using Visit Windows ...........35
8.1.1
Baseline.......................................................................................................................35
8.1.2
On-Treatment Parameters..........................................................................................35
8.2
Derived Dates .............................................................................................................37
8.3
Derived Parameters.....................................................................................................37
8.4
Study Therapy.............................................................................................................37
8.5
Concomitant Medications...........................................................................................38
8.6
Counting Rules for Adverse Events ...........................................................................38
8.7
Pharmacokinetic Evaluations......................................................................................39
8.7.1
Decimal Places for Pharmacokinetic Data ................................................................39
8.7.2
Pharmacokinetic Summaries ......................................................................................39
9
REFERENCES ...........................................................................................................40
APPENDIX 1
SNAPSHOT ALGORITHM......................................................................41
APPENDIX 2
GENOTYPIC AND PHENOTYPIC RESISTANCE................................43
APPENDIX 3
TIME TO LOSS OF VIROLOGIC RESPONSE.......................................47
APPENDIX 4
EQ-5D-3L SCORING PROGRAM - U.S. WEIGHTED ..........................49
APPENDIX 5
EQ-5D-3L SCORING PROGRAM - U.K. WEIGHTED..........................52
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
5
10
REFERENCES ...........................................................................................................53
11
DOCUMENT HISTORY ...........................................................................................53
LIST OF TABLES
Table 7.3.2.1-1:
Demographic Characteristics.....................................................................16
Table 7.3.2.1-2:
Baseline Disease Characteristics................................................................17
Table 7.3.2.1-3:
Other Baseline Characteristics...................................................................18
Table 7.6.1-1:
Adverse Event Summaries.........................................................................26
Table 8.1.2-1:
Visit Windows ...........................................................................................36
Table 9-1:
Snapshot Algorithm Analysis Visit Windows...........................................41
Table 9-2:
Genotypic Substitutions.............................................................................43
Table 9-3:
Cut-offs used by Monogram Biosciences to Determine Reduced 
Susceptibility..............................................................................................45
Table 11-1:
Document History......................................................................................53
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
6
1
BACKGROUND AND RATIONALE
Despite advances in prevention and care, HIV/AIDS remains a significant epidemic in both the 
US and worldwide. AIDS remains the 6th leading cause of death, internationally. Globally, 
approximately 35 million people were living with HIV infection in 2013. A number of these 
patients include those who are treatment-experienced. Note: the use of the term “treatment-
experienced” herein refers to subjects who have failed at least one or two antiretroviral (ARV) 
regimens and who may be harboring drug resistant virus (current or archived) to at least one drug 
class.
In contrast to current HIV treatment guidelines for treatment-naïve patients, the recommended 
composition of combination antiretroviral therapy (cART) is far less uniform for treatment-
experienced subjects. The level of detail in the DHHS and EACS guidelines leads to a lack of 
uniformity in treatment for patients in later lines of therapy. Moreover, drug related toxicities 
(both short and longer term) in treatment-experienced subjects necessitate vigilance and 
continued monitoring. Thus, there is a need for new and efficacious agents with novel 
mechanisms of action (MOA) and favorable safety/tolerability profiles. Given the aging HIV-1 
infected population and overall fewer number of ARV options for treatment-experienced 
patients, there is a need for a more simplified regimen that may have a better long-term safety 
profile such as that of a nucleoside- and booster-sparing cART regimen. This study evaluates the 
merits of a nucleoside-sparing cART regimen and a nucleoside/booster-sparing cART regimen in 
Stage 1 and 2, respectively.
Given the afore-mentioned challenges with existing treatment in ARV treatment-experienced 
adults, the two primary objectives of this two stage, Phase 2b study are to: 1) To study the 
efficacy of one dose (120mg) of BMS-955176 ( a novel HIV-1 maturation inhibitor) when given 
in combination with atazanavir boosted with ritonavir (ATV/r) 300/100mg and dolutegravir 
(DTG) 50mg in Stage 1, and 2) to study the efficacy of two doses (120 and 180mg) of 
BMS-955176 when given in combination with unboosted ATV 400mg and DTG 50mg in Stage 
2.
Ultimately this Phase 2b clinical trial will provide supportive data in the context of a therapeutic 
dose of BMS-955176 and the clinical safety/efficacy/resistance of the proposed component(s) of 
a single tablet regimen (STR, that is also a nucleoside/ritonavir sparing ARV strategy) for Phase 
3 trial development in HIV-1 infected treatment-experienced subjects. Specifically, two arms in 
Stage 2 will contain the individual ARV components of a potential STR: BMS-955176, ATV, 
and DTG.
Research Hypothesis:  
This Phase 2b study will evaluate whether the combination of BMS-955176 with ATV (with or 
without RTV) and DTG is efficacious, safe, and well-tolerated in HIV-1 infected treatment-
experience adults.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
7
Schedule of Analyses:
A first interim analysis will be conducted after approximately 50% of the randomized subjects 
have completed 24 weeks of therapy in Stage 1. This analysis will use the BMS equivalent of 
SDTM (Study Data Tabulation Model) data to facilitate the development of models for 
population pharmacokinetics, exposure-response relationships and viral kinetics.
A second interim analysis will be conducted after the last subject has completed 24 weeks of 
therapy in Stage 1. This will be a complete analysis of the available efficacy, safety and 
resistance data.
An interim analysis might be conducted after the last randomized subject in Stage 1 is on 
tratment for 48 weeks in case the continuation dose couldn’t be selected based on the Week 24 
results.
An interim analysis will be conducted after the last randomized subject in Stage 2 is on treatment 
for 24 weeks. The expectation is that the last subject in Stage 1 will have completed the Week 96 
visit by that time. 
An interim analysis will be conducted after the last randomized subject in Stage 2 completes the 
Week 48 visit. The analyses related to the first 48 weeks of treatment for Stage 2 will be 
performed.
The final analysis will be conducted after the last randomized subject in Stage 2 completes the 
Week 96 visit. 
2
OBJECTIVES
2.1
Study Design
This is a randomized, active-controlled, staged, open-label clinical trial.
The screening period begins on the day the subject signs on the informed consent form. If the 
subject meets all eligibility criteria, the subject is to be randomized within the 42-day screening 
period.
Approximately 200 treatment-experienced HIV-1 subjects will be randomized to one of five 
treatment arms (approximately 40 per arm) in a staged fashion. 
The data from the Week 24 analysis of Stage 1 and AI468038, including safety, efficacy and 
pharmacokinetics, will be examined to trigger the start of Stage 2 and confirm the two doses of 
BMS-955176 for study in Stage 2.
Stage 1:
In Stage 1, approximately 80 subjects will be randomly assigned 1:1 to one of two treatment 
arms and on Day 1, they will begin dosing with:

Arm 1: BMS-955176 120mg QD + ATV/r 300/100mg QD + DTG 50mg QD, or
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
8

Arm 2: TDF 300mg QD + ATV/r 300/100mg QD + DTG 50mg QD.
Stage 2:
In Stage 2, approximately 120 subjects will be randomly assigned 1:1:1 to one of three treatment 
arms and on Day 1, they will begin dosing with:

Arm 3: BMS-955176 120 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 4: BMS-955176 180 mg QD + ATV 400 mg QD + DTG 50 mg QD, or

Arm 5: TDF 300 mg QD + ATV/r 300/100 mg QD + DTG 50 mg QD.
Subjects in all arms will have the opportunity to participate in an elective Intensive PK substudy 
visit at Week 2 (window for visit: Day 12-16). Approximately 60 subjects, 12 subjects from each 
arm, are expected to participate in the substudy; BMS may allow the substudy to over-enroll in 
an effort to have a sufficient number of complete datasets.
Subjects are expected to be treated for the duration of 96 weeks. After Day 1 and the optional 
Intensive PK visit at Week 2, subjects are required to attend 12 more in-clinic study visits over 
the 96-week treatment period, as follows: 

Visits are conducted every 4 weeks from Week 4 through Week 16

Visits are conducted every 8 weeks from Week 24 through Week 48

Visits are conducted every 12 weeks from Week 60 through Week 96
Selection of Continuation Dose and Switch for Stage 1
Once all subjects in Stage 1 have reached Week 24, BMS will conduct an interim analysis of 
efficacy, safety, resistance and pharmacokinetics. An analysis of virologic futility will also occur 
at Week 24. If Arm 1 meets criteria for virologic futility at Week 24, the clinical trial will be 
terminated.
Based upon the Week 24 analysis of Arms 1 and 2, combined with the Week 24 analysis of all 
arms in the parallel AI468038 study, a continuation dose of BMS-955176 for Arm 1 will be 
selected for subjects in Arm 1. Subjects in the BMS-955176 treatment arm 1 may subsequently 
be transitioned to a selected continuation dose of BMS-955176. Subjects in the Arm containing 
TDF (i.e., Arm 2) will continue with the TDF treatment regimen. The assigned backbone will 
remain unaltered. The Week 24 efficacy, safety and pharmacokinetic analyses from Stage 1 and 
study AI468038 will also trigger the start of Stage 2. If the continuation dose cannot be clearly 
identified using the Week 24 data, the study will continue in original fashion until an analysis of 
the Week 48 data can be performed and the continuation dose is selected. If a continuation dose 
cannot be selected based upon the Week 24 data, this does not preclude the ability to start 
recruitment of Stage 2.
After the continuation dose is selected and once all of the logistics have been completed globally, 
the transition of the subjects in Arm 1 to the continuation dose will occur. It is anticipated that 
this transition will occur on or after all subjects have reached Week 48. 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
9
Selection of Continuation Dose and Switch for Stage 2
Once all subjects in Stage 2 have reached Week 24, BMS will conduct an interim analysis of 
efficacy, safety, resistance and pharmacokinetics. An analysis of virologic futility will also occur 
at Week 24. If a BMS-955176 dose arm meets criteria for virologic futility at Week 24, subjects 
in said arm will begin dosing with the next highest available remaining dose of BMS-955176.
The totality of data from AI468038 and AI468048 (Stage 1 and 2) will be used to select a 
continuation dose of BMS-955176 for Arms 3 and 4. Subjects in the BMS-955176 treatment 
arms 3 and 4 will subsequently be transitioned to the selected continuation dose of BMS-955176. 
It is anticipated that this transition may occur on or after all subjects in Stage 2 have reached 
Week 48. The assigned backbone will not change. Subjects in the TDF-containing arm (i.e., 
Arm 5) will continue with their assigned treatment regimen.
2.2
Treatment Assignment
Approximately 200 treatment-experienced HIV-1 subjects will be randomized to one of five 
treatment arms (approximately 40 per arm) in a staged fashion. 
Stage 1:
In Stage 1, approximately 80 subjects will be randomly assigned 1:1 to one of two treatment 
arms:

Arm 1: BMS-955176 120mg QD + ATV/r 300/100mg QD + DTG 50mg QD, or

Arm 2: TDF 300mg QD + ATV/r 300/100mg QD + DTG 50mg QD.
Stage 2:
In Stage 2, approximately 120 subjects will be randomly assigned 1:1:1 to one of three treatment 
arms:

Arm 3: BMS-955176 120mg QD + ATV 400mg QD + DTG 50mg QD, or

Arm 4: BMS-955176 180mg QD + ATV 400mg QD + DTG 50mg QD, or

Arm 5: TDF 300mg QD + ATV/r 300/100mg QD + DTG 50mg QD.
2.3
Blinding and Unblinding
This is an open-label study.
2.4
Protocol Amendments
The following protocol amendments and administrative letters have been processed and changes 
that may affect the statistical analysis are listed below:

Amendment 1 (Jan 28, 2015 - site specific): 

Permit the collection and storage of blood samples for use in future exploratory 
pharmacogenetic research.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
10

Amendment 2 (Jan 28, 2015 - country specific, Brazil)

To comply with the Brazilian law in force regarding post study access to therapy. 

Amendment 3 (Feb 13, 2015 - country specific, Argentina)

In response to a request from the Argentinean Health Authority: in case of pregnancy the 
study drug should be permanently discontinued.

Amendment 4 (March 19, 2015)

Incorporated information that more clarifies the Week 24 data (consisting of efficacy, 
safety and pharmacokinetic data) to be used to confirm the doses for Stage 2 and to 
trigger the start of Stage 2 of the study relative to other analyses conducted under the 
protocol for other purposes. 

Removed the requirement that all sparse PK samples need to be collected as pre-AM dose 
samples. Only one visit Weeks 4-24 (as opposed to all visits Week 4-24) needs to be 
performed in the morning and to have the blood collected as a pre-AM dose sampling.

Amendment 5 (June 3, 2015)

To mitigate the risk of randomizing subjects infected with HIV-1 with an unknown 
efficacy profile, exclusion criteria have been modified to now exclude subjects with 
Clade AE as well as those subjects who have failed a previous boosted PI- or Integrase 
strand transfer inhibitor (INSTI)-containing regimen for which resistance analyses were 
not conducted at the time of failure.

Pregnancy was added as a reason to be discontinued from the study and the practice of 
Rescreening was more clearly defined, an administrative change was made to clearly 
indicate that AIDS History is taken at Screening.

At Week 24, a Time to Loss of Virologic Response analysis will be conducted as a 
sensitivity analysis that compliments the snapshot analysis, and a definition of virologic 
rebound was added.

Amendment 6 (July 15, 2015 - country specific: Argentina)

Section 3.2: Eliminate bullet d) in order to be consistent with local regulations.
3
ENDPOINTS
3.1
Primary
Primary Objective Stage 1

To assess the antiviral efficacy of BMS-955176 120mg, and a TDF 300mg-containing arm, 
each when given in combination with ATV/r 300/100mg and DTG 50mg by determining the 
proportion of treatment-experienced subjects with plasma HIV-1 RNA < 40c/mL at Week 24 
in Stage 1.
Primary Objective Stage 2

To assess the antiviral efficacy of two doses (120 and 180mg) of BMS-955176, each when 
given in combination with unboosted ATV 400mg and DTG 50mg, and to assess the antiviral 
efficacy of TDF 300mg when given in combination with ATV/r 300/100mg and DTG 50mg 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
11
by determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 
40c/mL at Week 24 in Stage 2. 
3.2
Secondary

To assess the antiviral efficacy of BMS-955176 Arms, and TDF-containing regimens (TDF + 
ATV/r + DTG), by determining the proportion of treatment-experienced subjects with plasma 
HIV-1 RNA < 40c/mL at Weeks 48 and 96

To assess the antiviral efficacy of BMS-955176 Arms, and TDF-containing regimens, by 
determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA < 
200c/mL at Weeks 24, 48, 96

To assess the emergence of HIV drug resistance in samples selected for drug resistance 
testing

To assess efficacy of BMS-955176 Arms, and TDF-containing regimens, by using the mean 
changes from baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ T-
cells 

To assess the safety and tolerability of BMS-955176 in treatment-experienced subjects by 
measuring frequency of SAEs and AEs leading to discontinuation

To assess disease progression as measured by the occurrence of new AIDS defining events 
(CDC Class C events)

To characterize the pharmacokinetics of BMS-955176 when co-administered with ATV 
(with or without ritonavir) and DTG in treatment-experienced HIV-1 infected subjects. 
3.3
Exploratory

To determine the effect of BMS-955176 Arms, and TDF-containing regimens, on renal 
clinical parameters and biomarkers through Weeks 48 and 96

To determine the effect of BMS-955176 Arms, and TDF-containing regimens, on bone 
biomarkers through Weeks 12 and 24

To assess the impact of baseline (pre-therapy) Gag polymorphisms on the efficacy of BMS-
955176 by determining the proportion of treatment-experienced subjects with plasma HIV-1 
RNA < 40c/mL, HIV-1 RNA < 200c/mL, and the changes from baseline in log10 HIV-1 
RNA at Weeks 24, 48 and 96, by baseline polymorphisms 

To characterize the steady-state plasma PK of DTG when co-administered with BMS-955176 
and ATV (with or without RTV) in treatment-experienced subjects. The effect of BMS-
955176 on DTG PK in the presence of ATV (without RTV) may be assessed relative to 
historical data

To compare steady-state exposures of DTG when co-administered with BMS-955176 and 
ATV/RTV to DTG when co-administered with TDF and ATV/RTV

To characterize the PK of ATV when co-administered with DTG and BMS-955176, with or 
without RTV

To explore PK/PD and PK/viral kinetic (VK) relationships between BMS-955176, ATV, 
and/or DTG exposure and both efficacy and safety endpoints
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
12

To assess the impact of the study therapies on health-related quality of life measures.
4
ENDPOINTS
4.1
Primary Endpoints

Proportion of subjects with plasma HIV-1 RNA < 40c/mL at Week 24 for Stage 1, assessed 
using the snapshot algorithm 

Proportion of subjects with plasma HIV-1 RNA < 40c/mL at Week 24 for Stage 2, assessed 
using the snapshot algorithm
4.2
Secondary Endpoints

Proportion of subjects with plasma HIV-1 RNA < 40c/mL at Weeks 48 and 96, assessed 
using the snapshot algorithm

Proportion of subjects with plasma HIV-1 RNA < 200c/mL at Weeks 24, 48 and 96, assessed 
using the snapshot algorithm

Emergence of HIV drug resistance among samples selected for drug resistance testing will be 
assessed using the most recent version of the IAS-USA list of HIV-1 drug resistance 
mutations

Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the 
percentage of CD4+ T-cells over time will be assessed using on-treatment laboratory results, 
and pre-specified visit windows

Frequency of SAEs and AEs leading to discontinuation will be tabulated directly from the 
case report forms (CRFs). The summary will count the number of subjects that have at least 
one event

Occurrence of new AIDS defining events will be tabulated from the CRFs. The summary 
will count the number of subjects that have at least one event

Steady state PK parameters of BMS-955176: Cmax, Tmax, Ctau, C0 and AUC(TAU) will be 
assessed using the intensive PK data, collected at Week 2 from a subset of subjects
4.3
Exploratory Endpoints

Changes from baseline in renal biomarkers over time will be assessed using on-treatment 
laboratory results, and pre-specified visit windows

Changes from baseline in bone biomarkers over time will be assessed using on-treatment 
laboratory results, and pre-specified visit windows

Proportion of subjects with plasma HIV-1 RNA < c/mL and HIV-1 RNA < 200c/mL at 
Weeks 24, 48 and 96, by baseline polymorphism, will be assessed using the snapshot 
algorithm. The changes from baseline in log10 HIV-1 RNA at Weeks 24, 48 and 96, by 
baseline polymorphism will be assessed using on-treatment laboratory results, and pre-
specified visit windows.

Steady-state PK parameters of DTG: Cmax, Tmax, Ctau, C0 and AUC(TAU) will be assessed 
using the intensive PK data, collected at Week 2 from a subset of subjects
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
13

Steady-state PK parameters of ATV: Cmax, Tmax, Ctau, C0 and AUC(TAU) will be assessed 
using the intensive PK data, collected at Week 2 from a subset of subjects

Population PK modeling to obtain population-derived average steady state exposure of BMS-
955176 that will be used in exposure-response and PK/VK assessments. The population PK, 
exposure-response, and viral kinetic analyses will be described in a separate analysis plan.

Quality of life is assessed using the EQ-5D-3L and the Functional Assessment of HIV 
Infection (FAHI) instruments. 
5
SAMPLE SIZE AND POWER
This is an estimation study, without statistical testing, and hence there are no power 
considerations.
It is expected that response rate for the primary endpoint for all five arms will be somewhere 
around 80%.  With this response rate, and 40 subjects per arm, an exact Clopper-Pearson 95% 
confidence interval would run from roughly 64% to 91%.
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES
6.1
Study Periods
This study consists of the following periods:

Screening (or Pre-randomization) Period: begins on the day the subject signs the informed 
consent and continues through Day 1 prior to dosing. The screening period last about 42 
days.

Open-label Treatment Period (or On-treatment Period): begins on the first day of open-label 
therapy and ends after 96 weeks of dosing or early termination, whichever comes first.
6.2
Treatment Regimens
The treatment regimens are defined as follows:

As-randomized refers to the treatment regimen assigned at randomization. Accrual, 
disposition, demographic and baseline characteristics, protocol deviations and efficacy 
results will be presented as-randomized.

As-treated refers to the actual treatment regimen received. Subjects who receive an incorrect 
study therapy for the entire period of treatment are grouped according to the first incorrect 
study regimen received. Otherwise, subjects are grouped according to their randomized 
treatment regimen. Subjects who never receive study therapy, have their as-treated treatment 
regimen coded as “missing”. Results for exposure, concomitant medication, resistance, safety 
and PK parameters, and outcomes research scales will be presented as-treated.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
14
6.3
Populations for Analyses
Populations for analyses consist of enrolled, randomized and treated subjects:

Enrolled subjects are those who signed an informed consent form and were assigned a Patient 
Identification number (PID).

Randomized subjects are enrolled subjects who received a treatment assignment from the 
IVRS. The randomized subjects will be used to assess subject disposition.

Treated subjects (also referred to as mITT analysis set) are randomized subjects who 
received at least 1 dose of study therapy. The treated subjects will be used to assess 
demography and baseline characteristics, protocol deviations, exposure, concomitant 
medication, efficacy, resistance, safety and outcomes research scales.

PK population is defined as all treated subjects who have any available concentration-time 
data. The evaluable PK population is a sub-population including all treated subjects who 
have adequate PK profiles.
7
STATISTICAL ANALYSIS
This section describes the analyses for the Week 24 primary analysis and the Week 48 and 96 
secondary analyses.
Analyses do not exclude data obtained after the start of prohibited medication, unless otherwise 
specified.
7.1
General Methods
This is an estimation study. Formal comparisons of treatment arms will not be performed except 
for the virologic futility analyses performed at Week 24 of Stage 1 and Stage 2 (see 
Section 7.5.4).
Presentations will present treatment arms as the original treatment arms, before the potential 
movement to the continuation BMS-955176 dose. Data from Arms 2 and 5 will not be pooled
unless otherwise specified. Separate outputs will be created for each stage unless otherwise 
specified.
Categorical variables will be tabulated with counts and percentages.
Continuous variables will be summarized with univariate statistics.
Subjects must have a baseline measurement and at least one on-treatment measurement to be 
evaluable for change from baseline analyses. All data will be displayed for statistics that do not 
depend on a baseline measurement.
Laboratory parameters will be summarized using SI and US values and units.
Statistical analyses are carried out in SAS version 9.1.3 (Statistical Analysis System, SAS 
Institute, North Caroline, USA) or higher, unless otherwise indicated.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
15
7.2
Study Conduct
Protocol deviations that are programmable from the database and that could potentially affect the 
interpretability of the study results are deemed relevant protocol deviations. Relevant protocol 
deviations occurring during the study, are determined prior to unblinding. The proportion of 
subjects with relevant protocol deviations through the analysis time point is summarized by 
treatment arm and overall for the treated subjects.
The list of relevant deviations is provided below:

Subjects with Screening plasma HIV-1 RNA < 400c/mL

Subjects with Screening CD4 T-cell count < 50cells/mm3

Subjects with Screening Estimated eGFR < 60mL/min (CKD-EPI formula)

Subjects resistant to study drugs (unboosted ATV, FC < 2.2; DTG; and TDF) based on 
Screening genotype/phenotype report(s)

Subjects who received the wrong study medication

Subjects who took prohibited concomitant medications, as specified in the protocol, for more 
than 3 consecutive days.

Subjects with gaps in study medication dosing greater than 3 consecutive days.
7.3
Study Population
7.3.1
Subject Disposition
The disposition of subjects will be summarized separately for the pre-randomization period and 
the on-treatment period. 
The pre-randomization status will be summarized for all enrolled subjects. This summary will 
include the number of subjects enrolled, randomized, not randomized and the reasons for not 
being randomized.
The end of Week 96 subject status will be summarized by treatment arm and overall for the 
randomized subjects. This summary will include the number of subjects randomized, completing 
Week 96 and not completing Week 96. The reasons for not completing Week 96 will also be 
included.
A separate output will summarize the number of subjects in each population.
Subjects enrolled and randomized will be summarized by country and study site. . Enrollment by 
age group is summarized analogously. Age groups are: in utero; preterm newborn (gestational 
age < 37 weeks); newborns (0 to 27 days); infants and toddlers (28 days to 23 months); children 
(2 to 11 years); adolescents (12 to 17 years); adults (18 to 64 years); adults (65 to 84 years); 
adults (85 years).
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
16
7.3.2
Demographics and Other Characteristics
All baseline presentations will identify subjects with missing measurements. In tabulations of 
categorical variables, percentages are based on subjects with measurements.
7.3.2.1
Demographics and Other Baseline Characteristics
Demographic and other baseline characteristics (including disease characteristics) will be 
summarized by as-randomized treatment arm and overall for the treated subjects. Available 
demographic characteristics will also be summarized for subjects enrolled but not randomized.
Table 7.3.2.1-1:
Demographic Characteristics
Characteristic
Summarized as
Categories
Gender
Categorical
Male, Female
Age
Continuous and Categorical
< 50 , 50 years
Race
Categorical
White,
Black/African American,
American Indian/Alaska Native,
Asian,
Native Hawaiian/Other Pacific Islander,
Other
Ethnicity (US only)
Categorical
Hispanic/Latino
Non Hispanic/Latino
Geographic Region
Categorical
Europe
Asia
Australia
South America
North America
Africa
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
17
Table 7.3.2.1-2:
Baseline Disease Characteristics
Characteristic
Summarized as
Categories
Plasma HIV-1 RNA
Continuous (log10c/mL) and 
Categorical
<30,000c/mL
30,000 to < 100,000c/mL
100,000 to < 500,000c/ mL
500,000c/mL
CD4+ T-cell count
Continuous and Categorical
<50cells/mm3
50 to < 100cells/mm3
100 to < 200cells/mm3
200 to < 350cells/mm3
350 to < 500cells/mm3
500cells/mm3
CD4+ T-cell percentage
Continuous
CD8+ T-cell count
Continuous
HIV-1 Subtype
Categorical
IC50 for BMS-955176
Continuous
IC50 Fold Change for 
BMS-955176
Categorical
< 1.0
1.0 to < 5
5 to < 10
10 to < 100
100 to < 500
>= 500
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
18
Table 7.3.2.1-3:
Other Baseline Characteristics
Characteristic
Summarized as
Categories
Height
Continuous
Weight
Continuous
BMI
Continuous
Hematology:
Hemoglobin, 
Absolute Neutrophil Count(ANC), 
Platelets, 
White Blood Cell Count (WBC)
Categorical
Normal, Grade 1, Grade 2, Grade 3, Grade 4
Liver Function Tests:
Alanine Aminotransferase (ALT), 
Aspartate Aminotransferase (AST), 
Albumin, serum, low
Alkaline Phosphatase, 
Total Bilirubin
Categorical
Normal, Grade 1, Grade 2, Grade 3, Grade 4
Enzymes:
Creatinine Kinase (CK), 
Lipase
Categorical
Normal, Grade 1, Grade 2, Grade 3, Grade 4
Renal Function Tests:
Creatinine, 
Creatinine Clearance (eGFR),
Uric Acid
Categorical
Normal, Grade 1, Grade 2, Grade 3, Grade 4
Electrolytes:
Bicarbonate, serum, low
Calcium, serum, high
Calcium, serum, low
Potassium, serum, high
Potassium, serum, low
Sodium, serum, high
Sodium, serum, low
Categorical
Normal, Grade 1, Grade 2, Grade 3, Grade 4, 
Fasting Lipids:
Total Cholesterol, 
LDL-Cholesterol, 
Triglycerides
Categorical
Normal, Grade 1, Grade 2, Grade 3, Grade 4
Fasting Glucose:
Glucose, serum, high
Glucose, serum, low
Categorical
Normal, Grade 1, Grade 2, Grade 3, Grade 4, 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
19
Baseline laboratory values are graded using the DAIDS Toxicity Grades tables as presented in 
Appendix 3 of the protocol. 
Physical examination findings at baseline will be summarized by randomized treatment group 
and overall.
7.3.2.2
Pre-treatment CDC Class C AIDS Events
Pre-treatment CDC Class C AIDS events (as collected on the AIDS defining events CRF page)
will be summarized by as-treated treatment arm and overall for the treated subjects. Pre-
treatment events are those with an onset before the start of any study therapy. Documented 
clinical diagnoses are used to define AIDS (see Protocol Appendix 2).
7.3.2.3
Previous Medication
Previous medications are defined as those medications that are taken before the start of any study 
therapy. Previous medications will be summarized by as-treated treatment arm and overall for 
the treated subjects. Medications are presented alphabetically by anatomic class, therapeutic 
class and generic name. The WHO dictionary is used to code the non-study medication.
7.3.2.4
Baseline Resistance
Phenotypic resistance to a drug is defined as a fold change (i.e., ratio of the 50% inhibitory 
concentration (IC50) of the clinical isolate to the IC50 of the reference strain) which is greater 
than the cut-off for reduced susceptibility.
The number of subjects with phenotypic resistance at baseline will be summarized for all treated 
subjects, for subjects who had on-study resistance testing done and for treated subjects that are 
identified as protocol defined virologic failures (see Protocol Section 5.4.1.3) using the 
following, mutually exclusive categories:

No resistance to drugs in any class

1 NRTI

1 NNRTI

1 PI

1 INI

1 NRTI and 1 NNRTI

1 NRTI and 1 PI

1 NRTI and 1 INI

1 NNRTI and 1 PI

1 NNRTI and 1 INI

1 PI and 1 INI

1 NRTI and 1 NNRTI and 1 PI

1 NRTI and 1 NNRTI and 1 INI
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
20

1 NRTI and 1 PI and 1 INI

1 NNRTI and 1 PI and 1 INI

1 NRTI and 1 NNRTI and 1 PI and 1 INI
The number of subjects with phenotypic resistance will also be summarized by class and drug 
name.
The genotypic resistance profile at baseline will be summarized by treatment arm for all treated 
subjects, for subjects who had on-study resistance testing done and for treated subjects that are 
identified as protocol defined virologic failures. Tabulations will present genotypable isolates, 
those with PI substitutions from genotypable isolates, those with selected RT substitutions from 
genotypable isolates, and those with integrase substitutions from genotypable isolates using the 
most current version of the International AIDS Society-USA (IAS-USA) list (see 
APPENDIX 2). The genotypic resistance profile at baseline will also be summarized by baseline 
HIV subtype for all treated subjects.
In addition, baseline gag polymorphisms at positions 362, 364, 369 and 370 (relative to the wild 
type HxB2) will be summarized by treatment arm. This list of positions might be updated. The 
summary will report single mutations and combinations of mutations. The baseline gag 
polymorphisms at selected positions will also be summarized by baseline HIV subtype for all 
treated subjects.
Any deviation from the wild type virus (HxB2) in baseline gag sequencing will be summarized 
for treated subjects by treatment arm. This summary will also be provided by baseline HIV 
subtype.
The summaries for gag will be provided for treated subjects, for treated subjects who had on-
study resistance testing done and for treated subjects that are identified as protocol defined 
virologic failures.
7.4
Extent of Exposure
Extent of exposure is presented for treated subjects by as-treated treatment arm.
7.4.1
Study Therapy
Time (in days) on study therapy will be summarized by treatment arm. Time on study therapy is 
defined as the difference between the earliest last dose date of any component of the treatment 
arm and the first dose date of study treatment plus 1 day. 
Time on study therapy and average daily dose will be summarized for each individual drug 
component by treatment arm. Time on an individual drug component is defined as the number of 
days between the first dose date and the last dose date of the drug. The average daily dose is the 
total amount of drug in grams divided by the number of days between the first dose date and the 
last dose date of the drug.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
21
The time on BMS-955176 and average daily dose after the switch to the continuation dose will 
be summarized for subjects who switched to the continuation dose after Week 24, rather than 
starting on the continuation dose at the time of randomization. Time on BMS-955176 
continuation dose is defined as the difference between the last dose date of continuation dosing 
and the first dose date of continuation dosing plus 1 day. 
7.4.2
Discontinuation of Study Therapy
Time (in days) on any study therapy will be described by a Kaplan-Meier curve and life table 
with the Kaplan-Meier estimates.
Discontinuations from study therapy are considered events in this analysis. For subjects who 
have not discontinued, time on study therapy is censored at the last recorded dose stop date of 
any study therapy. For the purpose of this analysis, we will consider the start date and 
event/censor date regardless of any interruptions. 
7.4.3
Interruption or Delay of Study Therapy
Interruptions of study therapy greater than 3 consecutive days will be summarized by treatment 
arm and for each drug in the regimen. Interruptions are identified from complete dosing records 
in which either the number of units per day or the number of doses per day is zero.
7.4.4
Concomitant Therapy
Concomitant medications are defined as those taken at any time on or after the start date of study 
therapy and before or on the last dose date of study therapy. Concomitant medications will be 
summarized by treatment arm and overall for the treated subjects. Medications are presented 
alphabetically by anatomic class, therapeutic class and generic name. The WHO dictionary is 
used to code the non-study medication.
7.5
Efficacy
Efficacy endpoints are evaluated for treated subjects by as-randomized treatment arm during the 
treatment period through a specific analysis week. Measurements obtained on treatment and 
before or on the analysis week date (see Section 8.2) will be included.
7.5.1
Primary Efficacy Endpoint: Proportion of Subjects with Plasma HIV-1 
RNA < 40c/mL at the Week 24 Snapshot
The primary efficacy endpoint is the proportion of subjects with plasma HIV-1 RNA < 40c/mL 
at the Week 24 snapshot. The primary analysis will be based on a modified ITT (mITT) 
approach. A sensitivity analysis will be conducted using an observed values approach. The two 
approaches will be implemented as follows:

Modified ITT: The numerator will be based on subjects with plasma HIV-1 RNA < 40c/mL 
at Week 24. The denominator will be based on all treated subjects.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
22

Observed values: Similar to the mITT approach, the numerator will be based on subjects with 
plasma HIV-1 RNA < 40c/mL at Week 24. However, the denominator will be based on 
treated subjects with plasma HIV-1 RNA at Week 24.
Response rates will be tabulated by treatment arm with exact (Clopper-Pearson) binomial 95% 
confidence intervals.
This endpoint is assessed with the snapshot algorithm. The snapshot algorithm is described in 
detail in Appendix 1 of the CDER (2013) draft guidance1 on developing antiretroviral drugs (see 
also APPENDIX 1 of this SAP). If the draft guidance is superseded, and development timelines 
permit any needed changes, the instructions from the new guidance should be followed.
The main principle of the snapshot analysis is that the primary efficacy endpoint is intended to be 
primarily a virologic endpoint and not a clinical endpoint. The snapshot algorithm follows a 
“Virology First” hierarchy. The hierarchy for assessing percentages is “HIV-1 RNA < Limit of 
Detection” or “HIV-1 RNA Limit of Detection” first for any given time window followed by 
reasons for “No Virologic Data in the Window”.
The snapshot approach algorithm is based on the event occurring within a visit window which is 
outlined in Section 8.1. 
Optimized Background Therapy (OBT) Substitutions
Changes in background therapy are not allowed per protocol. Subjects who do change their dose 
for TDF in the event of treatment-limiting renal toxicity will be considered virologic failure if 
they have HIV-1 RNA > 40 at the time of the change.
Movement of a subject to the continuation dose of BMS-955176 will not be a cause for 
classifying a subject as a virologic failure.
The snapshot analysis must include a table that is of the same format shown in Table B (line 
1209) of the draft guidance. A more detailed presentation that breaks down the FDA categories 
into finer detail, may also be provided. The snapshot analysis will be accompanied by a detailed 
listing that facilitates finding the patients in each category described in the table.
The snapshot analysis is supplemented by a Time to Loss of Virologic Response (TLOVR) 
analysis at Weeks 24. Analyses are presented for the randomized treatment groups both 
separately and combined. TLOVR analyses are described in APPENDIX 3.
7.5.1.1
Summaries of Primary Efficacy Endpoint Within Subgroups
The primary efficacy endpoint will be summarized within the following subgroups using the 
mITT and the observed values approach:

Baseline viral load: < 100,000c/mL, 100,000c/mL

Baseline CD4 category: < 100cells/mm3, 100 to < 200cells/mm3, 200 to < 350cells/mm3, 
350 to < 500cells/mm3, 500cells/mm3

Gender
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
23

Race

HIV-1 clade
7.5.2
Secondary Efficacy Endpoints
7.5.2.1
Proportion of Subjects with Plasma HIV-1 RNA < 40c/mL at Weeks 48 
and 96
The proportion of subjects with HIV1 RNA < 40c/mL at Weeks 48 and 96 will be assessed 
analogously to the primary efficacy endpoint using the snapshot algorithm. Summaries within 
subgroups identified for the primary analysis will be provided for Week 48 and 96 using the 
mITT and the observed values approach. Also a time to loss of virologic response analysis will 
be done.
7.5.2.2
Proportion of Subjects with Plasma HIV-1 RNA < 200c/mL at the Week 
24, 48 and 96 Snapshot
The proportion of subjects with plasma HIV-1 RNA < 200c/mL at Week 24, 48 and 96 will be 
summarized using mITT and the observed values approach, analogously to the primary efficacy 
endpoint using the snapshot algorithm. No summaries within subgroups will be provided.
7.5.2.3
Change from Baseline in Plasma HIV-1 RNA (log10) over Time
The change from baseline in plasma HIV-1 RNA (log10) will be summarized over time for the 
treated subjects using observed values. The mean changes from baseline will be plotted at each 
scheduled visit (except Week 2) through Week 96 by treatment arm, with error bars representing 
1 standard error. The change from baseline in plasma HIV-1 RNA (log10) at Week 24, 48 and 96 
will be presented graphically using box plots. The change from baseline will also be provided for 
the subgroups identified for the primary analysis.
7.5.2.4
Changes from Baseline in CD4+ and CD8+ T-cell Count over Time
CD4+ and CD8+ T-cell counts and changes from baseline will be summarized at each scheduled 
visit through Week 96 by treatment arm using observed values. The mean changes from baseline 
will be plotted at each scheduled visit through Week 96 by treatment arm, with error bars 
representing 1 standard error. The change from baseline in CD4+ and CD8/ T-cell counts at 
Week 24, 48 and 96 will be presented graphically using box plots. Also the percentage of CD4+ 
T-cells and changes from baseline will be summarized at each scheduled visit through Week 96. 
The change from baseline will also be provided for the subgroups identified for the primary 
analysis.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
24
7.5.2.5
Newly-emergent Genotypic Substitutions, IC50 Fold Changes from 
Baseline and Newly-emergent Gag Polymorphisms 
Viral resistance is measured using the “PhenoSense GT plus Integrase” assay from Monogram 
(LabCorp). The PhenoSense GT plus Integrase is used to determine both genotypic and 
phenotypic resistance to Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside 
Reverse Transcriptase Inhibitors (NNRTIs), Integrase Inhibitors (INIs), and Protease Inhibitors 
(PIs). The “PhenoSense Gag” assay is used for determining phenotypic susceptibility to 
BMS-955176. HIV-1 Gag sequencing data will be obtained from the NGS-Gag Quantitative 
Sequencing (QS) assay. 
Genotypic substitutions and phenotypic resistance profiles focus on subjects with on-treatment 
isolates.
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change the cut-off 
for reduced susceptibility and an on-treatment fold change > the cut-off for reduced
susceptibility. The newly emergent phenotypic resistance profile (using all on-treatment isolates) 
will be tabulated by treatment arm for treated subjects with on-treatment resistance testing done. 
Newly emergent phenotypic resistance to BMS-955176 is defined as a baseline fold change IC50 
and an on-treatment fold change IC50 > 3. The newly emergent phenotypic resistance to 
BMS-955176 (using all on-treatment isolates) will be tabulated by treatment arm for treated 
subjects with on-treatment resistance testing done. 
Newly emergent genotypic substitutions (using all on-treatment isolates) are tabulated by 
treatment arm for treated subjects with on-treatment resistance testing done. The presentation 
will be similar to the one for baseline genotypic substitutions. 
The maximum change from baseline in BMS-955176 IC50 and the maximum BMS-955176 fold 
change IC50 (FC-IC50) through Week 96 will be summarized for all treated subjects with on-
treatment phenotypic resistance profile. In addition, the proportion of subjects with a > 3 fold 
increase from baseline in BMS-955176 FC-IC50 (i.e., BMS-955176 FC-IC50 on-treatment 
divided by BMS-955176 FC-IC50 at baseline > 3) will be summarized. The Gag polymorphisms 
will be summarized for subjects with a > 3 fold increase from baseline in BMS-955176 FC-IC50. 
These summaries will use all of the data present in the database at the time of lock.
Newly emergent Gag polymorphisms at the selected positions will be summarized by treatment 
arm for treated subjects with on-treatment resistance testing done, overall and by baseline HIV 
subtype. In addition, any newly emergent Gag deviation will be summarized for treated subjects 
with on-treatment resistance testing done, overall and by baseline HIV subtype.
All summaries described in this section will also be provided for treated subjects that are 
identified as protocol defined virologic failures.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
25
Protocol Defined Virologic Failure (PDVF) is defined by a subject meeting one of the following 
criteria (see Protocol, Section 5.4.1.2):

Confirmed > 1 log10c/mL increase in HIV-1 RNA at any time above nadir level where nadir
is 40c/mL

Confirmed HIV-1 RNA 400c/mL after Week 24

Confirmed HIV-1 RNA 40c/mL if prior suppression to < 40c/mL

Failure to have the last on-treatment HIV-1 RNA to < 400c/mL within Week 24, 48, or 96 
week snapshot window

Failure to achieve > 1 log10c/mL decrease in HIV-1 RNA by Week 8
7.5.3
Exploratory Efficacy Endpoints
7.5.3.1
Proportion of Subjects with Plasma HIV-1 RNA within Certain Range 
over Time
The proportion of subjects with HIV-1 RNA:

< 40c/mL

40 to < 100c/mL

toc/mL

200 to < 400c/mL

> 400c/mL
will be presented by visit using the observed values approach.
7.5.3.2
Efficacy Summaries by Baseline Gag Polymorphisms
To assess the impact of baseline gag polymorphisms the following efficacy endpoints will be 
summarized by all combinations of baseline gag polymorphisms at selected positions:

Proportion of subjects with plasma HIV-1 RNA < 40c/mL at Weeks 24, 48 and 96

Proportion of subjects with plasma HIV-1 RNA < 200c/mL at Weeks 24, 48 and 96

Change from baseline in log10 HIV-1 RNA at Weeks 4, 8, 12, 24, 48 and 96
7.5.4
Futility Analysis
An analysis of virologic futility will be performed at Week 24 when the last randomized subject 
in Stage 1 completes the Week 24 visit. This analysis will be conducted to evaluate whether the 
BMS-955176 arm shows significantly worse antiviral efficacy than the TDF arm. The proportion 
of subjects with HIV-1 RNA < 40c/mL at Week 24 will be evaluated using the FDA snapshot 
algorithm. The comparison of the BMS-955176 arm to the TDF arm will be made with one-sided 
Fisher’s exacts test, conducted at the 0.01 probability level.
An analysis of virologic futility will also be performed at Week 24 when the last randomized 
subject in Stage 2 completes the Week 24 visit. This analysis will be conducted to evaluate 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
26
whether the BMS-955176 arms show significantly worse antiviral efficacy than the TDF arm in 
Stage 2. The proportion of subjects with HIV-1 RNA < 40c/mL at Week 24 will be evaluated 
using the snapshot algorithm. The comparisons of Arms 3 and 4 (BMS-955176) to Arm 5 (TDF) 
will each be made with a one-sided, Fisher’s exact test, conducted at the 0.01 probability level.
7.6
Safety
Safety endpoints include the frequency of adverse events (AEs), serious adverse events (SAEs), 
non-serious adverse events, CDC Class C AIDS events, adverse events leading to 
discontinuations, deaths and other significant adverse events as reported on case report forms. 
Other safety endpoints include laboratory abnormalities, changes in laboratory parameters, 
changes in vital signs and physical measurements, and ECGs. Safety endpoints will not be 
evaluated through a specific analysis week. All safety data available in the database at the time 
of the lock will be included.
Safety summaries are provided for treated subjects by as-treated treatment arm, unless otherwise 
specified.
7.6.1
Overall Adverse Events
Adverse events will be classified by primary System Organ Class (SOC) and Preferred Term 
(PT) according to the latest version of the Medical Dictionary for Regulatory Activities 
(MedDRA) in production at BMS at the time of database lock.
AEs and SAEs with an onset on or after the start of study therapy through 30 days after the last 
dose of study therapy will be considered as occurring during study therapy. These will be 
summarized and presented by SOC and PT both in descending order of frequency over all 
treatment arms, unless otherwise specified.
Table 7.6.1-1:
Adverse Event Summaries
Endpoint
During Study Therapy
During Study Therapy, after
Switch to Continuation Dose
SAEs
X
X
SAEs leading to death a
X
SAEs related to study therapy and 
leading to death a
X
Non-SAEs a
X
AEs leading to discontinuation of study 
therapy
X
X
AEs - All Grades
X
AEs - Grade 2 to 4
X
AEs- Grade 3 to 4
X
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
27
Table 7.6.1-1:
Adverse Event Summaries
Endpoint
During Study Therapy
During Study Therapy, after
Switch to Continuation Dose
Related AEs - All Grades
X
Related AEs - Grade 2 to 4
X
Related AEs - Grade 3 to 4
X
CDC Class C AIDS Events
X
Events of Special Interest
X
Exposure-adjusted Events 
X
Exposure-adjusted SAEs a
X
Exposure-adjusted SAEs related to 
study therapy a
X
Exposure-adjusted non-SAEs a
X
a
ClinicalTrials.gov or EudraCT reporting requirement
7.6.2
Deaths
All deaths recorded on the status page, the AE page or SAE page of the CRF will be considered 
in the analyses. A listing of all deaths that occur will be produced for the enrolled subjects.
7.6.3
Serious Adverse Events
SAEs occurring during study therapy will be summarized by SOC and PT. SAEs leading to death 
and SAEs related to study therapy and leading to death will be summarized in a similar way.
A listing of all SAEs will be produced, displaying all SAEs (including pre-treatment events) for 
enrolled subjects.
7.6.4
Serious Adverse Events Emerging After Switch to Continuation 
Therapy
For subjects who switched to a continuation dose after Week 24, rather than starting on a 
continuation dose at the time of randomization, SAEs with an onset after the start date of 
continuation therapy through 30 days after the last dose of study therapy, will be summarized by 
SOC and PT.
7.6.5
Non-Serious Adverse Events
Non-serious adverse events occurring in at least 5% of the subjects treated will be summarized 
by SOC and PT.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
28
7.6.6
Adverse Events Leading to Discontinuation of Therapy
Adverse events leading to discontinuation will be summarized by SOC and PT.
7.6.7
Adverse  Events Leading to Discontinuation of Therapy After Switch to 
Continuation Therapy
For subjects who switched to a continuation dose after Week 24, rather than starting on a 
continuation dose at the time of randomization, AEs leading to discontinuation with an onset 
after the start date of continuation therapy will be summarized by SOC and PT.
7.6.8
Adverse Events by Relationship
Drug-related adverse events are those with ‘related’ or missing relationship to study drug. Drug-
related adverse events will be summarized by SOC and PT.
7.6.9
Adverse Events by Intensity
Adverse events and drug-related adverse events with the following grades:

all Grades,

Grade 2 to Grade 4,

Grade 3 to Grade 4,
will be summarized by SOC and PT.
Adverse events with missing intensity are included only in the summaries for all grades. If a 
subject has an adverse event with different intensities over time, then only the greatest intensity 
will be presented.
7.6.10
CDC Class C AIDS Events
CDC Class C AIDS events will be summarized and presented by SOC and PT.
7.6.11
Adverse Events of Special Interest
Separate summaries will be provided for the following events of special interest: gastrointestinal 
events. The list of events will be identified before database lock. The definition of 
gastrointestinal events will be based on existing Standardized MedDRA Queries (SMQs) if 
existing SMQs support the events of special interest requirements. If needed, a customized SMQ 
(cSMQ) will be developed. Gastrointestinal events will be summarized by SOC and PT.
7.6.12
Multiple Adverse Events
Several descriptive summaries of adverse events that take into account the number of 
occurrences that an AE was reported by individual subjects will be provided. In order to prepare 
these summaries, the CRF data will be processed according to standard BMS algorithms to 
categorize each line of subject data as a new occurrence or a continuation of an existing event. 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
29
This determination will be based upon onset and resolution dates. Each line of subject data will 
represent the maximum severity observed as well as the last known assessed relationship to study 
medication by the investigator.
This data will be presented as the rate per 100 years of patient exposure. Exposure to study 
medication will be calculated according to approved standard BMS algorithms as well.
As an example, if 5 subjects report 7 unique episodes of headache and had a combined 
cumulative exposure of 20 years to study medication, the incidence rate is reported as 7 / 20 *
100 or 35 cases per 100 patient years of exposure.
For adverse events with multiple occurrences, the following will be provided:

A table showing the total number and rate (exposure adjusted) of occurrences for general 
AEs occurring in at least 5% of the subjects treated.

A listing displaying the unique instances of all AEs (i.e., after duplicates have been 
eliminated and overlapping and contiguous occurrences of the same event have been 
collapsed).
Exposure-adjusted summaries will also be provided for SAEs, SAEs related to study therapy and 
non-SAEs.
7.6.13
Clinical Laboratory Evaluations
Laboratory parameters will be presented using SI and US values and units.
7.6.13.1
Laboratory Abnormalities
The incidence of laboratory abnormalities presenting the worst toxicity grade during the 
treatment period will be tabulated by treatment arm for all grades (Grades 1, 2, 3, 4) and Grades 
3 and 4.
Subjects with at least 1 measurement after the start of study therapy will be included in the 
summaries. Abnormalities are determined from laboratory measurements analyzed at the central 
or local laboratory. Grading categories for laboratory tests are determined using the DAIDS 
grading system (see Appendix 3 of the protocol).
This incidence will be further summarized by baseline toxicity grade.
Treatment emergent abnormalities by toxicity grade (increased to Grades 1, 2, 3, 4, and any 
grade) will also be summarized by baseline toxicity grade (normal, Grade 1 to 4, not reported) 
and total analogously. Treatment emergent abnormalities are those with a higher on-treatment 
toxicity grade than the baseline toxicity grade (including not reported baseline).
7.6.13.2
Laboratory Tests over Time
All summaries of laboratory data over time will use observed values. Visit windows are defined 
in Section 8.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
30
Observed values and changes from baseline in creatinine and creatinine clearance will be 
summarized at each scheduled visit by treatment arm.
Observed values, changes from baseline and percent changes from baseline will be summarized 
over time for the following laboratory tests:

Fasting Total cholesterol,

Fasting HDL-cholesterol

Fasting LDL-cholesterol,

Fasting Triglycerides.

Total:HDL cholesterol ratio
Values obtained after the start of serum lipid-reducing agents will be excluded from these lipid 
summaries. Mean percent changes from baseline using observed values will be plotted at each 
scheduled visit with error bars representing 1 standard error of the reported statistic.
7.6.14
Electrocardiograms
QRS, PR and QTc Fridericia intervals and changes from baseline will be summarized over time 
by treatment arm using observed values. Standard 95% confidence intervals for mean changes 
from baseline will also be provided.
The subject’s longest interval observed during the treatment period for these ECG parameters 
will be summarized categorically by treatment arm using the following categories:

QRS interval: < 100, 100 to < 110, 110 to < 120, 120 to < 130, 130 to < 140, 140msec;

PR interval: < 200, 200 to < 220, 220 to < 240, 240 to < 260, 260 to < 280, 280 to < 300, 
300msec;

QTcF interval: < 400, 400 to < 425, 425 to < 450, 450 to < 460, 460 to < 470, 470 to < 480, 
480 to < 490, 490msec.
The largest change from baseline in these intervals observed during the treatment period is also 
summarized categorically by treatment arm using the following categories:

QRS: < 0, 0 to < 10, 10 to < 20, 20 to < 30, 30 to < 40, 40msec;

PR: < 0, 0 to < 20, 20 to < 40, 40 to < 60, 60 to < 80, 80msec;

QTcF: < 0, 0 to < 10, 10 to < 20, 20 to < 30, 30 to < 40, 40msec.
7.6.15
Vital Signs
All summaries of vital signs over time will use observed values. Visit windows are defined in 
Section 8. Observed values and changes from baseline will be summarized over time. For blood 
pressure and heart rate, only sitting assessments will be included in the summaries.
Observed values and changes from baseline for body weight and BMI will be summarized over 
time.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
31
7.7
Clinical Biomarker Assessments
Renal and bone biomarkers values, changes from baseline and percent changes from baseline 
will be summarized over time using observed values. Visit windows are defined in Section 8. 
The renal biomarkers include urinary beta-2-microglobulin/creatinine and fractional excretion of 
phosphorous (FeP), defined as 

100 * [(urine phos x serum creatinine) / (serum phos x urine creatinine)]
The bone biomarkers include: N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-
linked C-telopeptide of Type 1 collagen (CTx).
The median change from baseline in FeP over time will be plotted with error bars representing 
IQR. 
The 
median
percent 
change 
from 
baseline 
in 
P1NP, 
CTx 
and 
urinary 
beta-2-microglobulin/creatinine over time will be plotted in a similar way.
7.8
Integrated Summaries
For the final analysis (i.e., when the last subject in Stage 2 completed the Week 96 visit), a 
number of integrated summaries will be provided. These outputs will include 4 columns: one for 
each of the treatment arms 1, 3 and 4 and one for the TDF containing arms (arms 2 and 5) 
combined. 
The following information will be summarized:

Week 96 subject status (see Section 7.3.1)

Demography and baseline disease characteristics (see Section 7.3.2.1)

Baseline resistance (see Section 7.3.2.4):

The number of treated subjects with phenotypic resistance using the earlier mentioned 
mutually exclusive categories, and by class and drug name.

The genotypic resistance profile for all treated subjects.

The baseline gag polymorphisms at selected positions.

Time on study therapy (see Section 7.4.1)

Newly emergent resistance for treated subjects with on-treatment resistance testing done (see 
Section 7.5.2.5):

Newly emergent phenotypic resistance profile 

Newly emergent phenotypic resistance to BMS-955176

Newly emergent genotypic substitutions

Newly emergent Gag polymorphisms at the selected positions

Any newly emergent deviation from the wild type virus in Gag sequencing 

Safety (see Section 7.6):

Overall AE summary

SAEs
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
32

AEs leading to discontinuation

Grade 2-4 related AEs

Grade 3-4 AEs

CDC Class C events

Gastrointestinal events

Grade 3-4 laboratory toxicities
7.9
Outcomes Research
7.9.1
EQ-5D-3L
As described in the SAP for BMS study CN162-007, the EuroQol (EQ-5D-3L) provides a simple 
but effective standardized measure of a subject’s quality of life and health state classification2. It 
is intended to provide both a compact descriptive profile and a single index value that will be 
used in the clinical and economic evaluation of health care. The questionnaire consists of 2 parts, 
which together are used to build a composite picture of the respondent’s health status.
In the first part, the “health state classification”, the respondent is asked to indicate his/her 
current health state, by ticking the most appropriate of three statements about each of the 5 
quality of life dimensions: mobility, self-care, usual activity, pain/discomfort, and 
anxiety/depression. Each of the 3 statements represents an increasing level of severity (1 = no 
problem, 2 = some or moderate problems, 3 = unable, or extreme problems). The string of five 
numbers, one for each dimension, indicates the aggregate health state. For example: “11111” 
indicates perfect health and “33333” indicates the worst health state.
The second part, “Visual Analogue Scale Thermometer”, evaluates the respondent’s current 
health-related quality of life by means of a 20cm visual analogue scale (VAS) with endpoints at 
100 (best imaginable health state) and 0 (worst imaginable health state).
The scores obtained from the 5 health state dimensions (first part of the questionnaire) will be 
converted to a US centric utility score based on the algorithm described by Shaw et al3. This 
utility score has range score from -0.019 (worse health state) to a maximum of 1.000 (best health 
state). APPENDIX 4 contains SAS code for calculating the US centric EQ-5D-3L utility score.  
The scores obtained from the 5 health state dimensions will also be converted to a UK centric 
utility score based on the algorithm described by Dolan4. APPENDIX 5 contains SAS code for 
calculating the UK utility scores.
For both the US centric and UK centric utility scores, values and changes from baseline are 
summarized as continuous parameters at baseline and all applicable, on-treatment analysis visits. 
Subjects must have paired measurements at baseline and the analysis visit to be evaluable. 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
33
7.9.2
FAHI
The FAHI consists of 5 subscales: Physical Well-Being, Emotional Well-Being, Function and 
Global Well-Being, Social Well-Being, and Cognitive functioning. Each scale consists of a 
number of questions, each of which has 5 possible responses: 0, 1, 2, 3 and 4. 
A detailed description of the FAHI structure and scoring algorithm is contained in internal BMS 
document, “FAHI Source Doc (16-DEC-2014).PDF”, which is available upon request. A 
summary of the scoring algorithm is provided below.
Negatively stated items are reversed by subtracting the response from 4. After reversing proper 
items, all subscale items are summed to a total which is the subscale score. Higher scores 
indicate better the quality of life. The score for each scale is the prorated sum of the items 
answered.  Thus, if a scale has 10 items, and only 6 are answered, the results of the six questions 
answered are summed and multiplied by 10. The result is then divided by 6.

The Physical Well-Being section of the questionnaire contains 13 questions, however only 10 
of them are used in scoring the scale.  These are questions GP1-GP7, BMT6, HI7 and HI12. 
Before computing the score for this scale, all of the responses are reversed by subtracting the 
response from 4.  

The Emotional Well-Being scale consists of 10 items.  Before computing the score for this 
scale, all of the responses are reversed by subtracting the response from 4.  

The Function and Global Well-Being scale consists of 13 items. Only one item, GE3, is 
reversed before the scale is scored.

The Social Well-Being scale consists of 8 items. None of these items are reversed before the 
scale is scored.

The Cognitive Functioning scale consists of three items. Two of these items, HI8 and HI9, 
are reversed before the scale is scored.
The scoring of any of the FAHI sub-scales is only considered valid as long as more than 50% of 
the subscale questions have been answered.
The total score for the FAHI is the sum of prorated scores from each of the five subscales. The 
overall score for the FAHI is considered valid if all of the subscales are considered to be valid.  
The analysis data set includes the overall score and each of the subscale scores by visit for each 
subject as well as indicator variables that show if the validity condition has been met for each of 
the subscales, as well as the FAHI overall.  Calculations for the FAHI total score and subscale 
scores use only valid data.  
FAHI total scores are summarized as continuous parameters at baseline and all applicable on-
treatment analysis visits.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
34
7.10
Pharmacokinetics
The following intensive PK parameters will be summarized (using mean, SD, median, minimum, 
maximum, geometric mean and %CV) for BMS-955176, DTG and ATV by treatment arm:

Cmax: maximum observed plasma concentration

Tmax: time of maximum observed plasma concentration

Ctau: observed plasma concentration at the end of a dosing interval

C0: observed pre-dose plasma concentration

AUC(TAU) area under the concentration-time curve in one dosing interval
The Pharmacokinetic (PK) population will be used for all listings. Evaluable PK population will 
be used for summary statistics and statistical analyses.
Subject plasma concentration-time profiles will be listed and summarized by treatment arm and 
nominal collection time for each analyte. Plots of individual plasma concentration profiles over 
time will be provided. Overlay of individual plasma concentration profiles over time will be 
provided by treatment arm. Plots of mean (+SD) plasma concentration profiles versus time will 
be presented for each analyte, and all treatments will be superimposed on the same plot for the 
analyte.
All individual PK parameters will be listed for each analyte including any exclusions and reasons 
for exclusion from summaries. Summary statistics will be tabulated for each PK parameter by 
treatment arm. Geometric means and coefficients of variation will be presented for Cmax, 
AUC(TAU), Ctau, and C0. Medians and ranges will be presented for Tmax. 
The effect of BMS-955176 on the exposure of DTG (in the presence of ATV/RTV 300/100mg) 
will be estimated by the geometric mean ratio, with 90% confidence interval, of the exposure 
data in Arm 1 over the reference ATV/r arm (Arm 2). These estimates will be generated using 
general linear models fitted to log-transformed data. The effect of BMS-955176 on the exposure 
of DTG (in the presence of ATV 400mg) will be estimated by the geometric mean ratio, with 
90% confidence intervals, of the exposure data in Arm 3 and Arm 4, separately, over historical 
data. These estimates will be generated using general linear models fitted to log-transformed 
data.
The population PK, exposure-response and viral kinetic analyses will be described in a separate 
analysis plan. Intensive and sparse pharmacokinetic data will be used in population PK, PK/PD 
and PK/VK. 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
35
8
CONVENTIONS
8.1
Derivation of Baseline and On-Treatment Parameters Using Visit 
Windows
8.1.1
Baseline
Baseline parameters are derived from pre-treatment measurements. Pre-treatment measurements 
are included for subjects in the following ways:

For treated subjects: measurements are included through the start of study therapy.

For randomized subjects who never received study therapy: measurements are included 
through randomization.

For enrolled subjects who were never randomized: all available measurements are included.
The following algorithm details the derivation of baseline parameters:

CD4+ and CD8+ T-cells: the last value on or before the start of study therapy. If there are 
multiple measurements on the same day from central and local laboratories, then the value 
from the central laboratory is selected.

Genotypic and phenotypic parameters: identified from the last typable resistance test on or 
before the start of study therapy. HIV subtype is identified from the first resistance test at 
which subtype was assessed. If there are multiple tests on the same day, the last test run is 
chosen.

All other parameters: the last value measured on or before the start of study therapy is 
selected. If there are multiple measurements on the same day, the value with the latest entry 
date/time is chosen : 

HIV-1 RNA: Values are assigned a value of 1 more (or 1 less) if an inequality “>” (“<”) 
is present. Values outside the upper (or lower) limit of quantification are assigned a value 
or 1 more (or 1 less) than the limit. Only values from the central laboratory will be used.
8.1.2
On-Treatment Parameters
Time is measured from the first dose of study therapy.
On-treatment parameters are derived from measurements after the start of study therapy through 
the last dose of study therapy plus 4 days for efficacy, biomarkers and outcomes research scales, 
plus 10 days for resistance parameters and plus 30 days for safety.
For the primary and secondary efficacy endpoints of proportion of subjects with plasma HIV-1 
RNA < 40c/mL at Weeks 24, 48 and 96, the snapshot algorithm and related window definition 
will be applied. The snapshot windows shown in the Table 8.1.2-1 below differ from those 
proposed by the FDA by 1 day. The FDA windowing appears to have the first study day as Day 
0, while the table below has the first study day as Day 1.
The windows for other parameters are based on the midpoint between planned study visits. For 
analysis through Week 96, the visit windows are presented in the following table:
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
36
Table 8.1.2-1:
Visit Windows
Visit
Target Day
HIV-1 RNA (Snapshot 
Algorithm)
Other Parameters
B/L
1
1
2
15
2 - 21
4
29
22 - 43
8
57
44 - 71
12
85
72 - 99
16
113
100 - 141
24
169
127 - 210 
(18-30 wks)
142 - 197
32
225
198 - 253
40
281
254 - 309 
48
337
295 - 378
(42-54 wks)
310 - 379
60
421
380 - 463
72
505
464 - 547
84
589
548 - 631
96
673
631-714
(90-102 wks)
632 - 715
Study days are calculated as:

Measurement date - first date of study therapy + 1 day, if measurement date if on or after 
start date of study therapy.

Measurement date - first date of study therapy, if measurement date is before start date of 
study therapy.
Weeks are study days divided by 7.
The following conventions are used to select the value to be used in the analysis:

HIV-1 RNA: analysis of the proportion of subjects with plasma HIV-1 RNA < 40c/mL at 
Week 24, 48 and 96 use the last plasma HIV-1 RNA value in the pre-defined visit window 
following the snapshot algorithm. For all other analyses or summaries of HIV-1 RNA, the 
value in the visit window that is closest to the target day of the planned visit (as determined 
by the absolute differences in days between the planned visit and the assessment date) will be 
used. In case of ties between observations located on different sides of the target day, the 
earlier assessment will be used. In case of ties located on the same side of the target day 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
37
(i.e., more than one value for the same day but different time), the value with the earlier entry 
date/time will be used. Only values from the central laboratory will be used.

Values are assigned a value of 1 more (or 1 less) if an inequality “>” (or “<”) is present. 
Values outside the upper (or lower) limit of quantification are assigned a value of 1 more 
(or 1 less) than the limit.

For other laboratory and non-laboratory parameters: if a subject has more than one 
measurement included within a window, the assessment closest to the target day will be used. 
In case of ties between observations located on different sides of the target day, the earlier 
assessment will be used. In case of ties located on the same side of the target day (i.e., more 
than one value for the same day but different time), the value with the earlier entry date/time 
will be used.
8.2
Derived Dates

Start date of any study therapy is the earliest start date of BMS-955176, TDF, ATV, RTV or 
DTG identified from dosing records with non-missing start date. This date is used to identify 
treated subjects and to distinguish pre-treatment from any on-study measurements.

Start date of continuation dosing of study therapy for BMS-955176 is the earliest start date of 
the continuation dose(s) of BMS-955176 with non-missing daily dose and non-missing start 
date. This date is used to identify treated subjects receiving the continuation dose(s) of BMS-
955176 and to distinguish on-study measurements in the original dosing period from on-
study measurements in the continuation dosing period.

Start date of serum lipid-reducing agents is the earliest start date of any concomitant or post-
treatment medication from the therapeutic class ‘serumlipidreducing agent’. This date is used 
to exclude data in longitudinal lipid analyses during treatment.

Analysis week date is the start date of study therapy plus the upperbound of the window 
defining the analysis week minus 1 day (see Section 8.1). This date is used to include data 
through the analysis week.
8.3
Derived Parameters
When deriving a parameter that requires more than one test measurement, the parameter must be 
derived using measurements from the same collection date, accession number and site code for 
each test.
8.4
Study Therapy
Time on therapy for each individual drug component is calculated from the first and last dates of 
dosing, regardless the interruptions. The first date of dosing is the minimum of the dosing start 
dates, and the last date of dosing is the maximum of dosing stop dates.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
38
8.5
Concomitant Medications
Start and stop date of all concomitant medications are collected on the CRF. In order to classify 
medication as prior, current or concomitant, partial, missing or invalid start and stop dates will be 
imputed where possible as follows:

If the reported start date is missing or invalid and the informed consent date is not missing or 
invalid, then the imputed start date is set equal to the informed consent date. If the consent 
date is missing or invalid and the birth date is not missing or invalid, then the imputed start 
date is set equal to the birth date. If the start date, the consent date and the birth date are all 
invalid or missing, then the imputed start date is set equal to missing.

If the reported start date is partially entered, then the imputed start date is set equal to the 
earliest possible reported start date based on the partial entered reported start date.

If the reported end date is missing, continuing, unknown or invalid, then the imputed end 
date is set equal to the most recent database extraction date.

If the reported end date of the medication is partial, then the imputed end date is set equal to 
the last possible reported end date based on the partial entered reported end date.
Imputed dates will not appear on the listings of non-study medication.
8.6
Counting Rules for Adverse Events
Where a subject has the same adverse event, based on preferred term, reported multiple times in 
a single analysis period, the subject will only be counted once at the preferred term level in 
adverse event frequency tables.
Where a subject has multiple adverse events within the same system organ class in a single 
analysis period, the subject will only be counted once at the system organ class level in adverse 
event frequency tables.
When a subject has the same adverse event, based on preferred term, reported multiple times in a 
single analysis period, the following criteria, in order of precedence, will be used to select the 
event to be included in the summary tables:

Relationship to study medication: related events will take precedence over unrelated events.

Intensity of the event: more intense events will take precedence over less intense events.

Onset date and time: earlier onset date/time events will take precedence over late onset 
date/time events.
When reporting adverse events by intensity, summary tables will also be provided based on the 
most intense event during the analysis period - independent of relationship to study medication. 
For these tables, the following criteria, in order of precedence, will be used to select the event to 
be included in the summary tables:

Intensity of the event

Onset date and time
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
39
8.7
Pharmacokinetic Evaluations
8.7.1
Decimal Places for Pharmacokinetic Data
The number of decimal places displayed in all listings will be determined by the number of 
decimal places in the raw data.  
Unless otherwise specified, minimum and maximum will be reported to the precision as the data 
collected, one more decimal place for the mean and median, and two more decimal places for the 
standard deviation.  The adjusted geometric mean, geometric mean ratio and the lower and upper 
limits of confidence interval will be displayed to three decimal places.
8.7.2
Pharmacokinetic Summaries
In-text Tables
For in-text pharmacokinetic tables, coefficient of variation (% CV) will be reported as integers. 
For other statistics, values of 100 or higher will be presented as integers, values of 10 - < 100 
will be displayed to one decimal place, and values of 1 - < 10 will be displayed to two decimal 
places. Values less than 1 will be displayed to three decimal places.  Ratios will also be 
displayed to three decimal places.
Handling of Non-Quantifiable Concentrations
For the summaries of plasma concentration-time data, concentrations that are less than the lower 
limit of quantification (LLOQ) should be displayed as “< LLOQ” in the listings and be treated as 
missing in summary tables and plots. For the purpose of calculating intensive PK parameters, 
pre-dose concentrations that are less than LLOQ and concentrations prior to the first quantifiable 
concentration that are less than LLOQ will be set to zero, and all other concentrations less than 
LLOQ will be set to missing.
Sparse PK concentrations for PK/PD and PK/VK correlations will be calculated by imputing 
values less than LLOQ as ½ * LLOQ.  
All available plasma concentration-time data and derived pharmacokinetic parameter values will 
be included in the PK data set and listed accordingly.
Treatment of Outliers
Individual plasma concentrations, if deemed to be anomalous, may be excluded from the analysis 
following a review of available documentation (e.g., bioanalytical report, clinical data). Any 
such exclusion will be clearly listed in the study report along with justification for exclusion.
Entire plasma concentration-time profiles for a subject may be excluded following review of 
available documentation (e.g., bioanalytical report, clinical data). However, results of analysis 
with and without the excluded profiles may be presented in the study report. Any such exclusion 
will be clearly listed in the study report along with justification for exclusion.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
40
PK Exclusions
Exclusion of one or more parameters or the entire dataset may be considered due to incomplete 
profile, or there is no sample around the suspected Cmax. In addition, subjects may be excluded 
from the analysis if they missed doses, had diarrhea, or vomited at or before a time equal to twice 
the median Tmax for immediate-release products, or vomited at any time during sampling after 
the administration of modified-release formulations.
9
REFERENCES
An interim analysis will be conducted after the last randomized subject in Stage 1 is on treatment 
for 24 weeks. The analyses related to the first 24 weeks of treatment for Stage 1 will be 
performed. 
An interim analysis might be conducted after the last randomized subject in Stage 1 is on 
tratment for 48 weeks in case the continuation dose couldn’t be selected based on the Week 24 
results.
An interim analysis will be conducted after the last randomized subject in Stage 2 is on treatment 
for 24 weeks. The expectation is that the last subject in Stage 1 will have completed the Week 96 
visit by that time. The analyses related to the first 24 weeks of treatment for Stage 2 will be 
performed as well as all analyses related to Stage 1 (except the futility analysis).
An interim analysis will be conducted after the last randomized subject in Stage 2 completes the 
Week 48 visit. The analyses related to the first 48 weeks of treatment for Stage 2 will be 
performed.
The final analysis will be conducted after the last randomized subject in Stage 2 completes the 
Week 96 visit. All analyses described in this plan will be performed for both Stages (except the 
futility analysis). This includes the integrated summaries described in Section 7.8.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
41
APPENDIX 1
SNAPSHOT ALGORITHM
The snapshot algorithm is described in detail in Appendix A of the CDER (2013) draft guidance 
on developing antiretroviral drugs1. If the draft guidance is superseded, and development 
timelines permit any needed changes, then the instructions from the new guidance should be 
followed. 
In some sections of the draft guidance, the responder cutoff is listed as HIV-1 RNA 
“< 50copies/mL”.  This is a carryover from earlier days when the assay limit of detection was 50. 
Currently approved assays have lower limits.  Hence, in implementing the snapshot algorithm, 
the assay limit of detection will replace the HIV-1 RNA limit of “< 50copies/mL”.
The analysis visit windows that appear in Table A of the draft guidance (line 1205) appear to use 
Day 0 as the start date. Windows that use Day 1 as the start date are in the following table.
Table 9-1:
Snapshot Algorithm Analysis Visit Windows
VISIT
Window  in Weeks
(Weeks indicate end of study week)
Days
(Inclusive of start & end points)
Week 24
18 through 30
127 through 210
Week 48
42 through 54
295 through 378
Week 96
90 through 102
631 through 714
Each snapshot analysis includes a summary of virologic outcomes at an analysis visit (e.g., Week 
24) that has the same format as Table B (line 1209) of the draft guidance. 
Each snapshot analysis may also include a summary of expanded virologic outcomes at an 
analysis visit. This summary has a similar format to Table B, but also displays the 95% CI for the 
response category “HIV-1 RNA < 40c/mL”, and breaks down the failure category “HIV RNA 
≥ 40c/mL” into 4 subcategories. Virologic outcomes are summarized according to the following 
categories:

HIV-1 RNA < 40c/mL

HIV-1 RNA 40c/mL

HIV-1 RNA 40c/mL in Week 24 window 

Discontinued study/study drug due to lack of efficacy. This includes subjects who 
discontinued study therapy due to lack of efficacy at any time from Day 1 through the 
Week 24 window if this resulted in no on-treatment HIV-1 RNA in the window.

Discontinued study/study drug due for other reasons. This includes subjects with last on-
treatment HIV-1 RNA ≥ 40c/mL who discontinued study therapy due to any reason 
except AE, death and lack of efficacy at any time from Day 1 through the Week 24 
window if this resulted in no on-treatment HIV-1 RNA in the window.  
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
42

No virologic data in Week 24 window

Discontinued study/study drug due to AE or death. This includes subjects who 
discontinued study therapy due to AE or death at any time from Day 1 through the Week 
24 window if this resulted in no on-treatment HIV-1 RNA in the window.

Discontinued study/study drug for other reasons. This includes subjects with last on-
treatment HIV-1 RNA < 40c/mL who discontinued study therapy for other reasons 
(withdrew consent, lost to follow-up, moved, etc.) at any time from Day 1 through the 
Week 24 window if this resulted in no on-treatment HIV-1 RNA in the window. 

On study but missing data in window
Each snapshot analysis may also include a by-subject listing that facilitates finding the subjects 
in each outcome category. The listing includes: subject ID; age/gender/race; as-randomized 
treatment group; assessment day; HIV-1 RNA on day of assessment; virologic outcome (HIV-1 
RNA < 40c/mL, HIV-1 RNA ≥ 40c/mL, or no virologic data in window); virologic outcome 
specification (see subcategories in the expanded virologic outcome summary); day of 
discontinuation of study therapy; and the reason for discontinuation of study therapy. The listing 
is sorted and paged by treatment group. Within treatment group, the subjects are sorted by 
virologic outcome and then by the virologic outcome specification.
An analysis data set contains at least the information specified starting on line 1346 (“Datasets 
for Snapshot Approach”). This analysis data set may contain additional variables, and have 
multiple uses besides the snapshot analysis. 
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
43
APPENDIX 2
GENOTYPIC AND PHENOTYPIC RESISTANCE
Genotypic Resistance
Genotypic resistance will be assessed by searching for all:

RT substitutions

PI substitutions

Integrase (IN) substitutions
that are listed in the most current version of the International AIDS Society-USA (IAS-USA) 
list.
The following table was prepared relative to the IAS-USA list from June/July of 20145. The 
table describes the categories and subcategories, by which the substitutions will be categorized. 
In the table below, slashes (“/”) between amino acid codes do indicate mixtures. The slashes 
indicate that any of the amino acids in the list qualify as substitutions.
Table 9-2:
Genotypic Substitutions
Category
Description of Relevant Substitutions
Protease Gene
Any PI substitution
At least one of the PI substitutions listed in the IAS-USA. 
L10C/F/I/R/V,  V11I,  G16E, 
K20I/M/R/T/V,  L24I,  
D30N,  V32I,  L33F/I/V,  E34Q,  M36I/L/V, 
K43T,  M46I/L,  I47A/V,  G48V, 
I50L/V,  F53L/Y,  I54A/L/M/S/T/V,  Q58E, 
D60E,  I62V,  L63P,  I64L/M/V,  H69K/R, 
A71I/L/T/V,  G73A/C/S/T,  T74P,  L76V,  V77I, 
V82A/F/I/L/S/T,  N83D,  I84V,  I85V,  N88D/S,  L89I/M/V, 
L90M,  I93L/M
Major PI Substitutions
Any of the major PI substitutions listed in the IAS-USA
D30N,  V32I, 
M46I/L,  I47A/V,  G48V, 
I50L/V,  I54L/M,  Q58E, 
T74P, L76V, 
V82A/F/L/S/T,  N83D,  I84V,  N88S, 
L90M
Major PI substitutions are sub-tabulated by codon.
Minor PI Substitutions
Any of the minor PI substitutions listed in the IAS-USA
L10C/F/I/R/V,   V11I,   G16E,  
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
44
Table 9-2:
Genotypic Substitutions
Category
Description of Relevant Substitutions
K20I/M/R/T/V,  L24I ,
L33F/I/V,  E34Q,  M36I/L/V,  
K43T,   
F53L/Y,  I54A/S/V/T,   
D60E,  I62V,  L63P,  I64L/M/V, H69K/R,  
A71I/L/T/V,  G73A/C/S/T,  V77I,  
V82I,  I85V,  N88D, L89I/M/V,  
I93L/M
Minor PI substitutions are sub-tabulated by codon.
Reverse Transcriptase Gene
Any RT substitution
At least one of the nRTI or NNRTI substitutions listed in the IAS-USA. 
RT substitutions are sub-tabulated into nRTI and NNRTI substitutions. 
nRTI
At least one of the nRTI substitutions listed in the IAS-USA
nRTI substitutions are further sub-tabulated into: 69 Insertion Complex, 
151 Complex, TAMS and Other.
69 insertion complex
Substitution at codon 69 with a double amino acid insertion and at least 
one of the following: M41L, A62V, K70R, L210W, T215Y/F, 
K219Q/E
151 complex
Q151M and at least one of the following: A62V, V75I, F77L, F116Y
Thymidine Analogue-
Associated Mutations (TAMS)
At least one of the following: M41L, D67N, K70R, L210W, T215Y/F, 
K219Q/E
Other
At least one of the other nRTI substitutions not covered above: 
K65R/E/N, K70E, L74V, Y115F, M184V/I
NNRTI
At least one of the substitutions listed in the IAS-USA for any of the 
NNRTIs:
V90I, A98G, 
L100I, K101E/H/P, K103N/S,V106A/I/M, V108I, 
E138A/G/K/Q/R, 
V179D/F/L/T, 
Y181C/I/V, Y188C/L/H, 
G190S/A, 
H221Y, P225H, F227C, 
M230I/L.
NNRTI substitutions are tabulated by codon.
Integrase Gene
Any Integrase Substitutions
At least one of the substitutions listed in the IAS-USA for integrase 
inhibitors
T66I/A/K
L74M
E92Q/G,  T97A
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
45
Table 9-2:
Genotypic Substitutions
Category
Description of Relevant Substitutions
F121Y
E138A/K
G140A/S
Y143R/H/C,  S147G, Q148H/K/R
N155H 
Integrase substitutions are tabulated by codon
Phenotypic Resistance
The phenotypic resistance to a drug is defined as a fold change (i.e., ratio of the 50% inhibitory 
concentration (IC50) of the clinical isolate to the IC50 of the reference strain) greater than the cut-
off for reduced susceptibility. The following table displays cut-offs used by Monogram 
Biosciences, Inc. to determine reduced susceptibility to each drug. 
The phenotypic resistance status, as determined by Monogram (for ARVs other than BMS-
955176) should be available in the clinical database. Hence, programming these cutoffs should 
be unnecessary.
Note: Monogram may use TFV as a code for tenofovir in phenotypic data files.
Table 9-3:
Cut-offs used by Monogram Biosciences to Determine Reduced 
Susceptibility
Class
Drug
Reduced Susceptibility Cut-off
PI
Atazanovir (ATV)
2.2
Atazanavir/Ritonavir (ATV/r)
5.2
Darunavir/Ritonavir (DRV/r)
10
Fosamprenavir/Ritonavir (AMP/r)
4
Indinavir/Ritonavir (IDV/r)
10
Lopinavir/Ritonavir (LPV/r)
9
Nelfinavir (NFV)
3.6
Ritonavir (RTV)
2.5
Saquinavir/Ritonavir (SQV/r)
2.3
Tipranavir/Ritonavir (TPV/r)
2
NNRTI
Delavirdine (DLV)
6.2
Efavirenz (EFV)
3
Etravirine (ETR)
2.9
Nevirapine (NVP)
4.5
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
46
Table 9-3:
Cut-offs used by Monogram Biosciences to Determine Reduced 
Susceptibility
Class
Drug
Reduced Susceptibility Cut-off
Rilpivirine (RPV)
2.5
NRTI
Abacavir (ABC)
4.5
Didanosine (ddI)
1.3
Emtricitabine (FTC)
3.5
Lamivudine (3TC)
3.5
Stavudine (d4T)
1.7
Tenofovir (TDF)
1.4
Zidovudine (ZDV)
1.9
IN
Raltegravir (RAL)
2.2
Dolutegravir (DTG)
4
Elvitegravir (EVG)
3.5
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
47
APPENDIX 3
TIME TO LOSS OF VIROLOGIC RESPONSE
This appendix describes the Time to Loss of Virologic Response (TLOVR) algorithm for 
analyses at Week 24, 48 and 96. The instructions that follow are based on the FDA guidance 
from 20026. Guidance from the European Union7 indicates that snapshot analyses should be 
supplemented by at TLOVR analysis.
For this study, the TLOVR analyses are done on the mITT data sets. The assay limit used in the 
TLOVR analysis is the limit of detection. 
TLOVR has two components, a time-to-failure (life table) analysis, and a tabulation of treatment 
outcomes at each particular time point (e.g. Week 24).  
The time to failure data are analyzed using the Kaplan-Meier method.  The presentation will 
include a K-M curve, estimates of the response rates at the end of weeks 24, 48 and 96 and 95% 
confidence intervals for the estimate. The time-to-failure analysis is based on the following rules 
(FDA, 2002):

“For 2 and 3 below, discard all visits with no data. In what follows, visit means visit with an 
observed viral load. All available visits, including off-schedule visits and post-week 96 visits, 
should be used for the calculation. Data should not be interpolated for visits or time points 
with missing data. 

Subjects who never achieved confirmed HIV RNA levels below the assay limit (on two 
consecutive visits) before any of the following events will be considered to have failed at 
time 0. 
a) Death 
b) Introduction of a new antiretroviral drug to the regimen. Exceptions may be made for 
certain pre-specified changes in background therapy where the reason for change is due 
to toxicity or intolerance of background therapy and not the study drug or control. 
c) Last available visit 

For all subjects who have confirmed HIV RNA levels below an assay limit (two consecutive 
visits below an assay limit), the time to failure is the earliest of the choices below, with 
modification specified in 4: 
a) Time of the event as described in 2b 
b) Time of loss to follow-up 
c) Time of confirmed levels above an assay limit. Confirmed is defined as two consecutive 
visits greater than an assay limit or one visit greater than an assay limit followed by loss 
to follow-up. 
d) Time of death 

If the time to virologic failure defined above is immediately preceded by a single missing 
scheduled visit or multiple consecutive missing scheduled visits, the time of virologic failure 
is replaced by the time of the first such missing visit.”
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
48
The tabulation of treatment outcomes shows the proportions of success and failure for various 
reasons.  For a subject, the reason for failure is based on the primary reason for the earliest 
treatment failure. For any visit, subjects who achieved confirmed virologic success, defined as 
two consecutive visits below the assay limit of detection, but have not failed according the above 
loss of virologic success algorithm are considered successes.  All others should be classified into 
the appropriate categories, which are shown in the FDA draft guidance.  
The visit windows used in tabulating treatment outcomes are the same visit windows used for the 
snapshot algorithm. For subjects who failed for multiple reasons at the earliest time of failure, 
the precedence of failure classification is: death, virologic rebound and then premature 
discontinuation. For example, if virologic rebound and premature discontinuation occur on the 
same day, then the reason for failure is virologic rebound.
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
49
APPENDIX 4
EQ-5D-3L SCORING PROGRAM - U.S. WEIGHTED
This SAS scoring algorithm was downloaded on January 20, 2015 from: 
http://archive.ahrq.gov/professionals/clinicians-providers/resources/rice/EQ5Dscore.html 
/* EQ-5D U.S. PREFERENCE-WEIGHTED INDEX */
/* Author: 
*/
/* Date:  May 20, 2004 */
/* Program was written with SAS Release 8.02 for Windows. */
/* The scoring algorithm presented below was taken from:  Shaw JW, Johnson JA, Coons SJ.
U.S. Valuation of the EQ-5D Health States:  Development and Testing of the D1 Valuation Model.
Medical Care. Submitted 2004. */
/* This program computes the U.S. preference-weighted index score using self-reported EQ-5D data.
It is presumed that the data set includes the following five variables:
Dimension               Variable Name     Range
--------------------------------------------------
Mobility                MO                1-3
Self-care               SC                1-3
Usual activities        UA                1-3
Pain/discomfort         PD                1-3
Anxiety/depression      AD                1-3
--------------------------------------------------
where a 1 indicates no problems, a 2 indicates moderate problems, and a 3 indicates severe
problems.  The variables containing responses for the five dimensions must be named as above
(in capital letters).  Missing values should be left blank (ie, a '.' should not be substituted
for a missing value).  The index score will not be generated when responses are missing for 1 or
more of the five dimensions.
In the data step, the user should specify the location (LIBNAME) and name of the data set to
be analyzed (DATANAME).  It is recommended that the index values be saved to a new data set
(NEWDATANAME) in the desired library. */
/* SAS Data Step */
data LIBNAME.DATANAME ; set LIBNAME.NEWDATANAME ;
10.0
Approved
2.0
v
930093621
PPD


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
50
/* Generate Dummy Variables for Levels 2 and 3 of Five Dimensions */
m1 =0 ;
m2 =0 ;
s1 =0 ;
s2 =0 ;
u1 =0 ;
u2 =0 ;
p1 =0 ;
p2 =0 ;
a1 =0 ;
a2 =0 ;
if MO = 2 then m1 = 1 ;
if MO = 3 then m2 = 1 ;
if SC = 2 then s1 = 1 ;
if SC = 3 then s2 = 1 ;
if UA = 2 then u1 = 1 ;
if UA = 3 then u2 = 1 ;
if PD = 2 then p1 = 1 ;
if PD = 3 then p2 = 1 ;
if AD = 2 then a1 = 1 ;
if AD = 3 then a2 = 1 ;
/* Generate Interaction Terms (I2, I2-squared, I3, I3-squared) */
m0 = 0 ;
s0 = 0 ;
u0 = 0 ;
p0 = 0 ;
a0 = 0 ;
if m1 = 0 and m2 = 0 then m0 = 1 ;
if s1 = 0 and s2 = 0 then s0 = 1 ;
if u1 = 0 and u2 = 0 then u0 = 1 ;
if p1 = 0 and p2 = 0 then p0 = 1 ;
if a1 = 0 and a2 = 0 then a0 = 1 ;
i2 = m1 + s1 + u1 + p1 + a1 ;
i2 = i2 - 1 ;
if i2<0 then i2 = 0 ;
i22 = i2*i2 ;
i3 = m2 + s2 + u2 + p2 + a2 ;
i3 = i3 - 1 ;
if i3<0 then i3 = 0 ;
i32 = i3*i3 ;
/* Generate D1 Term */
i1 = m0 + s0 + u0 + p0 + a0 ;
d1 = 4 - i1 ;
if d1<0 then d1 = 0 ;
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
51
/* Generate Raw Index Score */
pred = .146016*m1 + .557685*m2 + .1753425*s1 + .4711896*s2 + .1397295*u1 + .3742594*u2 + .1728907*p1 + .5371011*p2 + .156223*a1 + 
.4501876*a2 + -.1395949*d1 + .0106868*i22  + -.1215579*i3 + -.0147963*i32 ;
EQ_index = 1 - pred ;
if (MO = .) or (SC = .) or (UA = .) or (PD = .) or (AD = .) then EQ_index = .  ;/* Drop Variables Generated by Program */
drop m1 m2 s1 s2 u1 u2 p1 p2 a1 a2 m0 s0 u0 p0 a0 i2 i22 i3 i32 d1 pred nvector ;
run ;
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
52
APPENDIX 5
EQ-5D-3L SCORING PROGRAM - U.K. WEIGHTED
The following SAS code is an example of computing UK centric utility scores. The code was taken from the BMS SAP for study 
CN162-0072. 
utility = 1;
if mobility=1 then mob=0;
else if mobility=2 then mob=-0.069;
else if mobility=3 then mob=-0.314;
if selfcare=1 then self=0;
else if selfcare=2 then self=-0.104;
else if selfcare=3 then self=-0.214;
if usualact=1 then usual=0;
else if usualact=2 then usual=-0.036;
else if usualact=3 then usual=-0.094;
if paindis=1 then pain=0;
else if paindis=2 then pain=-0.123;
else if paindis=3 then pain=-0.386;
if anxdep=1 then anxiety=0;
else if anxdep=2 then anxiety=-0.071;
else if anxdep=3 then anxiety=-0.236;
utility = utility + mob + self + usual + pain + anxiety;
if mobility in (2,3) or selfcare in (2,3) or usualact in (2,3) or paindis in (2,3) or anxdep in (2,3)
then utility = utility - 0.081;
if mobility=3 or selfcare=3 or usualact=3 or paindis=3 or anxdep=3 then utility = utility -0.269;
10.0
Approved
2.0
v
930093621


Statistical Analysis Plan
AI468048
BMS-955176
hiv maturation inhibitor
53
10
REFERENCES
1. Guidance for industry: Human Immunodeficiency Virus-1 Infection: Developing 
Antiretroviral Drugs for Treatment. US Department of Health and Human Services, Food and 
Drug Administration, Center for Drug Evaluation and Research (CDER). Draft Guidance. 
June, 2013.
2. Statistical Analysis Plan for CN162-007, version 2, BMS DCN 930065069
3. Shaw, J.W., et al, 2005, "US Valuation of the EQ-5D Heath States Development and Testing 
of the D1 Valuation Model", Medical Care, vol. 43, no. 3, 203-220.
4. Dolan P. (1997). Modeling valuations for EuroQol health states, Medical Care, 35, 1095-
1108
5. Johnson V, et al., Update of the Drug Resistance Mutations in HIV-1. Topics in HIV 
Medicine 2013; 21 (1): 4 - 12.
6. Guidance for industry: Antiretroviral Drugs Using Plasma HIV RNA Measurements -
Clinical Considerations for Accelerated and Traditional Approval.  US Department of Health 
and Human Services, Food and Drug Administration, Center for Drug Evaluation and 
Research (CDER). October, 2002.
7. Guideline on the clinical development medicinal products for the treatment HIV infection. 
EMEA/CPMP/EWP/633/02; Rev 3. 2013.
11
DOCUMENT HISTORY
Table 11-1:
Document History
Version 
Number
Author(s)
Description
1.0
Original version
2.0
Section 1: update schedule of analyses
Section 2.4: add protocol amendment 6
Section 7.2: add relevant protocol deviation related to screening eGFR
Section 7.3.2.4: add baseline resistance summaries for treated subjects that are 
identified as protocol defined virologic failures. 
Section 7.5.2.5: Include summary for newly emergent phenotypic resistance to 
BMS-955176.
For Gag: add summaries by HIV subtype.
Section 7.8: was added to describe the integrated outputs
Section 8.1: correct visit window for Weeks 16 and 24, and remove Week 20
Section 9: describe content of the reports in more detail
Update Table 10-1 based on 2014 IAS-USA
10.0
Approved
2.0
v
930093621
PPD
PPD


 
CONFIDENTIAL 
 
ViiV Healthcare and the GlaxoSmithKline group of companies 
AI468038/205891 
 
1 
 
Appendix to Reporting Analysis Plan for Study AI468048/205892 ---Final 
Analysis 
Compound Number: BMS-955176/GSK3532795 
Study Title 
A Phase 2b Randomized, Active-Controlled, Staged, Open-Label 
Trial to Investigate Safety and Efficacy of BMS-955176 in 
Combination with Dolutegravir and Atazanavir (with or without 
Ritonavir) in Treatment-Experienced HIV-1 Infected Adults 
Effective Date: 
09 November 2017 (This appendix should be attached to the 
amendment of Reporting and Analysis Plan for study 
AI468048/205892 Version 2.0 effective on 15 October 2016). 
Description: This appendix describes the plan for the final statistical analyses of study 
AI468048/205892. 
Author’s Name, Title and Functional Area:  
 Data Analyst Statistician, Clinical Statistics 
Approved through email by:  
 Statistics Leader, Clinical Statistics 
 Director Statistics, Statistics & Programming 
 Manager, Statistical Programming 
 Manager, Clinical Data Management 
 Manager, Clinical Development  
 Director, Clinical Development, Clinical Investigation Lead 
 Physician Product Lead 
 Medical Director/Safety Development Leader, SERM 
 Head Unit Physician, Medicine Development Leader 
 Clinical Development Scientist, Operations & Science Leader 
Copyright 2017 ViiV Healthcare and the GlaxoSmithKline group of companies. All 
rights reserved. Unauthorised copying or use of this information is prohibited. 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
2 
 
TABLE OF CONTENTS 
PAGE 
1. 
CHRONOLOGY ....................................................................................................... 3 
2. 
FINAL ANALYSIS..................................................................................................... 3 
3. 
LIST OF DISPLAYS ................................................................................................. 6 
3.1. 
Study Population ........................................................................................... 6 
3.1.1. 
Tables ............................................................................................ 6 
3.1.2. 
ICH Listings ................................................................................... 7 
3.1.3. 
Other Listings ................................................................................ 8 
3.2. 
Efficacy ......................................................................................................... 9 
3.2.1. 
Tables ............................................................................................ 9 
3.2.2. 
ICH Listings ................................................................................. 10 
3.2.3. 
Other Listings .............................................................................. 10 
3.3. 
Safety ......................................................................................................... 12 
3.3.1. 
Tables .......................................................................................... 12 
3.3.2. 
ICH Listings ................................................................................. 17 
3.4. 
Virology ...................................................................................................... 19 
3.4.1. 
Tables .......................................................................................... 19 
3.4.2. 
Other Listings .............................................................................. 20 
 
 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
3 
 
1. 
CHRONOLOGY 
15-OCT-2016 
09-NOV-2017 
Reporting and Analysis Plan for Study AI468048, Version 2.0 
Appendix of Analysis Plan for Study AI468048 (Final Analysis) 
2. 
FINAL ANALYSIS 
Per the company decision to end this study prior to all subjects reaching the primary 
endpoint, a simplified approach for the final report has been proposed by the project 
team. Hence the final analyses for AI468048 study as described in this appendix will be 
performed on subjects who were enrolled into this study, regardless of study stage, and 
will supersede what have been previously stated in the finalized BMS RAP Version 2.0. 
In addition, due to the GCP non-compliance of Site 
 (Dr. Juan Ballesteros in Chile) 
with ICH GCP E6 (R2) Guidelines, data obtained from this GCP non-compliant site will 
not be included in the final analyses (e.g., summary tables of selected efficacy and safety 
data); however, subject data listings will include all subjects enrolled in this study. 
Subject data listings for the GCP non-compliant Site 
 will also be provided. 
The details of the final reporting and analysis plan are described as below: 
1) Analysis Populations 
Due to the GCP non-compliance of Site 
 data obtained from this GCP non-
compliant site will be excluded in the final analyses.  
Populations for Analyses for this synoptic report are defined as follows: 
• Enrolled subjects are those who signed an informed consent form and 
were assigned a Patient Identification number (PID). 
• Randomized subjects are enrolled subjects who received a treatment 
assignment from the IVRS and will be used in subject data listings as 
specified. 
• Modified Randomized Subjects are enrolled subjects who received a 
treatment assignment from the IVRS, excluding subjects from Site 
 The 
modified randomized subjects will be used to assess subject disposition. 
• Treated Subjects are randomized subjects who received at least 1 dose of 
study therapy and will be used in subject data listings as specified. 
• Modified Treated Subjects are randomized subjects who received at least 1 
dose of study therapy, exclude subjects from Site 
 Modified treated 
subjects will be used to assess demography and baseline characteristics, 
PP
D
PP
D
PP
D
PP
D
PP
D


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
4 
 
protocol deviations, exposure, concomitant medication, efficacy, 
resistance and safety data. 
• Pharmacokinetic (PK) population is defined as all treated subjects who 
have any available concentration-time data. The evaluable PK population 
is a sub-population including all treated subjects who have adequate PK 
profiles. 
2) Demographic and baseline characteristic 
This report includes the analyses of demographics, baseline characteristics, and 
baseline resistance data based on Modified Treated Subjects population. Subject 
data listings will be based on Treated Subjects population. 
The detailed outputs for demographic and baseline characteristic data are listed in 
the Section 3.1 of List of Displays for Study Population. 
3) Simplified report on primary efficacy endpoint 
Selected summaries and analyses on primary efficacy endpoint will be performed 
for this final analysis, based on Modified Treated Subjects population. Subject 
data listings will be based on Treated Subjects population. 
The detailed outputs for primary efficacy endpoint data are listed in the Section 
3.2 of List of Displays for Efficacy. 
4) Secondary and Exploratory Efficacy Endpoints 
Analyses for secondary and exploratory efficacy endpoints, including 
pharmacokinetic and quality of life endpoints, will not be performed except for 
HIV-1 RNA, CD4+ counts, and drug resistance endpoints (see additional details 
in Section 3.4, Virology) which are subject to availability of the data and will be 
analyzed based on Modified Treated Subjects population. There will be no 
subgroups and no multivariate analysis performed for secondary and exploratory 
efficacy endpoints for this final analysis. Subject data listings based on Treated 
Subjects population except PK data which will be based PK population. 
The detailed outputs for primary secondary and exploratory efficacy endpoints are 
listed in the Section 3.2 of List of Displays for Efficacy. 
5) Safety displays 
Final safety analysis will be summarized based on Modified Treated Subjects 
population; however, subject data listings will be based on Treated Subjects 
population. Subject data listings will be based on Treated Subjects population. 
The detailed outputs are listed in the Section 3.3 of List of Displays for Safety. 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
5 
 
6) Virology 
HIV drug resistance data will be summarized based on Modified Treated Subjects 
population. Subject data listings will be based on Treated Subjects population. 
The detailed outputs for HIV drug resistance data are listed in the section of List 
of Display for Virology. 
7) General 
The display for TLFs will be based on BMS shells and will not utilize HARP for 
SAC. 
 
The list of displays has been updated as shown below. 
 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
6 
 
3. 
LIST OF DISPLAYS 
The data displays will be based on the BMS shell as specified in the column of BMS Table number/File Name/BMS Template, where 
applicable. The details information on BMS shell can be found in the Analysis Data Presentation Plan revision 2.0 for this study.  
The following data display numbering will be applied for RAP generated displays: 
Section 
Tables 
Study Population 
1.1 to 1.5 
Efficacy 
2.1 to 2.4 
Safety 
3.1 to 3.46 
Virology 
4.1 to 4.9 
Section 
Listings 
ICH Listings 
1 to 26 
Other Listings 
27 to 44 
 
3.1. 
Study Population 
3.1.1. 
Tables 
For Table and listing displays, Treated Subjects, Modified Treated Subjects, Randomized Subjects, and Modified Randomized Subjects 
populations will be used as specified below.  
Number 
Title 
BMS Table number/File Name/BMS Template 
1.1 
End of Study Subject Status Summary  
Modified Randomized Subjects 
Table S.2.1.1B / rt-ds-statuss1.lst / GS_DS_T_X_005 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
7 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
1.2 
Populations for Analysis Summary 
Table S.2.1.1C / rt-dm-populations1.lst / 
SS_DM_T_002 
1.3 
Demographic Characteristics Summary  
Modified Treated Subjects 
Table S.3.1.1 / rt-dm-summarys1.lst / 
GS_DM_T_X_002 
1.4 
Summary of Baseline Disease Characteristics  
Modified Treated Subjects 
Table S.3.2.1 / rt-dm-diseases1.lst / SS_DM_T_004 
1.5 
Summary of Baseline Physical Measurements  
Modified Treated Subjects 
Table S.3.3.1 / rt-pm-bsls1.lst / GS_PM_T_X_001 
 
3.1.2. 
ICH Listings 
Number 
Title 
BMS Table number/File Name/BMS Template 
1 
End of Study Subject Status  
Randomized Subjects 
Appendix 2.1.1B / rl-ds-statuss1.lst / 
GS_DS_L_X_005 
2 
Randomization Scheme and Codes  
Randomized Subjects 
Appendix 1.9.1 / rl-ds-randcode.lst / SS_DS_L_001 
3 
Subjects Excluded from Analysis  
Treated Subjects 
Appendix 2.2.1 / rl-dm-excls1.lst / SS_DM_L_001 
4 
Listing of Relevant Protocol Deviations  
Randomized Subjects 
Table S.2.3.1B / rl-pd-rels1.lst / SS_PD_L_001 
5 
Demographic Characteristics  
Treated Subjects 
Appendix 3.1.1A / rl-dm-demchars1.lst / 
GS_DM_L_X_001 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
8 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
6 
Non-Study Medication Previous and Concomitant Medications 
Treated Subjects 
Appendix 4.2.1 / rl-cm-meds1.lst / GS_CM_L_X_006 
 
3.1.3. 
Other Listings 
Number 
Title 
BMS Table number/File Name/BMS Template 
27 
Listing of Batch Numbers  
Treated Subjects 
Appendix 1.7.1 / rl-ex-batch.lst / SS_EX_L_001 
28 
Summary of Baseline Disease Characteristics  
Subjects Enrolled but Not Randomized 
Appendix 3.2.1A / rt-dm-diseasenrands1.lst / 
SS_DM_T_004 
29 
Listing of HIV Disease Characteristics  
Treated Subjects 
Appendix 3.2.1B / rl-dm-diseases1.lst / 
SS_DM_L_002 
30 
Physical Examination  
Treated Subjects 
Appendix 3.4.1 / rl-pe-lists1.lst / GS_PE_L_X_001 
31 
General Medical History  
Treated Subjects 
Appendix 3.7.1 / rl-mh-list1.lst / GS_MH_L_X_001 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
9 
 
3.2. 
Efficacy 
Summary and analyses for primary efficacy data, secondary efficacy data and exploratory efficacy data, unless indicated in Section 3.2.1 
below, will not be presented for the final analysis except for HIV Drug Resistance data from Modified Treated Subjects who underwent 
resistance testing will be summarized and presented, see additional details in Section 3.4.  
Subject data listings will be provided for primary efficacy data, secondary efficacy data, exploratory efficacy data, and available plasma 
concentration data based on Treated Subjects population in Sections 3.2.2 and 3.2.3. 
3.2.1. 
Tables 
Number 
Title 
BMS Table number/File Name/BMS Template 
2.1 
Detailed Summary of HIV-1 RNA < 40 c/mL Proportion of 
Responders at Week 24 Snapshot  
Modified Treated Subjects 
Table S.5.1.1A / rt-vl-resp40w24s1.lst / 
SS_VL_T_001 
2.2 
Summary of HIV-1 RNA < 40 c/mL Proportion of Responders by 
Scheduled Assessments Over Time  
Modified Treated Subjects (Observed)1 
Table S.5.1.1E / rt-vl-resp40w24obssubgs1.lst / 
SS_VL_T_003  
(By Weeks 24, 48, and 96 instead of By Subgroup)  
2.3 
Summary Statistics for Values and Change from Baseline Over Time 
CD4 Cell Count (cells/uL)  
Modified Treated Subjects (Observed)1 
Table S.5.7.1A / rt-lb-cd4s1.lst / SS_VL_T_006 
(Without “By Subgroup”) 
2.4 
Summary Statistics for Values and Change from Baseline Over Time 
CD4 Cell Percentage  
Modified Treated Subjects (Observed)1 
Table S.5.8.1A / rt-lb-cd4pcts1.lst / SS_VL_T_006 
(Without “By Subgroup”) 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
10 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
1 Add the following footnote to the tables 2.2-2.4: 
 
Note: Modified Treated Subjects (Observed): Consisting of subjects in the Treated Subjects Population excluding subjects who have no HIV-1 RNA result data 
in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor 
[October 10, 2016], will be used to evaluate efficacy in a sensitivity analysis. 
3.2.2. 
ICH Listings 
Number 
Title 
BMS Table number/File Name/BMS Template 
7 
Listing of Outcomes from HIV-1 RNA < 40 c/mL Snapshot 
Analysis Data for Subjects in the Week 24 Snapshot  
Treated Subjects 
Appendix 5.1.1A / rl-vl-outcome24s1.lst / 
SS_VL_L_004 
 
3.2.3. 
Other Listings 
Number 
Title 
BMS Table number/File Name/BMS Template 
32 
Listing of HIV-1 RNA  
Treated Subjects 
Appendix 5.1.1D / rl-vl-vllist1.lst / SS_VL_L_005 
33 
Listing of CD4+ and CD8+ T- Cell Count and Percentages  
Treated Subjects 
Appendix 5.1.1E / rl-lb-cd4cd81.lst / SS_VL_L_005 
34 
Listing of BMS-955176 Plasma Concentration – Time Data  
PK Population 
Appendix 8.2.1A / rl-pk-cpar1bmss1.lst / 
MS_PK_L_001 
35 
Listing of ATV Plasma Concentration – Time Data  
PK Population 
Appendix 8.2.1B / rl-pk-cpar1atvs1.lst / 
MS_PK_L_001 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
11 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
36 
Listing of DTG Plasma Concentration – Time Data  
PK Population 
Appendix 8.2.1C / rl-pk-cpar1dtgs1.lst / 
MS_PK_L_001 
 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
12 
 
3.3. 
Safety 
The Modified Treated Subjects population will be used in the safety summaries and analyses. All treated subjects will be used in the data 
listings. Subject data listings will be based on Treated Subjects population. 
3.3.1. 
Tables 
Number 
Title 
BMS Table number/File Name/BMS Template 
3.1 
Extent of Exposure to BMS-955176 Time on Therapy 
Modified Treated Subjects 
Table S.4.1.1A / rt-ex-bmss1.lst / SS_EX_T_001 
3.2 
Extent of Exposure to Tenofovir Time on Therapy  
Modified Treated Subjects 
Table S.4.1.1B / rt-ex-tdfs1.lst / SS_EX_T_001 
3.3 
Extent of Exposure to Atazanavir Time on Therapy  
Modified Treated Subjects 
Table S.4.1.1C / rt-ex-atvs1.lst / SS_EX_T_001 
3.4 
Extent of Exposure to Dolutegravir Time on Therapy  
Modified Treated Subjects 
Table S.4.1.1D / rt-ex-dtgs1.lst / SS_EX_T_001 
3.5 
Extent of Exposure to Ritonavir Time on Therapy  
Modified Treated Subjects 
Table S.4.1.1E / rt-ex-rtvs1.lst / SS_EX_T_001 
3.6 
Extent of Exposure to Treatment Regimen Time on Therapy  
Modified Treated Subjects 
Table S.4.1.1F / rt-ex-regimens1.lst / SS_EX_T_001 
3.7 
Adverse Events Overall Adverse Events Summary  
Modified Treated Subjects 
Table S.6.7.1 rt-ae-overallsums1.lst SS_AE_T_001 
3.8 
Summary of Serious Adverse Events  
Modified Treated Subjects 
Table S.6.2.1A / rt-ae-saes1.lst / GS_AE_T_X_001 
3.9 
Summary of Serious Adverse Event With Death As An Outcome  
Modified Treated Subjects 
Table S.6.2.1C / rt-ae-saeldeaths1eu.lst / 
GS_AE_T_X_001 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
13 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
3.10 
Summary of Drug Related Serious Adverse Event With Death As An 
Outcome  
Modified Treated Subjects 
Table S.6.2.2D / rt-ae-relsaeldeaths2eu.lst / 
GS_AE_T_X_001 
3.11 
Listing of Serious Adverse Events 
Modified Treated Subjects 
Table S.6.2.1E / rl-ae-saes1.lst / GS_AE_L_S_001 
3.12 
Death Listing  
Enrolled Subjects 
Table S.6.1.1 / rl-ae-deaths1.lst / SS_AE_L_001 
3.13 
Summary of Adverse Events Leading to Discontinuation of Study 
Medication 
Modified Treated Subjects 
Table S.6.3.1A / rt-ae-aediscs1.lst / GS_AE_T_X_001 
3.14 
Listing of Adverse Event Leading to Discontinuation of Study 
Medication 
Modified Treated Subjects 
Table S.6.3.1C / rl-ae-discs1.lst / GS_AE_L_X_001 
3.15 
Summary of Non-Serious Adverse Events Occurring in at Least 5 
Percent of Treated Subjects 
Modified Treated Subjects 
Table S.6.5.1A / rt-ae-nsae5pcts1.lst  / 
GS_AE_T_X_001 
3.16 
Summary of Grade 1 to 4 Adverse Events 
Modified Treated Subjects 
Table S.6.5.1B / rt-ae-grade1to4s1.lst / 
GS_AE_T_X_001 
3.17 
Summary of Grade 2 to 4 Adverse Events 
Modified Treated Subjects 
Table S.6.5.1C / rt-ae-grade2to4s1.lst / 
GS_AE_T_X_001 
3.18 
Summary of Grade 3 to 4 Adverse Events 
Modified Treated Subjects 
Table S.6.5.1D / rt-ae-grade3to4s1.lst / 
GS_AE_T_X_001 
3.19 
Summary of Grade 1 to 4 Related Adverse Events 
Modified Treated Subjects 
Table S.6.5.1E / rt-ae-relateds1.lst / GS_AE_T_X_001 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
14 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
3.20 
Summary of Grade 2 to 4 Related Adverse Events 
Modified Treated Subjects 
Table S.6.5.1F / rt-ae-relgrade2to4s1.lst / 
GS_AE_T_X_001 
3.21 
Summary of Grade 3 to 4 Related Adverse Events 
Modified Treated Subjects 
Table S.6.5.1G / rt-ae-relgrade3to4s1.lst / 
GS_AE_T_X_001 
3.22 
Summary of CDC Class C AIDS Events 
Modified Treated Subjects 
Table S.6.4.1A / rt-ae-cdcaes1.lst / GS_AE_T_X_001 
3.23 
Listing of Adverse Event 
CDC Class C AIDS Events 
Modified Treated Subjects 
Table S.6.4.1B / rl-ae-cdcaes1.lst / GS_AE_L_X_001 
3.24 
Summary of Gastrointestinal Events of Special Interest 
Modified Treated Subjects 
Table S.6.4.1C / rt-ae-giaes1.lst / GS_AE_T_X_001 
3.25 
Listing of Adverse Event 
Gastrointestinal Events of Special Interest 
Modified Treated Subjects 
Table S.6.4.1D / rl-ae-giaes1.lst / GS_AE_L_X_001 
3.26 
Summary of Worst Toxicity Grade 
Modified Treated Subjects 
Table S.7.1.1A / rt-lb-toxs1.lst / SS_LB_T_001 
3.27 
Summary of Grade 3-4 Toxicity 
Modified Treated Subjects 
Table S.7.1.1B / rt-lb-g34toxs1.lst / SS_LB_T_001 
3.28 
Summary of Treatment-Emergent Abnormalities 
Modified Treated Subjects 
Table S.7.1.1C / rt-lb-etoxs1.lst / SS_LB_T_001 
3.29 
Summary Statistics for Renal Function Values and Change 
from Baseline - SI Units 
Modified Treated Subjects 
Table S.7.2.1A / rt-lb-renals1.lst / SS_VL_T_006 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
15 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
3.30 
Summary Statistics for Renal Function Values and Change 
from Baseline - US Units 
Modified Treated Subjects 
Table S.7.2.1B / rt-zl-renals1.lst / SS_VL_T_006 
3.31 
Summary Statistics for Fasting Lipid Values and Change from 
Baseline - SI Units 
Modified Treated Subjects 
Table S.7.2.1C / rt-lb-lipidss1.lst / SS_VL_T_006 
3.32 
Summary Statistics for Fasting Lipid Values and Change from 
Baseline - US Units 
Modified Treated Subjects 
Table S.7.2.1D / rt-zl-lipidss1.lst / SS_VL_T_006 
3.33 
Summary Statistics for Fasting Lipid Values and Percent 
Change from Baseline - SI Units 
Modified Treated Subjects 
Table S.7.2.1E / rt-lb-pchglipidss1.lst / SS_VL_T_006 
3.34 
Summary Statistics for Fasting Lipid Values and Percent 
Change from Baseline - US Units 
Modified Treated Subjects 
Table S.7.2.1F / rt-zl-pchglipidss1.lst / SS_VL_T_006 
3.35 
Summary Statistics for Renal Biomarker Values and Change from 
Baseline - US Units  
Modified Treated Subjects 
Table S.7.5.1A / rt-zl-bmrenals1.lst / SS_VL_T_006 
3.36 
Summary Statistics for Renal Biomarker Values and Change from 
Baseline - SI Units  
Modified Treated Subjects 
Table S.7.5.1B / rt-lb-bmrenals1.lst / SS_VL_T_006 
3.37 
Summary Statistics for Renal Biomarker Values and Percent Change 
from Baseline - US Units  
Modified Treated Subjects 
Table S.7.5.1C / rt-zl-pchbmrenals1.lst / 
SS_VL_T_006 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
16 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
3.38 
Summary Statistics for Renal Biomarker Values and Percent Change 
from Baseline - SI Units  
Modified Treated Subjects 
Table S.7.5.1D / rt-lb-pchbmrenals1.lst / 
SS_VL_T_006 
3.39 
Summary Statistics for Bone Biomarker Values and Change from 
Baseline - US Units  
Modified Treated Subjects 
Table S.7.5.1E / rt-zl-bmbones1.lst / SS_VL_T_006 
3.40 
Summary Statistics for Bone Biomarker Values and Change from 
Baseline - SI Units  
Modified Treated Subjects 
Table S.7.5.1F / rt-lb-bmbones1.lst / SS_VL_T_006 
3.41 
Summary Statistics for Bone Biomarker Values and Percent Change 
from Baseline - US Units  
Modified Treated Subjects 
Table S.7.5.1G / rt-zl-pchbmbones1.lst / 
SS_VL_T_006 
3.42 
Summary Statistics for Bone Biomarker Values and Percent Change 
from Baseline - SI Units  
Modified Treated Subjects 
Table S.7.5.1H / rt-lb-pchbmbones1.lst / 
SS_VL_T_006 
3.43 
Summary of Electrocardiogram Values and Changes from 
Baseline over Time 
Modified Treated Subjects  
Appendix 7.3.1A / rt-eg-sumchgs1.lst / SS_EG_T_003 
3.44 
Summary of Electrocardiogram Change from Baseline Category 
Modified Treated Subjects 
Appendix 7.3.1B / rt-eg-changecats1.lst / 
SS_EG_T_001 
3.35 
Summary of Electrocardiogram Category 
Modified Treated Subjects 
Appendix 7.3.1C / rt-eg-cats1.lst / SS_EG_T_002 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
17 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
3.46 
Summary of Vital Sign Values and Changes from Baseline over 
Time 
Modified Treated Subjects 
Appendix 7.4.1A / rt-vs-sums1.lst / SS_VL_T_006 
 
3.3.2. 
ICH Listings 
Number 
Title 
BMS Table number/File Name/BMS Template 
8 
Listing of Study Medication Exposure by Subject Listing 
Treated Subjects 
Appendix 4.1.1A / rl-ex-lists1.lst / SS_EX_L_001 
9 
Listing of Adverse Event  
Treated Subjects 
Appendix 6.5.1 / rl-ae-lists1.lst / GS_AEL_X_001 
10 
Listing of Adverse Event Unique Events 
Treated Subjects 
Appendix 6.6.1 / rl-ae-uniques1.lst / 
GS_AE_L_U_002 
11 
Listing of Hematology - SI Units 
Treated Subjects 
Appendix 7.1.1A / rl-lb-hems1.lst / SS_LB_L_001 
12 
Listing of Liver Function Tests - SI Units 
Treated Subjects 
Appendix 7.1.1B / rl-lb-lfts1.lst / SS_LB_L_001 
13 
Listing of Enzymes - SI Units 
Treated Subjects 
Appendix 7.1.1C / rl-lb-enzs1.lst / SS_LB_L_001 
14 
Listing of Renal Function Tests - SI Units 
Treated Subjects 
Appendix 7.1.1D / rl-lb-rfts1.lst / SS_LB_L_001 
15 
Listing of Electrolytes - SI Units 
Treated Subjects 
Appendix 7.1.1E / rl-lb-elcs1.lst / SS_LB_L_001 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
18 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
16 
Listing of Fasting Lipids and Glucose – SI Units 
Treated Subjects 
Appendix 7.1.1F / rl-lb-flgs1.lst / SS_LB_L_001 
17 
Listing of Hematology - US Unit 
Treated Subjects 
Appendix 7.1.1G / rl-zl-hems1.lst / SS_LB_L_001 
18 
Listing of Liver Function Tests - US Unit 
Treated Subjects 
Appendix 7.1.1H / rl-zl-lfts1.lst / SS_LB_L_001 
19 
Listing of Enzymes - US Unit 
Treated Subjects 
Appendix 7.1.1I / rl-zl-enzs1.lst / SS_LB_L_001 
20 
Listing of Renal Function Tests - US Unit 
Treated Subjects 
Appendix 7.1.1J / rl-zl-rfts1.lst / SS_LB_L_001 
21 
Listing of Electrolytes - US Unit 
Treated Subjects 
Appendix 7.1.1K / rl-zl-elcs1.lst / SS_LB_L_001 
22 
Listing of Fasting Lipids and Glucose – US Unit 
Treated Subjects 
Appendix 7.1.1L / rl-zl-flgs1.lst / SS_LB_L_001 
23 
Listing of Differences in Categorization of SI and US Laboratory 
Test Results Treated Subjects 
Appendix 7.1.1M / rl-lb-diffunits1.lst / 
GS_LB_L_S_008 
24 
Listing of Pregnancy Test 
Treated Female Subjects 
Appendix 7.1.1N / rl-lb-pregs1.lst / GS_LB_L_X_006 
25 
Listing of Electrocardiogram 
Treated Subjects 
Appendix 7.3.1D / rl-eg-ecgs1.lst / GS_EG_L_X_001 
26 
Listing of Vital Signs 
Treated Subjects 
Appendix 7.4.1B / rl-vs-lists1.lst / GS_VS_L_X_006 
 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
19 
 
3.4. 
Virology 
The Modified Treated Subjects population with available virology data will be used in the summaries and analyses. All treated subjects 
with available virology data will be used in the data listings. 
3.4.1. 
Tables 
Number 
Title 
BMS Table number/File Name/BMS Template 
4.1 
Baseline Genotypic Resistance Profile  
Modified Treated Subjects 
Table S.3.9.1A / rt-gn-bases1.lst / SS_GN_T_001 
4.2 
Baseline Gag Polymorphisms at Selected Positions  
Modified Treated Subjects 
Table S.3.9.1C / rt-gn-bslgags1.lst / SS_GN_T_002 
4.3 
Baseline Gag Polymorphisms at Selected Positions  
Modified Treated Subjects Identified as Protocol Defined Virologic 
Failures 
Table S.3.9.1J / rt-gn-bslgagpdvfs1.lst / SS_GN_T_002 
4.4 
Newly Emergent Genotypic Resistance Profile  
Modified Treated Subjects with On-Treatment Genotypic Resistance 
Testing 
Table S.5.10.1A / rt-gn-news1.lst / SS_GN_T_001 
4.5 
Newly Emergent Genotypic Resistance Profile  
Modified Treated Subjects Identified as Protocol Defined Virologic 
Failures 
Table S.5.10.1B / rt-gn-newpdvfs1.lst / SS_GN_T_001 
4.6 
Emergent Gag Polymorphisms at Selected Positions  
Modified Treated Subjects with On-Treatment Gag Sequencing 
Table S.5.10.1C / rt-gn-newgags1.lst / SS_GN_T_002 
4.7 
Emergent Gag Polymorphisms at Selected Positions  
Modified Treated Subjects Identified as Protocol Defined Virologic 
Failures 
Table S.5.10.1D / rt-gn-newgagpdvfs1.lst / 
SS_GN_T_002 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
20 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
4.8 
Newly Emergent Phenotypic Resistance Profile  
Modified Treated Subjects with On-Treatment Phenotypic Resistance 
Profile 
Table S.5.10.1G / rt-pn-news1.lst / SS_PN_T_001 
4.9 
Newly Emergent Phenotypic Resistance Profile  
Modified Treated Subjects Identified as Protocol Defined Virologic 
Failures 
Table S.5.10.1H / rt-pn-newpdvfs1.lst / SS_PN_T_001 
 
3.4.2. 
Other Listings 
Number 
Title 
BMS Table number/File Name/BMS Template 
37 
Listing of Baseline Genotypic Substitutions  
Treated Subjects 
Appendix 3.9.1B / rl-gn-bsls1.lst / SS_GN_L_001 
38 
Listing of Baseline Gag Polymorphisms at Selected Positions 
Treated Subjects 
Appendix 3.9.1C / rl-gn-gagbsls1.lst / SS_GN_L_002 
39 
Listing of Baseline Gag Deviations from Wild Type Virus  
Treated Subjects 
Appendix 3.9.1D / rl-gn-gagbslanys1.lst / 
SS_GN_L_003 
40 
Listing of Protocol Defined Virologic Failures  
Treated Subjects 
Not Available / rl-vl-pdvf.lst / SS_VL_L_006 
41 
Listing of Genotypic Substitutions  
Treated Subjects with Baseline and On-Treatment Data 
Appendix 5.10.1A / rl-gn-ontrts1.lst / SS_GN_L_001 
42 
Listing of Gag Polymorphisms at Selected Positions  
Treated Subjects with Baseline and On-Treatment Data 
Appendix 5.10.1B / rl-gn-gagontrts1.lst / 
SS_GN_L_002 


 
CONFIDENTIAL 
 
 
 
AI468038/205891 
21 
 
Number 
Title 
BMS Table number/File Name/BMS Template 
43 
Listing of Newly Emergent Gag Deviations  
Treated Subjects with Baseline and On-Treatment Data 
Appendix 5.10.1C / rl-gn-gagontrts1.lst / 
SS_GN_L_003 
44 
Listing of Phenotypic Resistance  
Treated Subjects with Baseline and On-Treatment Data 
Appendix 5.10.1D / rl-pn-ontrt1.lst / SS_PN_L_001 
 
  


 
 
GLOBAL BIOMETRIC SCIENCES 
ANALYSIS DATA PRESENTATION PLAN 
 
BMS-955176 
HIV MATURATION INHIBITOR 
CLINICAL STUDY REPORT FOR AI438-048  
 
DOCUMENT REVISION: 2.0 
 
 


PPD
PPD
PPD
PPD
PPD


PPD
PPD
PPD
PPD
PPD
PPD


PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
2 
REVISION HISTORY 
Revision 
Date 
Revised By 
Changes Made -- Reasons for the Change 
1.0 
July 16, 2015 
 
Original issue 
2.0 
Oct 6, 2015 
 
Additional outputs for baseline resistance have been 
added based on the revised SAP v2.0 (see Tables 
S.3.9.xH-R) 
Additional outputs for on-treatment resistance have 
been added based on the revised SAP v2.0 (see Tables 
S.5.10.xR-W). 
Integrated outputs have been added as described in the 
revised SAP v2.0. 
Update the schedule of analysis: Week 48 Stage 1 
interim analysis only if continuation dose cannot be 
selected based on Week 24, Stage 1 results. The Week 
96 Stage 1 will be performed at the time of Week 24 
Stage 2. 
 
 
 
 
 
PPD
PPD


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
3 
TABLE OF CONTENTS 
ANALYSIS DATA PRESENTATION PLAN ...............................................................................1 
TABLE OF CONTENTS .................................................................................................................3 
TABLE OF CONTENTS: TEMPLATES .......................................................................................5 
1 
LIST OF DATA PRESENTATIONS ...........................................................................8 
1.1 
Codes Used for Deliverables ........................................................................................8 
1.2 
List ................................................................................................................................8 
2 
INTRODUCTION ......................................................................................................58 
2.1 
Guidance for DPP Users and Reviewers ....................................................................58 
2.2 
Referenced Documents ...............................................................................................58 
3 
GENERAL CRITERIA/CONVENTIONS .................................................................59 
3.1 
Exceptions to Global and/or Departmental Standards ................................................59 
3.2 
Populations .................................................................................................................59 
3.3 
Conventions ................................................................................................................60 
3.4 
Treatment Information ................................................................................................60 
3.5 
Graph Criteria/Conventions ........................................................................................60 
4 
PRESENTATION PLAN TEMPLATES AND METADATA ..................................62 
4.1 
Administrative Appendices ........................................................................................62 
4.2 
Study Conduct ............................................................................................................66 
4.2.1 
Protocol Deviations ....................................................................................................66 
4.3 
Study Population .........................................................................................................69 
4.3.1 
Disposition of Subjects ...............................................................................................69 
4.3.2 
Demographics and Baseline Characteristics .............................................................85 
4.3.3 
Medical History and Previous Treatments ...............................................................147 
4.4 
Extent Of Exposure ...................................................................................................153 
4.4.1 
Study Therapy and Treatment Compliance ..............................................................153 
4.4.2 
Concomitant Therapy ...............................................................................................170 
4.5 
Efficacy Results ........................................................................................................172 
4.6 
Safety Results ...........................................................................................................279 
4.6.1 
All Adverse Events ....................................................................................................279 
4.6.2 
Deaths .......................................................................................................................281 
4.6.3 
Serious Adverse Events .............................................................................................282 
4.6.4 
Adverse Events Leading to Discontinuation of Study Therapy ................................289 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
4 
4.6.5 
Other Significant Adverse Events .............................................................................294 
4.6.6 
Multiple Adverse Events ...........................................................................................307 
4.6.7 
Clinical Laboratory Evaluations ..............................................................................316 
4.6.8 
Electrocardiograms ..................................................................................................346 
4.6.9 
Vital Signs and Physical Findings ............................................................................354 
4.6.10 
Other Observations Related to Safety .......................................................................358 
4.7 
Pharmacokinetic Results ...........................................................................................369 
4.8 
Pharmacodynamic Results ........................................................................................406 
4.9 
Other Study Results ..................................................................................................406 
 
 
 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
5 
TABLE OF CONTENTS: TEMPLATES 
Template SS_EX_L_001: Batch Number Listing .........................................................................63 
Template SS_DS_L_001: Randomization Scheme and Codes .....................................................64 
Template SS_DM_T_001: Accrual Summary ...............................................................................65 
Template SS_PD_T_001: Relevant Protocol Deviation Summary ...............................................67 
Template SS_PD_L_001: Relevant Protocol Deviation Listing ...................................................68 
Template GS_DS_T_T_001: Pre-Randomization Subject Status .................................................70 
Template GS_DS_L_S_001: Pre-randomization Subject Status Listing.......................................72 
Template GS_DM_T_T_005 : Enrollment Summary ...................................................................74 
Template SS_DM_T_002: Counts and Percentages Table ............................................................76 
Template GS_DS_T_X_005 : End of Study Subjects Status ........................................................78 
Template GS_DS_L_X_005: End of Study Subject Status by Treatment Group .........................80 
Template SS_DM_T_002 : Population Summary .........................................................................82 
Template SS_DM_L_001: Listing of Subjects Excluded from the Efficacy Analysis .................84 
Template GS_DM_T_X_002: Demographic Characteristics Summary (incl. ‘Not 
reported’ category) .....................................................................................86 
Template GS_DM_T_T_002: Demographic Characteristics Summary (incl. ‘Not 
reported’ category) .....................................................................................89 
Template GS_DM_L_X_001: Demographics Listing by Treatment Group .................................91 
Template SS_DM_T_004 : Baseline Disease Characteristics .......................................................93 
Template SS_DM_L_002: Listing of HIV Disease Characteristics ..............................................97 
Template GS_PM_T_X_001: Physical Measurements Table .......................................................99 
Template GS_PE_T_X_001: Physical Examination by Treatment Group ..................................101 
Template GS_PE_L_X_001 : Physical Examination Listing by Treatment Group ....................103 
Template SS_GN_T_001: Baseline Genotypic Resistance Profile .............................................105 
Template SS_GN_L_001:Genotypic Resistance Listing .............................................................109 
Template SS_GN_T_002: Baseline Gag Polymorphisms at Selected Positions .........................111 
Template SS_GN_T_003: Baseline Gag Deviations from Wild Type ........................................119 
Template SS_GN_L_002: Gag Listing for Selected Positions ....................................................128 
Template SS_GN_L_003: Gag Listing of Deviations from the Wild Type Virus ......................130 
Template SS_PN_T_001: Baseline Phenotypic Resistance Categories ......................................132 
Template SS_PN_T_002: Phenotypic Resistance by Class and Drug Name ..............................137 
Template SS_PN_L_001: Phenotypic Resistance Listing ...........................................................142 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
6 
Template GS_LB_T_X_004: Laboratory Toxicity Grade Summary ..........................................144 
Template GS_AE_T_X_001: Adverse Event Summary by System Organ Class and 
Preferred Term .........................................................................................146 
Template GS_MH_T_X_001: Medical History Summary ..........................................................148 
Template GS_MH_L_X_001: Medical History Listing by Treatment Group ............................150 
Template GS_CM_T_X_001 : Non-Study Medication Summary ..............................................152 
Template SS_EX_T_001: Extent of Exposure Summary ............................................................154 
Template GS_EX_G_001: Kaplan-Meier Plot Grouped by Treatment with Censoring .............161 
Template SS_EX_T_002: Time on Study Therapy Life Table ...................................................163 
Template SS_EX_T_003: Summary of Interruptions Greater than 3 Days ................................165 
Template SS_EX_L_001: Study Medication Exposure Listing ..................................................167 
Template SS_EX_L_002: Study Medication Listing related to Continuation Dose ...................169 
Template GS_CM_L_X_006: Non-Study Medication Listing by Treatment Group ..................171 
Template SS_VL_T_001: Detailed Summary of HIV-1 < Y (by Subgroup) ..............................173 
Template SS_VL_T_002: Summary of HIV-1 < Y (by Subgroup) ............................................175 
Template SS_VL_T_003: Proportion of Responders (Observed) ...............................................199 
Template SS_VL_T_004: Treatment Outcomes Table Using the TLOVR Algorithm ...............207 
Template SS_VL_T_005: Proportion of Subjects with HIV-1 RNA within Certain Range .......213 
Template SS_VL_T_006 : Summary Statistics Over Time .........................................................215 
Template GS_LB_G_001: Box Plot ............................................................................................222 
Template GS_L_G_002: Longitudinal Line Plot Grouped by Treatment with Horizontal 
Shift and Reference Line .........................................................................231 
Template SS_VL_L_004: Listing of Outcomes from Snapshot Analysis ...................................235 
Template SS_VL_L_005: Listing of Viral Load .........................................................................239 
Template SS_LB_L_002: Listing of CD4 and CD8 ....................................................................241 
Template SS_PN_T_003: Maximum Change in IC50 Summary ................................................265 
Template SS_PN_T_004: Proportion of Subjects with > 3 Fold Increase in IC50 Fold 
Change .....................................................................................................270 
Template SS_VL_T_007: Proportion of Responders (mITT) - Futility Analysis .......................278 
Template SS_AE_T_001: Overall Adverse Events Summary ....................................................280 
Template SS_AE_L_001: Listing of Death .................................................................................282 
Template GS_AE_L_S_001: Adverse Event Listing (by Subject)..............................................287 
Template GS_AE_L_X_001: Adverse Event Listing (by Treatment Group) .............................292 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
7 
Template GS_AE_T_M_001: Exposure Adjusted Adverse Events Summary by SOC and 
Preferred Term .........................................................................................308 
Template GS_AE_L_U_002: Unique Adverse Event Listing .....................................................314 
Template SS_LB_T_001: Laboratory Test Worst Abnormalities Table by Baseline .................317 
Template SS_LB_T_002: Laboratory Test Treatment Emergent Abnormalities Table ..............320 
Template SS_LB_L_001: Laboratory Test Results Listing With Toxicity Grades .....................331 
Template GS_LB_L_S_008: Differences in Categorization of SI and US units .........................343 
Template GS_LB_L_X_006: Pregnancy Listing by Treatment Group .......................................345 
Template SS_EG_T_003 : ECG Summary Table with 95% CI ..................................................347 
Template SS_EG_T_001 : ECG Change from Baseline Category Summary .............................349 
Template SS_EG_T_002: ECG Category Summary ...................................................................351 
Template GS_EG_L_X_001: ECG Listing .................................................................................353 
Template GS_VS_L_X_006: Vital Signs Listing by Treatment Group ......................................356 
Template MS_PK_T_004:  Summary Statistics for PK Parameters ...........................................369 
Template MS_PK_T_005:  In-text Table for Summary Statistics for PK Parameters ................373 
Template MS_PK_T_006:  Statistical Analysis for PK Parameters ............................................377 
Template MS_PK_T_007:  In-text Table for Statistical Analysis for PK Parameters ................379 
Template MS_PK_L_005:  Listing for PK Parameters ...............................................................382 
Template MS_PK_L_001:  Listing of Plasma Concentration-Time Data ...................................386 
Template MS_PK_G_002:  Individual Plot of Plasma Concentrations vs. Time........................390 
Template MS_PK_G_001:  Overlay of Individual Matrix Concentration vs. Time ...................396 
Template MS_PK_G_006:  Mean Plot of Matrix Concentration vs. Time .................................401 
 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
8 
1 
LIST OF DATA PRESENTATIONS  
1.1 
Codes Used for Deliverables  
Code 
Description 
WK24S1 
Interim Analysis Week 24, Stage 1 
WK48S1 
Interim Analysis Week 48, Stage 1* 
WK96S1 
Final Analysis Week 96, Stage 1 (most likely at the time 
of Interim Analysis Week 24, Stage 2) 
WK24S2 
Interim Analysis Week 24, Stage 2 
WK48S2 
Interim Analysis Week 48, Stage 2 
WK96S2 
Final Analysis Week 96, Stage 2 
* The Week 48, Stage 1 interim analysis would only be performed in case a continuation dose cannot be selected based on 
the Week 24, Stage 1 interim analysis. 
Note: in order to make the distinction between the different database locks for each stage, the 
table numbers should have ‘-Wkxx’ attached to the table numbers mentioned in the rest of the 
DPP. For example, Table S.2.3.1A will become Table S.2.3.1A-Wk24 for the Stage 1 Week 24 
interim analysis. Table S.2.3.2A will become Table S.2.3.2A-Wk48 for the Stage 2 Week 48 
analysis. 
 
1.2 
List 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
1 
Appendix 1.7.1 
rl-ex-batchs1.lst 
SS_EX_L_001 
Listing of Batch Numbers 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
2 
Appendix 1.7.2 
rl-ex-batchs2.lst 
SS_EX_L_001 
Listing of Batch Numbers 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
3 
Appendix 1.9.1 
rl-ds-
randcodes1.lst 
SS_DS_L_001 
Randomization Scheme and 
Codes 
Randomized Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
4 
Appendix 1.9.2 
rl-ds-
randcodes2.lst 
SS_DS_L_001 
Randomization Scheme and 
Codes 
Randomized Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
5 
Appendix 
2.1.1E 
rt-dm-accruals1.lst 
SS_DM_T_001 
Accrual Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
6 
Appendix 
2.1.2E 
rt-dm-accruals2.lst 
SS_DM_T_001 
Accrual Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
9 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
7 
Table S.2.3.1A 
rt-pd-rels1.lst 
SS_PD_T_001 
Relevant Protocol Deviation 
Summary 
Randomized Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
8 
Table S.2.3.2A 
rt-pd-rels2.lst 
SS_PD_T_001 
Relevant Protocol Deviation 
Summary 
Randomized Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
9 
Table S.2.3.1B 
rl-pd-rels1.lst 
SS_PD_L_001 
Listing of Relevant Protocol 
Deviations 
Randomized Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
10 
Table S.2.3.2B 
rl-pd-rels2.lst 
SS_PD_L_001 
Listing of Relevant Protocol 
Deviations 
Randomized Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
11 
Table S.2.1.1A 
rt-ds-prerands1.lst 
GS_DS_T_T_001 
Pre-Randomization Subject 
Status 
Enrolled Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
12 
Table S.2.1.2A 
rt-ds-prerands2.lst 
GS_DS_T_T_001 
Pre-Randomization Subject 
Status 
Enrolled Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
13 
Appendix 
2.1.1A 
rl-ds-prerands1.lst 
GS_DS_L_S_001 
Pre-Randomized Subject Status 
Enrolled Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
14 
Appendix 
2.1.2A 
rl-ds-prerands2.lst 
GS_DS_L_S_001 
Pre-Randomized Subject Status 
Enrolled Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
15 
Appendix 
2.1.1C 
rt-dm-
enrolls1eu.lst 
GS_DM_T_T_005 
Enrollment Summary 
Number of Subjects at Each 
Study Site by Country 
Enrolled Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
16 
Appendix 
2.1.2C 
rt-dm-
enrolls2eu.lst 
GS_DM_T_T_005 
Enrollment Summary 
Number of Subjects at Each 
Study Site by Country 
Enrolled Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
17 
Appendix 
2.1.1D 
rt-dm-
enrages1eu.lst 
SS_DM_T_002 
Enrollment Summary  
Number of Subjects per Age 
Group 
Enrolled Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
18 
Appendix 
2.1.2D 
rt-dm-
enrages2eu.lst 
SS_DM_T_002 
Enrollment Summary  
Number of Subjects per Age 
Group 
Enrolled Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
19 
Table S.2.1.1B 
rt-ds-statuss1.lst 
GS_DS_T_X_005 
End of Study Subject Status 
Summary 
Randomized Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
20 
Table S.2.1.2B 
rt-ds-statuss2.lst 
GS_DS_T_X_005 
End of Study Subject Status 
Summary 
Randomized Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
10 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
21 
Table S.2.1.3B 
rt-ds-statuss12.lst 
GS_DS_T_X_005 
End of Study Subject Status 
Summary 
Randomized Subjects - Stage 1 
and 2 
WK96S2 
22 
Appendix 
2.1.1B 
rl-ds-statuss1.lst 
GS_DS_L_X_005 
End of Study Subject Status 
Randomized Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
23 
Appendix 
2.1.2B 
rl-ds-statuss2.lst 
GS_DS_L_X_005 
End of Study Subject Status 
Randomized Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
24 
Table S.2.1.1C 
rt-dm-
populations1.lst 
SS_DM_T_002 
Populations for Analysis 
Summary - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
25 
Table S.2.1.2C 
rt-dm-
populations2.lst 
SS_DM_T_002 
Populations for Analysis 
Summary - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
26 
Appendix 2.2.1 
rl-dm-excls1.lst 
SS_DM_L_001 
Subjects Excluded from 
Efficacy Analysis (mITT) 
Randomized Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
27 
Appendix 2.2.2 
rl-dm-excls2.lst 
SS_DM_L_001 
Subjects Excluded from 
Efficacy Analysis (mITT) 
Randomized Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
28 
Table S.3.1.1 
rt-dm-
summarys1.lst 
GS_DM_T_X_002 
Demographic Characteristics 
Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
29 
Table S.3.1.2 
rt-dm-
summarys2.lst 
GS_DM_T_X_002 
Demographic Characteristics 
Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
30 
Table S.3.1.3 
rt-dm-
summarys12.lst 
GS_DM_T_X_002 
Demographic Characteristics 
Summary 
Treated Subjects - Stage 1 and 2 
WK96S2 
31 
Appendix 
3.1.1B 
rt-dm-
sumenrolls1.lst 
GS_DM_T_T_002 
Demographic Characteristics 
Summary 
Subjects Enrolled but Not 
Randomized - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
32 
Appendix 
3.1.2B 
rt-dm-
sumenrolls2.lst 
GS_DM_T_T_002 
Demographic Characteristics 
Summary 
Subjects Enrolled but Not 
Randomized - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
33 
Appendix 
3.1.1A 
rl-dm-
demchars1.lst 
GS_DM_L_X_001 
Demographic Characteristics 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
34 
Appendix 
3.1.2A 
rl-dm-
demchars2.lst 
GS_DM_L_X_001 
Demographic Characteristics 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
11 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
35 
Table S.3.2.1 
rt-dm-diseases1.lst 
SS_DM_T_004 
Summary of Baseline Disease 
Characteristics 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
36 
Table S.3.2.2 
rt-dm-diseases2.lst 
SS_DM_T_004 
Summary of Baseline Disease 
Characteristics 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
37 
Table S.3.2.3 
rt-dm-
diseases12.lst 
SS_DM_T_004 
Summary of Baseline Disease 
Characteristics 
Treated Subjects - Stage 1 and 2 
WK96S2 
38 
Appendix 
3.2.1A 
rt-dm-
diseasenrands1.lst 
SS_DM_T_004 
Summary of Baseline Disease 
Characteristics 
Subjects Enrolled but Not 
Randomized - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
39 
Appendix 
3.2.2A 
rt-dm-
diseasenrands2.lst 
SS_DM_T_004 
Summary of Baseline Disease 
Characteristics 
Subjects Enrolled but Not 
Randomized - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
40 
Appendix 
3.2.1B 
rl-dm-diseases1.lst 
SS_DM_L_002 
Listing of HIV Disease 
Characteristics 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
41 
Appendix 
3.2.2B 
rl-dm-diseases2.lst 
SS_DM_L_002 
Listing of HIV Disease 
Characteristics 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
42 
Table S.3.3.1 
rt-pm-bsls1.lst 
GS_PM_T_X_001 
Physical Measurements 
Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
43 
Table S.3.3.2 
rt-pm-bsls2.lst 
GS_PM_T_X_001 
Physical Measurements 
Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
44 
Table S.3.4.1 
rt-pe-bslsums1.lst 
GS_PE_T_X_001 
Physical Examination Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
45 
Table S.3.4.2 
rt-pe-bslsums2.lst 
GS_PE_T_X_001 
Physical Examination Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
46 
Appendix 3.4.1 
rl-pe-lists1.lst 
GS_PE_L_X_001 
Physical Examination 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
47 
Appendix 3.4.2 
rl-pe-lists2.lst 
GS_PE_L_X_001 
Physical Examination 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
48 
Table S.3.9.1A 
rt-gn-bases1.lst 
SS_GN_T_001 
Baseline Genotypic Resistance 
Profile 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
49 
Table S.3.9.2A 
rt-gn-bases2.lst 
SS_GN_T_001 
Baseline Genotypic Resistance 
Profile 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
12 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
50 
Table S.3.9.3A 
rt-gn-bases12.lst 
SS_GN_T_001 
Baseline Genotypic Resistance 
Profile 
Treated Subjects - Stage 1 and 2 
WK96S2 
51 
Appendix 
3.9.1A 
rt-gn-
basebysubtypes1.ls
t 
SS_GN_T_001 
Baseline Genotypic Resistance 
Profile 
By HIV Subtype 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
52 
Appendix 
3.9.2A 
rt-gn-
basebysubtypes2.ls
t 
SS_GN_T_001 
Baseline Genotypic Resistance 
Profile 
By HIV Subtype 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
53 
Table S.3.9.1B 
rt-gn-baseots1.lst 
SS_GN_T_001 
Baseline Genotypic Resistance 
Profile 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
54 
Table S.3.9.2B 
rt-gn-baseots2.lst 
SS_GN_T_001 
Baseline Genotypic Resistance 
Profile 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
55 
Appendix 
3.9.1B 
rl-gn-bsls1.lst 
SS_GN_L_001 
Listing of Baseline Genotypic 
Substitutions 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
56 
Appendix 
3.9.2B 
rl-gn-bsls2.lst 
SS_GN_L_001 
Listing of Baseline Genotypic 
Substitutions 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
57 
Table S.3.9.1C 
rt-gn-bslgags1.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
58 
Table S.3.9.2C 
rt-gn-bslgags2.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
59 
Table S.3.9.3C 
rt-gn-bslgags12.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects - Stage 1 and 2 
WK96S2 
60 
Table S.3.9.1D 
rt-gn-
bslgagbysubtypes1
.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
61 
Table S.3.9.2D 
rt-gn-
bslgagbysubtypes2
.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
62 
Table S.3.9.3D 
rt-gn-
bslgagbysubtypes1
2.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects - Stage 1 and 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
13 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
63 
Table S.3.9.1H 
rt-gn-
bslgagontrts1.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
64 
Table S.3.9.2H 
rt-gn-
bslgagontrts2.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
65 
Table S.3.9.3H 
rt-gn-
bslgagontrts12.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 and 2 
WK96S2 
66 
Table S.3.9.1I 
rt-gn-
bslgagontrtbysubty
pes1.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
67 
Table S.3.9.2I 
rt-gn-
bslgagontrtbysubty
pes2.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
68 
Table S.3.9.3I 
rt-gn-
bslgagontrtbysubty
pes12.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 and 2 
WK96S2 
69 
Table S.3.9.1J 
rt-gn-
bslgagpdvfs1.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
70 
Table S.3.9.2J 
rt-gn-
bslgagpdvfs2.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
71 
Table S.3.9.3J 
rt-gn-
bslgagpdvfs12.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
14 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
72 
Table S.3.9.1K 
rt-gn-
bslgagpdvfbysubty
pes1.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
73 
Table S.3.9.2K 
rt-gn-
bslgagpdvfbysubty
pes2.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
74 
Table S.3.9.3K 
rt-gn-
bslgagpdvfbysubty
pes12.lst 
SS_GN_T_002 
Baseline Gag Polymorphisms at 
Selected Positions 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
75 
Table S.3.9.1E 
rt-gn-
bslgaganys1.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
76 
Table S.3.9.2E 
rt-gn-
bslgaganys2.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
77 
Table S.3.9.3E 
rt-gn-
bslgaganys12.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects - Stage 1 and 2 
WK96S2 
78 
Table S.3.9.1L 
rt-gn-
bslgaganybysubtyp
es1.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
79 
Table S.3.9.2L 
rt-gn-
bslgaganybysubtyp
es2.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
80 
Table S.3.9.3L 
rt-gn-
bslgaganybysubtyp
es12.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects - Stage 1 and 2 
WK96S2 
81 
Table S.3.9.1M 
rt-gn-
bslgaganyontrts1.ls
t 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
82 
Table S.3.9.2M 
rt-gn-
bslgaganyontrts2.ls
t 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
15 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
83 
Table S.3.9.3M 
rt-gn-
bslgaganyontrts12.
lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 and 2 
WK96S2 
84 
Table S.3.9.1N 
rt-gn-
bslgaganyontrtbysu
btypes1.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
85 
Table S.3.9.2N 
rt-gn-
bslgaganyontrtbysu
btypes2.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
86 
Table S.3.9.3N 
rt-gn-
bslgaganyontrtbysu
btypes12.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 and 2 
WK96S2 
87 
Table S.3.9.1O 
rt-gn-
bslgaganypdvfs1.ls
t 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
88 
Table S.3.9.2O 
rt-gn-
bslgaganypdvfs2.ls
t 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
89 
Table S.3.9.3O 
rt-gn-
bslgaganypdvfs12.l
st 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
90 
Table S.3.9.1P 
rt-gn-
bslgaganypdvfbysu
btypes1.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
91 
Table S.3.9.2P 
rt-gn-
bslgaganypdvfbysu
btypes2.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
16 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
92 
Table S.3.9.3P 
rt-gn-
bslgaganypdvfbysu
btypes12.lst 
SS_GN_T_003 
Baseline Gag Deviations from 
Wild Type Virus 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
93 
Appendix 
3.9.1C 
rl-gn-gagbsls1.lst 
SS_GN_L_002 
Listing of Baseline Gag 
Polymorphisms at Selected 
Positions 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
94 
Appendix 
3.9.2C 
rl-gn-gagbsls2.lst 
SS_GN_L_002 
Listing of Baseline Gag 
Polymorphisms at Selected 
Positions 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
95 
Appendix 
3.9.1D 
rl-gn-
gagbslanys1.lst 
SS_GN_L_003 
Listing of Baseline Gag 
Deviations from Wild Type 
Virus 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
96 
Appendix 
3.9.2D 
rl-gn-
gagbslanys2.lst 
SS_GN_L_003 
Listing of Baseline Gag 
Deviations from Wild Type 
Virus 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
97 
Table S.3.9.1F 
rt-pn-bsls1.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
98 
Table S.3.9.2F 
rt-pn-bsls2.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
99 
Table S.3.9.3F 
rt-pn-bsls12.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects - Stage 1 and 2 
WK96S2 
100 
Table S.3.9.1G 
rt-pn-bslots1.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
101 
Table S.3.9.2G 
rt-pn-bslots2.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
102 
Table S.3.9.3G 
rt-pn-bslots12.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects with On-
Treatment Resistance Testing - 
Stage 1 and 2 
WK96S2 
103 
Table S.3.9.1Q 
rt-pn-bslpdvfs1.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
17 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
104 
Table S.3.9.2Q 
rt-pn-bslpdvfs2.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
105 
Table S.3.9.3Q 
rt-pn-
bslpdvfs12.lst 
SS_PN_T_001 
Baseline Phenotypic Resistance 
Categories 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
106 
Table S.3.9.1H 
rt-pn-bsldrugs1.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1 
WK96S1, 
WK96S2 
107 
Table S.3.9.2H 
rt-pn-bsldrugs2.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
108 
Table S.3.9.3H 
rt-pn-
bsldrugs12.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects - Stage 1 and 2 
WK96S2 
109 
Table S.3.9.1I 
rt-pn-
bslotrtdrugs1.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Testing - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
110 
Table S.3.9.2I 
rt-pn-
bslotrtdrugs2.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Testing - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
111 
Table S.3.9.3I 
rt-pn-
bslotrtdrugs12.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Testing - Stage 1 and 
2 
WK96S2 
112 
Table S.3.9.1R 
rt-pn-
bsldrugpdvfs1.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Testing 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
113 
Table S.3.9.2R 
rt-pn-
bsldrugpdvfs2.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Testing 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
18 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
114 
Table S.3.9.3R 
rt-pn-
bsldrugpdvfs12.lst 
SS_PN_T_002 
Baseline Phenotypic Resistance 
by Class and Drug Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Testing 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
115 
Appendix 
3.9.1E 
rl-pn-bsls1.lst 
SS_PN_L_001 
Listing of Baseline Phenotypic 
Resistance 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1 
WK96S1, 
WK96S2 
116 
Appendix 
3.9.2E 
rl-pn-bsls2.lst 
SS_PN_L_001 
Listing of Baseline Phenotypic 
Resistance 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
117 
Table S.3.5.1 
rt-lb-bsltoxs1.lst 
GS_LB_T_X_004 
Baseline Laboratory Test 
Results Summary of Toxicity 
Grade 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
118 
Table S.3.5.2 
rt-lb-bsltoxs2.lst 
GS_LB_T_X_004 
Baseline Laboratory Test 
Results Summary of Toxicity 
Grade 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
119 
Table S.3.6.1 
rt-ae-preaidss1.lst 
GS_AE_T_X_001 
Adverse Events Summary 
Pre-treatment AIDS Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
120 
Table S.3.6.2 
rt-ae-preaidss2.lst 
GS_AE_T_X_001 
Adverse Events Summary 
Pre-treatment AIDS Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
121 
Table S.3.7.1 
rt-mh-sums1.lst 
GS_MH_T_X_001 
General Medical History 
Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
122 
Table S.3.7.2 
rt-mh-sums2.lst 
GS_MH_T_X_001 
General Medical History 
Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
123 
Appendix 3.7.1 
rl-mh-lists1.lst 
GS_MH_L_X_001 
General Medical History 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
124 
Appendix 3.7.2 
rl-mh-lists2.lst 
GS_MH_L_X_001 
General Medical History 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
125 
Table S.3.8.1 
rt-cm-premeds1.lst GS_CM_T_X_001 
Non-Study Medication 
Summary 
Previous Medication 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
126 
Table S.3.8.2 
rt-cm-premeds2.lst GS_CM_T_X_001 
Non-Study Medication 
Summary 
Previous Medication 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
19 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
127 
Table S.4.1.1A 
rt-ex-bmss1.lst 
SS_EX_T_001 
Extent of Exposure to BMS-
955176 
Time on Therapy 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
128 
Table S.4.1.2A 
rt-ex-bmss2.lst 
SS_EX_T_001 
Extent of Exposure to BMS-
955176 
Time on Therapy 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
129 
Table S.4.1.1B 
rt-ex-tdfs1.lst 
SS_EX_T_001 
Extent of Exposure to Tenofovir 
Time on Therapy 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
130 
Table S.4.1.2B 
rt-ex-tdfs2.lst 
SS_EX_T_001 
Extent of Exposure to Tenofovir 
Time on Therapy 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
131 
Table S.4.1.1C 
rt-ex-atvs1.lst 
SS_EX_T_001 
Extent of Exposure to 
Atazanavir 
Time on Therapy 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
132 
Table S.4.1.2C 
rt-ex-atvs2.lst 
SS_EX_T_001 
Extent of Exposure to 
Atazanavir 
Time on Therapy 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
133 
Table S.4.1.1D 
rt-ex-dtgs1.lst 
SS_EX_T_001 
Extent of Exposure to 
Dolutegravir 
Time on Therapy 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
134 
Table S.4.1.2D 
rt-ex-dtgs2.lst 
SS_EX_T_001 
Extent of Exposure to 
Dolutegravir 
Time on Therapy 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
135 
Table S.4.1.1E 
rt-ex-rtvs1.lst 
SS_EX_T_001 
Extent of Exposure to Ritonavir 
Time on Therapy 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
136 
Table S.4.1.2E 
rt-ex-rtvs2.lst 
SS_EX_T_001 
Extent of Exposure to Ritonavir 
Time on Therapy 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
137 
Table S.4.1.1F 
rt-ex-regimens1.lst 
SS_EX_T_001 
Extent of Exposure to Treatment 
Regimen 
Time on Therapy 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
138 
Table S.4.1.2F 
rt-ex-regimens2.lst 
SS_EX_T_001 
Extent of Exposure to Treatment 
Regimen 
Time on Therapy 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
139 
Table S.4.1.3F 
rt-ex-
regimens12.lst 
SS_EX_T_001 
Extent of Exposure to Treatment 
Regimen 
Time on Therapy 
Treated Subjects - Stage 1 and 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
20 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
140 
Table S.4.1.1G 
rt-ex-conts1.lst 
SS_EX_T_001 
Extent of Exposure to BMS-
955176 after Switch to 
Continuation Dose 
Time on Therapy 
Treated Subjects who Switched 
to Continuation Dose - Stage 1 
WK96S1, 
WK96S2 
141 
Table S.4.1.2G 
rt-ex-conts2.lst 
SS_EX_T_001 
Extent of Exposure to BMS-
955176 after Switch to 
Continuation Dose 
Time on Therapy 
Treated Subjects who Switched 
to Continuation Dose - Stage 2 
WK96S2 
142 
Figure S.4.1.1 
rg-ex-kms1 
GS_EX_G_001 
Time on Study Therapy 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
143 
Figure S.4.1.2 
rg-ex-kms2 
GS_EX_G_001 
Time on Study Therapy 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
144 
Table S.4.1.1H 
rt-ex-kms1.lst 
SS_EX_T_002 
Time of Study Therapy Life 
Table (Kaplan-Meier Estimates) 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
145 
Table S.4.1.2H 
rt-ex-kms2.lst 
SS_EX_T_002 
Time of Study Therapy Life 
Table (Kaplan-Meier Estimates) 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
146 
Table S.4.1.1I 
rt-ex-interrupts1.lst 
SS_EX_T_003 
Summary of Interruptions in 
Study Therapy Greater than 3 
Days 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
147 
Table S.4.1.2I 
rt-ex-interrupts2.lst 
SS_EX_T_003 
Summary of Interruptions in 
Study Therapy Greater than 3 
Days 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
148 
Appendix 
4.1.1A 
rl-ex-lists1.lst 
SS_EX_L_001 
Study Medication Exposure by 
Subject Listing 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
149 
Appendix 
4.1.2A 
rl-ex-lists2.lst 
SS_EX_L_001 
Study Medication Exposure by 
Subject Listing 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
150 
Appendix 
4.1.1B 
rl-ex-listcdoses1.lst 
SS_EX_L_002 
Listing of Time on Original and 
Continuation Dose 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
151 
Appendix 
4.1.2B 
rl-ex-listcdoses2.lst 
SS_EX_L_002 
Listing of Time on Original and 
Continuation Dose 
Treated Subjects - Stage 2 
WK96S2 
152 
Table S.4.2.1 
rt-cm-conmeds1.lst GS_CM_T_X_001 
Non-Study Medication 
Summary 
Concomitant Medication 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
21 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
153 
Table S.4.2.2 
rt-cm-conmeds2.lst GS_CM_T_X_001 
Non-Study Medication 
Summary 
Concomitant Medication 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
154 
Appendix 4.2.1 
rl-cm-meds1.lst 
GS_CM_L_X_006 
Non-Study Medication 
Previous and Concomitant 
Medications 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
155 
Appendix 4.2.2 
rl-cm-meds2.lst 
GS_CM_L_X_006 
Non-Study Medication 
Previous and Concomitant 
Medications 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
156 
Table S.5.1.1A 
rt-vl-
resp40w24s1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
157 
Table S.5.1.2A 
rt-vl-
resp40w24s2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
158 
Table S.5.1.1C 
rt-vl-
sumresp40w24s1.l
st 
SS_VL_T_002 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 24 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
159 
Table S.5.1.2C 
rt-vl-
sumresp40w24s2.l
st 
SS_VL_T_002 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 24 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
160 
Table S.5.1.1B 
rt-vl-
resp40w24subgs1.l
st 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
By Subgroup 
Treated Subjects (mITT) - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
161 
Table S.5.1.2B 
rt-vl-
resp40w24subgs2.l
st 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
By Subgroup 
Treated Subjects (mITT) - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
22 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
162 
Table S.5.2.1A 
rt-vl-
resp40w48s1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
163 
Table S.5.2.2A 
rt-vl-
resp40w48s2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK48S2, 
WK96S2 
164 
Table S.5.2.1C 
rt-vl-
sumresp40w48s1.l
st 
SS_VL_T_002 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 48 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
165 
Table S.5.2.2C 
rt-vl-
sumresp40w48s2.l
st 
SS_VL_T_002 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 48 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK48S2, 
WK96S2 
166 
Table S.5.2.1B 
rt-vl-
resp40w48subgs1.l
st 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
By Subgroup 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
167 
Table S.5.2.2B 
rt-vl-
resp40w48subgs2.l
st 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
By Subgroup 
Treated Subjects (mITT) - Stage 
2 
WK48S2, 
WK96S2 
168 
Table S.5.3.1A 
rt-vl-
resp40w96s1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
169 
Table S.5.3.2A 
rt-vl-
resp40w96s2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
23 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
170 
Table S.5.3.1C 
rt-vl-
sumresp40w96s1.l
st 
SS_VL_T_002 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 96 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
171 
Table S.5.3.2C 
rt-vl-
sumresp40w96s2.l
st 
SS_VL_T_002 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 96 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK96S2 
172 
Table S.5.3.1B 
rt-vl-
resp40w96subgs1.l
st 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
By Subgroup 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
173 
Table S.5.3.2B 
rt-vl-
resp40w96subgs2.l
st 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 40 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
By Subgroup 
Treated Subjects (mITT) - Stage 
2 
WK96S2 
174 
Table S.5.4.1A 
rt-vl-
resp200w24s1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
175 
Table S.5.4.2A 
rt-vl-
resp200w24s2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
176 
Table S.5.4.1B 
rt-vl-
resp200w24bpolys
1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
By Baseline Gag Polymorphism 
Treated Subjects (mITT) - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
177 
Table S.5.4.2B 
rt-vl-
resp200w24bpolys
2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 24 Snapshot 
By Baseline Gag Polymorphism 
Treated Subjects (mITT) - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
24 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
178 
Table S.5.4.1C 
rt-vl-
resp200w48s1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
179 
Table S.5.4.2C 
rt-vl-
resp200w48s2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK48S2, 
WK96S2 
180 
Table S.5.4.1D 
rt-vl-
resp200w48bpolys
1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
By Baseline Gag Polymorphism 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
181 
Table S.5.4.2D 
rt-vl-
resp200w48bpolys
2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 48 Snapshot 
By Baseline Gag Polymorphism 
Treated Subjects (mITT) - Stage 
2 
WK48S2, 
WK96S2 
182 
Table S.5.4.1E 
rt-vl-
resp200w96s1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
183 
Table S.5.4.2E 
rt-vl-
resp200w96s2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
Treated Subjects (mITT) - Stage 
2 
WK96S2 
184 
Table S.5.4.1F 
rt-vl-
resp200w96bpolys
1.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
By Baseline Gag Polymorphism 
Treated Subjects (mITT) - Stage 
1 
WK96S1, 
WK96S2 
185 
Table S.5.4.2F 
rt-vl-
resp200w96bpolys
2.lst 
SS_VL_T_001 
Detailed Summary of HIV-1 
RNA < 200 c/mL 
Proportion of Responders at 
Week 96 Snapshot 
By Baseline Gag Polymorphism 
Treated Subjects (mITT) - Stage 
2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
25 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
186 
Table S.5.1.1D 
rt-vl-
resp40w24obss1.ls
t 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 24  
Treated Subjects (Observed) - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
187 
Table S.5.1.2D 
rt-vl-
resp40w24obss2.ls
t 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 24  
Treated Subjects (Observed) - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
188 
Table S.5.1.1E 
rt-vl-
resp40w24obssubg
s1.lst 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 24  
By Subgroup 
Treated Subjects (Observed) - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
189 
Table S.5.1.2E 
rt-vl-
resp40w24obssubg
s2.lst 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 24  
By Subgroup 
Treated Subjects (Observed) - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
190 
Table S.5.2.1D 
rt-vl-
resp40w48obss1.ls
t 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 48  
Treated Subjects (Observed) - 
Stage 1 
WK96S1, 
WK96S2 
191 
Table S.5.2.2D 
rt-vl-
resp40w48obss2.ls
t 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 48  
Treated Subjects (Observed) - 
Stage 2 
WK48S2, 
WK96S2 
192 
Table S.5.2.1E 
rt-vl-
resp40w48obssubs
1.lst 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 48 
By Subgroup 
Treated Subjects (Observed) - 
Stage 1 
WK96S1, 
WK96S2 
193 
Table S.5.2.2E 
rt-vl-
resp40w48obssubg
s2.lst 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 48 
By Subgroup 
Treated Subjects (Observed) - 
Stage 2 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
26 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
194 
Table S.5.3.1D 
rt-vl-
resp40w96obss1.ls
t 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 96 
Treated Subjects (Observed) - 
Stage 1 
WK96S1, 
WK96S2 
195 
Table S.5.3.2D 
rt-vl-
resp40w96obss2.ls
t 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 96 
Treated Subjects (Observed) - 
Stage 2 
WK96S2 
196 
Table S.5.3.1E 
rt-vl-
resp40w96obssubg
s1.lst 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 96 
By Subgroup 
Treated Subjects (Observed) - 
Stage 1 
WK96S1, 
WK96S2 
197 
Table S.5.3.2E 
rt-vl-
resp40w96obssubg
s2.lst 
SS_VL_T_003 
Summary of HIV-1 RNA < 40 
c/mL 
Proportion of Responders at 
Week 96 
By Subgroup 
Treated Subjects (Observed) - 
Stage 2 
WK96S2 
198 
Table S.5.5.1A 
rt-vl-tlovr24s1.lst 
SS_VL_T_004 
Summary of Treatment 
Outcomes at Week 24 Using the 
TLOVR Algorithm 
Treated Subjects - Stage 1 
WK24S1 
199 
Table S.5.5.2A 
rt-vl-tlovr24s2.lst 
SS_VL_T_004 
Summary of Treatment 
Outcomes at Week 24 Using the 
TLOVR Algorithm 
Treated Subjects - Stage 2 
WK24S2 
200 
Table S.5.5.1B 
rt-vl-tlovr48s1.lst 
SS_VL_T_004 
Summary of Treatment 
Outcomes at Week 48 Using the 
TLOVR Algorithm 
Treated Subjects - Stage 1 
WK48S1 
201 
Table S.5.5.2B 
rt-vl-tlovr48s2.lst 
SS_VL_T_004 
Summary of Treatment 
Outcomes at Week 48 Using the 
TLOVR Algorithm 
Treated Subjects - Stage 2 
WK48S2 
202 
Table S.5.5.1C 
rt-vl-tlovr96s1.lst 
SS_VL_T_004 
Summary of Treatment 
Outcomes at Week 96 Using the 
TLOVR Algorithm 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
203 
Table S.5.5.2C 
rt-vl-tlovr96s2.lst 
SS_VL_T_004 
Summary of Treatment 
Outcomes at Week 96 Using the 
TLOVR Algorithm 
Treated Subjects - Stage 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
27 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
204 
Table S.5.5.1D 
rt-vl-klmtlovrs1.lst 
SS_EX_T_002 
Summary of Time to Loss of 
Virologic Response 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
205 
Table S.5.5.2D 
rt-vl-klmtlovrs2.lst 
SS_EX_T_002 
Summary of Time to Loss of 
Virologic Response 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
206 
Figure S.5.5.1E 
rg-vl-kmtlovrs1 
GS_EX_G_001 
Time to Loss of Virologic 
Response 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
207 
Figure S.5.5.2E 
rg-vl-kmtlovrs2 
GS_EX_G_001 
Time to Loss of Virologic 
Response 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
208 
Table S.5.6.1A 
rt-vl-props1.lst 
SS_VL_T_005 
Proportion of Subjects with 
HIV-1 RNA within Several 
Ranges 
Treated Subjects (Observed) - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
209 
Table S.5.6.2A 
rt-vl-props2.lst 
SS_VL_T_005 
Proportion of Subjects with 
HIV-1 RNA within Several 
Ranges 
Treated Subjects (Observed) - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
210 
Table S.5.6.1B 
rt-vl-sumchgs1.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
HIV-1 RNA (log10 c/mL) 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
211 
Table S.5.6.2B 
rt-vl-sumchgs2.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
HIV-1 RNA (log10 c/mL) 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
212 
Table S.5.7.1A 
rt-lb-cd4s1.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
CD4 Cell Count (cells/uL) 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
213 
Table S.5.7.2A 
rt-lb-cd4s2.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
CD4 Cell Count (cells/uL) 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
28 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
214 
Table S.5.8.1A 
rt-lb-cd4pcts1.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
CD4 Cell Percentage 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
215 
Table S.5.8.2A 
rt-lb-cd4pcts2.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
CD4 Cell Percentage 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
216 
Table S.5.9.1A 
rt-lb-cd8s1.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
CD8 Cell Count (cells/ul) 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
217 
Table S.5.9.2A 
rt-lb-cd8s2.lst 
SS_VL_T_006 
Summary Statistics for Values 
and Change from Baseline Over 
Time 
CD8 Cell Count (cells/ul) 
Overall and by Subgroup 
Treated Subjects (Observed) - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
218 
Figure S.5.6.1C 
rg-vl-box24s1 
GS_LB_G_001 
HIV-1 RNA (log10 c/mL) 
Change from Baseline to Week 
24 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
219 
Figure S.5.6.2C 
rg-vl-box24s2 
GS_LB_G_001 
HIV-1 RNA (log10 c/mL) 
Change from Baseline to Week 
24 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
220 
Figure S.5.6.1D 
rg-vl-box48s1 
GS_LB_G_001 
HIV-1 RNA (log10 c/mL) 
Change from Baseline to Week 
48 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
221 
Figure S.5.6.2D 
rg-vl-box48s2 
GS_LB_G_001 
HIV-1 RNA (log10 c/mL) 
Change from Baseline to Week 
48 
Treated Subjects - Stage 2 
WK48S2, 
WK96S2 
222 
Figure S.5.6.1E 
rg-vl-box96s1 
GS_LB_G_001 
HIV-1 RNA (log10 c/mL) 
Change from Baseline to Week 
96 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
223 
Figure S.5.6.2E 
rg-vl-box96s2 
GS_LB_G_001 
HIV-1 RNA (log10 c/mL) 
Change from Baseline to Week 
96 
Treated Subjects - Stage 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
29 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
224 
Figure S.5.7.1B 
rg-lb-cd4box24s1 
GS_LB_G_001 
CD4 Cell Count (cells/uL) 
Change from Baseline to Week 
24 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
225 
Figure S.5.7.2B 
rg-lb-cd4box24s2 
GS_LB_G_001 
CD4 Cell Count (cells/uL) 
Change from Baseline to Week 
24 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
226 
Figure S.5.7.1C 
rg-lb-cd4box48s1 
GS_LB_G_001 
CD4 Cell Count (cells/uL) 
Change from Baseline to Week 
48 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
227 
Figure S.5.7.2C 
rg-lb-cd4box48s2 
GS_LB_G_001 
CD4 Cell Count (cells/uL) 
Change from Baseline to Week 
48 
Treated Subjects - Stage 2 
WK48S2, 
WK96S2 
228 
Figure S.5.7.1D 
rg-lb-cd4box96s1 
GS_LB_G_001 
CD4 Cell Count (cells/uL) 
Change from Baseline to Week 
96 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
229 
Figure S.5.7.2D 
rg-lb-cd4box96s2 
GS_LB_G_001 
CD4 Cell Count (cells/uL) 
Change from Baseline to Week 
96 
Treated Subjects - Stage 2 
WK96S2 
230 
Figure S.5.9.1B 
rg-lb-cd8box24s1 
GS_LB_G_001 
CD8 Cell Count (cells/uL) 
Change from Baseline to Week 
24 
Treated Subjects -Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
231 
Figure S.5.9.2B 
rg-lb-cd8box24s2 
GS_LB_G_001 
CD8 Cell Count (cells/uL) 
Change from Baseline to Week 
24 
Treated Subjects -Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
232 
Figure S.5.9.1C 
rg-lb-cd8box48s1 
GS_LB_G_001 
CD8 Cell Count (cells/uL) 
Change from Baseline to Week 
48 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
233 
Figure S.5.9.2C 
rg-lb-cd8box48s2 
GS_LB_G_001 
CD8 Cell Count (cells/uL) 
Change from Baseline to Week 
48 
Treated Subjects - Stage 2 
WK48S2, 
WK96S2 
234 
Figure S.5.9.1D 
rg-lb-cd8box96s1 
GS_LB_G_001 
CD8 Cell Count (cells/uL) 
Change from Baseline to Week 
96 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
235 
Figure S.5.9.2D 
rg-lb-cd8box96s2 
GS_LB_G_001 
CD8 Cell Count (cells/uL) 
Change from Baseline to Week 
96 
Treated Subjects - Stage 2 
WK96S2 
236 
Figure S.5.6.1F 
rg-vl-times1 
GS_LB_G_002 
HIV-1 RNA (log10 c/mL) Mean 
Change from Baseline Over 
Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
30 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
237 
Figure S.5.6.2F 
rg-vl-times2 
GS_LB_G_002 
HIV-1 RNA (log10 c/mL) Mean 
Change from Baseline Over 
Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
238 
Figure S.5.7.1E 
rg-lb-cd4times1 
GS_LB_G_002 
CD4 (cells/uL) Mean Change 
from Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
239 
Figure S.5.7.2E 
rg-lb-cd4times2 
GS_LB_G_002 
CD4 (cells/uL) Mean Change 
from Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
240 
Figure S.5.9.1E 
rg-lb-cd8times1 
GS_LB_G_002 
CD8 (cells/uL) Mean Change 
from Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
241 
Figure S.5.9.2E 
rg-lb-cd8times2 
GS_LB_G_002 
CD8 (cells/uL) Mean Change 
from Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
242 
Appendix 
5.1.1A 
rl-vl-
outcome24s1.lst 
SS_VL_L_004 
Listing of Outcomes from HIV-
1 RNA < 40 c/mL Snapshot 
Analysis 
Data for Subjects in the Week 
24 Snapshot 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
243 
Appendix 
5.1.2A 
rl-vl-
outcome24s2.lst 
SS_VL_L_004 
Listing of Outcomes from HIV-
1 RNA < 40 c/mL Snapshot 
Analysis 
Data for Subjects in the Week 
24 Snapshot 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
244 
Appendix 
5.1.1B 
rl-vl-
outcome48s1.lst 
SS_VL_L_004 
Listing of Outcomes from HIV-
1 RNA < 40 c/mL Snapshot 
Analysis 
Data for Subjects in the Week 
48 Snapshot 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
245 
Appendix 
5.1.2B 
rl-vl-
outcome48s2.lst 
SS_VL_L_004 
Listing of Outcomes from HIV-
1 RNA < 40 c/mL Snapshot 
Analysis 
Data for Subjects in the Week 
48 Snapshot 
Treated Subjects - Stage 2 
WK48S2, 
WK96S2 
246 
Appendix 
5.1.1C 
rl-vl-
outcome96s1.lst 
SS_VL_L_004 
Listing of Outcomes from HIV-
1 RNA < 40 c/mL Snapshot 
Analysis 
Data for Subjects in the Week 
96 Snapshot 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
31 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
247 
Appendix 
5.1.2C 
rl-vl-
outcome96s2.lst 
SS_VL_L_004 
Listing of Outcomes from HIV-
1 RNA < 40 c/mL Snapshot 
Analysis 
Data for Subjects in the Week 
96 Snapshot 
Treated Subjects - Stage 2 
WK96S2 
248 
Appendix 
5.1.1D 
rl-vl-vllists1.lst 
SS_VL_L_005 
Listing of HIV-1 RNA 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
249 
Appendix 
5.1.2D 
rl-vl-vllists2.lst 
SS_VL_L_005 
Listing of HIV-1 RNA 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
250 
Appendix 
5.1.1E 
rl-lb-cd4cd8s1.lst 
SS_VL_L_005 
Listing of CD4+ and CD8+ T-
Cell Count and Percentages 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
251 
Appendix 
5.1.2E 
rl-lb-cd4cd8s2.lst 
SS_VL_L_005 
Listing of CD4+ and CD8+ T-
Cell Count and Percentages 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
252 
Table 
S.5.10.1A 
rt-gn-news1.lst 
SS_GN_T_001 
Newly Emergent Genotypic 
Resistance Profile 
Treated Subjects with On-
Treatment Genotypic Resistance 
Testing - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
253 
Table 
S.5.10.2A 
rt-gn-news2.lst 
SS_GN_T_001 
Newly Emergent Genotypic 
Resistance Profile 
Treated Subjects with On-
Treatment Genotypic Resistance 
Testing - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
254 
Table 
S.5.10.3A 
rt-gn-news12.lst 
SS_GN_T_001 
Newly Emergent Genotypic 
Resistance Profile 
Treated Subjects with On-
Treatment Genotypic Resistance 
Testing - Stage 1 and 2 
WK96S2 
255 
Table S.5.10.1B 
rt-gn-
newpdvfs1.lst 
SS_GN_T_001 
Newly Emergent Genotypic 
Resistance Profile 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
256 
Table S.5.10.2B 
rt-gn-
newpdvfs2.lst 
SS_GN_T_001 
Newly Emergent Genotypic 
Resistance Profile 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
257 
Table S.5.10.3B 
rt-gn-
newpdvfs12.lst 
SS_GN_T_001 
Newly Emergent Genotypic 
Resistance Profile 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
32 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
258 
Appendix 
5.10.1A 
rl-gn-ontrts1.lst 
SS_GN_L_001 
Listing of Genotypic 
Substitutions 
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
259 
Appendix 
5.10.2A 
rl-gn-ontrts2.lst 
SS_GN_L_001 
Listing of Genotypic 
Substitutions 
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
260 
Table S.5.10.1C rt-gn-newgags1.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
261 
Table S.5.10.2C rt-gn-newgags2.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
262 
Table S.5.10.3C 
rt-gn-
newgags12.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 and 2 
WK96S2 
263 
Table S.5.10.1R 
rt-gn-
newgagbysubtypes
1.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
By HIV Subtype 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
264 
Table S.5.10.2R 
rt-gn-
newgagbysubtypes
2.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
By HIV Subtype 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
265 
Table S.5.10.3R 
rt-gn-
newgagbysubtypes
12.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
By HIV Subtype 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 and 2 
WK96S2 
266 
Table 
S.5.10.1D 
rt-gn-
newgagpdvfs1.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
267 
Table 
S.5.10.2D 
rt-gn-
newgagpdvfs2.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
33 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
268 
Table 
S.5.10.3D 
rt-gn-
newgagpdvfs12.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
269 
Table S.5.10.1S 
rt-gn-
newgagpdvfbysubt
ypes1.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
270 
Table S.5.10.2S 
rt-gn-
newgagpdvfbysubt
ypes2.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
271 
Table S.5.10.3S 
rt-gn-
newgagpdvfbysubt
ypes12.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
at Selected Positions 
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
272 
Appendix 
5.10.1B 
rl-gn-gagontrts1.lst 
SS_GN_L_002 
Listing of Gag Polymorphisms 
at Selected Positions 
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
1 
WK24S1, 
WK48S1 
WK96S1, 
WK96S2 
273 
Appendix 
5.10.2B 
rl-gn-gagontrts2.lst 
SS_GN_L_002 
Listing of Gag Polymorphisms 
at Selected Positions 
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
274 
Table S.5.10.1E rt-gn-anygags1.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
275 
Table S.5.10.2E rt-gn-anygags2.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
276 
Table S.5.10.3E rt-gn-anygags12.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 and 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
34 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
277 
Table S.5.10.1T 
rt-gn-
anygagbysubtypes
1.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
By HIV Subtype 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
278 
Table S.5.10.2T 
rt-gn-
anygagbysubtypes
2.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
By HIV Subtype 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
279 
Table S.5.10.3T 
rt-gn-
anygagbysubtypes
12.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
By HIV Subtype 
Treated Subjects with On-
Treatment Gag Sequencing - 
Stage 1 and 2 
WK96S2 
280 
Table S.5.10.1F 
rt-gn-
anygagpdvfs1.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
281 
Table S.5.10.2F 
rt-gn-
anygagpdvfs2.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
282 
Table S.5.10.3F 
rt-gn-
anygagpdvfs12.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
283 
Table 
S.5.10.1U 
rt-gn-
anygagpdvfbysubt
ypes1.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
284 
Table 
S.5.10.2U 
rt-gn-
anygagpdvfbysubt
ypes2.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
285 
Table 
S.5.10.3U 
rt-gn-
anygagpdvfbysubt
ypes12.lst 
SS_GN_T_003 
Newly Emergent Gag 
Deviations  
By HIV Subtype 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
35 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
286 
Appendix 
5.10.1C 
rl-gn-gagontrts1.lst 
SS_GN_L_003 
Listing of Newly Emergent Gag 
Deviations  
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
287 
Appendix 
5.10.2C 
rl-gn-gagontrts2.lst 
SS_GN_L_003 
Listing of Newly Emergent Gag 
Deviations 
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
288 
Table 
S.5.10.1G 
rt-pn-news1.lst 
SS_PN_T_001 
Newly Emergent Phenotypic 
Resistance Profile 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
289 
Table 
S.5.10.2G 
rt-pn-news2.lst 
SS_PN_T_001 
Newly Emergent Phenotypic 
Resistance Profile 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
290 
Table 
S.5.10.3G 
rt-pn-news12.lst 
SS_PN_T_001 
Newly Emergent Phenotypic 
Resistance Profile 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 1 and 
2 
WK96S2 
291 
Table 
S.5.10.1H 
rt-pn-
newpdvfs1.lst 
SS_PN_T_001 
Newly Emergent Phenotypic 
Resistance Profile 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
292 
Table 
S.5.10.2H 
rt-pn-
newpdvfs2.lst 
SS_PN_T_001 
Newly Emergent Phenotypic 
Resistance Profile 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
293 
Table 
S.5.10.3H 
rt-pn-
newpdvfs12.lst 
SS_PN_T_001 
Newly Emergent Phenotypic 
Resistance Profile 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
294 
Table S.5.10.1I 
rt-pn-
newdrugs1.lst 
SS_PN_T_002 
Newly Emergent Phenotypic 
Resistance by Class and Drug 
Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
295 
Table S.5.10.2I 
rt-pn-
newdrugs2.lst 
SS_PN_T_002 
Newly Emergent Phenotypic 
Resistance by Class and Drug 
Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
36 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
296 
Table S.5.10.3I 
rt-pn-
newdrugs12.lst 
SS_PN_T_002 
Newly Emergent Phenotypic 
Resistance by Class and Drug 
Name 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 1 and 
2 
WK96S2 
297 
Table S.5.10.1J 
rt-pn-
newdrugpdvfs1.lst 
SS_PN_T_002 
Newly Emergent Phenotypic 
Resistance by Class and Drug 
Name 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
298 
Table S.5.10.2J 
rt-pn-
newdrugpdvfs2.lst 
SS_PN_T_002 
Newly Emergent Phenotypic 
Resistance by Class and Drug 
Name 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
299 
Table S.5.10.3J 
rt-pn-
newdrugpdvfs12.ls
t 
SS_PN_T_002 
Newly Emergent Phenotypic 
Resistance by Class and Drug 
Name 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 and 2 
WK96S2 
300 
Appendix 
5.10.1D 
rl-pn-ontrts1.lst 
SS_PN_L_001 
Listing of Phenotypic Resistance 
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
301 
Appendix 
5.10.2D 
rl-pn-ontrts2.lst 
SS_PN_L_001 
Listing of Phenotypic Resistance 
Treated Subjects with Baseline 
and On-Treatment Data - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
302 
Table 
S.5.10.1K 
rt-pn-maxic50s1.lst 
SS_PN_T_003 
Maximum Change from 
Baseline Summary for BMS-
955176 IC50 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
303 
Table 
S.5.10.2K 
rt-pn-maxic50s2.lst 
SS_PN_T_003 
Maximum Change from 
Baseline Summary for BMS-
955176 IC50 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
304 
Table S.5.10.1L 
rt-pn-
maxic50pdvfs1.lst 
SS_PN_T_003 
Maximum Change from 
Baseline Summary for BMS-
955176 IC50 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
37 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
305 
Table S.5.10.2L 
rt-pn-
maxic50pdvfs2.lst 
SS_PN_T_003 
Maximum Change from 
Baseline Summary for BMS-
955176 IC50 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
306 
Table 
S.5.10.1M 
rt-pn-
maxic50fcs1.lst 
SS_PN_T_003 
Summary for Maximum BMS-
955176 IC50 Fold Change 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
307 
Table 
S.5.10.2M 
rt-pn-
maxic50fcs2.lst 
SS_PN_T_003 
Summary for Maximum BMS-
955176 IC50 Fold Change 
Treated Subjects with On-
Treatment Phenotypic 
Resistance Profile - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
308 
Table 
S.5.10.1N 
rt-pn-
maxic50fcpdvfs1.l
st 
SS_PN_T_003 
Summary for Maximum BMS-
955176 IC50 Fold Change 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
309 
Table 
S.5.10.2N 
rt-pn-
maxic50fcpdvfs2.l
st 
SS_PN_T_003 
Summary for Maximum BMS-
955176 IC50 Fold Change 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
310 
Table 
S.5.10.1O 
rt-pn-props1.lst 
SS_PN_T_004 
Proportion of Subjects with 
Greater than 3 Fold Increase in 
BMS-955176 IC50 Fold Change 
Treated Subjects with Baseline 
and On-Treatment Phenotypic 
Resistance Profile - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
311 
Table 
S.5.10.2O 
rt-pn-props2.lst 
SS_PN_T_004 
Proportion of Subjects with 
Greater than 3 Fold Increase in 
BMS-955176 IC50 Fold Change 
Treated Subjects with Baseline 
and On-Treatment Phenotypic 
Resistance Profile - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
312 
Table 
S.5.10.3O 
rt-pn-props12.lst 
SS_PN_T_004 
Proportion of Subjects with 
Greater than 3 Fold Increase in 
BMS-955176 IC50 Fold Change 
Treated Subjects with Baseline 
and On-Treatment Phenotypic 
Resistance Profile - Stage 1 and 
2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
38 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
313 
Table S.5.10.1P 
rt-pn-
proppdvfs1.lst 
SS_PN_T_004 
Proportion of Subjects with 
Greater than 3 Fold Increase in 
BMS-955176 IC50 Fold Change 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures  
with Baseline and On-Treatment 
Phenotypic Resistance Profile - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
314 
Table S.5.10.2P 
rt-pn-
proppdvfs2.lst 
SS_PN_T_004 
Proportion of Subjects with 
Greater than 3 Fold Increase in 
BMS-955176 IC50 Fold Change 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures  
with Baseline and On-Treatment 
Phenotypic Resistance Profile - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
315 
Table S.5.10.3P 
rt-pn-
proppdvfs12.lst 
SS_PN_T_004 
Proportion of Subjects with 
Greater than 3 Fold Increase in 
BMS-955176 IC50 Fold Change 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures  
with Baseline and On-Treatment 
Phenotypic Resistance Profile - 
Stage 1 and 2 
WK96S2 
316 
Table 
S.5.10.1V 
rt-pn-
propnews1.lst 
SS_PN_T_004 
Proportion of Subjects with 
Newly Emergent Phenotypic 
Resistance to BMS-955176 
Treated Subjects with Baseline 
and On-Treatment Phenotypic 
Resistance Profile - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
317 
Table 
S.5.10.2V 
rt-pn-
propnews2.lst 
SS_PN_T_004 
Proportion of Subjects with 
Newly Emergent Phenotypic 
Resistance to BMS-955176 
Treated Subjects with Baseline 
and On-Treatment Phenotypic 
Resistance Profile - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
318 
Table 
S.5.10.3V 
rt-pn-
propnews12.lst 
SS_PN_T_004 
Proportion of Subjects with 
Newly Emergent Phenotypic 
Resistance to BMS-955176 
Treated Subjects with Baseline 
and On-Treatment Phenotypic 
Resistance Profile - Stage 1 and 
2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
39 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
319 
Table 
S.5.10.1W 
rt-pn-
propnewpdvfs1.lst 
SS_PN_T_004 
Proportion of Subjects with 
Newly Emergent Phenotypic 
Resistance to BMS-955176 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures  
with Baseline and On-Treatment 
Phenotypic Resistance Profile - 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
320 
Table 
S.5.10.2W 
rt-pn-
propnewpdvfs2.lst 
SS_PN_T_004 
Proportion of Subjects with 
Newly Emergent Phenotypic 
Resistance to BMS-955176 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures  
with Baseline and On-Treatment 
Phenotypic Resistance Profile - 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
321 
Table 
S.5.10.3W 
rt-pn-
propnewpdvfs12.ls
t 
SS_PN_T_004 
Proportion of Subjects with 
Newly Emergent Phenotypic 
Resistance to BMS-955176 
Treated Subjects Identified as 
Protocol Defined Virologic 
Failures  
with Baseline and On-Treatment 
Phenotypic Resistance Profile - 
Stage 1 and 2 
WK96S2 
322 
Table 
S.5.10.1Q 
rt-gn-
newgagincs1.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
Treated Subjects with Greater 
than 3 Fold Increase in BMS-
955176 IC50 Fold Change- 
Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
323 
Table 
S.5.10.2Q 
rt-gn-
newgagincs2.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms  
Treated Subjects with Greater 
than 3 Fold Increase in BMS-
955176 IC50 Fold Change- 
Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
324 
Table 
S.5.10.3Q 
rt-gn-
newgagincs12.lst 
SS_GN_T_002 
Emergent Gag Polymorphisms 
Treated Subjects with Greater 
than 3 Fold Increase in BMS-
955176 IC50 Fold Change- 
Stage 1 and 2 
WK96S2 
325 
Table S.5.11.1 
rt-vl-futw24s1.lst 
SS_VL_T_007 
Test for Virologic Futility Based 
on HIV-1 RNA < 40 c/mL 
Proportion of Responders at 
Week 24  (mITT) 
Treated Subjects - Stage 1 
WK24S1 
326 
Table S.5.11.2 
rt-vl-futw24s2.lst 
SS_VL_T_007 
Test for Virologic Futility Based 
on HIV-1 RNA < 40 c/mL 
Proportion of Responders at 
Week 24  (mITT) 
Treated Subjects - Stage 2 
WK24S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
40 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
327 
Table S.6.7.1 
rt-ae-
overallsums1.lst 
SS_AE_T_001 
Adverse Events 
Overall Adverse Events 
Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
328 
Table S.6.7.2 
rt-ae-
overallsums2.lst 
SS_AE_T_001 
Adverse Events 
Overall Adverse Events 
Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
329 
Table S.6.7.3 
rt-ae-
overallsums12.lst 
SS_AE_T_001 
Adverse Events 
Overall Adverse Events 
Summary 
Treated Subjects - Stage 1 and 2 
WK96S2 
330 
Table S.6.1.1 
rl-ae-deaths1.lst 
SS_AE_L_001 
Death Listing 
Enrolled Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
331 
Table S.6.1.2 
rl-ae-deaths2.lst 
SS_AE_L_001 
Death Listing 
Enrolled Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
332 
Table S.6.2.1A 
rt-ae-saes1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Serious Adverse Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
333 
Table S.6.2.2A 
rt-ae-saes2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Serious Adverse Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
334 
Table S.6.2.3A 
rt-ae-saes12.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Serious Adverse Events 
Treated Subjects - Stage 1 and 2 
WK96S2 
335 
Table S.6.2.1B 
rt-ae-saeconts1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Serious Adverse Events After 
Switch to Continuation Dose 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
336 
Table S.6.2.2B 
rt-ae-saeconts2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Serious Adverse Events After 
Switch to Continuation Dose 
Treated Subjects - Stage 2 
WK96S2 
337 
Table S.6.2.1C 
rt-ae-
saeldeaths1eu.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Serious Adverse Event With 
Death As An Outcome 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
338 
Table S.6.2.2C 
rt-ae-
saeldeaths2eu.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Serious Adverse Event With 
Death As An Outcome 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
339 
Table S.6.2.1D 
rt-ae-
relsaeldeaths1eu.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Drug Related Serious Adverse 
Event With Death As An 
Outcome 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
41 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
340 
Table S.6.2.2D 
rt-ae-
relsaeldeaths2eu.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Drug Related Serious Adverse 
Event With Death As An 
Outcome 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
341 
Table S.6.2.1E 
rl-ae-saes1.lst 
GS_AE_L_S_001 
Adverse Event 
Serious Adverse Events 
Enrolled Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
342 
Table S.6.2.2E 
rl-ae-saes2.lst 
GS_AE_L_S_001 
Adverse Event 
Serious Adverse Events 
Enrolled Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
343 
Table S.6.3.1A 
rt-ae-aediscs1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Adverse Events Leading to 
Discontinuation of Study 
Medication 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
344 
Table S.6.3.2A 
rt-ae-aediscs2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Adverse Events Leading to 
Discontinuation of Study 
Medication 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
345 
Table S.6.3.3A 
rt-ae-aediscs12.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Adverse Events Leading to 
Discontinuation of Study 
Medication 
Treated Subjects - Stage 1 and 2 
WK96S2 
346 
Table S.6.3.1B 
rt-ae-
aediscconts1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Adverse Events Leading to 
Discontinuation of Study 
Medication After Switch to 
Continuation Dose 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
347 
Table S.6.3.2B 
rt-ae-
aediscconts2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Adverse Events Leading to 
Discontinuation of Study 
Medication After Switch to 
Continuation Dose 
Treated Subjects - Stage 2 
WK96S2 
348 
Table S.6.3.1C 
rl-ae-discs1.lst 
GS_AE_L_X_001 
Adverse Event 
Adverse Events Leading to 
Discontinuation of Study 
Medication 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
349 
Table S.6.3.2C 
rl-ae-discs2.lst 
GS_AE_L_X_001 
Adverse Event 
Adverse Events Leading to 
Discontinuation of Study 
Medication 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
42 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
350 
Table S.6.5.1A rt-ae-nsae5pcts1.lst GS_AE_T_X_001 
Adverse Event Summary 
Non-Serious Adverse Events 
Occurring in at Least 5 Percent 
of Treated Subjects 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
351 
Table S.6.5.2A rt-ae-nsae5pcts2.lst GS_AE_T_X_001 
Adverse Event Summary 
Non-Serious Adverse Events 
Occurring in at Least 5 Percent 
of Treated Subjects 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
352 
Table S.6.5.1B 
rt-ae-
grade1to4s1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 1 to 4 Adverse Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
353 
Table S.6.5.2B 
rt-ae-
grade1to4s2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 1 to 4 Adverse Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
354 
Table S.6.5.1C 
rt-ae-
grade2to4s1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 2 to 4 Adverse Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
355 
Table S.6.5.2C 
rt-ae-
grade2to4s2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 2 to 4 Adverse Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
356 
Table S.6.5.1D 
rt-ae-
grade3to4s1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 3 to 4 Adverse Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
357 
Table S.6.5.2D 
rt-ae-
grade3to4s2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 3 to 4 Adverse Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
358 
Table S.6.5.3D 
rt-ae-
grade3to4s12.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 3 to 4 Adverse Events 
Treated Subjects - Stage 1 and 2 
WK96S2 
359 
Table S.6.5.1E 
rt-ae-relateds1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 1 to 4 Related Adverse 
Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
360 
Table S.6.5.2E 
rt-ae-relateds2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 1 to 4 Related Adverse 
Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
361 
Table S.6.5.1F 
rt-ae-
relgrade2to4s1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 2 to 4 Related Adverse 
Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
362 
Table S.6.5.2F 
rt-ae-
relgrade2to4s2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 2 to 4 Related Adverse 
Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
43 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
363 
Table S.6.5.3F 
rt-ae-
relgrade2to4s12.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 2 to 4 Related Adverse 
Events 
Treated Subjects - Stage 1 and 2 
WK96S2 
364 
Table S.6.5.1G 
rt-ae-
relgrade3to4s1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 3 to 4 Related Adverse 
Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
365 
Table S.6.5.2G 
rt-ae-
relgrade3to4s2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Grade 3 to 4 Related Adverse 
Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
366 
Appendix 6.5.1 
rl-ae-lists1.lst 
GS_AEL_X_001 
Adverse Event 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
367 
Appendix 6.5.2 
rl-ae-lists2.lst 
GS_AEL_X_001 
Adverse Event 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
368 
Table S.6.4.1A 
rt-ae-cdcaes1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
CDC Class C AIDS Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
369 
Table S.6.4.2A 
rt-ae-cdcaes2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
CDC Class C AIDS Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
370 
Table S.6.4.3A 
rt-ae-cdcaes12.lst 
GS_AE_T_X_001 
Adverse Event Summary 
CDC Class C AIDS Events 
Treated Subjects - Stage 1 and 2 
WK96S2 
371 
Table S.6.4.1B 
rl-ae-cdcaes1.lst 
GS_AEL_X_001 
Adverse Event 
CDC Class C AIDS Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
372 
Table S.6.4.2B 
rl-ae-cdcaes2.lst 
GS_AEL_X_001 
Adverse Event 
CDC Class C AIDS Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
373 
Table S.6.4.1C 
rt-ae-giaes1.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Gastrointestinal Events of 
Special Interest 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
374 
Table S.6.4.2C 
rt-ae-giaes2.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Gastrointestinal Events of 
Special Interest 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
375 
Table S.6.4.3C 
rt-ae-giaes12.lst 
GS_AE_T_X_001 
Adverse Event Summary 
Gastrointestinal Events of 
Special Interest 
Treated Subjects - Stage 1 and 2 
WK96S2 
376 
Table S.6.4.1D 
rl-ae-giaes1.lst 
GS_AE_L_X_001 
Adverse Event 
Gastrointestinal Events of 
Special Interest 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
44 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
377 
Table S.6.4.2D 
rl-ae-giaes2.lst 
GS_AE_L_X_001 
Adverse Event 
Gastrointestinal Events of 
Special Interest 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
378 
Table S.6.6.1A 
rt-ae-
expadjusts1.lst 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Events Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
379 
Table S.6.6.2A 
rt-ae-
expadjusts2.lst 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Events Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
380 
Table S.6.6.1B 
rt-ae-
expadjsaes1eu.lst 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Events Summary 
Including Multiple Occurrences 
of Unique Adverse Events 
Treated Subjects - Stage 1 
Serious Adverse Events 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
381 
Table S.6.6.2B 
rt-ae-
expadjsaes2eu.lst 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Events Summary 
Including Multiple Occurrences 
of Unique Adverse Events 
Treated Subjects - Stage 2 
Serious Adverse Events 
WK24S2, 
WK48S2, 
WK96S2 
382 
Table S.6.6.1C 
rt-ae-
expadjrelsaes1eu.ls
t 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Events Summary 
Including Multiple Occurrences 
of Unique Adverse Events 
Treated Subjects - Stage 1 
Drug Related Serious Adverse 
Events 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
383 
Table S.6.6.2C 
rt-ae-
expadjrelsaes2eu.ls
t 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Events Summary 
Including Multiple Occurrences 
of Unique Adverse Events 
Treated Subjects - Stage 2 
Drug Related Serious Adverse 
Events 
WK24S2, 
WK48S2, 
WK96S2 
384 
Table S.6.6.1D 
rt-ae-
expadjnsae5pcts1e
u.lst 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Event Summary  
Including Multiple Occurrences 
of Unique Adverse Events 
Treated Subjects - Stage 1 
Non-Serious Adverse Events 
Using a Global Cutoff of 5 
Percent 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
385 
Table S.6.6.2D 
rt-ae-
expadjnsae5pcts2e
u.lst 
GS_AE_T_M_001 
Exposure Adjusted Adverse 
Event Summary 
Including Multiple Occurrences 
of Unique Adverse Events 
Treated Subjects - Stage 2 
Non-Serious Adverse Events 
Using a Global Cutoff of 5 
Percent 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
45 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
386 
Appendix 6.6.1 
rl-ae-uniques1.lst 
GS_AE_L_U_002 
Adverse Event 
Unique Events 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
387 
Appendix 6.6.2 
rl-ae-uniques2.lst 
GS_AE_L_U_002 
Adverse Event 
Unique Events 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
388 
Table S.7.1.1A 
rt-lb-toxs1.lst 
SS_LB_T_001 
Laboratory Test Results 
Summary of Worst Toxicity 
Grade 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
389 
Table S.7.1.2A 
rt-lb-toxs2.lst 
SS_LB_T_001 
Laboratory Test Results 
Summary of Worst Toxicity 
Grade 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
390 
Table S.7.1.1B 
rt-lb-g34toxs1.lst 
SS_LB_T_001 
Laboratory Test Results  
Summary of Grade 3-4 Toxicity 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
391 
Table S.7.1.2B 
rt-lb-g34toxs2.lst 
SS_LB_T_001 
Laboratory Test Results  
Summary of Grade 3-4 Toxicity 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
392 
Table S.7.1.3B 
rt-lb-g34toxs12.lst 
SS_LB_T_001 
Laboratory Test Results  
Summary of Grade 3-4 Toxicity 
Treated Subjects - Stage 1 and 2 
WK96S2 
393 
Table S.7.1.1C 
rt-lb-etoxs1.lst 
SS_LB_T_001 
Laboratory Test Results 
Summary of Treatment-
Emergent Abnormalities 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
394 
Table S.7.1.2C 
rt-lb-etoxs2.lst 
SS_LB_T_001 
Laboratory Test Results 
Summary of Treatment-
Emergent Abnormalities 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
395 
Table S.7.2.1A 
rt-lb-renals1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Function Values and Change 
from Baseline - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
396 
Table S.7.2.2A 
rt-lb-renals2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Function Values and Change 
from Baseline - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
397 
Table S.7.2.1B 
rt-zl-renals1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Function Values and Change 
from Baseline - US Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
398 
Table S.7.2.2B 
rt-zl-renals2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Function Values and Change 
from Baseline - US Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
46 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
399 
Table S.7.2.1C 
rt-lb-lipidss1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Change from 
Baseline - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
400 
Table S.7.2.2C 
rt-lb-lipidss2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Change from 
Baseline - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
401 
Table S.7.2.1D 
rt-zl-lipidss1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Change from 
Baseline - US Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
402 
Table S.7.2.2D 
rt-zl-lipidss2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Change from 
Baseline - US Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
403 
Table S.7.2.1E 
rt-lb-
pchglipidss1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Percent 
Change from Baseline - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
404 
Table S.7.2.2E 
rt-lb-
pchglipidss2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Percent 
Change from Baseline - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
405 
Table S.7.2.1F 
rt-zl-
pchglipidss1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Percent 
Change from Baseline - US 
Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
406 
Table S.7.2.2F 
rt-zl-
pchglipidss2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Fasting 
Lipid Values and Percent 
Change from Baseline - US 
Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
407 
Figure S.7.2.1A 
rg-lb-tchols1 
GS_LB_G_002 
Fasting Total Cholesterol 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
408 
Figure S.7.2.2A 
rg-lb-tchols2 
GS_LB_G_002 
Fasting Total Cholesterol 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
47 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
409 
Figure S.7.2.1B 
rg-lb-ldlcs1 
GS_LB_G_002 
Fasting LDL-Cholesterol 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
410 
Figure S.7.2.2B 
rg-lb-ldlcs2 
GS_LB_G_002 
Fasting LDL-Cholesterol 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
411 
Figure S.7.2.1C 
rg-lb-hdlcs1 
GS_LB_G_002 
Fasting HDL-Cholesterol 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
412 
Figure S.7.2.2C 
rg-lb-hdlcs2 
GS_LB_G_002 
Fasting HDL-Cholesterol 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
413 
Figure S.7.2.1D 
rg-lb-trigs1 
GS_LB_G_002 
Fasting Total Triglycerides 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
414 
Figure S.7.2.2D 
rg-lb-trigs2 
GS_LB_G_002 
Fasting Total Triglycerides 
(mg/dL) Mean Percent Change 
from Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
415 
Appendix 
7.1.1A 
rl-lb-hems1.lst 
SS_LB_L_001 
Hematology - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
416 
Appendix 
7.1.2A 
rl-lb-hems2.lst 
SS_LB_L_001 
Hematology - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
417 
Appendix 
7.1.1B 
rl-lb-lfts1.lst 
SS_LB_L_001 
Liver Function Tests - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
418 
Appendix 
7.1.2B 
rl-lb-lfts2.lst 
SS_LB_L_001 
Liver Function Tests - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
419 
Appendix 
7.1.1C 
rl-lb-enzs1.lst 
SS_LB_L_001 
Enzymes - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
420 
Appendix 
7.1.2C 
rl-lb-enzs2.lst 
SS_LB_L_001 
Enzymes - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
421 
Appendix 
7.1.1D 
rl-lb-rfts1.lst 
SS_LB_L_001 
Renal Function Tests - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
422 
Appendix 
7.1.2D 
rl-lb-rfts2.lst 
SS_LB_L_001 
Renal Function Tests - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
48 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
423 
Appendix 
7.1.1E 
rl-lb-elcs1.lst 
SS_LB_L_001 
Electrolytes - SI Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
424 
Appendix 
7.1.2E 
rl-lb-elcs2.lst 
SS_LB_L_001 
Electrolytes - SI Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
425 
Appendix 
7.1.1F 
rl-lb-flgs1.lst 
SS_LB_L_001 
Fasting Lipids and Glucose - SI 
Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
426 
Appendix 
7.1.2F 
rl-lb-flgs2.lst 
SS_LB_L_001 
Fasting Lipids and Glucose - SI 
Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
427 
Appendix 
7.1.1G 
rl-zl-hems1.lst 
SS_LB_L_001 
Hematology - US Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
428 
Appendix 
7.1.2G 
rl-zl-hems2.lst 
SS_LB_L_001 
Hematology - US Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
429 
Appendix 
7.1.1H 
rl-zl-lfts1.lst 
SS_LB_L_001 
Liver Function Tests - US Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
430 
Appendix 
7.1.2H 
rl-zl-lfts2.lst 
SS_LB_L_001 
Liver Function Tests - US Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
431 
Appendix 
7.1.1I 
rl-zl-enzs1.lst 
SS_LB_L_001 
Enzymes - US Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
432 
Appendix 
7.1.2I 
rl-zl-enzs2.lst 
SS_LB_L_001 
Enzymes - US Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
433 
Appendix 
7.1.1J 
rl-zl-rfts1.lst 
SS_LB_L_001 
Renal Function Tests - US Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
434 
Appendix 
7.1.2J 
rl-zl-rfts2.lst 
SS_LB_L_001 
Renal Function Tests - US Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
435 
Appendix 
7.1.1K 
rl-zl-elcs1.lst 
SS_LB_L_001 
Electrolytes - US Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
436 
Appendix 
7.1.2K 
rl-zl-elcs2.lst 
SS_LB_L_001 
Electrolytes - US Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
437 
Appendix 
7.1.1L 
rl-zl-flgs1.lst 
SS_LB_L_001 
Fasting Lipids and Glucose - US 
Units 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
49 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
438 
Appendix 
7.1.2L 
rl-zl-flgs2.lst 
SS_LB_L_001 
Fasting Lipids and Glucose - US 
Units 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
439 
Appendix 
7.1.1M 
rl-lb-diffunits1.lst 
GS_LB_L_S_008 
Differences in Categorization of 
SI and US Laboratory Test 
Results 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
440 
Appendix 
7.1.2M 
rl-lb-diffunits2.lst 
GS_LB_L_S_008 
Differences in Categorization of 
SI and US Laboratory Test 
Results 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
441 
Appendix 
7.1.1N 
rl-lb-pregs1.lst 
GS_LB_L_X_006 
Pregnancy Test 
Treated Female Subjects - Stage 
1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
442 
Appendix 
7.1.2N 
rl-lb-pregs2.lst 
GS_LB_L_X_006 
Pregnancy Test 
Treated Female Subjects - Stage 
2 
WK24S2, 
WK48S2, 
WK96S2 
443 
Appendix 
7.3.1A 
rt-eg-sumchgs1.lst 
SS_EG_T_003 
Electrocardiogram Summary of 
Values and Changes from 
Baseline over Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
444 
Appendix 
7.3.2A 
rt-eg-sumchgs2.lst 
SS_EG_T_003 
Electrocardiogram Summary of 
Values and Changes from 
Baseline over Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
445 
Appendix 
7.3.1B 
rt-eg-
changecats1.lst 
SS_EG_T_001 
Electrocardiogram Change from 
Baseline Category Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
446 
Appendix 
7.3.2B 
rt-eg-
changecats2.lst 
SS_EG_T_001 
Electrocardiogram Change from 
Baseline Category Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
447 
Appendix 
7.3.1C 
rt-eg-cats1.lst 
SS_EG_T_002 
Electrocardiogram Category 
Summary 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
448 
Appendix 
7.3.2C 
rt-eg-cats2.lst 
SS_EG_T_002 
Electrocardiogram Category 
Summary 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
449 
Appendix 
7.3.1D 
rl-eg-ecgs1.lst 
GS_EG_L_X_001 
Electrocardiogram 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
450 
Appendix 
7.3.2D 
rl-eg-ecgs2.lst 
GS_EG_L_X_001 
Electrocardiogram 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
451 
Appendix 
7.4.1A 
rt-vs-sums1.lst 
SS_VL_T_006 
Vital Sign Summary of Values 
and Changes from Baseline over 
Time  
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
50 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
452 
Appendix 
7.4.2A 
rt-vs-sums2.lst 
SS_VL_T_006 
Vital Sign Summary of Values 
and Changes from Baseline over 
Time  
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
453 
Appendix 
7.4.1B 
rl-vs-lists1.lst 
GS_VS_L_X_006 
Vital Signs 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
454 
Appendix 
7.4.2B 
rl-vs-lists2.lst 
GS_VS_L_X_006 
Vital Signs 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
455 
Appendix 
7.4.1C 
rt-pm-sums1.lst 
SS_VL_T_006 
Physical Measurements 
Summary of Values and 
Changes from Baseline over 
Time 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
456 
Appendix 
7.4.2C 
rt-pm-sums2.lst 
SS_VL_T_006 
Physical Measurements 
Summary of Values and 
Changes from Baseline over 
Time 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
457 
Table S.7.5.1A 
rt-lb-bmrenals1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Change 
from Baseline - US Units 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
458 
Table S.7.5.2A 
rt-lb-bmrenals2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Change 
from Baseline - US Units 
Treated Subjects - Stage 2 
WK96S2 
459 
Table S.7.5.1B 
rt-zl-bmrenals1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Change 
from Baseline - SI Units 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
460 
Table S.7.5.2B 
rt-zl-bmrenals2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Change 
from Baseline - SI Units 
Treated Subjects - Stage 2 
WK96S2 
461 
Table S.7.5.1C 
rt-lb-
pchbmrenals1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Percent 
Change from Baseline - US 
Units 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
462 
Table S.7.5.2C 
rt-lb-
pchbmrenals2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Percent 
Change from Baseline - US 
Units 
Treated Subjects - Stage 2 
WK96S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
51 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
463 
Table S.7.5.1D 
rt-zl-
pchbmrenals1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Percent 
Change from Baseline - SI Units 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
464 
Table S.7.5.2D 
rt-zl-
pchbmrenals2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Renal 
Biomarker Values and Percent 
Change from Baseline - SI Units 
Treated Subjects - Stage 2 
WK96S2 
465 
Table S.7.5.1E 
rt-lb-bmbones1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Change 
from Baseline - US Units 
Treated Subjects - Stage 1 
WK24S1 
466 
Table S.7.5.2E 
rt-lb-bmbones2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Change 
from Baseline - US Units 
Treated Subjects - Stage 2 
WK24S2 
467 
Table S.7.5.1F 
rt-zl-bmbones1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Change 
from Baseline - SI Units 
Treated Subjects - Stage 1 
WK24S1 
468 
Table S.7.5.2F 
rt-zl-bmbones2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Change 
from Baseline - SI Units 
Treated Subjects - Stage 2 
WK24S2 
469 
Table S.7.5.1G 
rt-lb-
pchbmbones1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Percent 
Change from Baseline - US 
Units 
Treated Subjects - Stage 1 
WK24S1 
470 
Table S.7.5.2G 
rt-lb-
pchbmbones2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Percent 
Change from Baseline - US 
Units 
Treated Subjects - Stage 2 
WK24S2 
471 
Table S.7.5.1H 
rt-zl-
pchbmbones1.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Percent 
Change from Baseline - SI Units 
Treated Subjects - Stage 1 
WK24S1 
472 
Table S.7.5.2H 
rt-zl-
pchbmbones2.lst 
SS_VL_T_006 
Laboratory Test Results  
Summary Statistics for Bone 
Biomarker Values and Percent 
Change from Baseline - SI Units 
Treated Subjects - Stage 2 
WK24S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
52 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
473 
Figure S.7.5.1A 
rg-lb-ub2s1 
GS_LB_G_002 
Urinary Beta-2-
Microglobulin/Creatinine 
Median Percent Change from 
Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1 
474 
Figure S.7.5.2A 
rg-lb-ub2s2 
GS_LB_G_002 
Urinary Beta-2-
Microglobulin/Creatinine 
Median Percent Change from 
Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2 
475 
Figure S.7.5.1B 
rg-lb-feps1 
GS_LB_G_002 
Fractional Excretion of 
Phosphorous Median Change 
from Baseline Over Time 
Treated Subjects - Stage 1 
WK24S1 
476 
Figure S.7.5.2B 
rg-lb-feps2 
GS_LB_G_002 
Fractional Excretion of 
Phosphorous Median Change 
from Baseline Over Time 
Treated Subjects - Stage 2 
WK24S2 
477 
Figure S.7.5.1C 
rg-lb-pchp1nps1 
GS_LB_G_002 
N-Terminal Propeptide of Type 
1 Procollagen Median Percent 
Change from Baseline Over 
Time 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
478 
Figure S.7.5.2C 
rg-lb-pchp1nps2 
GS_LB_G_002 
N-Terminal Propeptide of Type 
1 Procollagen Median Percent 
Change from Baseline Over 
Time 
Treated Subjects - Stage 2 
WK96S2 
479 
Figure S.7.5.1D 
rg-lb-pchctxs1 
GS_LB_G_002 
Cross-Linked C-Telopeptide of 
Type 1 Collagen Median Percent 
Change from Baseline Over 
Time 
Treated Subjects - Stage 1 
WK96S1, 
WK96S2 
480 
Figure S.7.5.2D 
rg-lb-pchctxs2 
GS_LB_G_002 
Cross-Linked C-Telopeptide of 
Type 1 Collagen Median Percent 
Change from Baseline Over 
Time 
Treated Subjects - Stage 2 
WK96S2 
481 
Table S.8.1.1A rt-pk-sumbmss1.lst 
MS_PK_T_004 
Summary Statistics of BMS-
955176 Pharmacokinetic 
Parameters  
Evaluable PK Population - Stage 
1 
WK24S1 
482 
Table S.8.1.2A rt-pk-sumbmss2.lst 
MS_PK_T_004 
Summary Statistics of BMS-
955176 Pharmacokinetic 
Parameters  
Evaluable PK Population - Stage 
2 
WK24S2 
483 
Table S.8.1.1B 
rt-pk-sumatvs1.lst 
MS_PK_T_004 
Summary Statistics of ATV 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
1 
WK24S1 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
53 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
484 
Table S.8.1.2B 
rt-pk-sumatvs2.lst 
MS_PK_T_004 
Summary Statistics of ATV 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
2 
WK24S2 
485 
Table S.8.1.1C 
rt-pk-sumdtgs1.lst 
MS_PK_T_004 
Summary Statistics of DTG 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
1 
WK24S1 
486 
Table S.8.1.2C 
rt-pk-sumdtgs2.lst 
MS_PK_T_004 
Summary Statistics of DTG 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
2 
WK24S2 
487 
Table 9.2.1A 
rt-pk-
itsumbmss1.lst 
MS_PK_T_005 
Summary Statistics of BMS-
955176 Pharmacokinetic 
Parameters  
Evaluable PK Population - Stage 
1 
WK24S1 
488 
Table 9.2.2A 
rt-pk-
itsumbmss2.lst 
MS_PK_T_005 
Summary Statistics of BMS-
955176 Pharmacokinetic 
Parameters  
Evaluable PK Population - Stage 
2 
WK24S2 
489 
Table 9.3.1A 
rt-pk-
itsumdtgs1.lst 
MS_PK_T_005 
Summary Statistics of DTG 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
1 
WK24S1 
490 
Table 9.3.2A 
rt-pk-
itsumdtgs2.lst 
MS_PK_T_005 
Summary Statistics of DTG 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
2 
WK24S2 
491 
Table 9.4.1A 
rt-pk-itsumatvs1.lst 
MS_PK_T_005 
Summary Statistics of ATV 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
1 
WK24S1 
492 
Table 9.4.2A 
rt-pk-itsumatvs2.lst 
MS_PK_T_005 
Summary Statistics of ATV 
Pharmacokinetic Parameters  
Evaluable PK Population - Stage 
2 
WK24S2 
493 
Table  
S.8.2.5.1A 
rt-pk-
mixedbmsdtgs1.lst 
MS_PK_T_006 
Effect of BMS-955176 on 
Exposure of DTG 
PK Parameters DTG Cmax, 
Ctau and AUC(TAU) 
BMS-955176 120 mg QD+ 
ATV/r + DTG versus TDF + 
ATV/r + DTG 
Evaluable PK Population - Stage 
1 
WK24S1 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
54 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
494 
Table  
S.8.2.5.2A 
rt-pk-
mixedbms120dtgs2
.lst 
MS_PK_T_006 
Effect of BMS-955176 on 
Exposure of DTG 
PK Parameters DTG Cmax, 
Ctau and AUC(TAU) 
BMS-955176 120 mg QD+ 
ATV + DTG versus Historical 
Data 
Evaluable PK Population - Stage 
2 
WK24S2 
495 
Table  
S.8.2.5.2B 
rt-pk-
mixedbms180dtgs2
.lst 
MS_PK_T_006 
Effect of BMS-955176 on 
Exposure of DTG 
PK Parameters DTG Cmax, 
Ctau and AUC(TAU) 
BMS-955176 180 mg QD+ 
ATV + DTG versus Historical 
Data 
Evaluable PK Population - Stage 
2 
WK24S2 
496 
Table  9.3.1.1A 
rt-pk-
itmixedbmss1.lst 
MS_PK_T_007 
In-text Table of Effect of BMS-
955176 on Exposure of DTG 
PK Parameters DTG Cmax, 
Ctau and AUC(TAU) 
BMS-955176 120 mg QD+ 
ATV/r + DTG versus TDF + 
ATV/r + DTG 
Evaluable PK Population - Stage 
1 
WK24S1 
497 
Table  9.3.1.2A 
rt-pk-
itmixedbms120s2.l
st 
MS_PK_T_007 
In-text Table of Effect of BMS-
955176 on Exposure of DTG 
PK Parameters DTG Cmax, 
Ctau and AUC(TAU) 
BMS-955176 120 mg QD+ 
ATV + DTG versus TDF + 
ATV/r + DTG 
Evaluable PK Population - Stage 
2 
WK24S2 
498 
Table  9.3.1.2B 
rt-pk-
itmixedbms180s2.l
st 
MS_PK_T_007 
In-text Table of Effect of BMS-
955176 on Exposure of DTG 
PK Parameters DTG Cmax, 
Ctau and AUC(TAU) 
BMS-955176 180 mg QD+ 
ATV + DTG versus TDF + 
ATV/r + DTG 
Evaluable PK Population - Stage 
2 
WK24S2 
499 
Appendix 
8.2.5A 
rl-pk-
listbms01s1.lst 
MS_PK_L_005 
Listing of BMS-955176 
Pharmacokinetic Parameters 
PK Population - Stage 1 
WK24S1 
500 
Appendix 
8.2.5A 
rl-pk-
listbms01s2.lst 
MS_PK_L_005 
Listing of BMS-955176 
Pharmacokinetic Parameters 
PK Population - Stage 2 
WK24S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
55 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
501 
Appendix 
8.2.5B 
rl-pk-listatv01s1.lst 
MS_PK_L_005 
Listing of ATV Pharmacokinetic 
Parameters 
PK Population - Stage 1 
WK24S1 
502 
Appendix 
8.2.5B 
rl-pk-listatv01s2.lst 
MS_PK_L_005 
Listing of ATV Pharmacokinetic 
Parameters 
PK Population - Stage 2 
WK24S2 
503 
Appendix 
8.2.5C 
rl-pk-
listdtg01s1.lst 
MS_PK_L_005 
Listing of DTG Pharmacokinetic 
Parameters 
PK Population - Stage 1 
WK24S1 
504 
Appendix 
8.2.5C 
rl-pk-
listdtg01s2.lst 
MS_PK_L_005 
Listing of DTG Pharmacokinetic 
Parameters 
PK Population - Stage 2 
WK24S2 
505 
Appendix 
8.2.1A 
rl-pk-
cpar1bmss1.lst 
MS_PK_L_001 
Listing of BMS-955176 Plasma 
Concentration – Time Data 
PK Population - Stage 1 
WK24S1 
506 
Appendix 
8.2.1A 
rl-pk-
cpar1bmss2.lst 
MS_PK_L_001 
Listing of BMS-955176 Plasma 
Concentration – Time Data 
PK Population - Stage 2 
WK24S2 
507 
Appendix 
8.2.1B 
rl-pk-cpar1atvs1.lst 
MS_PK_L_001 
Listing of ATV Plasma 
Concentration – Time Data 
PK Population - Stage 1 
WK24S1 
508 
Appendix 
8.2.1B 
rl-pk-cpar1atvs2.lst 
MS_PK_L_001 
Listing of ATV Plasma 
Concentration – Time Data 
PK Population - Stage 2 
WK24S2 
509 
Appendix 
8.2.1C 
rl-pk-
cpar1dtgs1.lst 
MS_PK_L_001 
Listing of DTG Plasma 
Concentration – Time Data 
PK Population - Stage 1 
WK24S1 
510 
Appendix 
8.2.1C 
rl-pk-
cpar1dtgs2.lst 
MS_PK_L_001 
Listing of DTG Plasma 
Concentration – Time Data 
PK Population - Stage 2 
WK24S2 
511 
Figure S.8.2.3A 
rg-pk-
cpar3bmss1.lst 
MS_PK_G_002 
Plots of Individual BMS-955176 
Plasma Concentration Profiles 
vs. Time  
Evaluable PK Population - Stage 
1 
WK24S1 
512 
Figure S.8.2.3A 
rg-pk-
cpar3bmss2.lst 
MS_PK_G_002 
Plots of Individual BMS-955176 
Plasma Concentration Profiles 
vs. Time  
Evaluable PK Population - Stage 
2 
WK24S2 
513 
Figure S.8.2.3B 
rg-pk-
cpar3atvs1.lst 
MS_PK_G_002 
Plots of Individual ATV Plasma 
Concentration Profiles vs. Time  
Evaluable PK Population- Stage 
1 
WK24S1 
514 
Figure S.8.2.3B 
rg-pk-
cpar3atvs2.lst 
MS_PK_G_002 
Plots of Individual ATV Plasma 
Concentration Profiles vs. Time  
Evaluable PK Population- Stage 
2 
WK24S2 
515 
Figure S.8.2.3C 
rg-pk-
cpar3dtgs1.lst 
MS_PK_G_002 
Plots of Individual DTG Plasma 
Concentration Profiles vs. Time  
Evaluable PK Population - Stage 
1 
WK24S1 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
56 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
516 
Figure S.8.2.3C 
rg-pk-
cpar3dtgs2.lst 
MS_PK_G_002 
Plots of Individual DTG Plasma 
Concentration Profiles vs. Time  
Evaluable PK Population - Stage 
2 
WK24S2 
517 
Figure S.8.2.1A 
rg-pk-
cpar1bmss1.lst 
MS_PK_G_001 
Overlay of Individual BMS-
955176 Plasma Concentration 
Profile vs. Time by Treatment 
Evaluable PK Population - Stage 
1 
WK24S1 
518 
Figure S.8.2.1A 
rg-pk-
cpar1bmss2.lst 
MS_PK_G_001 
Overlay of Individual BMS-
955176 Plasma Concentration 
Profile vs. Time by Treatment 
Evaluable PK Population - Stage 
2 
WK24S2 
519 
Figure S.8.2.1B 
rg-pk-
cpar1atvs1.lst 
MS_PK_G_001 
Overlay of Individual ATV 
Plasma Concentration Profile vs. 
Time by Treatment 
Evaluable PK Population - Stage 
1 
WK24S1 
520 
Figure S.8.2.1B 
rg-pk-
cpar1atvs2.lst 
MS_PK_G_001 
Overlay of Individual ATV 
Plasma Concentration Profile vs. 
Time by Treatment 
Evaluable PK Population - Stage 
2 
WK24S2 
521 
Figure S.8.2.1A 
rg-pk-
cpar1dtgs1.lst 
MS_PK_G_001 
Overlay of Individual DTG 
Plasma Concentration Profile vs. 
Time by Treatment 
Evaluable PK Population - Stage 
1 
WK24S1 
522 
Figure S.8.2.1A 
rg-pk-
cpar1dtgs2.lst 
MS_PK_G_001 
Overlay of Individual DTG 
Plasma Concentration Profile vs. 
Time by Treatment 
Evaluable PK Population - Stage 
2 
WK24S2 
523 
Figure S.8.2.6A 
rg-pk-
cpar6bmss1.lst 
MS_PK_G_006 
Mean (+SD) BMS-955176 
Plasma Concentration Profile vs. 
Time   
Evaluable PK Population - Stage 
1 
WK24S1 
524 
Figure S.8.2.6A 
rg-pk-
cpar6bmss2.lst 
MS_PK_G_006 
Mean (+SD) BMS-955176 
Plasma Concentration Profile vs. 
Time   
Evaluable PK Population - Stage 
2 
WK24S2 
525 
Figure S.8.2.6B 
rg-pk-
cpar6atvs1.lst 
MS_PK_G_006 
Mean (+SD) ATV Plasma 
Concentration Profile vs. Time   
Evaluable PK Population - Stage 
1 
WK24S1 
526 
Figure S.8.2.6B 
rg-pk-
cpar6atvs2.lst 
MS_PK_G_006 
Mean (+SD) ATV Plasma 
Concentration Profile vs. Time   
Evaluable PK Population - Stage 
2 
WK24S2 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
57 
No. 
Table No. 
Output File 
Name 
Template ID 
Title and Population 
Purpose 
527 
Figure S.8.2.6C 
rg-pk-
cpar6dtgs1.lst 
MS_PK_G_006 
Mean (+SD) DTG Plasma 
Concentration Profile vs. Time   
Evaluable PK Population - Stage 
1 
WK24S1 
528 
Figure S.8.2.6C 
rg-pk-
cpar6dtgs2.lst 
MS_PK_G_006 
Mean (+SD) DTG Plasma 
Concentration Profile vs. Time   
Evaluable PK Population - Stage 
2 
WK24S2 
529 
Appendix 
10.1.1 
rt-qs-eq5ds1.lst 
SS_VL_T_006 
EQ-5D-3L Summary of US and 
UK Centric Scores and Changes 
From Baseline Over Time on 
Treatment 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
530 
Appendix 
10.1.2 
rt-qs-eq5ds2.lst 
SS_VL_T_006 
EQ-5D-3L Summary of US and 
UK Centric Scores and Changes 
From Baseline Over Time on 
Treatment 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
531 
Appendix 
10.2.1 
rt-qs-fahis1.lst 
SS_VL_T_006 
FAHI Summary of Total Scores 
Over Time on Treatment 
Treated Subjects - Stage 1 
WK24S1, 
WK48S1, 
WK96S1, 
WK96S2 
532 
Appendix 
10.2.2 
rt-qs-fahis2.lst 
SS_VL_T_006 
FAHI Summary of Total Scores 
Over Time on Treatment 
Treated Subjects - Stage 2 
WK24S2, 
WK48S2, 
WK96S2 
 
 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
58 
2 
INTRODUCTION 
2.1 
Guidance for DPP Users and Reviewers 
The Analysis Data Presentation Plan (DPP) contains comprehensive specifications for the 
development of data displays for an analysis.   
Within the Analysis DPP, the following templates will reside: 
Templates and Metadata Tables: 
• Global Standard Templates (GS): The layout of these templates is a Global Standard. 
Global Standard templates will be placed into the DPP without modifications.  
• Project Specific Templates (PS): The layout of these templates is constructed and described 
in the Core DPP. Project Specific templates will be placed into the DPP without 
modifications. 
• For Early Development Only - Model Document Specific Template (MS): The layout of 
these templates is constructed and described in the Early Development Standardized DPP 
Template. 
• Study Specific Templates (SS): The layout of these templates is constructed for and 
described in the Analysis DPP.  
A Metadata Table will contain information on the exact layout for a table, listing or graph. 
Text presented within a template and highlighted in grey: 
DPP Conventions: 
• is a generic indicator for the type of endpoint or phrase that should replace it (Measure or 
Period for example)  
• represents an optional item for a particular template presentation (P-value or 
Tablets/Capsules, for example).  
The highlighted text in grey will remain as such in the template and the appropriate endpoint or 
phrase and the specifications to include within a specific table or listing in lieu of the highlighted 
text in grey will be described in the metadata tables. This will allow multiple tables to refer to the 
same table template. 
2.2 
Referenced Documents 
The following documents were referenced in the creation of this document. 
Document 
Revision 
GBS General Requirements for Statistical Outputs 
v [Click to enter 
version: x.x] 
Statistical Analysis Plan 
v 2.0 
 
 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
59 
3 
GENERAL CRITERIA/CONVENTIONS 
3.1 
Exceptions to Global and/or Departmental Standards 
Location of 
Documentation 
Standards Document 
Exception 
https://external.bms.com
/teams/GBS-
bms955176/genprogdoc
s/Forms/AllItems.aspx 
Demographics Domain Requirements 
Specification 
Standards Request #8246: Add countries 
within geographic regions to Template 
GS_DM_T_X_002 and 
GS_DM_T_T_002. Add 2 columns 
"Geographic Region" and "Country" to 
end of Template GS_DM_L_X_001. 
https://external.bms.com
/teams/GBS-
bms955176/genprogdoc
s/Forms/AllItems.aspx 
Laboratory Test Results (SI Units) (US 
Units) Domain Requirements 
Specifications, Physical Measurements 
Domain Requirements Specifications, 
Vital Signs Domain Requirements 
Specifications 
Standards Request #8247, #8251, #8255: 
Display N, mean, SD, median, IQR for 
values and changes from baseline over 
time, with the option to specify absolute 
or percent changes (see Template 
SS_VL_T_006). 
https://external.bms.com
/teams/GBS-
bms955176/genprogdoc
s/Forms/AllItems.aspx 
Laboratory Test Results (SI Units) (US 
Units) Domain Requirements 
Specifications 
Standards Request #8252: Display select 
lab tests in side-by-side columns in all 
lab listings, similar to GS_LB_L_S_007, 
not just LFTs (see Template 
SS_LB_L_001). 
https://external.bms.com
/teams/GBS-
bms955176/genprogdoc
s/Forms/AllItems.aspx 
Electrocardiogram Domain Requirements 
Specification 
Standards Request #8248: Modify 
Template GS_EG_T_X_005 to replace 
min and max with median, Q1, Q3, and 
add 95% CI for mean change from 
baseline (see Template SS_EG_T_003). 
https://external.bms.com
/teams/GBS-
bms955176/genprogdoc
s/Forms/AllItems.aspx 
Laboratory Test Results (SI Units) (US 
Units) Domain Requirements 
Specifications 
Standards Request #8253: Display select 
toxicities (eg, Grade 1-4) by baseline tox 
grade categories (all, normal, Grade 1, 2, 
3, 4, not reported) with multiple 
treatment group columns on the same 
page (see Template SS_LB_T_001). 
https://external.bms.com
/teams/GBS-
bms955176/genprogdoc
s/Forms/AllItems.aspx 
Laboratory Test Results (SI Units) (US 
Units) Domain Requirements 
Specifications 
Standards Request #8254: Display 
treatment emergent lab abnormalities 
(increased to grade 1, increased to grade 
2, increased to grade 3, increased to 
grade 4, increased to any grade) by 
baseline tox grade categories (all, 
normal, Grade 1 to 4, not reported) (see 
Template SS_LB_T_002). 
 
3.2 
Populations 
Name as to Appear on 
Output 
Name used in SAP (if different) 
Definition when no SAP available 
Enrolled Subjects 
 
 
Randomized Subjects 
 
 
Treated Subjects 
 
 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
60 
Name as to Appear on 
Output 
Name used in SAP (if different) 
Definition when no SAP available 
PK Population 
 
 
Evaluable PK Population 
 
 
 
3.3 
Conventions 
[Click to enter text] 
3.4 
Treatment Information  
Drug Name 
Column Headers to use in 
Tables 
Order Of 
Column 
Label to use in Listings (if different) 
Stage 1: 
 
 
 
BMS-955176  
BMS-955176 120 mg + 
ATV/r + DTG 
1 
 
Tenofovir 
TDF 300 mg + ATV/r + DTG 
2 
 
Stage 2: 
 
 
 
BMS-955176  
BMS-955176 120 mg + ATV 
+ DTG 
1 
 
BMS-955176  
BMS-955176 180 mg + ATV 
+ DTG 
2 
 
Tenofovir 
TDF 300 mg + ATV/r + DTG 
3 
 
Stage 1 and 2 
combined: 
 
 
 
BMS-955176  
ST1 BMS-955176 120 mg + 
ATV/r + DTG 
1 
 
BMS-955176  
ST2 BMS-955176 120 mg + 
ATV + DTG 
2 
 
BMS-955176  
ST2 BMS-955176 180 mg + 
ATV + DTG 
3 
 
Stage 1+Stage 2 
Tenofovir 
ST1+ST2 TDF 300 mg + 
ATV/r + DTG 
4 
 
 
3.5 
Graph Criteria/Conventions  
Attribute 
Parameter 
Value/Line 
Symbol 
BMS-955176 120 mg + 
ATV/r + DTG 
Open triangle 
BMS-955176 120 mg + 
ATV + DTG 
Open circle 
BMS-955176 180 mg + 
ATV + DTG 
Open square 


Analysis Data Presentation Plan 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
61 
Attribute 
Parameter 
Value/Line 
TDF 300 mg + ATV/r + 
DTG 
Full circle 
Line style 
BMS-955176 120 mg + 
ATV/r + DTG 
Dotted line  
BMS-955176 120 mg + 
ATV + DTG 
Dashed 
BMS-955176 180 mg + 
ATV + DTG 
Dashed/Dotted line 
TDF 300 mg + ATV/r + 
DTG 
Solid 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
4 
PRESENTATION PLAN TEMPLATES AND METADATA 
4.1 
Administrative Appendices 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
63 
Template SS_EX_L_001: Batch Number Listing 
--------------------------------------------------------------------------------------------------------------------------------- 
 
 
 
Commercial 
 
 
 
 
 
 
         
Date Kit 
 
 
 
Batch  
 
 
 
 
 
 
  Kit  
Assigned 
 Drug  
Number         Subject ID 
 
Age/Gender/Race 
  Number 
by IVRS 
----------------------------
---------------------------------------------------------------------------------- 
<Drug Name> 
XXXXXXXX 
(43/F/B) 
 
  XXXXX  
10MAR2003 
 
 
 
 
 
 
 
 
  XXXXX  
10MAR2003 
 
 
 
 
 
 
(43/F/B) 
 
  XXXXX  
10MAR2003 
 
 
 
 
 
 
 
 
  XXXXX  
10MAR2003 
 
 
 
 
 
 
 
 
  XXXXX  
30FEB2004 
 
<Drug Name#2> XXXXXXXX 
(43/F/B) 
 
  XXXXX  
10MAR2003 
 
 
 
 
 
 
 
 
  XXXXX  
10MAR2003 
--------------------------------------------------------------------------------------------------------------------------------- 
 
Parameter 
Values 
Template ID 
SS_EX_L_001 
Output File Name 
rl-ex-batchs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 1.7.1 
Title 1 
Listing of Batch Numbers 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
SS_EX_L_001 
Output File Name 
rl-ex-batchs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 1.7.2 
Title 1 
Listing of Batch Numbers 
Title 2 
Treated Subjects - Stage 2 
 
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
64 
Template SS_DS_L_001: Randomization Scheme and Codes 
------------------------------------------------------------------------------------------------------------------------------------ 
Subject ID                        Randomized                Randomization                 As Treated         
  (Age/Gender/Race)               Treatment Group           Date                         Treatment Group                   
----------------------------------------------------------------------------------------------------------------------- 
                          TRT A                27OCT2003                     TRT A 
  (59/F/O)          
 
                           TRT A                27OCT2003                     TRT B 
  (59/F/O)          
---------------------------------------------------------------------------------------------------------------------------------- 
 
Parameter 
Values 
Template ID 
SS_DS_L_001 
Output File Name 
rl-ds-randcodes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 1.9.1 
Title 1 
Randomization Scheme and Codes 
Title 2 
Randomized Subjects - Stage 1 
Programming notes 
Sorted by site and subject identifier. The listing should also be “paged” by site. 
 
Parameter 
Values 
Template ID 
SS_DS_L_001 
Output File Name 
rl-ds-randcodes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 1.9.2 
Title 1 
Randomization Scheme and Codes 
Title 2 
Randomized Subjects - Stage 2 
Programming notes 
Sorted by site and subject identifier. The listing should also be “paged” by site. 
 
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
65 
Template SS_DM_T_001: Accrual Summary 
------------------------------------------------------------------------------------------------------------------------------------               
 Site                                                        TRT A               TRT B               TRT C               Total 
   Treatment Initiation Month  
 
 
         N=XXX  
      N=XXX 
 
    N=XXX               N=XXX 
------------------------------------------------------------------------------------------------------------------------------------               
 
Site 
                                                      XXX (XX.X)          XXX (XX.X)          XXX (XX.X)       XXX (XX.X) 
  Calendar Month/Year 1                                      XXX (XX.X)          XXX (XX.X)          XXX (XX.X)       XXX (XX.X) 
  Calendar Month/Year 2                                      XXX (XX.X)          XXX (XX.X)          XXX (XX.X)       XXX (XX.X) 
  ...
Site
  Calendar Month/Year 1                                      XXX (XX.X)          XXX (XX.X)          XXX (XX.X)       XXX (XX.X) 
  Calendar Month/Year 2                                      XXX (XX.X)          XXX (XX.X)          XXX (XX.X)       XXX (XX.X) 
  ... 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_DM_T_001 
Output File Name 
rt-dm-accruals1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 2.1.1E 
Title 1 
Accrual Summary 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
SS_DM_T_001 
Output File Name 
rt-dm-accruals2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 2.1.2E 
Title 1 
Accrual Summary 
Title 2 
Treated Subjects - Stage 2 
 
PP
D
PP
D


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
66 
4.2 
Study Conduct  
4.2.1 
Protocol Deviations 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
67 
Template SS_PD_T_001: Relevant Protocol Deviation Summary 
---------------------------------------------------------------------------------------------------------------------------------- 
   
 
 
 
 
                   
 
                                                                 Group A     Group B        Group C     Group D         Total  
Deviation                                                            N = XX       N = XX        N = XX      N = XX        N = XX  
---------------------------------------------------------------------------------------------------------------------------------- 
ANY DEVIATION                                                        XX (XX.X)   XX (XX.X)     XX (XX.X)     XX (XX.X)   XX (XX.X) 
 
INFORMED CONSENT NOT OBTAINED, OR OBTAINED AFTER ENROLLMENT          XX (XX.X)   XX (XX.X)     XX (XX.X)     XX (XX.X)   XX (XX.X) 
QUALIFYING HIV 1 RNA < 5,000 C/ML OR MISSING PRIOR TO RANDOMIZATION  XX (XX.X)   XX (XX.X)     XX (XX.X)     XX (XX.X)   XX (XX.X) 
CD4 < 200 CELLS/UL MISSING PRIOR TO RANDOMIZATION                   XX (XX.X)   XX (XX.X)     XX (XX.X)     XX (XX.X)   XX (XX.X) 
PRIOR ANTIRETROVIRAL THERAPY 
≥ 1 WEEK OF EXPOSURE
                    XX (XX.X)   XX (XX.X)     XX (XX.X)     XX (XX.X)   XX (XX.X) 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_PD_T_001 
Output File Name 
rt-pd-rels1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.2.3.1A 
Title 1 
Relevant Protocol Deviation Summary 
Title 2 
Randomized Subjects - Stage 1 
Layout notes 
Include the relevant protocol deviations listed in the SAP. 
 
Parameter 
Values 
Template ID 
SS_PD_T_001 
Output File Name 
rt-pd-rels2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.2.3.2A 
Title 1 
Relevant Protocol Deviation Summary 
Title 2 
Randomized Subjects - Stage 2 
Layout notes 
Include the relevant protocol deviations listed in the SAP. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
68 
Template SS_PD_L_001: Relevant Protocol Deviation Listing 
---------------------------------------------------------------------------------------------------------------------------------- 
Subject ID          
  (Age/Gender/Race) 
    Treatment Group                Deviation 
---------------------------------------------------------------------------------------------------------------------------------- 
                      XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
  (54/M/C) 
    TRT B 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_PD_L_001 
Output File Name 
rl-pd-rels1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.2.3.1B 
Title 1 
Listing of Relevant Protocol Deviations 
Title 2 
Randomized Subjects - Stage 1 
Layout notes 
Include the relevant protocol deviations listed in the SAP. 
Programming notes 
Sorted by treatment group, site and subject identifier 
 
Parameter 
Values 
Template ID 
SS_PD_L_001 
Output File Name 
rl-pd-rels2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.2.3.2B 
Title 1 
Listing of Relevant Protocol Deviations 
Title 2 
Randomized Subjects - Stage 2 
Layout notes 
Include the relevant protocol deviations listed in the SAP. 
Programming notes 
Sorted by treatment group, site and subject identifier 
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
69 
4.3 
Study Population   
4.3.1 
Disposition of Subjects 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
70 
Template GS_DS_T_T_001: Pre-Randomization Subject Status 
Protocol: TA123456                                             Draft                                                     Page 1 of 1     
                                                Pre-Randomized Subject Status Summary 
                                                        All Enrolled Subjects 
 
                                  ------------------------------------------------------------------ 
                                                                                      Total     
                                  ------------------------------------------------------------------ 
                                                                                                   
                                  SUBJECTS ENROLLED                                   468         
                                                                                                   
                                  SUBJECTS RANDOMIZED (%)                             445 ( 95.1) 
                                                                                                   
                                  SUBJECTS NOT RANDOMIZED (%)                          23 (  4.9) 
                                                                                                   
                                  REASON FOR NOT BEING RANDOMIZED (%)                              
                                    SUBJECT WITHDREW CONSENT                            4 (  0.9) 
                                    POOR/NON-COMPLIANCE                                 3 (  0.6) 
                                    SUBJECT NO LONGER MEETS STUDY CRITERIA             12 (  2.6) 
                                    ADMINISTRATIVE REASON BY SPONSOR                    1 (  0.2) 
                                    OTHER                                               3 (  0.6) 
------------------------------------------------------------------------------------------------------------------------------------ 
Percentages based on subjects enrolled                                                                 
Program Source: /wwbdm/ndp/prime/gssr/devtest/sta/test/domain_example/status1.sas                                 16NOV2004:10:37:00 
 
Parameter 
Values 
Template ID 
GS_DS_T_T_001 
Output File Name 
rt-ds-prerands1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.2.1.1A 
Title 1 
Pre-Randomization Subject Status 
Title 2 
Enrolled Subjects - Stage 1 
Footnote 1 
Percentages based on subjects enrolled. 
 
Parameter 
Values 
Template ID 
GS_DS_T_T_001 
Output File Name 
rt-ds-prerands2.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
71 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.2.1.2A 
Title 1 
Pre-Randomization Subject Status 
Title 2 
Enrolled Subjects - Stage 2 
Footnote 1 
Percentages based on subjects enrolled. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
72 
Template GS_DS_L_S_001: Pre-randomization Subject Status Listing 
Protocol: TA123456                                             Draft                                                     Page 1 of 2 
Pre-Randomized Subject Status 
All Enrolled Subjects 
                                                
------------------------------------------------------------------------------------------------------------------------------------ 
Subject ID                                          
  (Age/Gender/Race)   Date       Randomized  Reason Subject Will Not be Randomized             
----------------------------------------------------------------------------------------------------------------------- 
        27OCT2003  YES 
  (47/M/C) 
         05NOV2003  NO          SUBJECT NO LONGER MEETS STUDY CRITERIA: VIRAL LOAD < 50 COPIES AT SCREENING VISIT 
  (31/M/C)                                    
 
        13FEB2004  YES 
  (24/F/B)  
 
      09FEB2004  NO          SUBJECT WITHDREW CONSENT: SHE IS AFRAID OF BEGINNING A NEW TREATMENT 
  (41/F/C)                                                          
 
      27NOV2003  YES 
  (21/F/B) 
 
       09OCT2003  NO          OTHER: SOCIAL SITUATION/PATIENTS WISH 
  (39/M/C) 
      05APR2004  YES 
  (46/M/C) 
      05APR2004  YES 
  (32/M/C) 
       05APR2004  NO          LOST TO FOLLOW-UP: 05APR2004 
  (38/M/C) 
       25SEP2003  YES 
  (44/M/C) 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/sta/test/sta_lst.sas                                                07SEP2004:14:35:00 
 
Parameter 
Values 
Template ID 
GS_DS_L_S_001 
Output File Name 
rl-ds-prerands1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
73 
Table No. 
Appendix 2.1.1A 
Title 1 
Pre-Randomized Subject Status 
Title 2 
Enrolled Subjects - Stage 1 
Programming notes 
Sorted by site and subject identifier 
 
Parameter 
Values 
Template ID 
GS_DS_L_S_001 
Output File Name 
rl-ds-prerands2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 2.1.2A 
Title 1 
Pre-Randomized Subject Status 
Title 2 
Enrolled Subjects - Stage 2 
Programming notes 
Sorted by site and subject identifier 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
74 
Template GS_DM_T_T_005 : Enrollment Summary 
Protocol: CV123456                                       Confidential                                                  Page 1 of 2 
                                                     Enrollment Summary 
                                     Number Of Subjects At Each Study Site By Country    
 
                           --------------------------------------------------------------------------------- 
                           Country (%)                                     ENROLLED               RANDOMIZED                      
                             Site Number (%)                               N = 200                 N = 150                      
                           --------------------------------------------------------------------------------- 
 
                                                                                                                               
                           AU
ALIA                                    136 ( 78.0)              109 ( 72.7)               
                             
                                        10 (  5.0)                8 (  5.3)               
                            
                                        12 (  6.0)                9 (  6.0)               
                            
                                         8 (  4.0)                6 (  4.0)               
                            
                                         9 (  4.5)                7 (  4.7)             
                            
                                        15 (  7.5)               12 (  8.0)               
                            
                                         4 (  2.0)                3 (  2.0)               
                            
                                         7 (  3.5)                7 (  4.7)               
                            
                                         5 (  2.5)                5 (  3.3)               
                            
                                         9 (  4.5)                8 (  5.3)              
                            
                                         8 (  4.0)                5 (  3.3)               
                            
                                         6 (  3.0)                5 (  3.3)               
                            
                                        13 (  6.5)               10 (  6.7)               
                            
                                         5 (  2.5)                4 (  2.7)              
                            
                                         9 (  4.5)                8 (  5.3)                 
                            
                                         8 (  4.0)                7 (  4.7)               
                             
                                         7 (  3.5)                5 (  3.3)               
                                                                                                                               
                           CANADA                                        49 ( 24.5)               40 ( 26.7)               
                             
                                         7 (  3.5)                5 (  3.3)               
                             
                                         5 (  2.5)                3 (  2.0)               
                             
                                         5 (  2.5)                4 (  2.7)               
                             
                                        11 (  5.5)                9 (  6.0)               
                             
                                         9 (  4.5)                8 (  5.3)               
                             
                                         6 (  3.0)                6 (  4.0)               
                             
                                         6 (  3.0)                5 (  3.3)              
 
                           CHILE                                          14(  7.0)               12 (  8.0)             
                             
                                          7 (  3.5)                6 (  4.0)             
       
 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                  
Program Source: /gbs/prod/clin/programs/cv/123/456/country.sas                                                    18FEB2005:10:59:00 
 
Parameter 
Values 
Template ID 
GS_DM_T_T_005 
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
75 
Output File Name 
rt-dm-enrolls1eu.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 2.1.1C 
Title 1 
Enrollment Summary 
Title 2 
Number of Subjects at Each Study Site by Country 
Title 3 
Enrolled Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_DM_T_T_005 
Output File Name 
rt-dm-enrolls2eu.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 2.1.2C 
Title 1 
Enrollment Summary 
Title 2 
Number of Subjects at Each Study Site by Country 
Title 3 
Enrolled Subjects - Stage 2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
Template SS_DM_T_002: Counts and Percentages Table 
Protocol: AI438XXX 
                                                                                                Page 1 of X 
<Title 1> 
<Title 2> 
 
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
                   ------------------------------------------------------------------------------------ 
                   <Col Header 1> (%)                                       Group 1          Group 2      
                     <Col Header 2> (%)                                     N = XXX          N = XXX 
                   ------------------------------------------------------------------------------------     
                                 
                   <EVENT 1>                                             XXX (XXX.X)       XXX (XXX.X)       
                     <SUBEVENT 1>                                        XXX (XXX.X)       XXX (XXX.X) 
                     ... 
                     <SUBEVENT X>                                        XXX (XXX.X)       XXX (XXX.X) 
  
                   ... <ADDITIONAL EVENTS> 
 
                   <EVENT X>                                             XXX (XXX.X)       XXX (XXX.X)       
                     <SUBEVENT 1>                                        XXX (XXX.X)       XXX (XXX.X) 
                     ... 
                     <SUBEVENT X>                                        XXX (XXX.X)       XXX (XXX.X) 
     
                    
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
<Footnote 1> 
<Footnote 2> 
<Footnote 3> 
Program Source: <TBD>                                                                                             DDMMMYYYY:HR:MM:SS               
 
 
Parameter 
Values 
Template ID 
SS_DM_T_002 
Output File Name 
rt-dm-enrages1eu.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 2.1.1D 
Title 1 
Enrollment Summary  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
77 
Title 2 
Number of Subjects per Age Group 
Title 3 
Enrolled Subjects - Stage 1 
Layout notes 
Col 1 Header: Age Group (%). Events 1 through 9 are the following (display even if 0 total counts): IN UTERO; PRETERM 
NEWBORN (GESTATIONAL AGE < 37 WEEKS); NEWBORNS (0 TO 27 DAYS); INFANTS AND TODDLERS (28 DAYS 
TO 23 MONTHS); CHILDREN (2 TO 11 YEARS); ADOLESCENTS (12 TO 17 YEARS); ADULTS (18 TO 64 YEARS); 
FROM 65 TO 84 YEARS; 85 YEARS AND OVER. 
 
Parameter 
Values 
Template ID 
SS_DM_T_002 
Output File Name 
rt-dm-enrages2eu.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 2.1.2D 
Title 1 
Enrollment Summary  
Title 2 
Number of Subjects per Age Group 
Title 3 
Enrolled Subjects - Stage 2 
Layout notes 
Col 1 Header: Age Group (%). Events 1 through 9 are the following (display even if 0 total counts): IN UTERO; PRETERM 
NEWBORN (GESTATIONAL AGE < 37 WEEKS); NEWBORNS (0 TO 27 DAYS); INFANTS AND TODDLERS (28 DAYS 
TO 23 MONTHS); CHILDREN (2 TO 11 YEARS); ADOLESCENTS (12 TO 17 YEARS); ADULTS (18 TO 64 YEARS); 
FROM 65 TO 84 YEARS; 85 YEARS AND OVER. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
78 
Template GS_DS_T_X_005 : End of Study Subjects Status 
Protocol: TA123456                                             Draft                                                     Page 1 of 1     
                                                 End of Study Subject Status Summary 
                                               Descriptive text of population basis 
 
------------------------------------------------------------------------------------------------------------------------------------          
                                                          TRT A               TRT B               TRT C               Total 
------------------------------------------------------------------------------------------------------------------------------------         
 
SUBJECTS                                                  150                 145                 150                 445            
 
SUBJECTS COMPLETING THE STUDY (%)                         146 ( 97.3)         142 ( 97.9)         147 ( 98.0)         435 ( 97.8)    
                                                                                                                              
SUBJECTS NOT COMPLETING THE STUDY (%)                       4 (  2.7)           3 (  2.1)           3 (  2.0)          10 (  2.2)    
                                                                                                                              
REASON FOR NOT COMPLETING THE STUDY (%)                                                                                 
  LACK OF EFFICACY                                          1 (  0.7)           1 (  0.7)           0                   2 (  0.4)    
  ADVERSE EVENT                                             2 (  1.3)           0                   1 (  0.7)           3 (  0.7)    
  SUBJECT WITHDREW CONSENT                                  1 (  0.7)           1 (  0.7)           2 (  1.3)           4 (  0.9)    
  LOST TO FOLLOW-UP                                         0                   1 (  0.7)           0                   1 (  0.2) 
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Percentages based on subjects population basis                          
Program Source: /wwbdm/ndp/prime/gssr/devtest/sta/test/domain_example/status4r.sas                                16NOV2004:10:37:00 
 
Parameter 
Values 
Template ID 
GS_DS_T_X_005 
Output File Name 
rt-ds-statuss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.2.1.1B 
Title 1 
End of Study Subject Status Summary 
Title 2 
Randomized Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_DS_T_X_005 
Output File Name 
rt-ds-statuss2.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
79 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.2.1.2B 
Title 1 
End of Study Subject Status Summary 
Title 2 
Randomized Subjects - Stage 2 
 
Parameter 
Values 
Template ID 
GS_DS_T_X_005 
Output File Name 
rt-ds-statuss12.lst 
Purpose 
 WK96S2 
Table No. 
Table S.2.1.3B 
Title 1 
End of Study Subject Status Summary 
Title 2 
Randomized Subjects - Stage 1 and 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
80 
Template GS_DS_L_X_005: End of Study Subject Status by Treatment Group 
Protocol: TA123456                                             Draft                                                     Page 1 of 2 
End of Study Subject Status  
Descriptive text of population basis 
 
Treatment Group: TRT A  
------------------------------------------------------------------------------------------------------------------------------------ 
                                                    
Subject ID                                   Completed   
  (Age/Gender/Race)   Period      Date       Study      Reason Subject Did Not Complete Study 
------------------------------------------------------------------------------------------------------------------------------------ 
         ON STUDY    09JUL2004  YES 
  (48/M/C) 
 
        ON STUDY    17FEB2004  NO         ADVERSE EVENT: DUE TO AE OF HYPOTHYROIDISM BY MEDICAL MONITOR 
  (62/F/C) 
 
        ON STUDY    29JUN2004  NO         SUBJECT WITHDREW CONSENT: TOO LONG OF COMMUTE, LEAVING AREA FOR SUMMER 
  (63/F/C) 
 
        ON STUDY    14MAY2004  NO         LACK OF EFFICACY: FPG WITH A RESULT OF 15.1 MMOL/L AFTER RETEST 
  (62/F/C) 
 
       ON STUDY               NO         LOST TO FOLLOW-UP 
  (59/F/C) 
 
        ON STUDY    23AUG2004  YES 
  (61/F/C) 
 
        ON STUDY    10JUN2004  NO         DEATH 
  (67/M/C) 
        ON STUDY    23AUG2004  YES 
  (64/M/C) 
 
       ON STUDY    16APR2004  NO         POOR/NON-COMPLIANCE: MEDICATION NOT TAKEN ACC. TO INVESTIGATOR'S INSTRUCTION 
  (67/F/C)                                                       
       ON STUDY    26AUG2004  YES 
  (62/M/C) 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/sta/test/sta_lst2.sas                                               07SEP2004:14:35:00 
 
Parameter 
Values 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
81 
Template ID 
GS_DS_L_X_005 
Output File Name 
rl-ds-statuss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 2.1.1B 
Title 1 
End of Study Subject Status 
Title 2 
Randomized Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_DS_L_X_005 
Output File Name 
rl-ds-statuss2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 2.1.2B 
Title 1 
End of Study Subject Status 
Title 2 
Randomized Subjects - Stage 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
82 
Template SS_DM_T_002 : Population Summary 
  ---------------------------------------------------------------------------------------------------------------------------------- 
                                                 Trt A             Trt B           Trt C             Trt D             Total        
  ---------------------------------------------------------------------------------------------------------------------------------- 
                                                                                                                                     
  RANDOMIZED SUBJECTS (A)                           XX               XX              XX                XX                XX   
 
  TREATED SUBJECTS (B)                              XX               XX              XX                XX                XX   
 
                                                                                                                                    
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_DM_T_002 
Output File Name 
rt-dm-populations1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.2.1.1C 
Title 1 
Populations for Analysis Summary - Stage 1 
Footnote 1 
(A) Randomized subjects in the treatment group to which they were randomized. 
Footnote 2 
(B) Subjects who took at least one dose of study medication in the treatment group to which they were randomized  
Footnote 3 
unless subjects have never received the study medication they were randomized, in which case subjects will be included 
Footnote 4 
in the treatment group based on the first treatment received. 
 
Parameter 
Values 
Template ID 
SS_DM_T_002 
Output File Name 
rt-dm-populations2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.2.1.2C 
Title 1 
Populations for Analysis Summary - Stage 2 
Footnote 1 
(A) Randomized subjects in the treatment group to which they were randomized. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
83 
Footnote 2 
(B) Subjects who took at least one dose of study medication in the treatment group to which they were randomized  
Footnote 3 
unless subjects have never received the study medication they were randomized, in which case subjects will be included 
Footnote 4 
in the treatment group based on the first treatment received. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
84 
Template SS_DM_L_001: Listing of Subjects Excluded from the Efficacy Analysis 
 
Treatment Group: TRT A  
------------------------------------------------------------------------------------------------------------------------------------ 
                                                    
Subject ID             
  (Age/Gender/Race)   Reason Subject Excluded from Efficacy Analysis                           Discontinuation Reason 
------------------------------------------------------------------------------------------------------------------------------------ 
         RANDOMIZED, BUT NOT TREATED                                              LOST TO FOLLOW-UP  
  (48/M/C) 
        RANDOMIZED, BUT NOT TREATED                                              SUBJECT WITHDREW CONSENT: TOO LONG OF 
  (62/F/C)                                                                                     COMMUTE, LEAVING AREA FOR SUMMER 
 
 
Parameter 
Values 
Template ID 
SS_DM_L_001 
Output File Name 
rl-dm-excls1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 2.2.1 
Title 1 
Subjects Excluded from Efficacy Analysis (mITT) 
Title 2 
Randomized Subjects - Stage 1 
Programming notes 
Reason for being excluded should always be: RANDOMIZED, BUT NOT TREATED. 
Sorted by treatment group, site and subject identifier. 
 
Parameter 
Values 
Template ID 
SS_DM_L_001 
Output File Name 
rl-dm-excls2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 2.2.2 
Title 1 
Subjects Excluded from Efficacy Analysis (mITT) 
Title 2 
Randomized Subjects - Stage 2 
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
85 
Programming notes 
Reason for being excluded should always be: RANDOMIZED, BUT NOT TREATED. 
Sorted by treatment group, site and subject identifier. 
 
4.3.2 
Demographics and Baseline Characteristics 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
86 
Template GS_DM_T_X_002: Demographic Characteristics Summary (incl. ‘Not reported’ category) 
Protocol: CA259001                                             Draft                                                     Page 1 of 1      
                                                 Demographic Characteristics Summary                                                    
                                                        All Treated Subjects                                                          
                                                                                                                                       
----------------------------------------------------------------------------------------------------------------------------------     
                                                      TRT A                 TRT B                 TRT C                 Total          
                                                    N = 1113              N = 1111              N = 1107              N = 3331         
----------------------------------------------------------------------------------------------------------------------------------    
                                                                                                                                      
AGE (Units)                                                                                                                                  
  N                                                 1112                  1109                  1107                  3328             
  MEAN                                                72                    71                    72                    72             
  MEDIAN                                              72                    71                    71                    71             
  MIN , MAX                                       0 , 94                0 , 95               59 , 94                0 , 95            
  Q1 , Q3                                        66 , 77               66 , 76               66 , 77               66 , 77            
  STANDARD DEVIATION                                   7.2                   7.7                   6.8                   7.2           
                                                                                                                                      
AGE CATEGORIZATION (%)                                                                                                                  
  < 50                                               232 ( 17.3)           248 ( 18.3)           246 ( 18.0)           726 ( 17.9)     
  >= 50                                              880 ( 78.9)           861 ( 77.1)           861 ( 78.8)          2602 ( 78.3)     
  NOT REPORTED                                         1 ( <0.1)             2 (  0.2)             0                     3 ( <0.1)     
                                                                                                                                        
GENDER (%)                                                                                                                            
  MALE                                               445 ( 40.1)           437 ( 39.1)           441 ( 39.6)          1323 ( 39.6)     
  FEMALE                                             666 ( 59.7)           669 ( 60.4)           659 ( 59.8)          1994 ( 60.0)     
  NOT REPORTED                                         2 (  0.2)             5 (  0.4)             7 (  0.6)            14 (  0.4)     
                                                                                                                                      
RACE (%)                                                                                                                               
  WHITE                                             1041 ( 93.3)          1042 ( 93.3)          1041 ( 93.4)          3124 ( 93.3)     
  BLACK OR AFRICAN AMERICAN                           26 (  2.3)            24 (  2.1)            20 (  2.5)            70 (  2.3)     
  ASIAN                                                4 (  0.4)             5 (  0.4)             3 (  0.3)            12 (  0.4)     
  OTHER                                               42 (  4.0)            40 (  4.1)            42 (  3.8)           124 (  4.0)     
  NOT REPORTED                                         0                     0                     1 ( <0.1)             1 ( <0.1)     
                                                                                                                                      
ETHNICITY (%)                                                                                                                            
  HISPANIC/LATINO                                     24 (  2.4)            35 (  3.1)            33 (  2.8)            92 (  2.8)     
  NOT HISPANIC/LATINO                               1089 ( 97.6)          1076 ( 96.9)          1073 ( 97.1)          3238 ( 97.2)     
  NOT REPORTED                                         0                     0                     1 ( <0.1)             1 ( <0.1)    
 
------------------------------------------------------------------------------------------------------------------------------------  
Program Source: /wwbdm/ndp/prime/gssr/devtest/dem/test/dem_tbl_mod.sas                                            30DEC2004:14:45:05  
 
 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
87 
Parameter 
Values 
Template ID 
GS_DM_T_X_002 
Output File Name 
rt-dm-summarys1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.1.1 
Title 1 
Demographic Characteristics Summary 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
See SAP Table 7.3.2.1-1. Add “COUNTRY BY GEOGRAPHIC REGION (%)” after “ETHNICITY (%)”. Indent countries 2 
spaces underneath regions. 
 
Parameter 
Values 
Template ID 
GS_DM_T_X_002 
Output File Name 
rt-dm-summarys2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.1.2 
Title 1 
Demographic Characteristics Summary 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
See SAP Table 7.3.2.1-1. Add “COUNTRY BY GEOGRAPHIC REGION (%)” after “ETHNICITY (%)”. Indent countries 2 
spaces underneath regions. 
 
Parameter 
Values 
Template ID 
GS_DM_T_X_002 
Output File Name 
rt-dm-summarys12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.1.3 
Title 1 
Demographic Characteristics Summary 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
88 
Title 2 
Treated Subjects - Stage 1 and 2 
Layout notes 
See SAP Table 7.3.2.1-1. Add “COUNTRY BY GEOGRAPHIC REGION (%)” after “ETHNICITY (%)”. Indent countries 2 
spaces underneath regions. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
89 
Template GS_DM_T_T_002: Demographic Characteristics Summary (incl. ‘Not reported’ category) 
Protocol: CA259001                                             Draft                                                     Page 1 of 1     
                                                 Demographic Characteristics Summary 
                                                        All Treated Subjects 
 
                                 ---------------------------------------------------------------- 
                                                                                       Total      
                                                                                     N = 3348     
                                 ---------------------------------------------------------------- 
                                                                                                    
                                 AGE (Units)                                                               
                                   N                                                 3345         
                                   MEAN                                                72         
                                   MEDIAN                                              71         
                                   MIN , MAX                                       0 , 95    
                                   Q1 , Q3                                        66 , 77    
                                   STANDARD DEVIATION                                   7.2       
                                                                                                    
                                 AGE CATEGORIZATION (%)                                             
                                   < 65                                               598 ( 17.9) 
                                   65 - 85                                           2620 ( 78.3) 
                                   NOT REPORTED                                         3 ( <0.1) 
                                                                                                    
                                 GENDER (%)                                                         
                                   MALE                                              1323 ( 39.6) 
                                   FEMALE                                            1994 ( 60.0) 
                                   NOT REPORTED                                        14 (  0.4) 
                                                                                                    
                                 RACE (%)                                                           
                                   WHITE                                             3124 ( 93.3) 
                                   BLACK OR AFRICAN AMERICAN                           78 (  2.3) 
                                   ASIAN                                               12 (  0.4) 
                                   OTHER                                              133 (  4.0) 
                                   NOT REPORTED                                         1 ( <0.1) 
                                                                                                    
                                ETHNICITY (%)                                                      
                                   HISPANIC/LATINO                                     93 (  2.8) 
                                   NOT HISPANIC/LATINO                               3254 ( 97.2) 
                                   NOT REPORTED                                         1 ( <0.1)  
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/dem/test/dem_tbl_mod.sas                                            30DEC2004:14:46:08 
 
Parameter 
Values 
Template ID 
GS_DM_T_T_002 
Output File Name 
rt-dm-sumenrolls1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
90 
Table No. 
Appendix 3.1.1B 
Title 1 
Demographic Characteristics Summary 
Title 2 
Subjects Enrolled but Not Randomized - Stage 1 
Layout notes 
See SAP Table 7.3.2.1-1. Add “COUNTRY BY GEOGRAPHIC REGION (%)” after “ETHNICITY (%)”. Indent countries 2 
spaces underneath regions. 
 
Parameter 
Values 
Template ID 
GS_DM_T_T_002 
Output File Name 
rt-dm-sumenrolls2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.1.2B 
Title 1 
Demographic Characteristics Summary 
Title 2 
Subjects Enrolled but Not Randomized - Stage 2 
Layout notes 
See SAP Table 7.3.2.1-1. Add “COUNTRY BY GEOGRAPHIC REGION (%)” after “ETHNICITY (%)”. Indent countries 2 
spaces underneath regions. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
91 
Template GS_DM_L_X_001: Demographics Listing by Treatment Group 
Protocol: CV131148                                             Draft                                                    Page 1 of 11  
                                                   Demographic Characteristics 
                                                        All Treated Subjects     
 
Treatment Group: TRT A                                                  
------------------------------------------------------------------------------------------------------------------------------------ 
                      Informed                                                                      
                      Consent       Birth       
Subject ID            Date          Date         Age   Gender   Ethnicity                Race 
----------------------
-------------------------------------------------------------------------------------------               
        22NOV2002     
2001      1   MALE     HISPANIC/LATINO          WHITE 
        07DEC2003     
2003     10M  MALE                              OTHER: WHITE SOUTH AFRICAN                         
        12JUN2003     
2002      6M  MALE     HISPANIC/LATINO          WHITE 
        17FEB2003     
2002      1   MALE     NOT HISPANIC/LATINO      WHITE              
        24APR2003     
2001      2   MALE     NOT HISPANIC/LATINO      WHITE              
        14MAY2003     
2000      3   FEMALE   NOT HISPANIC/LATINO      WHITE               
        25DEC2001     
2001      2D  FEMALE   NOT HISPANIC/LATINO      WHITE              
---------------------------------------------------------------------------------------------------------------------- 
Program Source: /wwbdm/ndp/prime/gssr/devtest/dem/test/dem_lst.sas                                                30DEC2004:15:50:44   
 
Parameter 
Values 
Template ID 
GS_DM_L_X_001 
Output File Name 
rl-dm-demchars1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.1.1A 
Title 1 
Demographic Characteristics 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Add 2 columns “Country” and “Geographic Region” after “Race”. 
 
Parameter 
Values 
Template ID 
GS_DM_L_X_001 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
92 
Output File Name 
rl-dm-demchars2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.1.2A 
Title 1 
Demographic Characteristics 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Add 2 columns “Country” and “Geographic Region” after “Race”. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
93 
Template SS_DM_T_004 : Baseline Disease Characteristics 
---------------------------------------------------------------------------------------------------------------------------------- 
 
                         Group A                  Group B         Group C 
      Group D                Total         
 
 
                       N = XX                 N = XX              N = XX         N = XX      
       N = XX     
---------------------------------------------------------------------------------------------------------------------------------- 
 
HIV SUBTYPE                                                                                                     
  A                           XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)        
  B                           XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)        
  <ADDITIONAL SUBTYPES>       XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X) 
 
Plasma HIV-1 RNA (log10 c/mL) 
  N                              XX                     XX                 XX               XX   
 
  XX          
  MEAN                         XX.X                   XX.X                 XX.X            XX.X                   XX.X        
  MEDIAN                       XX.X                   XX.X                 XX.X            XX.X                   XX.X 
  MIN , MAX                 XX.X , XX.X            XX.X , XX.X         XX.X , XX.X     XX.X , XX.X            XX.X , XX.X     
  Q1 , Q3                   XX.X , XX.X            XX.X , XX.X         XX.X , XX.X     XX.X , XX.X            XX.X , XX.X     
  STANDARD DEVIATION           XX.XX                  XX.XX                XX.XX           XX.XX                  XX.XX       
                                                                                                                              
HIV-1 RNA CATEGORIZATION                                                                                                     
  < 30,000 c/mL              XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  30,000 to < 100,000 c/mL   XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X) 
  100,000 to < 500,000 c/mL  XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  ≥ 500,000 c/mL             XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  NOT REPORTED               XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
                                                                                                                              
CD4+ T-cell counts (cells/uL) 
  N                              XX                     XX                 XX               XX   
 
  XX          
  MEAN                         XX.X                   XX.X                 XX.X            XX.X                   XX.X        
  MEDIAN                       XX.X                   XX.X                 XX.X            XX.X                   XX.X 
  MIN , MAX                 XX.X , XX.X            XX.X , XX.X         XX.X , XX.X       XX.X , XX.X            XX.X , XX.X   
  Q1 , Q3                   XX.X , XX.X            XX.X , XX.X         XX.X , XX.X       XX.X , XX.X            XX.X , XX.X   
  STANDARD DEVIATION           XX.XX                  XX.XX                XX.XX            XX.XX                  XX.XX      
                                                                                                                              
CD4+ T-cell CATEGORIZATION                                                                                                    
  < 50 cells/uL              XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  50 to < 100 cells/uL       XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X) 
  100 to < 200 cells/uL      XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  200 to < 350 cells/uL      XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  350 to < 500 cells/uL      XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  ≥ 500 cells/uL             XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
  NOT REPORTED               XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)       
 
CD4+ T-cell percentage 
  N                              XX                     XX                 XX               XX   
 
  XX          
  MEAN                         XX.X                   XX.X                 XX.X            XX.X                   XX.X        
  MEDIAN                       XX.X                   XX.X                 XX.X            XX.X                   XX.X 
  MIN , MAX                 XX.X , XX.X            XX.X , XX.X         XX.X , XX.X       XX.X , XX.X            XX.X , XX.X   
  Q1 , Q3                   XX.X , XX.X            XX.X , XX.X         XX.X , XX.X       XX.X , XX.X            XX.X , XX.X   
  STANDARD DEVIATION           XX.XX                  XX.XX                XX.XX            XX.XX                  XX.XX      
                                                                                                                               


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
94 
CD8+ T-cell counts (cells/uL) 
  N                              XX                     XX                 XX               XX   
 
  XX          
  MEAN                         XX.X                   XX.X                 XX.X            XX.X                   XX.X        
  MEDIAN                       XX.X                   XX.X                 XX.X            XX.X                   XX.X 
  MIN , MAX                 XX.X , XX.X            XX.X , XX.X        XX.X , XX.X       XX.X , XX.X            XX.X , XX.X    
  Q1 , Q3                   XX.X , XX.X            XX.X , XX.X        XX.X , XX.X       XX.X , XX.X            XX.X , XX.X    
  STANDARD DEVIATION           XX.XX                  XX.XX              XX.XX             XX.XX                  XX.XX       
                                                                                                                              
BMS-955176 IC50 (μM) 
  N                              XX                     XX                 XX               XX                   XX          
  MEAN                         XX.X                   XX.X               XX.X              XX.X                 XX.X          
  Geometric Mean  
(Coefficient of Variation)  
MEDIAN                       XX.X                   XX.X                 XX.X              XX.X                 XX.X 
  MIN , MAX                 XX.X , XX.X            XX.X , XX.X        XX.X , XX.X       XX.X , XX.X          XX.X , XX.X      
  Q1 , Q3                   XX.X , XX.X            XX.X , XX.X        XX.X , XX.X       XX.X , XX.X          XX.X , XX.X      
  STANDARD DEVIATION           XX.XX                  XX.XX              XX.XX             XX.XX                XX.XX         
                                                                                                                              
BMS-955176 IC50 FOLD CHANGE 
  < 1.0                      xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
  1.0 to < 5.0               xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
  5.0 to < 10                xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
  10  to < 100               xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
  100 to < 500               xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
  >= 500                     xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
 
AIDS STATUS 
  YES                        xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
  NO                         xx ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)              XX ( XX.X)         
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_DM_T_004 
Output File Name 
rt-dm-diseases1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.2.1 
Title 1 
Summary of Baseline Disease Characteristics 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Include all HIV subtypes available in the database. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
95 
Parameter 
Values 
Template ID 
SS_DM_T_004 
Output File Name 
rt-dm-diseases2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.2.2 
Title 1 
Summary of Baseline Disease Characteristics 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Include all HIV subtypes available in the database. 
 
Parameter 
Values 
Template ID 
SS_DM_T_004 
Output File Name 
rt-dm-diseases12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.2.3 
Title 1 
Summary of Baseline Disease Characteristics 
Title 2 
Treated Subjects - Stage 1 and 2 
Layout notes 
Include all HIV subtypes available in the database. 
 
Parameter 
Values 
Template ID 
SS_DM_T_004 
Output File Name 
rt-dm-diseasenrands1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.2.1A 
Title 1 
Summary of Baseline Disease Characteristics 
Title 2 
Subjects Enrolled but Not Randomized - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
96 
Layout notes 
Include only the ‘Total’ column.  
Include all HIV subtypes available in the database. 
 
Parameter 
Values 
Template ID 
SS_DM_T_004 
Output File Name 
rt-dm-diseasenrands2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.2.2A 
Title 1 
Summary of Baseline Disease Characteristics 
Title 2 
Subjects Enrolled but Not Randomized - Stage 2 
Layout notes 
Include only the ‘Total’ column.  
Include all HIV subtypes available in the database. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
97 
Template SS_DM_L_002: Listing of HIV Disease Characteristics 
Treatment Group: TRT A  
----------------------------------------------------------------------------------------------------------------------------------- 
                       Plasma HIV-1 Level             CD4+ T-cell count        
                       -----------------             -----------------        
                       Result    Category            Result    Category      CD4 T-cell  CD8+          HIV        IC50      IC Fold 
Subject ID            (log10 c/mL)  (c/mL)           (cells/uL) (cells/uL)   (percent)   cells/uL)     Subtype   (μM)        Change 
----------------------------------------------------------------------------------------------------------------- 
         x.x     <30,000               xx     < 200            xx         xx            xxxx      xx          xx  
         x.x    30,000 to < 100,000    xx    350 to < 500      xx         xx            xxxx      xx          xx  
         x.x    100,000 to < 500,000   xx    200 to < 350      xx         xx            xxxx      xx          xx  
         x.x     ≥ 500,000             xx    200 to < 350      xx         xx            xxxx      xx          xx  
         x.x     ≥ 500,000             xx    350 to < 500      xx         xx            xxxx      xx          xx  
         x.x     ≥ 500,000             xx     ≥ 500            xx         xx            xxxx      xx          xx  
         x.x     ≥ 500,000             xx    350 to < 500      xx         xx            xxxx      xx          xx  
         x.x     ≥ 500,000             xx    350 to < 500      xx         xx            xxxx      xx          xx  
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_DM_L_002 
Output File Name 
rl-dm-diseases1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.2.1B 
Title 1 
Listing of HIV Disease Characteristics 
Title 2 
Treated Subjects - Stage 1 
Programming notes 
Sorted by treatment group, site and subject identifier 
 
Parameter 
Values 
Template ID 
SS_DM_L_002 
Output File Name 
rl-dm-diseases2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.2.2B 
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
98 
Title 1 
Listing of HIV Disease Characteristics 
Title 2 
Treated Subjects - Stage 2 
Programming notes 
Sorted by treatment group, site and subject identifier 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
99 
Template GS_PM_T_X_001: Physical Measurements Table 
Protocol: CA259001                                              Draft                                                    Page 1 of 2     
                                                   Physical Measurements Summary 
                                                        All Treated Subjects 
 
    ---------------------------------------------------------------------------------------------------------------------------       
                                                  TRT A                 TRT B                 TRT C                 Total             
    Period/Visit                                N = 1366              N = 1382              N = 1338              N = 4086            
    ---------------------------------------------------------------------------------------------------------------------------       
                     
    SCREENING/DAY -1 
                                                                                                              
      HEIGHT (CM)                                                                                                                     
        N                                        1366                  1382                  1338                  4086               
        MEAN                                      170.6                 170.6                 170.6                 170.6             
        MEDIAN                                    171.0                 171.0                 171.0                 171.0             
        MIN , MAX                         147.3 , 198.1         149.0 , 198.1         143.5 , 198.1         143.5 , 198.1             
        STANDARD DEVIATION                          3.62                  3.73                  3.69                  3.68            
                                                                                                                                      
      WEIGHT (KG)                                                                                                                     
        N                                        1366                  1382                  1338                  4086               
        MEAN                                       87.7                  88.1                  88.7                  88.2             
        MEDIAN                                     85.3                  86.5                  85.7                  85.7             
        MIN , MAX                          51.0 , 158.1          41.5 , 149.2          38.4 , 144.5          38.4 , 158.1             
        STANDARD DEVIATION                         18.63                 21.01                 19.39                 19.71            
                                                                                                                                      
      BODY MASS INDEX (KG/M2)                                                                                                         
        N                                        1366                  1382                  1338                  4086               
        MEAN                                       30.11                 30.25                 30.46                 30.27            
        MEDIAN                                     29.31                 29.74                 29.49                 29.48            
        MIN , MAX                          17.44 , 54.07         14.19 , 51.02         13.13 , 47.95         13.13 , 54.07            
        STANDARD DEVIATION                          6.252                 7.017                 6.523                 6.607           
                                                                                                                                      
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/phm/test/domain_example/phm_tbl1.sas                                15DEC2004:16:21:00 
 
Parameter 
Values 
Template ID 
GS_PM_T_X_001 
Output File Name 
rt-pm-bsls1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.3.1 
Title 1 
Physical Measurements Summary 
Title 2 
Treated Subjects - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
100 
 
Parameter 
Values 
Template ID 
GS_PM_T_X_001 
Output File Name 
rt-pm-bsls2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.3.2 
Title 1 
Physical Measurements Summary 
Title 2 
Treated Subjects - Stage 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
101 
Template GS_PE_T_X_001: Physical Examination by Treatment Group 
Protocol: TA123456                                             Draft                                                     Page 1 of 1 
                                                      Physical Examination Summary 
                                                         All Treated Subjects  
 
 ----------------------------------------------------------------------------------------------------------------------------------- 
                                                          TRT A                TRT B                TRT C                Total        
 Period/Visit                                            N = 16               N = 17               N = 17               N = 50       
 ----------------------------------------------------------------------------------------------------------------------------------- 
                                                                                                                                     
 SCREENING/DAY 1                                                                                                                     
    
   SUBJECTS WITH ABNORMAL PHYSICAL EXAMINATION (%)         10 ( 62.5)           14 ( 82.4)           14 ( 82.4)           38 ( 76.0) 
     
     GENERAL APPEARANCE                                     0                    1 (  5.9)            0                    1 (  2.0) 
     HEAD, EARS, EYES, NOSE, THROAT                         5 ( 31.3)           12 ( 70.6)            5 ( 29.4)           22 ( 44.0) 
     NECK                                                   0                    0                    0                    0         
     CARDIOVASCULAR                                         0                    0                    0                    0         
     LUNGS                                                  0                    0                    1 (  5.9)            1 (  2.0) 
     ABDOMEN                                                1 (  6.3)            2 ( 11.8)            1 (  5.9)            4 (  8.0) 
     LYMPH NODES                                            0                    0                    0                    0         
     GENITOURINARY                                          0                    0                    0                    0         
     EXTREMITIES                                            3 ( 18.8)            2 ( 11.8)            4 ( 23.5)            9 ( 18.0) 
     NEUROLOGICAL                                           0                    0                    1 (  5.9)            1 (  2.0) 
     SKIN                                                   8 ( 50.0)           10 ( 58.8)            8 ( 47.1)           26 ( 52.0) 
     MUSCULOSKELETAL                                        0                    1 (  5.9)            1 (  5.9)            2 (  4.0) 
     OTHER                                                  8 ( 50.0)            7 ( 41.2)            8 ( 47.1)           23 ( 46.0) 
 
 SCREENING/DAY 5                                                                                                                     
    
   SUBJECTS WITH ABNORMAL PHYSICAL EXAMINATION (%)         10 ( 62.5)           14 ( 82.4)           14 ( 82.4)           38 ( 76.0) 
     
     GENERAL APPEARANCE                                     0                    1 (  5.9)            0                    1 (  2.0) 
     HEAD, EARS, EYES, NOSE, THROAT                         5 ( 31.3)           12 ( 70.6)            5 ( 29.4)           22 ( 44.0) 
     NECK                                                   0                    0                    0                    0         
     CARDIOVASCULAR                                         0                    0                    0                    0         
     LUNGS                                                  0                    0                    1 (  5.9)            1 (  2.0) 
     ABDOMEN                                                1 (  6.3)            2 ( 11.8)            1 (  5.9)            4 (  8.0) 
     LYMPH NODES                                            0                    0                    0                    0         
     GENITOURINARY                                          0                    0                    0                    0         
     EXTREMITIES                                            3 ( 18.8)            2 ( 11.8)            4 ( 23.5)            9 ( 18.0) 
     NEUROLOGICAL                                           0                    0                    1 (  5.9)            1 (  2.0) 
     SKIN                                                   8 ( 50.0)           10 ( 58.8)            8 ( 47.1)           26 ( 52.0) 
     MUSCULOSKELETAL                                        0                    1 (  5.9)            1 (  5.9)            2 (  4.0) 
     OTHER                                                  8 ( 50.0)            7 ( 41.2)            8 ( 47.1)           23 ( 46.0) 
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/mhx/test/domain_example/phx_tbl.sas                                 21SEP2004:10:31:00 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
102 
Parameter 
Values 
Template ID 
GS_PE_T_X_001 
Output File Name 
rt-pe-bslsums1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.4.1 
Title 1 
Physical Examination Summary 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Include all examinations present in the database. 
 
Parameter 
Values 
Template ID 
GS_PE_T_X_001 
Output File Name 
rt-pe-bslsums2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.4.2 
Title 1 
Physical Examination Summary 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Include all examinations present in the database. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
103 
Template GS_PE_L_X_001 : Physical Examination Listing by Treatment Group 
Protocol: TA123456                                             Draft                                                   Page 1 of 958 
Physical Examination 
All Treated Subjects 
Treatment Group: DRUG C  
----------------------------------------------------------------------------------------------------------------------------------- 
                             Period                                                                                                 
                               Visit                                                                                                
Subject ID                       Exam Date     Exanimation          Exam                                                 
  (Age/Gender/Race)                Study Day   Criteria             Result      Abnormality                              
--------------------------------------------------------------------------------------------------------------------- 
                SCREENING         GENERAL APPEARANCE   NORMAL                                               
  (46/M/C)                     A1
    HEENT                ABNORMAL    R EYE MILD NYSTIGMUS NCS                 
                                
    NECK                 ABNORMAL    CAROTID PULSES DIMINISHED SYMETRICALLY WITHOUT     
                                         -14                                    BRUITS NCS                                         
                                               CARDIOVASCULAR       ABNORMAL    MSM GRADE I-II / III NCS                 
                                               LUNGS                NORMAL                                               
                                               ABDOMEN              NORMAL                                               
                                               LYMPH NODES          NORMAL                                               
                                               GENITOURINARY        NOT DONE                                             
                                               EXTREMITIES          ABNORMAL    BILATERAL TRACE NO PITTING ANKLE EDEMA   
                                               NEUROLOGICAL         NORMAL                                               
                                               SKIN                 ABNORMAL    ABRASION R BENIGN MOLES NEVI & ACROCHORITONS       
                                               MUSCULOSKELETAL      ABNORMAL    BILAT HAND W/MCP&PIP RA CHNGS,TR SYNOVITIS L MCP   
                                                                                3&4,R MCP 3,4,5,TR SYNOVITIS WRIST BILAT,MILD BILAT 
                                                                                TRAPESIUS TIGHTNES SYMETRICALLY, SHOULDERS DECR     
                                                                                FROM ABDUCT 90 DEGREES SYMETRICALLY W/ANTERIOR TPS  
                                                                                                                        
                 PRE-TREAT         GENERAL APPEARANCE   NORMAL                                               
  (55/F/C)                     A3              HEENT                NORMAL                                               
                                
    NECK                 NORMAL                                               
                                          -1   CARDIOVASCULAR       NORMAL                                               
                                               LUNGS                NORMAL                                               
                                               ABDOMEN              NORMAL                                               
 
 
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/phy/test/phy_lst.sas                                                28FEB2005:15:09:00 
 
Parameter 
Values 
Template ID 
GS_PE_L_X_001 
Output File Name 
rl-pe-lists1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
104 
Table No. 
Appendix 3.4.1 
Title 1 
Physical Examination 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_PE_L_X_001 
Output File Name 
rl-pe-lists2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.4.2 
Title 1 
Physical Examination 
Title 2 
Treated Subjects - Stage 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
105 
Template SS_GN_T_001: Baseline Genotypic Resistance Profile 
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
              
 
 
 
 
 
Group A         Group B 
   Group C 
     Group D      
        
 
 
 
 
 
 
N = XX           N = XX   
   N = XX  
     N=XX 
    
------------------------------------------------------------------------------------------------------------------------------------ 
TESTED  
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
SEQUENCED 
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
 
ANY PI SUBSTITUTIONS  
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  PI substitutions#1  
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  PI substitutions#2  
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  PI substitutions#3  
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  PI substitutions#4  
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  <ADDITIONAL SUBSTITUTIONS> . . . 
 
SELECTED RT SUBSTITUTIONS 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  nRTI SUBSTITUTIONS  
 
 
 
 
 
    nRTI substitutions#1 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
    nRTI substitutions#2 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
    <ADDITIONAL SUBSTITUTIONS> . . . 
 
  NNRTI SUBSTITUTIONS  
 
 
 
 
 
    NNRTI substitutions#1 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
    NNRTI substitutions#2 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
INTEGRASE (RAL) SUBSTITUTIONS  
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  RAL substitutions#1  
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-bases1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1A 
Title 1 
Baseline Genotypic Resistance Profile 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Mutations extracted from data are based on IAS-USA list updated June 2014. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
106 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-bases2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2A 
Title 1 
Baseline Genotypic Resistance Profile 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Mutations extracted from data are based on IAS-USA list updated June 2014. 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-bases12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3A 
Title 1 
Baseline Genotypic Resistance Profile 
Title 2 
Treated Subjects - Stage 1 and 2 
Footnote 1 
Mutations extracted from data are based on IAS-USA list updated June 2014. 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-basebysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.9.1A 
Title 1 
Baseline Genotypic Resistance Profile 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
107 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
Mutations extracted from data are based on IAS-USA list updated June 2014. 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-basebysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.9.2A 
Title 1 
Baseline Genotypic Resistance Profile 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
Mutations extracted from data are based on IAS-USA list updated June 2014. 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-baseots1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1B 
Title 1 
Baseline Genotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 
Footnote 1 
Mutations extracted from data are based on IAS-USA list updated June 2014. 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
108 
Output File Name 
rt-gn-baseots2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2B 
Title 1 
Baseline Genotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 2 
Footnote 1 
Mutations extracted from data are based on IAS-USA list updated June 2014. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
109 
Template SS_GN_L_001:Genotypic Resistance Listing 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                    Period                                                                           
Subject ID                                            Visit                                                                          
  (Age/Gender/Race)                                     Date                                                                         
    Treatment Group     Current Treatment                 Study Day  RT Substitutions     PI Substitutions     RAL Substitutions     
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                       
          PRE-TREATMENT               PRE-TREATMENT    Q102K, K103K,        R41K, Q61H           V72I, S81R,           
  (54/F/C)                                            SCREENING      K103N, I142I,                             S81S, V113I,          
    ATV/r/RAL/TDF                                       
    I142V, C162S,                             T124A, V201I,         
                                                                -42  I178L, R211K,                             Y227F, S230N,         
                                                                     A272P, K275R,                             R231K, V234L,         
                                                                     R277K, Q278H                              A265V                 
                                                                                                                                     
                        ATV300mg QD+RTV100mg QD+    STAGE 1          Q102K, K103K,        R41K, Q61H           V72I, V113I,          
                        RAL400mg BID+TDF300mg QD      WE
    K103N, I142I,                             T124A, V201I,         
                                                        
   I142V, C162S,                             Y227F, S230N,         
                                                                119  I178L, R211K,                             R231K, V234L,         
                                                                     A272P, K275R,                             A265V                 
                                                                     R277K, Q278H,                                                   
                                                                     P294P, P294S                                                    
                                                                                                                     
        PRE-TREATMENT               PRE-TREATMENT    Q102K, K103N,        E35D, M36I,          E10D, M50I,           
  (62/M/C)                                            SCREENING      K122E, K122K,        M36M, N37D,          M50M, V72I,           
    ATV/r/RAL/TDF                                       
   D123D, D123E,        R57K, R57R,          L101I, V113I,         
                                                                -38  D123K, D123N,        I62V, L63H,          S119P, T125A,         
                                                                     V179I, V179V,        I93L                 K156N, G193E,         
                                                                     Q207N, H208H,                             G193G, G193K,         
                                                                     H208Y, R211K,                             G193R, V201I,         
                                                                     A272P, T286A,                             S230N, D232E,         
                                                                     V293I, E297K                              V234L, D256E,         
                                                                                                               D278A, Q285P,         
                                                                                                               Q285Q                 
                                                                                                                                     
  
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_GN_L_001 
Output File Name 
rl-gn-bsls1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.9.1B 
Title 1 
Listing of Baseline Genotypic Substitutions 
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
110 
Title 2 
Treated Subjects - Stage 1 
Programming notes 
Please include only the pre-treatment assessments. 
 
Parameter 
Values 
Template ID 
SS_GN_L_001 
Output File Name 
rl-gn-bsls2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.9.2B 
Title 1 
Listing of Baseline Genotypic Substitutions 
Title 2 
Treated Subjects - Stage 2 
Programming notes 
Please include only the pre-treatment assessments. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
111 
Template SS_GN_T_002: Baseline Gag Polymorphisms at Selected Positions 
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
              
 
 
 
 
 
Group A         Group B 
   Group C 
     Group D      
        
 
 
 
 
 
 
N = XX           N = XX   
   N = XX  
     N=XX 
    
------------------------------------------------------------------------------------------------------------------------------------ 
TESTED  
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
SEQUENCED 
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
SELECTED SUBSTITUTIONS 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITION 362  
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITION 364  
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITION 369  
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITION 370  
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
  POSITIONS 362 AND 364 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITIONS 362 AND 369 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITIONS 362 AND 370 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITIONS 364 AND 369 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITIONS 364 AND 370 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITIONS 369 AND 370 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
  POSITIONS 362, 364 AND 369  
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITIONS 362, 364 AND 370  
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  POSITIONS 364, 369 AND 370  
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
  POSITIONS 362, 364, 369 AND 370 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgags1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1C 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects - Stage 1 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
112 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgags2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2C 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgags12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3C 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1D 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 1 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
113 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2D 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3D 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagontrts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1H 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
114 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagontrts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2H 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagontrts12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3H 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagontrtbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1I 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
115 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagontrtbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2I 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Resistance Testing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagontrtbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3I 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1J 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
116 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2J 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3J 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
117 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagpdvfbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1K 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagpdvfbysubtypes2.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
118 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2K 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-bslgagpdvfbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3K 
Title 1 
Baseline Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
119 
Template SS_GN_T_003: Baseline Gag Deviations from Wild Type  
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
              
 
 
 
 
 
Group A         Group B 
   Group C 
     Group D      
        
 
 
 
 
 
 
N = XX           N = XX   
   N = XX  
     N=XX 
    
------------------------------------------------------------------------------------------------------------------------------------ 
TESTED  
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
SEQUENCED 
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
ANY DEVIATION  
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  DEV 1  
   
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  DEV 2    
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  DEV 3  
   
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  DEV 4    
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganys1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1E 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganys2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
120 
Table No. 
Table S.3.9.2E 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganys12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3E 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects - Stage 1 and 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganybysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1L 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
121 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganybysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2L 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganybysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3L 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects - Stage 1 and 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganyontrts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1M 
Title 1 
Baseline Gag Deviations from Wild Type Virus 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
122 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganyontrts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2M 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganyontrts12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3M 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 and 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganyontrtbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
123 
Table No. 
Table S.3.9.1N 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganyontrtbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2N 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Resistance Testing - Stage 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganyontrtbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3N 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 and 2 
Layout notes 
Include any deviation from the wild type virus detected in the database. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
124 
 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganypdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1O 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganypdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2O 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
125 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganypdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3O 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganypdvfbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1P 
Title 1 
Baseline Gag Deviations from Wild Type Virus 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
126 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganypdvfbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2P 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Include any deviation from the wild type virus detected in the database. 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
127 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-bslgaganypdvfbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3P 
Title 1 
Baseline Gag Deviations from Wild Type Virus 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Include any deviation from the wild type virus detected in the database. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
128 
Template SS_GN_L_002: Gag Listing for Selected Positions 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                            Period                                                                           
Subject ID                                                    Visit                                                                          
  (Age/Gender/Race)     HIV                                     Date                                                                         
    Treatment Group     Subtype  Current Treatment            Study Day  Position 362  Position 364   Position 369   Position 370    
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
         B        PRE-TREATMENT               PRE-TREATMENT     xxx              xxx           xxx              xxx 
  (54/F/C)                                                     SC
     
    ATV/r/RAL/TDF                                               
     
                                                                         -42   
                                                                      
                                                                      
                                                                                                                                     
                                 ATV300mg QD+RTV100mg QD+    STAGE 1           xxx              xxx           xxx              xxx            
                                 RAL400mg BID+TDF300mg QD      WE
     
                                                                 
     
                                                                         119   
                                                                      
                                                                                                                     
        C        PRE-TREATMENT               PRE-TREATMENT     xxx              xxx           xxx              xxx 
  (62/M/C)                                                     SCREENING       
    ATV/r/RAL/TDF                                                
    
                                                                         -38   
                                                                      
                                                                                                                
                                                                                                                    
                                                                                                                                     
  
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_GN_L_002 
Output File Name 
rl-gn-gagbsls1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.9.1C 
Title 1 
Listing of Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects - Stage 1 
Programming notes 
Please include only the pre-treatment assessments. 
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
129 
 
Parameter 
Values 
Template ID 
SS_GN_L_002 
Output File Name 
rl-gn-gagbsls2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.9.2C 
Title 1 
Listing of Baseline Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects - Stage 2 
Programming notes 
Please include only the pre-treatment assessments. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
130 
Template SS_GN_L_003: Gag Listing of Deviations from the Wild Type Virus 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                            Period                                                                           
Subject ID                                                    Visit                                                                          
  (Age/Gender/Race)     HIV                                     Date                                                                         
    Treatment Group     Subtype  Current Treatment                 Study Day      Deviations    
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                        
          C        PRE-TREATMENT               PRE-TREATMENT        xxx, xxx, xxx, xxx 
  (54/F/C)                                                    SC
     
    ATV/r/RAL/TDF                                               
    
                                                                        -42   
                                                                      
                                                                      
                                                                                                                                     
                                 ATV300mg QD+RTV100mg QD+    STAGE 1              xxx, xxx, xxx, xxx 
                                 RAL400mg BID+TDF300mg QD      WEEK 16         
                                                                 
    
                                                                         119   
                                                                      
                                                                                                                       
         B        PRE-TREATMENT               PRE-TREATMENT        xxx 
  (62/M/C)                                                     SC
     
    ATV/r/RAL/TDF                                                
     
                                                                         -38   
                                                                      
                                                                                                                
                                                                                                                    
                                                                                                                                     
  
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_GN_L_003 
Output File Name 
rl-gn-gagbslanys1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.9.1D 
Title 1 
Listing of Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects - Stage 1 
Programming notes 
Please include only the pre-treatment assessments. 
 
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
131 
Parameter 
Values 
Template ID 
SS_GN_L_003 
Output File Name 
rl-gn-gagbslanys2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.9.2D 
Title 1 
Listing of Baseline Gag Deviations from Wild Type Virus 
Title 2 
Treated Subjects - Stage 2 
Programming notes 
Please include only the pre-treatment assessments. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
132 
Template SS_PN_T_001: Baseline Phenotypic Resistance Categories 
------------------------------------------------------------------------------------------------------------------------------------ 
 
              
 
 
 
 
 
Group A         Group B 
   Group C 
     Group D      
        
 
 
 
 
 
 
N = XX          N = XX   
   N = XX  
     N=XX 
    
------------------------------------------------------------------------------------------------------------------------------------ 
 
PHENOTYPIC TESTING AT BASELINE 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
PHENOTYPABLE  
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
RESISTANCE CATEGORY 
  NO RESISTANCE TO DRUGS IN ANY CLASS 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  ≥1 NRTI 
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  ≥1 nNRTI 
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  ≥1 PI  
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  ≥1 INI 
 
 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 NRTI) AND (≥1 nNRTI) 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 NRTI) AND (≥1 PI) 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 NRTI) AND (≥1 INI) 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 nNRTI) AND (≥1 PI) 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 nNRTI) AND (≥1 INI) 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 PI) AND (≥1 INI) 
 
 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 NRTI) AND (≥1 nNRTI) AND (≥1 PI) 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 NRTI) AND (
≥1 nNRTI) AND (≥1 INI
) 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 NRTI) AND (≥1 PI) AND ( ≥1 
INI)  
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 nNRTI) AND (
≥1 PI) AND (≥1 INI
) 
 
 
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
  (≥1 NRTI) AND (≥1 nNRTI) AND (≥1 PI) AND ( ≥1 INI)  
XX/XX (XX.X)    XX/XX (XX.X)     XX/XX (XX.X)     XX/XX (XX.X)  
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bsls1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1F 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
133 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bsls2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2F 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects - Stage 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bsls12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3F 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bslots1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1G 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
134 
Output File Name 
rt-pn-bslots2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2G 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bslots12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3G 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects with On-Treatment Resistance Testing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bslpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1Q 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
135 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bslpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2Q 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-bslpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3Q 
Title 1 
Baseline Phenotypic Resistance Categories 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
136 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
137 
Template SS_PN_T_002: Phenotypic Resistance by Class and Drug Name 
                                                 TRT A            TRT B            TRT C            TRT D           TRT E            
                                                 N = 10           N = 15           N = 14           N = 15          N = 11           
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
PHENOTYPIC TESTING                               10/10 (100.0)    15/15 (100.0)    14/14 (100.0)    15/15 (100.0)    11/11 (100.0)   
                                                                                                                                     
PHENOTYPABLE                                      9/10 ( 90.0)    14/15 ( 93.3)    14/14 (100.0)    15/15 (100.0)    11/11 (100.0)   
                                                                                                                                     
PHENOTYPE                                                                                                                            
  PI                                              1/9  ( 11.1)     0/14             1/14 (  7.1)     2/15 ( 13.3)     0/11           
    AMP                                           0/9              0/14             0/14             0/15             0/11           
    AMP/R                                         0/9              0/14             0/14             0/15             0/11           
    ATV                                           1/9  ( 11.1)     0/14             0/14             1/15 (  6.7)     0/11           
    ATV/R                                         0/9              0/14             0/14             0/15             0/11           
    DRV/R                                         0/9              0/14             0/14             0/15             0/11           
    IDV/R                                         0/9              0/14             0/14             0/15             0/11           
    LPV/R                                         0/9              0/14             0/14             0/15             0/11           
    NFV                                           0/9              0/14             0/14             0/15             0/11           
    RTV                                           1/9  ( 11.1)     0/14             0/14             1/15 (  6.7)     0/11           
    SQV                                           0/9              0/14             0/14             0/15             0/11           
    SQV/R                                         1/9  ( 11.1)     0/14             0/14             1/15 (  6.7)     0/11           
    TPV/R                                         1/9  ( 11.1)     0/14             1/14 (  7.1)     2/15 ( 13.3)     0/11           
                                                                                                                                     
  NNRTI                                           1/9  ( 11.1)     2/14 ( 14.3)     0/14             0/15             1/11 (  9.1)   
    DLV                                           1/9  ( 11.1)     1/14 (  7.1)     0/14             0/15             1/11 (  9.1)   
    EFV                                           1/9  ( 11.1)     1/14 (  7.1)     0/14             0/15             1/11 (  9.1)   
    ETR                                           0/9              0/14             0/14             0/15             0/11           
    NVP                                           1/9  ( 11.1)     0/14             0/14             0/15             1/11 (  9.1)   
                                                                                                                                     
  NRTI                                            1/9  ( 11.1)     1/14 (  7.1)     1/14 (  7.1)     0/15             0/11           
    3TC                                           0/9              0/14             0/14             0/15             0/11           
    ABC                                           0/9              0/14             0/14             0/15             0/11           
    D4T                                           0/9              0/14             0/14             0/15             0/11           
    DDI                                           0/9              1/14 (  7.1)     1/14 (  7.1)     0/15             0/11           
    FTC                                           0/9              0/14             0/14             0/15             0/11           
    TFV                                           1/9  ( 11.1)     1/14 (  7.1)     0/14             0/15             0/11           
    ZDV                                           1/9  ( 11.1)     1/14 (  7.1)     0/14             0/15             0/11           
  
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /projects/bms208451/stats/primary/prog/tables/rt-pn-new.sas                                       13MAR2015:05:25:28 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
138 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bsldrugs1.lst 
Purpose 
WK24S1, WK48S1 WK96S1, WK96S2 
Table No. 
Table S.3.9.1H 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bsldrugs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2H 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects - Stage 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bsldrugs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3H 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects - Stage 1 and 2 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
139 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bslotrtdrugs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1I 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Testing - Stage 1 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bslotrtdrugs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2I 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Testing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bslotrtdrugs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3I 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Testing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
140 
Output File Name 
rt-pn-bsldrugpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.9.1R 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Testing 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bsldrugpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.9.2R 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Testing 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
141 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-bsldrugpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.3.9.3R 
Title 1 
Baseline Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Testing 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
142 
Template SS_PN_L_001: Phenotypic Resistance Listing 
------------------------------------------------------------------------------------------------------------------------------------ 
 
                      Current                        BMS-955176              RT                    PI                   RAL          
Subject ID            Treatment/                  ----------------- -------------------- ---------------------- -------------------- 
  (Age/Gender/Race)   Period/          Date/           IC50/ IC50           IC50/ IC50             IC50/ IC50           IC50/ IC50   
    Treatment Group   Visit            Study Day  Susc Fold Change  Susc    Fold Change  Susc      Fold Change  Susc    Fold Change  
------------------------------------------------------------------------------------------------------------------------------------ 
                         
                                                                                   
        PRE-TREATMENT/   
     0.00017/0.13 3TC (S) 3.79/1.41    AMP/R (S) 0.0167/1.26  RAL (S) 0.00762/0.88 
  (43/M/B)            PRE-TREATMENT/         -42                    ABC (S) 0.7/0.95     ATV (S)   0.00361/1.18                      
    BMS-663068        SCREENING                                     D4T (S) 0.66/1.06    ATV/R (S) 0.00361/1.18                      
    1200 mg QD/                                                     DDI (S) 7.52/1.04    DRV/R (S) 0.00099/1.28                      
    RAL/TDF                                                         FTC (S) 1.13/1.32    IDV/R (S) 0.0105/1.34                       
                                                                    TFV (S) 0.996/0.92   LPV/R (S) 0.0075/1.24                       
                                                                    ZDV (S) 0.029/1.21   NFV (S)   0.0248/1.85                       
                                                                    DLV (S) 0.0451/1.63  RTV (S)   0.0316/1.37                       
                                                                    EFV (S) 0.0054/1.24  SQV/R (S) 0.0054/1.24                       
                                                                    ETR (S) 0.0028/1.39  TPV/R (S) 0.1154/1.16                       
                                                                    NVP (S) 0.131/1.31                                               
                                       
                                                                                   
                      BMS1200mg QD+    
     NR/          3TC (S) 3.76/1.41    AMP/R (S) 0.02/1.56    RAL (S) 0.02064/1.33 
                      RAL400mg BID+           35                    ABC (S) 0.98/1.04    ATV (S)   0.00414/1.66                      
                      TDF300mg QD/                                  D4T (S) 0.77/1.06    ATV/R (S) 0.00414/1.66                      
                      STAGE 1/                                      DDI (S) 9.19/1.12    DRV/R (S) 0.00142/1.55                      
                      WEEK 4                                        FTC (S) 1.47/1.26    IDV/R (S) 0.0119/1.63                       
                                                                    TFV (S) 0.976/0.99   LPV/R (S) 0.0068/1.25                       
                                                                    ZDV (S) 0.047/1.60   NFV (S)   0.0281/2.83                       
                                                                    DLV (S) 0.0696/1.94  RTV (S)   0.046/1.97                        
                                                                    EFV (S) 0.0063/1.50  SQV/R (S) 0.0068/1.60                       
                                                                    ETR (S) 0.00326/1.55 TPV/R (P) 0.1843/2.06                       
                                                                    NVP (S) 0.185/1.91                                               
                                                                                                                                     
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_PN_L_001 
Output File Name 
rl-pn-bsls1.lst 
Purpose 
WK24S1, WK48S1 WK96S1, WK96S2 
Table No. 
Appendix 3.9.1E 
Title 1 
Listing of Baseline Phenotypic Resistance 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Susc = Susceptibility 
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
143 
Footnote 2 
P = Partial, R = Resistance, S = Susceptible 
Programming notes 
Please include only the pre-treatment assessments. 
 
Parameter 
Values 
Template ID 
SS_PN_L_001 
Output File Name 
rl-pn-bsls2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 3.9.2E 
Title 1 
Listing of Baseline Phenotypic Resistance 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Susc = Susceptibility 
Footnote 2 
P = Partial, R = Resistance, S = Susceptible 
Programming notes 
Please include only the pre-treatment assessments. 
 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
144 
Template GS_LB_T_X_004: Laboratory Toxicity Grade Summary 
Protocol: BMS234303                                            Draft                                                   Page 1 of 1 
Laboratory Test Results Summary of Worst Toxicity Grade 
All Treated Subjects 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Lab Test Description                       Group 1           Group 2          Group 3           Group 4            Total   
  Toxicity Grade                           N = 83            N = 50           N = 50            N = 25            N = 208 
------------------------------------------------------------------------------------------------------------------------------------ 
 
BLOOD UREA NITROGEN                                                                                                                  
  CRITERION 1                                 71 ( 85.5)        10 ( 20.0)        0                 0                81 ( 38.9) 
  CRITERION 2                                  7 (  8.4)         5 ( 10.0)        0                 0                12 (  5.8) 
  NOT REPORTED                                 5 (  0.6)        35 ( 70.0)       50 (100.0)        25 (100.0)       115 ( 55.3) 
                                                                                                                                     
LDL-C/HDL-C RATIO (DIRECT)                                                                                                           
  CRITERION 1                                 33 ( 39.8)        20 ( 40.0)        0                 0                53 ( 25.5) 
  CRITERION 2                                 39 ( 47.0)        20 ( 40.0)        0                 0                59 ( 28.4) 
  NOT REPORTED                                11 ( 13.3)        10 ( 20.0)       50 (100.0)        25 (100.0)        96 ( 46.1) 
                                                                                                                                     
TOTAL PROTEIN                                                                                                                        
  CRITERION 1                                 75 ( 90.4)         0               10 ( 20.0)         0                85 ( 40.9) 
  CRITERION 2                                  3 (  3.6)         0                2 (  4.0)         0                 5 (  2.4) 
  NOT REPORTED                                 5 (  0.6)        50 (100.0)       38 ( 76.0)        25 (100.0)       118 ( 56.7) 
                                                                                                                                  
CHLORIDE                                                                                                                             
  CRITERION 1                                 74 ( 89.2)         0                0                20 ( 80.0)        94 ( 45.2) 
  CRITERION 2                                  4 (  4.8)         0                0                 2 (  8.0)         6 (  2.9) 
  NOT REPORTED                                 5 (  0.6)        50 (100.0)       50 (100.0)         3 ( 12.0)       108 ( 51.9) 
 
 
------------------------------------------------------------------------------------------------------------------------------------  
Toxicity Scale: Descriptive text of toxicity scale 
Program Source: /wwbdm/ndp/prime/gssr/devtest/lab/test/labsum.b.sas                                               07SEP2004:14:35:00 
 
 
Parameter 
Values 
Template ID 
GS_LB_T_X_004 
Output File Name 
rt-lb-bsltoxs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.5.1 
Title 1 
Baseline Laboratory Test Results Summary of Toxicity Grade 
Title 2 
Treated Subjects - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
145 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
Parameter 
Values 
Template ID 
GS_LB_T_X_004 
Output File Name 
rt-lb-bsltoxs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.5.2 
Title 1 
Baseline Laboratory Test Results Summary of Toxicity Grade 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
146 
Template GS_AE_T_X_001: Adverse Event Summary by System Organ Class and Preferred Term 
Protocol: CV131154                                           Confidential                                               Page 1 of 21 
Adverse Event Summary 
All Treated Subjects 
 
------------------------------------------------------------------------------------------------------------------------------------ 
System Organ Class (%)                           TRT A                   TRT B                   TRT C                   Total       
  Preferred Term (%)                            N = 200                 N = 959                 N = 482                 N = 1641     
------------------------------------------------------------------------------------------------------------------------------------ 
 
TOTAL SUBJECTS WITH AN EVENT                    100 ( 50.0)             866 ( 90.3)             417 ( 86.5)             1383 ( 89.0) 
                                                                                                                               
BLOOD AND LYMPHATIC SYSTEM DISORDERS              6 (  3.0)              51 (  5.3)              39 (  8.1)               96 (  5.9)  
  ANAEMIA                                         0                      17 (  1.8)              16 (  3.3)               33 (  2.3)  
  LEUKOPENIA                                      0                      17 (  1.8)               5 (  1.0)               22 (  1.5)  
  EOSINOPHILIA                                    0                       5 (  0.5)               3 (  0.6)                8 (  0.6)  
  LYMPHADENOPATHY                                 0                       0                       7 (  1.5)                7 (  0.5)  
  LEUKOCYTOSIS                                    0                       1 (  0.1)               5 (  1.0)                6 (  0.4)  
  THROMBOCYTOPENIA                                4 (  2.0)               4 (  0.4)               1 (  0.2)                9 (  0.5)  
  IRON DEFICIENCY ANAEMIA                         0                       2 (  0.2)               1 (  0.2)                3 (  0.2)  
  BONE MARROW TOXICITY                            0                       1 (  0.1)               1 (  0.2)                2 (  0.1)  
  ANAEMIA FOLATE DEFICIENCY                       0                       1 (  0.1)               0                        1 ( <0.1)  
  ANAEMIA OF CHRONIC DISEASE                      0                       1 (  0.1)               0                        1 ( <0.1)  
  BASOPHILIA                                      0                       1 (  0.1)               0                        1 ( <0.1)  
  BONE MARROW DEPRESSION                          0                       1 (  0.1)               0                        1 ( <0.1)  
  LYMPH NODE PAIN                                 2                       1 (  0.1)               0                        1 ( <0.1)  
  MONOCYTOSIS                                     0                       0                       1 (  0.2)                1 ( <0.1)  
  NEUTROPENIA                                     0                       1 (  0.1)               0                        1 ( <0.1)  
  THROMBOCYTHAEMIA                                0                       1 (  0.1)               0                        1 ( <0.1)  
                                                                                                                                
CARDIAC DISORDERS                                10 (  5.0)              54 (  5.6)              36 (  7.5)              100 (  6.1)  
  PALPITATIONS                                    0                      21 (  2.2)               8 (  1.7)               29 (  2.0)  
  TACHYCARDIA                                     5 (  2.5)              13 (  1.4)               4 (  0.8)               22 (  1.3)  
  CARDIAC FAILURE CONGESTIVE                      5 (  2.5)               3 (  0.3)               3 (  0.6)               11 (  0.7)  
  BRADYCARDIA                                     0                       4 (  0.4)               1 (  0.2)                5 (  0.3)  
  SINUS BRADYCARDIA                               0                       1 (  0.1)               4 (  0.8)                5 (  0.3)  
  ARRHYTHMIA                                      0                       1 (  0.1)               3 (  0.6)                4 (  0.3)  
  ATRIAL FIBRILLATION                             0                       2 (  0.2)               2 (  0.4)                4 (  0.3)  
 
UNASSIGNED                                        1 (  0.5)               0                       0                        1 ( <0.1) 
  UNASSIGNED                                      1 (  0.5)               0                       0                        1 ( <0.1) 
       
 
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
MedDRA Version: 7.1                                                                                                                    
Program Source: /wwbdm/ndp/prime/msr/devtest/test/sample1.sas                                                     18FEB2005:10:59:00 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
147 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-preaidss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.6.1 
Title 1 
Adverse Events Summary 
Title 2 
Pre-treatment AIDS Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-preaidss2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.6.2 
Title 1 
Adverse Events Summary 
Title 2 
Pre-treatment AIDS Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
4.3.3 
Medical History and Previous Treatments 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
148 
Template GS_MH_T_X_001: Medical History Summary 
Protocol: TA001001                                             Draft                                                     Page 1 of 1 
                                                  General Medical History Summary 
                                                        All Treated Subjects 
 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                     TRT A                 TRT B                 TRT C                 Total 
                                                    N = 16                N = 17                N = 17                N = 50 
------------------------------------------------------------------------------------------------------------------------------------ 
 
SUBJECTS WITH ABNORMAL MEDICAL HISTORY (%)            16 (100.0)            16 ( 94.1)            16 ( 94.1)            48 ( 96.0) 
 
BODY SYSTEM (%) 
  HEAD, EYES, EARS, NOSE, THROAT                      12 ( 75.0)            11 ( 64.7)            10 ( 58.8)            33 ( 66.0) 
  CARDIOVASCULAR                                       3 ( 18.8)             5 ( 29.4)             4 ( 23.5)            12 ( 24.0) 
  PERIPHERAL VASCULAR                                  0                     3 ( 17.6)             0                     3 (  6.0) 
  RESPIRATORY                                          2 ( 12.5)             1 (  5.9)             1 (  5.9)             4 (  8.0) 
  GASTROINTESTINAL                                     6 ( 37.5)             5 ( 29.4)             5 ( 29.4)            16 ( 32.0) 
  HEPATOBILIARY                                        2 ( 12.5)             0                     1 (  5.9)             3 (  6.0) 
  RENAL                                                2 ( 12.5)             0                     1 (  5.9)             3 (  6.0) 
  GENITOURINARY                                        6 ( 37.5)             7 ( 41.2)             6 ( 35.3)            19 ( 38.0) 
  ENDOCRINE-METABOLIC                                 16 (100.0)            16 ( 94.1)            16 ( 94.1)            48 ( 96.0) 
  HEMATOLOGIC-LYMPHATIC                                0                     1 (  5.9)             0                     1 (  2.0) 
  MUSCULOSKELETAL                                     11 ( 68.8)            10 ( 58.8)             9 ( 52.9)            30 ( 60.0) 
  DERMATOLOGIC                                         4 ( 25.0)             6 ( 35.3)             4 ( 23.5)            14 ( 28.0) 
  NEUROLOGIC                                           8 ( 50.0)             5 ( 29.4)             6 ( 35.3)            19 ( 38.0) 
  PSYCHIATRIC                                          3 ( 18.8)             2 ( 11.8)             3 ( 17.6)             8 ( 16.0) 
  ALLERGIES                                            3 ( 18.8)             3 ( 17.6)             3 ( 17.6)             9 ( 18.0) 
  NEOPLASIA                                            1 (  6.3)             0                     0                     1 (  2.0) 
  ALCOHOL USE                                          9 ( 56.3)             4 ( 23.5)             8 ( 47.1)            21 ( 42.0) 
  TOBACCO USE                                          4 ( 25.0)             6 ( 35.3)             5 ( 29.4)            15 ( 30.0) 
  DRUG ABUSE                                           0                     0                     0                     0 
  OTHER                                                2 ( 12.5)             3 ( 17.6)             2 ( 11.8)             7 ( 14.0) 
------------------------------------------------------------------------------------------------------------------------------------ 
 
 
Parameter 
Values 
Template ID 
GS_MH_T_X_001 
Output File Name 
rt-mh-sums1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.3.7.1 
Title 1 
General Medical History Summary 
Title 2 
Treated Subjects - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
149 
 
Parameter 
Values 
Template ID 
GS_MH_T_X_001 
Output File Name 
rt-mh-sums2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.7.2 
Title 1 
General Medical History Summary 
Title 2 
Treated Subjects - Stage 2 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
150 
Template GS_MH_L_X_001: Medical History Listing by Treatment Group 
Protocol: CV131148                                             Draft                                                   Page 1 of 100 
                                                       General Medical History 
                                                        All Treated Subjects 
Treatment Group: TRT A 
------------------------------------------------------------------------------------------------------------------------------------ 
Subject ID 
  (Age/Gender/Race)          System                            Condition(s) 
------------------------------------------------------------------------------------------------------------------------------------ 
                HEAD, EARS, EYES, NOSE, THROAT    CEREBRO VASCULAR 
  (79/M/C)                   CARDIOVASCULAR                    SEE PREVIOUS PAGE 
                             PERIPHERAL VASCULAR               PERIPHERAL PULSATIONS NOT PALPABLE 
                             RESPIRATORY                       NULOL COPD 
                             GASTROINTESTINAL                  GASTRIC ,ULCER - ANAL BLEEDING - RECTUM POLYP & RESECTION 
                             ALLERGIES                         PENICILLINE 
               CARDIOVASCULAR                    CHF 
  (83/F/C)                   RESPIRATORY                       BRONCHITIS 
                             GASTROINTESTINAL                  CHOLELITHIASIS WITH CHOLECYSECTOMY 
                             MUSCULOSKELETAL                   ARTHROSIS - SPINAL STENOSIS 
                             PSYCHIATRIC                       DEPRESSION 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/mhx/test/mhx_lst.sas                                                06APR2004:17:58:02 
 
Parameter 
Values 
Template ID 
GS_MH_L_X_001 
Output File Name 
rl-mh-lists1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 3.7.1 
Title 1 
General Medical History 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_MH_L_X_001 
Output File Name 
rl-mh-lists2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
151 
Table No. 
Appendix 3.7.2 
Title 1 
General Medical History 
Title 2 
Treated Subjects - Stage 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
152 
Template GS_CM_T_X_001 : Non-Study Medication Summary 
Protocol: CV168006                                             Draft                                                    Page 1 of 58 
                                                     Non-Study Medication Summary 
                                                          Medication Category 
                                                          All Treated Subjects 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Anatomic Class (%)                                                                                                                   
  Therapeutic Class (%)                                                 TRT A           TRT B           TRT C           Total     
    Generic Name (%)                                                   N = 5443        N = 6443        N = 6123        N = 19009   
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
TOTAL SUBJECTS USING MEDICATION                                        6134 ( 95.2)    6134 ( 95.2)    5884 ( 96.1)    19009 ( 95.6) 
                                                                                                                                     
ALIMENTARY TRACT & METABOLISM                                           431 (  6.7)     431 (  6.7)     425 (  6.9)     1287 (  6.8) 
                                                                                                                                     
  ANABOLIC STEROID                                                        0               0               1 ( <0.1)        1 ( <0.1) 
    PRASTERONE                                                            0               0               1 ( <0.1)        1 ( <0.1) 
                                                                                                                                     
  ANTACID                                                                31 (  0.5)      31 (  0.5)      46 (  0.8)      108 (  0.6) 
    ALOH/CACO/MGOH                                                        1 ( <0.1)       1 ( <0.1)       0                2 ( <0.1) 
    ALOH/MAGTRI                                                           0               0               1 ( <0.1)        1 ( <0.1) 
    ALOH/MGOH                                                             2 ( <0.1)       2 ( <0.1)       3 ( <0.1)        7 ( <0.1) 
    ALOH/MGOH/OXETAC                                                      2 ( <0.1)       1 ( <0.1)       0                3 ( <0.1) 
    ANTACID                                                               7 ( <0.1)       7 (  0.1)      11 (  0.2)       25 (  0.1) 
    CACO/FAMO/MGOH                                                        7 ( <0.1)       1 ( <0.1)       1 ( <0.1)        9 ( <0.1) 
    CALCIUM CARBONATE                                                    13 (  0.2)      13 (  0.2)      22 (  0.4)       48 (  0.3) 
    DIHYDROXYALUMINIUM SODIUM CARBINATE                                   0               0               6 (  0.1)        6 ( <0.1) 
  
  ANTIDIARRHEA/INTEST ANTIINFLAM                                          2 ( <0.1)       2 (< 0.1)       1 ( <0.1)        5 ( <0.1) 
    ANTIDIARRHEAL                                                         2 ( <0.1)       2 (< 0.1)       1 ( <0.1)        5 ( <0.1) 
                                                                                                                                     
  ANTIDIARRHEAL MICROORGANISM                                             5 ( <0.1)       5 (  0.1)       3 ( <0.1)       13 (  0.1) 
    LACTOBACILLUS ACIDOPHILUS                                             4 ( <0.1)       4 (  0.1)       3 ( <0.1)       11 (  0.1) 
    SACCHAROMYCES BOULARDII                                               1 ( <0.1)       1 (< 0.1)       0                2 ( <0.1) 
 
UNASSIGNED                                                                2 ( <0.1)       2 ( <0.1)       2 ( <0.1)        6 ( <0.1) 
  UNASSIGNED                                                              1 ( <0.1)       1 ( <0.1)       0                2 ( <0.1) 
    UNASSIGNED                                                            1 ( <0.1)       1 ( <0.1)       2 ( <0.1)        4 ( <0.1) 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/checkraw/cmtbl.sas                                                  29OCT2004:18:53:00 
 
Parameter 
Values 
Template ID 
GS_CM_T_X_001 
Output File Name 
rt-cm-premeds1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
153 
Table No. 
Table S.3.8.1 
Title 1 
Non-Study Medication Summary 
Title 2 
Previous Medication 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
Previous medication is defined as any medication that was taken before the start of study medication. 
 
Parameter 
Values 
Template ID 
GS_CM_T_X_001 
Output File Name 
rt-cm-premeds2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.3.8.2 
Title 1 
Non-Study Medication Summary 
Title 2 
Previous Medication 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
Previous medication is defined as any medication that was taken before the start of study medication. 
 
 
4.4 
Extent Of Exposure 
4.4.1 
Study Therapy and Treatment Compliance 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
154 
Template SS_EX_T_001: Extent of Exposure Summary 
---------------------------------------------------------------------------------------------------------------------------------- 
   
 
 
 
 
 
 
 
                   
 
                           
 
 
Group A                Group B 
     Group C         Group D             
 
 
                        
 
        N = XX                 N = XX              N = XX           N = XX             
---------------------------------------------------------------------------------------------------------------------------------- 
                                                                                                                                   
  N                               
 
 
   XX                     XX                 XX               XX                
  MEAN                          
 
 
  XX.X                   XX.X  
        XX.X             XX.X              
  MEDIAN                        
 
 
  XX.X                   XX.X  
        XX.X             XX.X              
  MIN , MAX                   
 
       XX.X , XX.X            XX.X , XX.X        XX.X , XX.X      XX.X , XX.X          
  Q1 , Q3                                          XX.X , XX.X            XX.X , XX.X        XX.X , XX.X      XX.X , XX.X          
  STANDARD DEVIATION                                 XX.XX                  XX.XX               XX.XX            XX.XX             
  
  MEAN DAILY DOSE (mg) 
 
 
 
 XXX.X  
 
   XXX.X  
       XXX.X           XXX.X  
                                                                                                                           
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-bmss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1A 
Title 1 
Extent of Exposure to BMS-955176 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-bmss2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2A 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
155 
Title 1 
Extent of Exposure to BMS-955176 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-tdfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1B 
Title 1 
Extent of Exposure to Tenofovir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-tdfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2B 
Title 1 
Extent of Exposure to Tenofovir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Include Mean Daily Dose 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
156 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-atvs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1C 
Title 1 
Extent of Exposure to Atazanavir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-atvs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2C 
Title 1 
Extent of Exposure to Atazanavir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-dtgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1D 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
157 
Title 1 
Extent of Exposure to Dolutegravir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-dtgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2D 
Title 1 
Extent of Exposure to Dolutegravir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-rtvs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1E 
Title 1 
Extent of Exposure to Ritonavir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Include Mean Daily Dose 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
158 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-rtvs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2E 
Title 1 
Extent of Exposure to Ritonavir 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-regimens1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1F 
Title 1 
Extent of Exposure to Treatment Regimen 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Do not include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-regimens2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2F 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
159 
Title 1 
Extent of Exposure to Treatment Regimen 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Do not include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-regimens12.lst 
Purpose 
WK96S2 
Table No. 
Table S.4.1.3F 
Title 1 
Extent of Exposure to Treatment Regimen 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects - Stage 1 and 2 
Layout notes 
Do not include Mean Daily Dose 
 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-conts1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.4.1.1G 
Title 1 
Extent of Exposure to BMS-955176 after Switch to Continuation Dose 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects who Switched to Continuation Dose - Stage 1 
Layout notes 
Include Mean Daily Dose 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
160 
Parameter 
Values 
Template ID 
SS_EX_T_001 
Output File Name 
rt-ex-conts2.lst 
Purpose 
WK96S2 
Table No. 
Table S.4.1.2G 
Title 1 
Extent of Exposure to BMS-955176 after Switch to Continuation Dose 
Title 2 
Time on Therapy 
Title 3 
Treated Subjects who Switched to Continuation Dose - Stage 2 
Layout notes 
Include Mean Daily Dose 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
161 
Template GS_EX_G_001: Kaplan-Meier Plot Grouped by Treatment with Censoring 
 
Parameter 
Values 
Template ID 
GS_EX_G_001 
Output File Name 
rg-ex-kms1 
0.0
0.1
0.2
0.3
0.4
0.5
Probability of Event
0
5
10
15
20
25
30
Time (Weeks)
Number of Subjects at Risk
DrgA Xmg
DrgA Ymg
DrgA Zmg
DrgB Xmg
61
58
58
53
38
12
0
62
54
51
50
38
16
0
61
57
55
49
34
13
0
63
60
57
53
36
14
0
DrugA Xmg (events: 6/61)
DrugA Ymg (events: 12/62)
DrugA Zmg (events: 8/61)
DrugB Xmg (events: 7/63)
Serious Events (incl. Deaths) up to 30 days post-trt included
Non-Serious events up to last day of treatement included. Symbols represent censored observation
<Special Events> are based upon a predefined list of MEDDRA Preferred Terms.
Program Path:  /home/banckenf/sgtest
20OCT2008:06:57:24
Program Name: sgissue0005.sas


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
162 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.4.1.1 
Title 1 
Time on Study Therapy 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: Proportion of Subjects on Study Therapy 
X-axis label: Time (Weeks) 
 
Parameter 
Values 
Template ID 
GS_EX_G_001 
Output File Name 
rg-ex-kms2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.4.1.2 
Title 1 
Time on Study Therapy 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: Proportion of Subjects on Study Therapy 
X-axis label: Time (Weeks) 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
163 
Template SS_EX_T_002: Time on Study Therapy Life Table 
                 ------------------------------------------------------------------------------------------------- 
                               Group A (N=194)                 GROUP B (N=203)                GROUP C (N=201)      
                             ---------------------------  ---------------------------  --------------------------- 
                                        Proportion (%)               Proportion (%)               Proportion (%)   
                 Week (a)     n    N#      (95% CI)        n    N#      (95% CI)        n    N#      (95% CI)      
                                                                                                                   
                 ------------------------------------------------------------------------------------------------- 
                                                                                                                   
                 < 4           0  194   0.0  ( 0.0- 0.0)    0  203   0.0  ( 0.0- 0.0)    0  201   0.0  ( 0.0- 0.0) 
                 4 - < 8       0  189   0.0  ( 0.0- 0.0)    0  201   0.0  ( 0.0- 0.0)    0  197   0.0  ( 0.0- 0.0) 
                 8 - < 12      0  186   0.0  ( 0.0- 0.0)    0  196   0.0  ( 0.0- 0.0)    1  194   0.5  ( 0.0- 1.5) 
                 12 - < 16     0  185   0.0  ( 0.0- 0.0)    0  193   0.0  ( 0.0- 0.0)    3  192   1.6  ( 0.0- 3.3) 
                 16 - < 20     1  184   0.5  ( 0.0- 1.6)    5  188   2.7  ( 0.4- 5.0)    5  184   2.6  ( 0.4- 4.9) 
                 20 - < 24     1  181   0.5  ( 0.0- 1.6)    5  179   2.7  ( 0.4- 5.0)    8  181   4.2  ( 1.4- 7.1) 
                 24 - < 28     1  181   0.5  ( 0.0- 1.6)    7  179   3.8  ( 1.0- 6.6)   11  178   5.9  ( 2.5- 9.3) 
                 28 - < 32     1  180   0.5  ( 0.0- 1.6)   11  174   6.0  ( 2.6- 9.5)   18  171   9.8  ( 5.5-14.0) 
                 32 - < 36     1  180   0.5  ( 0.0- 1.6)   13  169   7.1  ( 3.4-10.9)   21  163  11.5  ( 6.8-16.1) 
                 36 - < 40     1  180   0.5  ( 0.0- 1.6)   13  164   7.1  ( 3.4-10.9)   22  156  12.0  ( 7.3-16.8) 
                 40 - < 44     1  177   0.5  ( 0.0- 1.6)   14  163   7.7  ( 3.8-11.6)   25  154  13.8  ( 8.7-18.8) 
                 44 - < 48     1  175   0.5  ( 0.0- 1.6)   15  161   8.3  ( 4.3-12.3)   25  150  13.8  ( 8.7-18.8) 
                 48 - < 52     1  137   0.5  ( 0.0- 1.6)   15  129   8.3  ( 4.3-12.3)   26  116  16.0  ( 9.5-22.5) 
                 52 - < 56     1    4                      15    4                      26    4                    
                 ------------------------------------------------------------------------------------------------- 
 
Parameter 
Values 
Template ID 
SS_EX_T_002 
Output File Name 
rt-ex-kms1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1H 
Title 1 
Time of Study Therapy Life Table (Kaplan-Meier Estimates) 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
(a) Cumulative proportion without events at end of interval. 
 
Parameter 
Values 
Template ID 
SS_EX_T_002 
Output File Name 
rt-ex-kms2.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
164 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2H 
Title 1 
Time of Study Therapy Life Table (Kaplan-Meier Estimates) 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
(a) Cumulative proportion without events at end of interval. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
165 
Template SS_EX_T_003: Summary of Interruptions Greater than 3 Days 
---------------------------------------------------------------------------------------------------------------------------------- 
                                                                       Treatment Regimen 
                                          ------------------------------------------------------------------------------ 
 
                           
 
Group A           Group B 
    Group C 
     Group D        Group E                        
Drug                           
        N = XX             N = XX         N = XX         N = XX           N = XX      
        
----------------------------------------------------------------------------------------------------------------------------------- 
DRUG 1 
  N                            
 
   XX                XX              XX              XX      
  MEAN                         
 
  XX.X              XX.X 
       XX.X            XX.X                
  MEDIAN                       
 
  XX.X              XX.X 
       XX.X            XX.X                    
  MIN , MAX                   
       XX.X , XX.X        XX.X , XX.X    XX.X , XX.X     XX.X , XX.X              
  Q1 , Q3                                   XX.X , XX.X       XX.X , XX.X     XX.X , XX.X     XX.X , XX.X             
  STANDARD DEVIATION                           XX.XX             XX.XX           XX.XX           XX.XX                   
 
  
DRUG 2 
  N                            
 
   XX                XX              XX              XX             XX        
  MEAN                         
 
  XX.X              XX.X 
       XX.X            XX.X           XX.X               
  MEDIAN                       
 
  XX.X              XX.X 
       XX.X            XX.X           XX.X                   
  MIN , MAX                   
       XX.X , XX.X        XX.X , XX.X    XX.X , XX.X     XX.X , XX.X    XX.X , XX.X            
  Q1 , Q3                                   XX.X , XX.X       XX.X , XX.X     XX.X , XX.X     XX.X , XX.X    XX.X , XX.X            
  STANDARD DEVIATION                           XX.XX             XX.XX           XX.XX           XX.XX          XX.XX                  
 
 
DRUG 3 
  N                            
 
   XX                XX              XX              XX             XX        
  MEAN                         
 
  XX.X              XX.X 
       XX.X            XX.X           XX.X               
  MEDIAN                       
 
  XX.X              XX.X 
       XX.X            XX.X           XX.X                   
  MIN , MAX                   
       XX.X , XX.X        XX.X , XX.X    XX.X , XX.X     XX.X , XX.X    XX.X , XX.X            
  Q1 , Q3                                   XX.X , XX.X       XX.X , XX.X     XX.X , XX.X     XX.X , XX.X    XX.X , XX.X            
  STANDARD DEVIATION                           XX.XX             XX.XX           XX.XX           XX.XX          XX.XX                  
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_EX_T_003 
Output File Name 
rt-ex-interrupts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.1.1I 
Title 1 
Summary of Interruptions in Study Therapy Greater than 3 Days 
Title 2 
Treated Subjects - Stage 1 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
166 
Parameter 
Values 
Template ID 
SS_EX_T_003 
Output File Name 
rt-ex-interrupts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.1.2I 
Title 1 
Summary of Interruptions in Study Therapy Greater than 3 Days 
Title 2 
Treated Subjects - Stage 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
167 
Template SS_EX_L_001: Study Medication Exposure Listing 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Subject Number                                                                                                                       
  (Age/Gender/Race)                                                                                                                  
    Treatment Group                Drug           Start Date  Stop Date   Daily Dose  Reason for Modification                        
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                         
                      BMS-663068     04NOV2013   04NOV2013       0       DOSING ERROR                                   
  (50/M/B)                                                                                                                           
    BMS-663068 1200 mg QD/RAL/TDF                                                                                                    
                                                  05NOV2013   15NOV2013    1200       NO CHANGE                                      
                                                  16NOV2013   16NOV2013       0       DOSING ERROR                                   
                                                  17NOV2013   19NOV2013    1200       NO CHANGE                                      
                                                  20NOV2013   31JAN2014    1200       NO CHANGE                                      
                                                  01FEB2014   13FEB2014       0       OTHER                                          
                                                  14FEB2014   06MAY2014    1200       NO CHANGE                                      
                                                  07MAY2014   29JUL2014    1200       NO CHANGE                                      
                                   RALTEGRAVIR    27OCT2011   10NOV2012     800       NO CHANGE                                      
                                                  11NOV2012   19DEC2012       0       OTHER                                          
                                                  20DEC2012   07FEB2013     800       NO CHANGE                                      
                                                  08FEB2013   08FEB2013       0       DOSING ERROR                                   
                                                  09FEB2013   18MAR2013     800       NO CHANGE                                      
                                                  19MAR2013   19MAR2013       0       DOSING ERROR                                   
                                                  20MAR2013   21MAR2013     800       NO CHANGE                                      
                                                  22MAR2013   23MAR2013       0       DOSING ERROR                                   
                                                  24MAR2013   23SEP2013     800       NO CHANGE                                      
                                                  24SEP2013   25SEP2013       0       DOSING ERROR                                   
                                                  26SEP2013   31JAN2014     800       NO CHANGE                                      
                                                  01FEB2014   13FEB2014       0       OTHER                                          
                                                  14FEB2014   06MAY2014     800       NO CHANGE                                      
                                                  07MAY2014   29JUL2014     800       NO CHANGE                                      
                                   TENOFOVIR      27OCT2011   10NOV2012     300       NO CHANGE                                      
                                                  11NOV2012   19DEC2012       0       OTHER                                          
                                                  20DEC2012   07FEB2013     300       NO CHANGE                                      
                                                  08FEB2013   08FEB2013       0       DOSING ERROR                                   
                                                  09FEB2013   18MAR2013     300       NO CHANGE                                      
                                                  19MAR2013   19MAR2013       0       DOSING ERROR                                   
                                                  20MAR2013   21MAR2013     300       NO CHANGE                                      
                                                  22MAR2013   23MAR2013       0       DOSING ERROR                                   
                                                  24MAR2013   23SEP2013     300       NO CHANGE                                      
  
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_EX_L_001 
Output File Name 
rl-ex-lists1.lst 
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
168 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 4.1.1A 
Title 1 
Study Medication Exposure by Subject Listing 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
SS_EX_L_001 
Output File Name 
rl-ex-lists2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 4.1.2A 
Title 1 
Study Medication Exposure by Subject Listing 
Title 2 
Treated Subjects - Stage 2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
169 
Template SS_EX_L_002: Study Medication Listing related to Continuation Dose 
Treatment Group: DRUG C  
 
------------------------------------------------------------------------------------------------------------------------------------ 
Subject Number                     Tim on                 Date/Study Day        Time on 
  (Age/Gender/Race)                Randomized             of Switch to          Continuation 
                                   Dose                   Continuation Dose     Dose                        
------------------------------------------------------------------------------------------------------------------------------------ 
                                              
                                                                 
                      280                   
/ 281       364                                                  
                                             
                                                                 
                      285                   
/ 286       370                                                  
                                             
                                                                 
                       298                   
/ 299       351                                                  
  (50/M/B)                                                
                                                                 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_EX_L_002 
Output File Name 
rl-ex-listcdoses1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Appendix 4.1.1B 
Title 1 
Listing of Time on Original and Continuation Dose 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
SS_EX_L_002 
Output File Name 
rl-ex-listcdoses2.lst 
Purpose 
WK96S2 
Table No. 
Appendix 4.1.2B 
Title 1 
Listing of Time on Original and Continuation Dose 
Title 2 
Treated Subjects - Stage 2 
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
170 
 
4.4.2 
Concomitant Therapy 
Parameter 
Values 
Template ID 
GS_CM_T_X_001 
Output File Name 
rt-cm-conmeds1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.4.2.1 
Title 1 
Non-Study Medication Summary 
Title 2 
Concomitant Medication 
Title 3 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_CM_T_X_001 
Output File Name 
rt-cm-conmeds2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.4.2.2 
Title 1 
Non-Study Medication Summary 
Title 2 
Concomitant Medication 
Title 3 
Treated Subjects - Stage 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
171 
Template GS_CM_L_X_006: Non-Study Medication Listing by Treatment Group 
Protocol: CV181008                                                     Draft                                            Page 1 of 89 
                                                              Non-Study Medication 
                                                               Medication Category 
                                                              All Treated Subjects 
Treatment Group: TRT A 
------------------------------------------------------------------------------------------------------------------------------------ 
                                            Start           Anatomic Class                                                           
                          Period              Stop            Therapeutic Class                                     
Subject ID                  Visit               Study Day       Generic Name                                          
  (Age/Gender/Race)           Current Trt         TRD#            Reported Medication                                Use 
----------------------------
----------------------------------------------------------------------------- 
          SHORT TERM        
    ALIMENTARY TRACT & METABOLISM                            OTHER   
  (43/F/B)                  WEEK 1          
      ORAL BLOOD GLUCOSE LOWERING DRUG                      
                              ABC 10        
 1       METFORMIN                                               
                                                  1D              GLUCOPHAGE   
                                            
                          SHORT TERM       
    ALIMENTARY TRACT & METABOLISM                            OTHER           
                            WEEK 1         
      ORAL BLOOD GLUCOSE LOWERING DRUG                                       
                              ABC 10                    1       GLIPIZIDE                                                            
                                                  1D              GLUCOTROL XL   
                                            
                          SHORT TERM        
    NERVOUS SYSTEM                                           ADVERSE EVENT  
                            WEEK 1          
      OTHER ANALGESIC & ANTIPYRETIC                                          
                              ABC 10        
 2       ACETAMINOPHEN                                                        
                                                  2D              TYLENOL     
                                            
 
                          SHORT TERM        
     ALIMENTARY TRACT & METABOLISM                            OTHER          
                            WEEK 1          
       ORAL BLOOD GLUCOSE LOWERING DRUG                                       
                              ABC 10                    2       GLIPIZIDE                                                            
                                                  2D              GLUCOTROL XL  
                                            
                          SHORT TERM       
    ALIMENTARY TRACT & METABOLISM                            OTHER          
                            WEEK 1         
      ORAL BLOOD GLUCOSE LOWERING DRUG                                       
                              ABC 10                    2       METFORMIN                                                            
                                                  2D              GLUCOPHAGE   
                                                                                                         
------------------------------------------------------------------------------------------------------------------------------------ 
# Time relative to most recent dose                                                                                              
Program Source: /wwbdm/ndp/prime/gssr/devtest/checkraw/cmlist.sas                                                 29OCT2004:18:53:00 
 
Parameter 
Values 
Template ID 
GS_CM_L_X_006 
Output File Name 
rl-cm-meds1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
172 
Table No. 
Appendix 4.2.1 
Title 1 
Non-Study Medication 
Title 2 
Previous and Concomitant Medications 
Title 3 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_CM_L_X_006 
Output File Name 
rl-cm-meds2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 4.2.2 
Title 1 
Non-Study Medication 
Title 2 
Previous and Concomitant Medications 
Title 3 
Treated Subjects - Stage 2 
 
4.5 
Efficacy Results 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
173 
Template SS_VL_T_001: Detailed Summary of HIV-1 < Y (by Subgroup) 
 
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
                                                            BMS-986001        BMS-986001        BMS-986001                           
                                                            100 mg QD/        200 mg QD/        400 mg QD/                           
                                                            EFV/3TC           EFV/3TC           EFV/3TC           TDF/EFV/3TC        
                                                            N = XX            N = XX            N = XX            N = XX             
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
NUMBER OF RESPONDERS (A)                                     57 ( 87.7)        54 ( 80.6)        62 ( 93.9)        88 ( 88.9)        
  95% CI                                                    (77.2 - 94.5)     (69.1 - 89.2)     (85.2 - 98.3)     (81.0 - 94.3)      
NUMBER OF VIROLOGIC FAILURES                                  X (XXX.X)         X (XXX.X)         X (XXX.X)         X (XXX.X)        
  HIV-1 RNA >= 40 c/mL (B)                                    X (XXX.X)         X (XXX.X)         X (XXX.X)         X (XXX.X)        
  DISC. STUDY/STUDY DRUG DUE TO LACK OF EFFICACY (C)          X (XXX.X)         X (XXX.X)         X (XXX.X)         X (XXX.X)        
  DISC. STUDY/STUDY DRUG FOR OTHER REASONS (D)                X (XXX.X)         X (XXX.X)         X (XXX.X)         X (XXX.X)        
NO VIROLOGIC DATA                                                                                                                    
  DISC. STUDY/STUDY DRUG DUE TO AE OR DEATH (E)               0                 4 (  6.0)         0                 2 (  2.0)        
  DISC. STUDY/STUDY DRUG FOR OTHER REASONS (F)                0                 0                 0                 2 (  2.0)        
  MISSING DATA DURING WINDOW BUT ON STUDY                     0                 0                 0                 0                
  
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w24s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.1.1A 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
174 
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w24s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.1.2A 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
175 
Template SS_VL_T_002: Summary of HIV-1 < Y (by Subgroup) 
 
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
                                                            BMS-986001        BMS-986001        BMS-986001                           
                                                            100 mg QD/        200 mg QD/        400 mg QD/                           
                                                            EFV/3TC           EFV/3TC           EFV/3TC           TDF/EFV/3TC        
                                                            N = XX            N = XX            N = XX            N = XX             
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
NUMBER OF RESPONDERS (A)                                     57 ( 87.7)        54 ( 80.6)        62 ( 93.9)        88 ( 88.9)        
  95% CI                                                    (77.2 - 94.5)     (69.1 - 89.2)     (85.2 - 98.3)     (81.0 - 94.3)      
NUMBER OF VIROLOGIC FAILURES (B)                              X (XXX.X)         X (XXX.X)         X (XXX.X)         X (XXX.X)        
NO VIROLOGIC DATA                                                                                                                    
  DISC. STUDY/STUDY DRUG DUE TO AE OR DEATH (C)               0                 4 (  6.0)         0                 2 (  2.0)        
  DISC. STUDY/STUDY DRUG FOR OTHER REASONS (D)                0                 0                 0                 2 (  2.0)        
  MISSING DATA DURING WINDOW BUT ON STUDY                     0                 0                 0                 0                
  
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_VL_T_002 
Output File Name 
rt-vl-sumresp40w24s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.1.1C 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects who are >= 50 copies in the visit window. It also includes subjects who discontinued prior to the visit 
window for lack or loss of efficacy or any reasons except AE and death at any time point from Day 1 through the time window if 
this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 50 c/mL. 
Footnote 3 
(C) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
176 
Footnote 4 
(D) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_002 
Output File Name 
rt-vl-sumresp40w24s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.1.2C 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects who are >= 50 copies in the visit window. It also includes subjects who discontinued prior to the visit 
window for lack or loss of efficacy or any reasons except AE and death at any time point from Day 1 through the time window if 
this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 50 c/mL. 
Footnote 3 
(C) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 4 
(D) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w24subgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.1.1B 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
177 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Baseline Gag Polymorphism: all combinations of baseline gag polymorphisms at selected positions 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w24subgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.1.2B 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
178 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Baseline Gag Polymorphism: all combinations of baseline gag polymorphisms at selected positions 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w48s1.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
179 
Purpose 
 WK96S1, WK96S2 
Table No. 
Table S.5.2.1A 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w48s2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Table S.5.2.2A 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
180 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_002 
Output File Name 
rt-vl-sumresp40w48s1.lst 
Purpose 
 WK96S1, WK96S2 
Table No. 
Table S.5.2.1C 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects who are >= 50 copies in the visit window. It also includes subjects who discontinued prior to the visit 
window for lack or loss of efficacy or any reasons except AE and death at any time point from Day 1 through the time window if 
this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 50 c/mL. 
Footnote 3 
(C) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 4 
(D) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
181 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_002 
Output File Name 
rt-vl-sumresp40w48s2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Table S.5.2.2C 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects who are >= 50 copies in the visit window. It also includes subjects who discontinued prior to the visit 
window for lack or loss of efficacy or any reasons except AE and death at any time point from Day 1 through the time window if 
this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 50 c/mL. 
Footnote 3 
(C) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 4 
(D) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w48subgs1.lst 
Purpose 
 WK96S1, WK96S2 
Table No. 
Table S.5.2.1B 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
182 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Baseline Gag Polymorphism: all combinations of baseline gag polymorphisms at selected positions 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w48subgs2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Table S.5.2.2B 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
183 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Baseline Gag Polymorphism: all combinations of baseline gag polymorphisms at selected positions 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w96s1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.3.1A 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
184 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 96 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w96s2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.3.2A 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 96 visit window. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
185 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_002 
Output File Name 
rt-vl-sumresp40w96s1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.3.1C 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects who are >= 50 copies in the visit window. It also includes subjects who discontinued prior to the visit 
window for lack or loss of efficacy or any reasons except AE and death at any time point from Day 1 through the time window if 
this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 50 c/mL. 
Footnote 3 
(C) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 4 
(D) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
186 
Parameter 
Values 
Template ID 
SS_VL_T_002 
Output File Name 
rt-vl-sumresp40w96s2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.3.2C 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects who are >= 50 copies in the visit window. It also includes subjects who discontinued prior to the visit 
window for lack or loss of efficacy or any reasons except AE and death at any time point from Day 1 through the time window if 
this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 50 c/mL. 
Footnote 3 
(C) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 4 
(D) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w96subgs1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.3.1B 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (mITT) - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
187 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 96 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Baseline Gag Polymorphism: all combinations of baseline gag polymorphisms at selected positions 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp40w96subgs2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.3.2B 
Title 1 
Detailed Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
By Subgroup 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
188 
Title 4 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 40 c/mL within the Week 96 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 40 
c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 40 c/mL 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Baseline Gag Polymorphism: all combinations of baseline gag polymorphisms at selected positions 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w24s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.4.1A 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
189 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w24s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.4.2A 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
190 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w24bpolys1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.4.1B 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
By Baseline Gag Polymorphism 
Title 4 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
Subgroups are all combinations of baseline gag polymorphisms at selected positions 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
191 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w24bpolys2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.4.2B 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 24 Snapshot 
Title 3 
By Baseline Gag Polymorphism 
Title 4 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 24 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
Subgroups are all combinations of baseline gag polymorphisms at selected positions 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w48s1.lst 
Purpose 
 WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
192 
Table No. 
Table S.5.4.1C 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w48s2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Table S.5.4.2C 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
193 
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w48bpolys1.lst 
Purpose 
 WK96S1, WK96S2 
Table No. 
Table S.5.4.1D 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
By Baseline Gag Polymorphism 
Title 4 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
194 
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
Subgroups are all combinations of baseline gag polymorphisms at selected positions 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w48bpolys2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Table S.5.4.2D 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 48 Snapshot 
Title 3 
By Baseline Gag Polymorphism 
Title 4 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 48 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
Subgroups are all combinations of baseline gag polymorphisms at selected positions 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
195 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w96s1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.4.1E 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 96 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
No subgroup presentation 
 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w96s2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.4.2E 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
196 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 96 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w96bpolys1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.4.1F 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
By Baseline Gag Polymorphism 
Title 4 
Treated Subjects (mITT) - Stage 1 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
197 
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 96 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
Subgroups are all combinations of baseline gag polymorphisms at selected positions 
 
 
Parameter 
Values 
Template ID 
SS_VL_T_001 
Output File Name 
rt-vl-resp200w96bpolys2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.4.2F 
Title 1 
Detailed Summary of HIV-1 RNA < 200 c/mL 
Title 2 
Proportion of Responders at Week 96 Snapshot 
Title 3 
By Baseline Gag Polymorphism 
Title 4 
Treated Subjects (mITT) - Stage 2 
Footnote 1 
(A) Response is assessed with the snapshot algorithm, which uses the last plasma HIV-1 RNA value in the predefined visit 
window to classify a subject's response status.   
Footnote 2 
(B) Includes subjects having HIV-1 RNA >= 200 c/mL within the Week 96 visit window. 
Footnote 3 
(C) Includes subjects who discontinued due to lack of efficacy at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window.    
Footnote 4 
(D) Includes subjects who discontinued due to any reasons except AE, death and lack of efficacy at any time point from Day 1 
through the time window if this resulted in no virologic data on treatment during the specified window and last HIV-1 RNA >= 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
198 
200 c/mL.    
Footnote 5 
(E) Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted 
in  no virologic data on treatment during the specified window 
Footnote 6 
(F) Other includes: withdrew consent, loss to follow-up, moved etc. with last HIV-1 RNA < 200 c/mL 
Layout notes 
Subgroups are all combinations of baseline gag polymorphisms at selected positions 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
199 
Template SS_VL_T_003: Proportion of Responders (Observed) 
---------------------------------------------------------------------------------------------------------------------------------- 
   
 
 
 
 
 
 
 
 
                   
 
                           
 
 
 
Group A              Group B    
  Group C 
    Group D                        
     
 
                        
 
 
 N = XX               N = XX             N = XX          N = XX      
        
---------------------------------------------------------------------------------------------------------------------------------- 
SUBGROUP 1 
                                                                                                                               
NUMBER OF RESPONDERS (a) 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)       XX ( XX.X)         
  95% CI 
 
 
                            (XX.X – XX.X)         (XX.X – XX.X)    (XX.X – XX.X)    (XX.X – XX.X)     
 
 
SUBGROUP 2 
                                                                                                                               
NUMBER OF RESPONDERS (a) 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)       XX ( XX.X)         
  95% CI 
 
 
                            (XX.X – XX.X)         (XX.X – XX.X)    (XX.X – XX.X)    (XX.X – XX.X)     
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w24obss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.1.1D 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24  
Title 3 
Treated Subjects (Observed) - Stage 1 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w24obss2.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
200 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.1.2D 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24  
Title 3 
Treated Subjects (Observed) - Stage 2 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w24obssubgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.1.1E 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24  
Title 3 
By Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 1 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
201 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w24obssubgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.1.2E 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24  
Title 3 
By Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 2 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w48obss1.lst 
Purpose 
 WK96S1, WK96S2 
Table No. 
Table S.5.2.1D 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
202 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48  
Title 3 
Treated Subjects (Observed) - Stage 1 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w48obss2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Table S.5.2.2D 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48  
Title 3 
Treated Subjects (Observed) - Stage 2 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w48obssubs1.lst 
Purpose 
 WK96S1, WK96S2 
Table No. 
Table S.5.2.1E 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
203 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 1 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w48obssubgs2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Table S.5.2.2E 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 48 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 2 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
204 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w96obss1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.3.1D 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 
Title 3 
Treated Subjects (Observed) - Stage 1 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
No subgroup presentation 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w96obss2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.3.2D 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 
Title 3 
Treated Subjects (Observed) - Stage 2 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
No subgroup presentation 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
205 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w96obssubgs1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.3.1E 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 1 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_003 
Output File Name 
rt-vl-resp40w96obssubgs2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.3.2E 
Title 1 
Summary of HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 96 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
206 
Title 3 
By Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 2 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Layout notes 
Subgroups are:  
• 
Baseline  HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4  < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, 
Other 
• 
HIV-1 Clade: Include all clades available in the database 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
207 
Template SS_VL_T_004: Treatment Outcomes Table Using the TLOVR Algorithm  
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                          Trt A                         Trt B 
Outcome (%)                                                              N = XXX                       N = XXX 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
HIV-1 RNA < 40 C/ML (A)                                                 XXX (XXX.X)                   XXX (XXX.X)                              
  95% CI                                                              (XXX.X, XXX.X)                (XXX.X, XXX.X) 
 
HIV-1 RNA >= 40 C/ML                                                    XXX (XXX.X)                   XXX (XXX.X)          
  VIROLOGIC REBOUND (B)                                                 XXX (XXX.X)                   XXX (XXX.X) 
  NEVER SUPPRESSED THROUGH WEEK 24 (C)                                  XXX (XXX.X)                   XXX (XXX.X) 
  DRUG CHANGE DUE TO LACK OF EFFICACY                                   XXX (XXX.X)                   XXX (XXX.X) 
 
DEATH                                                                   XXX (XXX.X)                   XXX (XXX.X) 
 
DRUG CHANGE OR DISCONTINUATION DUE TO AE                                XXX (XXX.X)                   XXX (XXX.X) 
 
DRUG CHANGE OR DISCONTINUATION DUE TO OTHER REASONS                     XXX (XXX.X)                   XXX (XXX.X)    
 
Parameter 
Values 
Template ID 
SS_VL_T_004 
Output File Name 
rt-vl-tlovr24s1.lst 
Purpose 
WK24S1 
Table No. 
Table S.5.5.1A 
Title 1 
Summary of Treatment Outcomes at Week 24 Using the TLOVR Algorithm 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
(A) Virologic response (HIV-1 RNA < 40 c/mL at >= 2 consecutive visits) through Week 24 without intervening failure. 
Footnote 2 
(B) Virologic response and subsequent HIV-1 RNA >= 40 c/mL at >= 2 consecutive visits or last visit followed by discontinuation 
of 
Footnote 3 
study therapy through Week 24. 
Footnote 4 
(C) Never achieved virologic response through Week 24. 
 
Parameter 
Values 
Template ID 
SS_VL_T_004 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
208 
Output File Name 
rt-vl-tlovr24s2.lst 
Purpose 
WK24S2 
Table No. 
Table S.5.5.2A 
Title 1 
Summary of Treatment Outcomes at Week 24 Using the TLOVR Algorithm 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
(A) Virologic response (HIV-1 RNA < 40 c/mL at >= 2 consecutive visits) through Week 24 without intervening failure. 
Footnote 2 
(B) Virologic response and subsequent HIV-1 RNA >= 40 c/mL at >= 2 consecutive visits or last visit followed by discontinuation 
of 
Footnote 3 
study therapy through Week 24. 
Footnote 4 
(C) Never achieved virologic response through Week 24. 
 
Parameter 
Values 
Template ID 
SS_VL_T_004 
Output File Name 
rt-vl-tlovr48s1.lst 
Purpose 
WK48S1 
Table No. 
Table S.5.5.1B 
Title 1 
Summary of Treatment Outcomes at Week 48 Using the TLOVR Algorithm 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
(A) Virologic response (HIV-1 RNA < 40 c/mL at >= 2 consecutive visits) through Week 48 without intervening failure. 
Footnote 2 
(B) Virologic response and subsequent HIV-1 RNA >= 40 c/mL at >= 2 consecutive visits or last visit followed by discontinuation 
of 
Footnote 3 
study therapy through Week 48. 
Footnote 4 
(C) Never achieved virologic response through Week 48. 
 
Parameter 
Values 
Template ID 
SS_VL_T_004 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
209 
Output File Name 
rt-vl-tlovr48s2.lst 
Purpose 
WK48S2 
Table No. 
Table S.5.5.2B 
Title 1 
Summary of Treatment Outcomes at Week 48 Using the TLOVR Algorithm 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
(A) Virologic response (HIV-1 RNA < 40 c/mL at >= 2 consecutive visits) through Week 48 without intervening failure. 
Footnote 2 
(B) Virologic response and subsequent HIV-1 RNA >= 40 c/mL at >= 2 consecutive visits or last visit followed by discontinuation 
of 
Footnote 3 
study therapy through Week 48. 
Footnote 4 
(C) Never achieved virologic response through Week 48. 
 
Parameter 
Values 
Template ID 
SS_VL_T_004 
Output File Name 
rt-vl-tlovr96s1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.5.5.1C 
Title 1 
Summary of Treatment Outcomes at Week 96 Using the TLOVR Algorithm 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
(A) Virologic response (HIV-1 RNA < 40 c/mL at >= 2 consecutive visits) through Week 96 without intervening failure. 
Footnote 2 
(B) Virologic response and subsequent HIV-1 RNA >= 40 c/mL at >= 2 consecutive visits or last visit followed by discontinuation 
of 
Footnote 3 
study therapy through Week 96. 
Footnote 4 
(C) Never achieved virologic response through Week 96. 
 
Parameter 
Values 
Template ID 
SS_VL_T_004 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
210 
Output File Name 
rt-vl-tlovr96s2.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.5.2C 
Title 1 
Summary of Treatment Outcomes at Week 96 Using the TLOVR Algorithm 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
(A) Virologic response (HIV-1 RNA < 40 c/mL at >= 2 consecutive visits) through Week 96 without intervening failure. 
Footnote 2 
(B) Virologic response and subsequent HIV-1 RNA >= 40 c/mL at >= 2 consecutive visits or last visit followed by discontinuation 
of 
Footnote 3 
study therapy through Week 96. 
Footnote 4 
(C) Never achieved virologic response through Week 96. 
 
Parameter 
Values 
Template ID 
SS_EX_T_002 
Output File Name 
rt-vl-klmtlovrs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.5.1D 
Title 1 
Summary of Time to Loss of Virologic Response 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
(a) Cumulative proportion without events at end of interval. 
Layout notes 
Use 4-week intervals 
 
Parameter 
Values 
Template ID 
SS_EX_T_002 
Output File Name 
rt-vl-klmtlovrs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
211 
Table No. 
Table S.5.5.2D 
Title 1 
Summary of Time to Loss of Virologic Response 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
(a) Cumulative proportion without events at end of interval. 
Layout notes 
Use 4-week intervals 
 
Parameter 
Values 
Template ID 
GS_EX_G_001 
Output File Name 
rg-vl-kmtlovrs1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.5.5.1E 
Title 1 
Time to Loss of Virologic Response 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
• 
X-axis label: Weeks 
• 
X-axis tick labels: B/L, 4, 8, and every 4 weeks up to timepoint with data in any group 
• 
Y-axis label: Percent Without Failure 
• 
Y-axis ticks: 0 to 100 by 10 
• 
Censoring symbols: none 
 
Parameter 
Values 
Template ID 
GS_EX_G_001 
Output File Name 
rg-vl-kmtlovrs2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.5.5.2E 
Title 1 
Time to Loss of Virologic Response 
Title 2 
Treated Subjects - Stage 2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
212 
Layout notes 
• 
X-axis label: Weeks 
• 
X-axis tick labels: B/L, 4, 8, and every 4 weeks up to timepoint with data in any group 
• 
Y-axis label: Percent Without Failure 
• 
Y-axis ticks: 0 to 100 by 10 
• 
Censoring symbols: none 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
213 
Template SS_VL_T_005: Proportion of Subjects with HIV-1 RNA within Certain Range 
---------------------------------------------------------------------------------------------------------------------------------- 
  
 
 
 
 
 
 
 
 
                   
 
                           
 
 
Group A               Group B            Group C 
     Group D                        
Weeks 
 
                        
 
 N = XX                N = XX             N = XX          N = XX      
        
---------------------------------------------------------------------------------------------------------------------------------- 
                                                                                                                               
WEEK 1  
 
 
 
 
 
   
 
   < 40 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  40 to < 100 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  100 to < 200 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  200 to < 400 c/mL 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  > 400 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
 
WEEK 2  
 
 
 
 
 
   
 
   < 40 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  40 to < 100 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  100 to < 200 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  200 to < 400 c/mL 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  > 400 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
 
WEEK 4  
 
 
 
 
 
   
 
   < 40 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  40 to < 100 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  100 to < 200 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  200 to < 400 c/mL 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  > 400 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
 
<additional weeks> 
 
 
 
 
 
 
   
 
   < 40 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  40 to < 100 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  100 to < 200 c/mL  
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  200 to < 400 c/mL 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
  > 400 c/mL 
 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)      XX ( XX.X)         
 
                                                                                                                           
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_VL_T_005 
Output File Name 
rt-vl-props1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
214 
Table No. 
Table S.5.6.1A 
Title 1 
Proportion of Subjects with HIV-1 RNA within Several Ranges 
Title 2 
Treated Subjects (Observed) - Stage 1 
Programming notes 
The following weeks need to be included: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
 
Parameter 
Values 
Template ID 
SS_VL_T_005 
Output File Name 
rt-vl-props2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.6.2A 
Title 1 
Proportion of Subjects with HIV-1 RNA within Several Ranges 
Title 2 
Treated Subjects (Observed) - Stage 2 
Programming notes 
The following weeks need to be included: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
215 
Template SS_VL_T_006 : Summary Statistics Over Time 
Protocol: AIxxxXXX 
                                                                                                Page 1 of X 
<Domain> Summary of Values and Changes From Baseline Over Time 
<Title 2> 
 
<Parameter> (<Units>) 
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
----------------------------------------------------------------------------------------------------------------------------- 
Period                                                Percentiles                      Change From Baseline                  
  Visit                                         ----------------------    ---------------------------------------------------  
    Group          N        Mean       SD         Q1     Median    Q3      N     Mean       SD        Q1      Median     Q3         
-----------------------------------------------------------------------------------------------------------------------------  
        
PRE-TRT 
  B/L      
    Group 1        XXX     XXX.X     XXX.XX     XXX.X   XXX.X    XXX.X    XXX   XXX.X     XXX.XX     XXX.X     XXX.X    XXX.X  
    Group 2        XXX     XXX.X     XXX.XX     XXX.X   XXX.X    XXX.X    XXX   XXX.X     XXX.XX     XXX.X     XXX.X    XXX.X 
 
ON TRT 
  WK XX      
    Group 1        XXX     XXX.X     XXX.XX     XXX.X   XXX.X    XXX.X    XXX   XXX.X     XXX.XX     XXX.X     XXX.X    XXX.X  
    Group 2        XXX     XXX.X     XXX.XX     XXX.X   XXX.X    XXX.X    XXX   XXX.X     XXX.XX     XXX.X     XXX.X    XXX.X         
 
... <ADDITIONAL PERIODS AND VISITS> 
-----------------------------------------------------------------------------------------------------------          
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-vl-sumchgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.6.1B 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 
Title 2 
HIV-1 RNA (log10 c/mL) 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 1 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
216 
For the baseline Gag polymorphism: include also Week 4, 8 and 12. 
Programming notes 
Subgroups are: 
• 
Baseline Gag Polymorphism 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 
• 
HIV-1 Clade: any clade available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-vl-sumchgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.6.2B 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 
Title 2 
HIV-1 RNA (log10 c/mL) 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 2 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 
For the baseline Gag polymorphism: include also Week 4, 8 and 12. 
Programming notes 
Subgroups are: 
• 
Baseline Gag Polymorphism 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 
• 
HIV-1 Clade: any clade available in the database 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
217 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-cd4s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.7.1A 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 
Title 2 
CD4 Cell Count (cells/uL) 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 1 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 
Programming notes 
Subgroups are: 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 
• 
HIV-1 Clade: any clade available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-cd4s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.7.2A 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 
Title 2 
CD4 Cell Count (cells/uL) 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
218 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 2 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 
Programming notes 
Subgroups are: 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 
• 
HIV-1 Clade: any clade available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-cd4pcts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.8.1A 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 
Title 2 
CD4 Cell Percentage 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 1 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 
Programming notes 
Subgroups are: 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
219 
• 
HIV-1 Clade: any clade available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-cd4pcts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.8.2A 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 
Title 2 
CD4 Cell Percentage 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 2 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 
Programming notes 
Subgroups are: 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 
• 
HIV-1 Clade: any clade available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-cd8s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.9.1A 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
220 
Title 2 
CD8 Cell Count (cells/ul) 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 1 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 
Programming notes 
Subgroups are: 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 
• 
HIV-1 Clade: any clade available in the database 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-cd8s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.9.2A 
Title 1 
Summary Statistics for Values and Change from Baseline Over Time 
Title 2 
CD8 Cell Count (cells/ul) 
Title 3 
Overall and by Subgroup 
Title 4 
Treated Subjects (Observed) - Stage 2 
Layout notes 
The following weeks need to be included for the overall summary: baseline, Week 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84 and 96. 
The following weeks need to be included for the subgroup summaries: baseline, Week 24, 48 and 96. 
Programming notes 
Subgroups are: 
• 
Baseline Viral Load Category: HIV-1 RNA < 100,000 c/mL , >=100,000 c/mL 
• 
Baseline CD4 Category: < 100, 100 to < 200, 200 to < 350, 350 to < 500, >= 500 cells/uL 
• 
Gender: Male, Female 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
221 
• 
Race: White, Black/African American, American Indian/Alaska Native, Asian, Native Hawaiian/Other Pacific Islander, Other 
• 
HIV-1 Clade: any clade available in the database 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
222 
Template GS_LB_G_001: Box Plot 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-vl-box24s1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.5.6.1C 
PLA
IBI 5
mg/d
IBI 25/5
mg/d
IBI 10
mg/d
IBI 25
mg/d
IBI 50
mg/d
IBI OL 100
mg/wk
0
2
4
6
8
10
12
14
16
0
2
4
6
8
10
12
14
16
N=63
N=61
N=62
N=61
N=63
N=63
N=60
Duration of ST Treatment (Weeks)
Treatment Group
Outliers 
Mean 
Duration computed as the difference between the last and first short-term dosing date plus on
Program Path:  /home/banckenf/sgtest/boxplot
RUN DATE: 11SEP2008:15:29:12
Program Name: box1.sas


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
223 
Title 1 
HIV-1 RNA (log10 c/mL) Change from Baseline to Week 24 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 24. 
Layout notes 
Y-axis label: HIV-1 RNA Change from Baseline (log10 c/mL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-vl-box24s2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.5.6.2C 
Title 1 
HIV-1 RNA (log10 c/mL) Change from Baseline to Week 24 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 24. 
Layout notes 
Y-axis label: HIV-1 RNA Change from Baseline (log10 c/mL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-vl-box48s1 
Purpose 
 WK96S1, WK96S2 
Table No. 
Figure S.5.6.1D 
Title 1 
HIV-1 RNA (log10 c/mL) Change from Baseline to Week 48 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 48. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
224 
Layout notes 
Y-axis label: HIV-1 RNA Change from Baseline (log10 c/mL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-vl-box48s2 
Purpose 
WK48S2, WK96S2 
Table No. 
Figure S.5.6.2D 
Title 1 
HIV-1 RNA (log10 c/mL) Change from Baseline to Week 48 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 48. 
Layout notes 
Y-axis label: HIV-1 RNA Change from Baseline (log10 c/mL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-vl-box96s1 
Purpose 
WK96S1, WK96S2 
Table No. 
Figure S.5.6.1E 
Title 1 
HIV-1 RNA (log10 c/mL) Change from Baseline to Week 96 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 96. 
Layout notes 
Y-axis label: HIV-1 RNA Change from Baseline (log10 c/mL) 
X-axis label: Treatment Group 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
225 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-vl-box96s2 
Purpose 
WK96S2 
Table No. 
Figure S.5.6.2E 
Title 1 
HIV-1 RNA (log10 c/mL) Change from Baseline to Week 96 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 96. 
Layout notes 
Y-axis label: HIV-1 RNA Change from Baseline (log10 c/mL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd4box24s1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.5.7.1B 
Title 1 
CD4 Cell Count (cells/uL) Change from Baseline to Week 24 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 24. 
Layout notes 
Y-axis label: CD4 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd4box24s2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
226 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.5.7.2B 
Title 1 
CD4 Cell Count (cells/uL) Change from Baseline to Week 24 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 24. 
Layout notes 
Y-axis label: CD4 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd4box48s1 
Purpose 
 WK96S1, WK96S2 
Table No. 
Figure S.5.7.1C 
Title 1 
CD4 Cell Count (cells/uL) Change from Baseline to Week 48 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 48. 
Layout notes 
Y-axis label: CD4 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd4box48s2 
Purpose 
WK48S2, WK96S2 
Table No. 
Figure S.5.7.2C 
Title 1 
CD4 Cell Count (cells/uL) Change from Baseline to Week 48 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
227 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 48. 
Layout notes 
Y-axis label: CD4 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd4box96s1 
Purpose 
WK96S1, WK96S2 
Table No. 
Figure S.5.7.1D 
Title 1 
CD4 Cell Count (cells/uL) Change from Baseline to Week 96 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 96. 
Layout notes 
Y-axis label: CD4 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd4box96s2 
Purpose 
WK96S2 
Table No. 
Figure S.5.7.2D 
Title 1 
CD4 Cell Count (cells/uL) Change from Baseline to Week 96 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 96. 
Layout notes 
Y-axis label: CD4 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
228 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd8box24s1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.5.9.1B 
Title 1 
CD8 Cell Count (cells/uL) Change from Baseline to Week 24 
Title 2 
Treated Subjects -Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 24. 
Layout notes 
Y-axis label: CD8 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd8box24s2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.5.9.2B 
Title 1 
CD8 Cell Count (cells/uL) Change from Baseline to Week 24 
Title 2 
Treated Subjects -Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 24. 
Layout notes 
Y-axis label: CD8 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
229 
Output File Name 
rg-lb-cd8box48s1 
Purpose 
 WK96S1, WK96S2 
Table No. 
Figure S.5.9.1C 
Title 1 
CD8 Cell Count (cells/uL) Change from Baseline to Week 48 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 48. 
Layout notes 
Y-axis label: CD8 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd8box48s2 
Purpose 
WK48S2, WK96S2 
Table No. 
Figure S.5.9.2C 
Title 1 
CD8 Cell Count (cells/uL) Change from Baseline to Week 48 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 48. 
Layout notes 
Y-axis label: CD8 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd8box96s1 
Purpose 
WK96S1, WK96S2 
Table No. 
Figure S.5.9.1D 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
230 
Title 1 
CD8 Cell Count (cells/uL) Change from Baseline to Week 96 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
N is the number of subjects with data at baseline and at Week 96. 
Layout notes 
Y-axis label: CD8 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
Parameter 
Values 
Template ID 
GS_LB_G_001 
Output File Name 
rg-lb-cd8box96s2 
Purpose 
WK96S2 
Table No. 
Figure S.5.9.2D 
Title 1 
CD8 Cell Count (cells/uL) Change from Baseline to Week 96 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
N is the number of subjects with data at baseline and at Week 96. 
Layout notes 
Y-axis label: CD8 Cell Count Change from Baseline (cells/uL) 
X-axis label: Treatment Group 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
231 
Template GS_L_G_002: Longitudinal Line Plot Grouped by Treatment with Horizontal Shift and Reference Line 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-vl-times1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.5.6.1F 
Title 1 
HIV-1 RNA (log10 c/mL) Mean Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: HIV-1 RNA (log10 c/mL)  Mean Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
232 
Template ID 
GS_LB_G_002 
Output File Name 
rg-vl-times2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.5.6.2F 
Title 1 
HIV-1 RNA (log10 c/mL) Mean Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: HIV-1 RNA (log10 c/mL)  Mean Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-cd4times1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.5.7.1E 
Title 1 
CD4 (cells/uL) Mean Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: CD4 Mean Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-cd4times2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.5.7.2E 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
233 
Title 1 
CD4 (cells/uL) Mean Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: CD4 Mean Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-cd8times1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.5.9.1E 
Title 1 
CD8 (cells/uL) Mean Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: CD8 Mean Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-cd8times2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.5.9.2E 
Title 1 
CD8 (cells/uL) Mean Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: CD8 Mean Change from Baseline (SE) 
X-axis label: Time (Weeks) 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
234 
Include horizontal reference line at Y=0. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
235 
Template SS_VL_L_004: Listing of Outcomes from Snapshot Analysis 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Subject ID          Randomized            Assessment Day      Response           Specification                  Disc.     Disc.                
  (Age/Gender/Race) Treatment Group         HIV-1 RNA (c/mL)                                                      Day      Reason               
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                         
       BMS-986001 600 mg QD/ 01FEB2013/        NO VIROLOGIC DATA    DISC. STUDY/STUDY DRUG       10FEB2013   OTHER                
  25/M/C            EFV/3TC                 8754                               DUE TO AE OR DEATH                                     
                                                                                                                         
      BMS-986001 1200 mg QD/ 20DEC2012        RESPONDER                                                                 
  24/F/B            EFV/3TC                 <40                                                                                      
 
                                                                                                                         
      BMS-986001 600 mg QD/ 01MAR2013         VIROLOGIC FAILURE   HIV-1 RNA >= 40 c/mL                                   
  26/M/C            EFV/3TC                 1350                                                                                     
                                                                                                                                     
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_VL_L_004 
Output File Name 
rl-vl-outcome24s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 5.1.1A 
Title 1 
Listing of Outcomes from HIV-1 RNA < 40 c/mL Snapshot Analysis 
Title 2 
Data for Subjects in the Week 24 Snapshot 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
HIV-1 RNA assessments used for the response evaluation are listed. 
Programming notes 
Listing should be sorted by Treatment group, response and specification.  
 
Parameter 
Values 
Template ID 
SS_VL_L_004 
Output File Name 
rl-vl-outcome24s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
236 
Table No. 
Appendix 5.1.2A 
Title 1 
Listing of Outcomes from HIV-1 RNA < 40 c/mL Snapshot Analysis 
Title 2 
Data for Subjects in the Week 24 Snapshot 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
HIV-1 RNA assessments used for the response evaluation are listed. 
Programming notes 
Listing should be sorted by Treatment group, response and specification.  
 
 
Parameter 
Values 
Template ID 
SS_VL_L_004 
Output File Name 
rl-vl-outcome48s1.lst 
Purpose 
 WK96S1, WK96S2 
Table No. 
Appendix 5.1.1B 
Title 1 
Listing of Outcomes from HIV-1 RNA < 40 c/mL Snapshot Analysis 
Title 2 
Data for Subjects in the Week 48 Snapshot 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
HIV-1 RNA assessments used for the response evaluation are listed. 
Programming notes 
Listing should be sorted by Treatment group, response and specification.  
 
Parameter 
Values 
Template ID 
SS_VL_L_004 
Output File Name 
rl-vl-outcome48s2.lst 
Purpose 
WK48S2, WK96S2 
Table No. 
Appendix 5.1.2B 
Title 1 
Listing of Outcomes from HIV-1 RNA < 40 c/mL Snapshot Analysis 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
237 
Title 2 
Data for Subjects in the Week 48 Snapshot 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
HIV-1 RNA assessments used for the response evaluation are listed. 
Programming notes 
Listing should be sorted by Treatment group, response and specification.  
 
Parameter 
Values 
Template ID 
SS_VL_L_004 
Output File Name 
rl-vl-outcome96s1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Appendix 5.1.1C 
Title 1 
Listing of Outcomes from HIV-1 RNA < 40 c/mL Snapshot Analysis 
Title 2 
Data for Subjects in the Week 96 Snapshot 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
HIV-1 RNA assessments used for the response evaluation are listed. 
Programming notes 
Listing should be sorted by Treatment group, response and specification.  
 
Parameter 
Values 
Template ID 
SS_VL_L_004 
Output File Name 
rl-vl-outcome96s2.lst 
Purpose 
WK96S2 
Table No. 
Appendix 5.1.2C 
Title 1 
Listing of Outcomes from HIV-1 RNA < 40 c/mL Snapshot Analysis 
Title 2 
Data for Subjects in the Week 96 Snapshot 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
HIV-1 RNA assessments used for the response evaluation are listed. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
238 
Programming notes 
Listing should be sorted by Treatment group, response and specification.  
 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
239 
Template SS_VL_L_005: Listing of Viral Load 
 
Treatment Group: DRUG A                                                                                                    
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                        Treatment                                  
Subject ID            Current                                Lab        Start            HIV-1 RNA    HIV-1 RNA               
  (Age/Gender/Race)   Treatment    Period        Visit       Date       Study Day        (c/mL)      (log10 c/mL)   Assay     
------------------------------------------------------------------------------------------------------------------------------------
-- 
                       SCRN          A00       
     -16           1500000       6.18         U 
  (56/M/C)         DRUG A 250 MG    ON TRT        B01       
      1              45000       4.65         S 
                   DRUG A 300 MG    ON TRT        B02       
      25             23000       4.36         U 
                   DRUG A 200 MG    ON TRT        B03       
      30               450       2.65         S 
                   DRUG A 200 MG    ON TRT        B04       
      30                45       1.65         U 
                       SCRN          A00       
     -16           1500000       6.18         U 
  (56/M/C)         DRUG A 250 MG    ON TRT        B01       
       1             45000       4.65         U 
                   DRUG A 300 MG    ON TRT        B02       
       2             23000       4.36         U 
                   DRUG A 200 MG    ON TRT        B03       
       5               450       2.65         U 
                   DRUG A 300 MG    ON TRT        B02       
       6             23000       4.36         S 
                   DRUG A 200 MG    ON TRT        B03       
       7               450       2.65         U 
                   DRUG A 200 MG    ON TRT        B04       
      36                45       1.65         U 
                   DRUG A 300 MG    ON TRT        B05       
      62             23000       4.36         U 
                   DRUG A 200 MG    ON TRT        B06       
      90               450       2.65         S 
                   DRUG A 200 MG    ON TRT        B06       
     118                45       1.65         A 
                   DRUG A 200 MG    ON TRT        B06       
     146                45       1.65         A 
------------------------------------------------------------
------------------------------------------------------------- 
ASSAY:  S = ROCHE AMPLICOR STANDARD ASSAY   U = ROCHE AMPLICOR ULTRA-SENSITIVE ASSAY   A = ABBOTT REALTIME M2000 ASSAY        
 
Parameter 
Values 
Template ID 
SS_VL_L_005 
Output File Name 
rl-vl-vllists1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 5.1.1D 
Title 1 
Listing of HIV-1 RNA 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
240 
Template ID 
SS_VL_L_005 
Output File Name 
rl-vl-vllists2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 5.1.2D 
Title 1 
Listing of HIV-1 RNA 
Title 2 
Treated Subjects - Stage 2 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
241 
Template SS_LB_L_002: Listing of CD4 and CD8 
 
Treatment Group: DRUG A                                                                                                    
------------------------------------------------------------------------------------------------------------------------------------ 
 
                                                                                                                                
                                                          Treatment                                                           
Subject                                         Lab       Start            CD4+          CD4+          CD8+          CD8+           
  (Age/Gender/Race)  Period        Visit        Date      Study Day        (cells/ul)    percentage    (cells/ul)    percentage     
------------------------------------------------------------------------------------------------------------------------------------ 
                                  
                                                                          
       PRE-TREATMENT SCREENING   
  -34               557       30.0              937       51.0         
  (38/M/B)                                     
                                                                         
                     STAGE 1       DAY 1       
    8               633       31.0             1025       51.0         
                     STAGE 1       WEEK 2      
   21               633       31.0              998       49.0         
                     STAGE 1       WEEK 4      
   35               583       32.0              842       46.0         
                     STAGE 1       WEEK 8      
   62               594       30.0              844       43.0         
                     STAGE 1       WEEK 12     
   91               628       39.0              660       40.0         
                     STAGE 1       WEEK 16     
  119               650       40.0              613       38.0         
                     STAGE 1       WEEK 20     
  145               743       38.0              761       39.0         
                     STAGE 1       WEEK 24     
  173               710       42.0              571       34.0         
                     STAGE 1       WEEK 32     
  226               642       40.0              567       35.0         
                     STAGE 1       WEEK 40     
  285               615       42.0              503       34.0         
                     STAGE 1       WEEK 48     
  349               696       45.0              506       33.0         
                     STAGE 1       WEEK 56     
  394               727       46.0              515       33.0         
                     STAGE 1       WEEK 64     
  453               644       45.0              443       31.0         
                     STAGE 1       WEEK 72     
  511               696       46.0              465       31.0         
                     STAGE 1       WEEK 80     
  567               630       44.0              399       28.0         
                     STAGE 1       WEEK 88     
  622               845       51.0              474       29.0         
                     STAGE 1       WEEK 96     
  679               784       47.0              479       29.0         
                     STAGE 2       WEEK 108    
  758               772       45.0              491       29.0         
                     STAGE 2       WEEK 120    
  848               936       48.0              555       28.0         
                     STAGE 2       WEEK 132    
  926               780       47.0              479       29.0         
                     STAGE 2       WEEK 144    
 1043               798       49.0              448       27.0         
                                               
                                                                          
 
Parameter 
Values 
Template ID 
SS_VL_L_005 
Output File Name 
rl-lb-cd4cd8s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 5.1.1E 
Title 1 
Listing of CD4+ and CD8+ T-Cell Count and Percentages 
Title 2 
Treated Subjects - Stage 1 
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
242 
 
Parameter 
Values 
Template ID 
SS_VL_L_005 
Output File Name 
rl-lb-cd4cd8s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 5.1.2E 
Title 1 
Listing of CD4+ and CD8+ T-Cell Count and Percentages 
Title 2 
Treated Subjects - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-news1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1A 
Title 1 
Newly Emergent Genotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Genotypic Resistance Testing - Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-news2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2A 
Title 1 
Newly Emergent Genotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Genotypic Resistance Testing - Stage 2 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
243 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-news12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3A 
Title 1 
Newly Emergent Genotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Genotypic Resistance Testing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-newpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1B 
Title 1 
Newly Emergent Genotypic Resistance Profile 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-newpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
244 
Table No. 
Table S.5.10.2B 
Title 1 
Newly Emergent Genotypic Resistance Profile 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_001 
Output File Name 
rt-gn-newpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3B 
Title 1 
Newly Emergent Genotypic Resistance Profile 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_L_001 
Output File Name 
rl-gn-ontrts1.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
245 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 5.10.1A 
Title 1 
Listing of Genotypic Substitutions 
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_L_001 
Output File Name 
rl-gn-ontrts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 5.10.2A 
Title 1 
Listing of Genotypic Substitutions 
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgags1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1C 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgags2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
246 
Table No. 
Table S.5.10.2C 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with On-Treatment Gag Sequencing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgags12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3C 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1R 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
247 
Table No. 
Table S.5.10.2R 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Gag Sequencing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3R 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1D 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
248 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2D 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3D 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
249 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagpdvfbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1S 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagpdvfbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2S 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
250 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagpdvfbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3S 
Title 1 
Emergent Gag Polymorphisms at Selected Positions 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_L_002 
Output File Name 
rl-gn-gagontrts1.lst 
Purpose 
WK24S1, WK48S1 WK96S1, WK96S2 
Table No. 
Appendix 5.10.1B 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
251 
Title 1 
Listing of Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_L_002 
Output File Name 
rl-gn-gagontrts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 5.10.2B 
Title 1 
Listing of Gag Polymorphisms at Selected Positions 
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygags1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1E 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygags2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2E 
Title 1 
Newly Emergent Gag Deviations  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
252 
Title 2 
Treated Subjects with On-Treatment Gag Sequencing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygags12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3E 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1T 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2T 
Title 1 
Newly Emergent Gag Deviations  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
253 
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Gag Sequencing - Stage 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3T 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects with On-Treatment Gag Sequencing - Stage 1 and 2 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1F 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
254 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2F 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3F 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
255 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagpdvfbysubtypes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1U 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagpdvfbysubtypes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2U 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
256 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_T_003 
Output File Name 
rt-gn-anygagpdvfbysubtypes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3U 
Title 1 
Newly Emergent Gag Deviations  
Title 2 
By HIV Subtype 
Title 3 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_GN_L_003 
Output File Name 
rl-gn-gagontrts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 5.10.1C 
Title 1 
Listing of Newly Emergent Gag Deviations  
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
257 
 
Parameter 
Values 
Template ID 
SS_GN_L_003 
Output File Name 
rl-gn-gagontrts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 5.10.2C 
Title 1 
Listing of Newly Emergent Gag Deviations 
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 2 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-news1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1G 
Title 1 
Newly Emergent Phenotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 1 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-news2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2G 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
258 
Title 1 
Newly Emergent Phenotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-news12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3G 
Title 1 
Newly Emergent Phenotypic Resistance Profile 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 1 and 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-newpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1H 
Title 1 
Newly Emergent Phenotypic Resistance Profile 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
259 
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
Footnote 3 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 4 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 5 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 6 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 7 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 
Output File Name 
rt-pn-newpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2H 
Title 1 
Newly Emergent Phenotypic Resistance Profile 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
Footnote 3 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 4 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 5 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 6 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 7 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
260 
Output File Name 
rt-pn-newpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3H 
Title 1 
Newly Emergent Phenotypic Resistance Profile 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
Footnote 3 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 4 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 5 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 6 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 7 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-newdrugs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1I 
Title 1 
Newly Emergent Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 1 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
261 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-newdrugs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2I 
Title 1 
Newly Emergent Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-newdrugs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3I 
Title 1 
Newly Emergent Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 1 and 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-newdrugpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1J 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
262 
Title 1 
Newly Emergent Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
Footnote 3 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 4 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 5 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 6 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 7 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-newdrugpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2J 
Title 1 
Newly Emergent Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
Footnote 3 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 4 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 5 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 6 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 7 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
263 
 
Parameter 
Values 
Template ID 
SS_PN_T_002 
Output File Name 
rt-pn-newdrugpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3J 
Title 1 
Newly Emergent Phenotypic Resistance by Class and Drug Name 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 and 2 
Footnote 1 
Newly emergent phenotypic resistance to a drug is defined as a baseline fold change less than or equal to the cut-off for reduced 
susceptibility  
Footnote 2 
and an on-treatment fold change greater than the cut-off for reduced susceptibility. 
Footnote 3 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 4 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 5 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 6 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 7 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_L_001 
Output File Name 
rl-pn-ontrts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 5.10.1D 
Title 1 
Listing of Phenotypic Resistance 
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 1 
Footnote 1 
Susc = Susceptibility 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
264 
Footnote 2 
P = Partial, R = Resistance, S = Susceptible 
 
Parameter 
Values 
Template ID 
SS_PN_L_001 
Output File Name 
rl-pn-ontrts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 5.10.2D 
Title 1 
Listing of Phenotypic Resistance 
Title 2 
Treated Subjects with Baseline and On-Treatment Data - Stage 2 
Footnote 1 
Susc = Susceptibility 
Footnote 2 
P = Partial, R = Resistance, S = Susceptible 
 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
265 
Template SS_PN_T_003: Maximum Change in IC50 Summary 
------------------------------------------------------------------------------------------------------------------------------------ 
 
                                  TRT A                    TRT B                    TRT C                    TRT D                   
ASSESSMENT                        N = 10                   N = 15                   N = 14                   N = 15                  
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
BASELINE                                                                                                                             
  N                                3                       11                        6                        5                      
  MEAN (SD)                        0.042480 (0.0276698)     0.012479 (0.0220447)     0.002700 (0.0059675)     0.009394 (0.0149333)   
  GEOMETRIC MEAN                   0.033159 (65.1)          0.001733 (176.7)         0.000490 (221.0)         0.001608 (159.0)       
  (COEFFICIENT OF VARIATION)                                                                                                         
                                                                                                                                     
MAXIMUM ON TREATMENT                                                                                                                 
  N                                2                        9                        6                        5                      
  MEAN (SD)                        0.096295 (0.1327734)     0.718214 (1.6357205)     0.121485 (0.2291942)     1.038524 (2.2150816)   
  GEOMETRIC MEAN                   0.021409 (137.9)         0.019219 (227.7)         0.006114 (188.7)         0.022420 (213.3)       
  (COEFFICIENT OF VARIATION)                                                                                                         
                                                                                                                                     
MAXIMUM CHANGE FROM BASELINE                                                                                                         
  MEAN (SD)                        0.063335 (0.1013496)     0.703029 (1.6328842)     0.118785 (0.2306211)     1.029130 (2.2200751)   
  MEDIAN                           0.063335                 0.007120                 0.003155                 0.041980               
  MIN , MAX                       -0.00833 , 0.13500       -0.00007 , 4.98500       -0.00005 , 0.57797       -0.00011 , 4.99979      
                                                                                                                                     
  
 
Parameter 
Values 
Template ID 
SS_PN_T_003 
Output File Name 
rt-pn-maxic50s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1K 
Title 1 
Maximum Change from Baseline Summary for BMS-955176 IC50 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 1 
Layout notes 
Assessment = BMS-955176 IC50 
 
Parameter 
Values 
Template ID 
SS_PN_T_003 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
266 
Output File Name 
rt-pn-maxic50s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2K 
Title 1 
Maximum Change from Baseline Summary for BMS-955176 IC50 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 2 
Layout notes 
Assessment = BMS-955176 IC50 
 
Parameter 
Values 
Template ID 
SS_PN_T_003 
Output File Name 
rt-pn-maxic50pdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1L 
Title 1 
Maximum Change from Baseline Summary for BMS-955176 IC50 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Assessment = BMS-955176 IC50 
 
Parameter 
Values 
Template ID 
SS_PN_T_003 
Output File Name 
rt-pn-maxic50pdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
267 
Table No. 
Table S.5.10.2L 
Title 1 
Maximum Change from Baseline Summary for BMS-955176 IC50 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Assessment = BMS-955176 IC50 
 
Parameter 
Values 
Template ID 
SS_PN_T_003 
Output File Name 
rt-pn-maxic50fcs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1M 
Title 1 
Summary for Maximum BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 1 
Layout notes 
Assessment = BMS-955176 IC50 Fold Change 
Only include the ‘MAXIMUM ON TREATMENT’ part 
 
Parameter 
Values 
Template ID 
SS_PN_T_003 
Output File Name 
rt-pn-maxic50fcs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2M 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
268 
Title 1 
Summary for Maximum BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects with On-Treatment Phenotypic Resistance Profile - Stage 2 
Layout notes 
Assessment = BMS-955176 IC50 Fold Change 
Only include the ‘MAXIMUM ON TREATMENT’ part 
 
Parameter 
Values 
Template ID 
SS_PN_T_003 
Output File Name 
rt-pn-maxic50fcpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1N 
Title 1 
Summary for Maximum BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Assessment = BMS-955176 IC50 Fold Change  
Only include the ‘MAXIMUM ON TREATMENT’ part 
 
Parameter 
Values 
Template ID 
SS_PN_T_003 
Output File Name 
rt-pn-maxic50fcpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2N 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
269 
Title 1 
Summary for Maximum BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Layout notes 
Assessment = BMS-955176 IC50 Fold Change  
Only include the ‘MAXIMUM ON TREATMENT’ part 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
270 
Template SS_PN_T_004: Proportion of Subjects with > 3 Fold Increase in IC50 Fold Change 
---------------------------------------------------------------------------------------------------------------------------------- 
   
 
 
 
 
 
 
 
 
                   
 
                           
 
 
 
Group A             Group B    
  Group C 
    Group D                        
     
 
                        
 
 
 N = XX               N = XX             N = XX          N = XX      
        
---------------------------------------------------------------------------------------------------------------------------------- 
                                                                                                                               
NUMBER (%) OF SUBJECTS  
 
 
 
 
XX ( XX.X)          XX ( XX.X) 
   XX ( XX.X)       XX ( XX.X)         
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-props1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1O 
Title 1 
Proportion of Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 
Footnote 1 
A > 3 fold increase from baseline in BMS-955176 FC-IC50 is defined as BMS-955176 FC-IC50 on-treatment divided by BMS-
955176 FC-IC50 at baseline >3. 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-props2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2O 
Title 1 
Proportion of Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 2 
Footnote 1 
A > 3 fold increase from baseline in BMS-955176 FC-IC50 is defined as BMS-955176 FC-IC50 on-treatment divided by BMS-
955176 FC-IC50 at baseline >3. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
271 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-props12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3O 
Title 1 
Proportion of Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 and 2 
Footnote 1 
A > 3 fold increase from baseline in BMS-955176 FC-IC50 is defined as BMS-955176 FC-IC50 on-treatment divided by BMS-
955176 FC-IC50 at baseline >3. 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-proppdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1P 
Title 1 
Proportion of Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures  
Title 3 
with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 
Footnote 1 
A > 3 fold increase from baseline in BMS-955176 FC-IC50 is defined as BMS-955176 FC-IC50 on-treatment divided by BMS-
955176 FC-IC50 at baseline >3. 
Footnote 2 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 3 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 4 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 5 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 6 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
272 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-proppdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2P 
Title 1 
Proportion of Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures  
Title 3 
with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 2 
Footnote 1 
A > 3 fold increase from baseline in BMS-955176 FC-IC50 is defined as BMS-955176 FC-IC50 on-treatment divided by BMS-
955176 FC-IC50 at baseline >3. 
Footnote 2 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 3 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 4 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 5 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 6 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-proppdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3P 
Title 1 
Proportion of Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures  
Title 3 
with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 and 2 
Footnote 1 
A > 3 fold increase from baseline in BMS-955176 FC-IC50 is defined as BMS-955176 FC-IC50 on-treatment divided by BMS-
955176 FC-IC50 at baseline >3. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
273 
Footnote 2 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 3 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 4 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 5 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 6 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-propnews1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1V 
Title 1 
Proportion of Subjects with Newly Emergent Phenotypic Resistance to BMS-955176 
Title 2 
Treated Subjects with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 
Footnote 1 
Newly emergent phenotypic resistance to BMS-955176 is defined as a baseline fold change <= 3  
Footnote 2 
and an on-treatment fold change >3 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-propnews2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2V 
Title 1 
Proportion of Subjects with Newly Emergent Phenotypic Resistance to BMS-955176 
Title 2 
Treated Subjects with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 2 
Footnote 1 
Newly emergent phenotypic resistance to BMS-955176 is defined as a baseline fold change <= 3  
Footnote 2 
and an on-treatment fold change >3 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
274 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-propnews12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3V 
Title 1 
Proportion of Subjects with Newly Emergent Phenotypic Resistance to BMS-955176 
Title 2 
Treated Subjects with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 and 2 
Footnote 1 
Newly emergent phenotypic resistance to BMS-955176 is defined as a baseline fold change <= 3  
Footnote 2 
and an on-treatment fold change >3 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-propnewpdvfs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1W 
Title 1 
Proportion of Subjects with Newly Emergent Phenotypic Resistance to BMS-955176 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures  
Title 3 
with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Footnote 6 
Newly emergent phenotypic resistance to BMS-955176 is defined as a baseline fold change <= 3  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
275 
Footnote 7 
and an on-treatment fold change >3 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-propnewpdvfs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2W 
Title 1 
Proportion of Subjects with Newly Emergent Phenotypic Resistance to BMS-955176 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures  
Title 3 
with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Footnote 6 
Newly emergent phenotypic resistance to BMS-955176 is defined as a baseline fold change <= 3  
Footnote 7 
and an on-treatment fold change >3 
 
Parameter 
Values 
Template ID 
SS_PN_T_004 
Output File Name 
rt-pn-propnewpdvfs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3W 
Title 1 
Proportion of Subjects with Newly Emergent Phenotypic Resistance to BMS-955176 
Title 2 
Treated Subjects Identified as Protocol Defined Virologic Failures  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
276 
Title 3 
with Baseline and On-Treatment Phenotypic Resistance Profile - Stage 1 and 2 
Footnote 1 
Protocol Defined Virologic Failure is defined by a subject meeting one of the following criteria: 
Footnote 2 
1) Confirmed > 1 log10 c/mL increase in HIV-1 RNA at anytime above nadir level where nadir is ≥ 40 c/mL 
Footnote 3 
2) Confirmed HIV-1 RNA ≥ 40 c/mL if prior suppression to < 40 c/mL 
Footnote 4 
3) Failure to have the last on-treatment HIV-1 RNA to < 400 c/mL within Week 24, 48, or 96 week snapshot window 
Footnote 5 
4) Failure to achieve > 1 log10 c/mL decrease in HIV-1 RNA by Week 8 
Footnote 6 
Newly emergent phenotypic resistance to BMS-955176 is defined as a baseline fold change <= 3  
Footnote 7 
and an on-treatment fold change >3 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagincs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.5.10.1Q 
Title 1 
Emergent Gag Polymorphisms 
Title 2 
Treated Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change- Stage 1 
 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagincs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.5.10.2Q 
Title 1 
Emergent Gag Polymorphisms  
Title 2 
Treated Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change- Stage 2 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
277 
Parameter 
Values 
Template ID 
SS_GN_T_002 
Output File Name 
rt-gn-newgagincs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.5.10.3Q 
Title 1 
Emergent Gag Polymorphisms 
Title 2 
Treated Subjects with Greater than 3 Fold Increase in BMS-955176 IC50 Fold Change- Stage 1 and 2 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
278 
Template SS_VL_T_007: Proportion of Responders (mITT) - Futility Analysis 
---------------------------------------------------------------------------------------------------------------------------------- 
   
 
 
 
 
 
 
 
 
                   
 
                           
 
 
 
Group A              Group B    
  Group C 
    Group D                        
     
 
                        
 
 
 N = XX               N = XX             N = XX          N = XX      
        
---------------------------------------------------------------------------------------------------------------------------------- 
                                                                                                                               
NUMBER OF RESPONDERS (a) 
 
 
 
 
XX ( XX.X)            XX ( XX.X) 
   XX ( XX.X)       XX ( XX.X)         
  95% CI 
 
 
                            (XX.X – XX.X)         (XX.X – XX.X)    (XX.X – XX.X)    (XX.X – XX.X)     
 
P-value (b)                                                   xxx                  xxx               xxx              
------------------------------------------------------------------------------------------------------------------------------------ 
 
 
Parameter 
Values 
Template ID 
SS_VL_T_007 
Output File Name 
rt-vl-futw24s1.lst 
Purpose 
WK24S1 
Table No. 
Table S.5.11.1 
Title 1 
Test for Virologic Futility Based on HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24  (mITT) 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Footnote 2 
(b) Based on one-sided Fisher’s exact test. 
 
Parameter 
Values 
Template ID 
SS_VL_T_007 
Output File Name 
rt-vl-futw24s2.lst 
Purpose 
WK24S2 
Table No. 
Table S.5.11.2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
279 
Title 1 
Test for Virologic Futility Based on HIV-1 RNA < 40 c/mL 
Title 2 
Proportion of Responders at Week 24  (mITT) 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
(a) Response is assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a subject’s response 
status. 
Footnote 2 
(b) Based on one-sided Fisher’s exact test. 
 
 
4.6 
Safety Results 
4.6.1 
All Adverse Events 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
280 
Template SS_AE_T_001: Overall Adverse Events Summary 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                          TRT A             TRT B             TRT C               All Subjects       
                                                          N = XXX           N = XXX           N = XXX             N = XXXX     
-------------------------------------------------------------------------------------------------------------------------------- 
 
SUBJECTS WITH ONE OR MORE ADVERSE EVENTS                  XXX ( XX.X)       XXX ( XX.X)       XX ( XX.X)         XXXX ( XX.X) 
SUBJECTS WHO DIED                                         XXX ( XX.X)       XXX ( XX.X)       XX ( XX.X)         XXXX ( XX.X) 
SUBJECTS WITH SERIOUS ADVERSE EVENTS                      XXX ( XX.X)       XXX ( XX.X)       XX ( XX.X)         XXXX ( XX.X) 
SUBJECTS WITH RELATED ADVERSE EVENTS                      XXX ( XX.X)       XXX ( XX.X)       XX ( XX.X)         XXXX ( XX.X) 
SUBJECTS WITH ADVERSE EVENT LEADING TO DISCONTINUATION    XXX ( XX.X)       XXX ( XX.X)       XX ( XX.X)         XXXX ( XX.X) 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_AE_T_001 
Output File Name 
rt-ae-overallsums1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.7.1 
Title 1 
Adverse Events 
Title 2 
Overall Adverse Events Summary 
Title 3 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
SS_AE_T_001 
Output File Name 
rt-ae-overallsums2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.7.2 
Title 1 
Adverse Events 
Title 2 
Overall Adverse Events Summary 
Title 3 
Treated Subjects - Stage 2 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
281 
Parameter 
Values 
Template ID 
SS_AE_T_001 
Output File Name 
rt-ae-overallsums12.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.7.3 
Title 1 
Adverse Events 
Title 2 
Overall Adverse Events Summary 
Title 3 
Treated Subjects - Stage 1 and 2 
 
4.6.2 
Deaths 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
282 
Template SS_AE_L_001: Listing of Death 
------------------------------------------------------------------------------------------------------------------------------------ 
 
Subject ID                                                                                                                           
  (Age/Gender/Race)                 Current Trt                                                                                      
    Treatment Group                   Period                            Death Date     Death Day      Cause of Death                 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
 
Parameter 
Values 
Template ID 
SS_AE_L_001 
Output File Name 
rl-ae-deaths1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.1.1 
Title 1 
Death Listing 
Title 2 
Enrolled Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
SS_AE_L_001 
Output File Name 
rl-ae-deaths2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.1.2 
Title 1 
Death Listing 
Title 2 
Enrolled Subjects - Stage 2 
 
4.6.3 
Serious Adverse Events 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
283 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-saes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.2.1A 
Title 1 
Adverse Event Summary 
Title 2 
Serious Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-saes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.2.2A 
Title 1 
Adverse Event Summary 
Title 2 
Serious Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-saes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.2.3A 
Title 1 
Adverse Event Summary 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
284 
Title 2 
Serious Adverse Events 
Title 3 
Treated Subjects - Stage 1 and 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-saeconts1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.6.2.1B 
Title 1 
Adverse Event Summary 
Title 2 
Serious Adverse Events After Switch to Continuation Dose 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-saeconts2.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.2.2B 
Title 1 
Adverse Event Summary 
Title 2 
Serious Adverse Events After Switch to Continuation Dose 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
285 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-saeldeaths1eu.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.2.1C 
Title 1 
Adverse Event Summary 
Title 2 
Serious Adverse Event With Death As An Outcome 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-saeldeaths2eu.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.2.2C 
Title 1 
Adverse Event Summary 
Title 2 
Serious Adverse Event With Death As An Outcome 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relsaeldeaths1eu.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.2.1D 
Title 1 
Adverse Event Summary 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
286 
Title 2 
Drug Related Serious Adverse Event With Death As An Outcome 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relsaeldeaths2eu.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.2.2D 
Title 1 
Adverse Event Summary 
Title 2 
Drug Related Serious Adverse Event With Death As An Outcome 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
287 
Template GS_AE_L_S_001: Adverse Event Listing (by Subject) 
Protocol: IM101031                                          Confidential                                                Page 1 of 95 
                                                           Adverse Event                                                                           
                                                        All Treated Subjects                                                                       
 
------------------------------------------------------------------------------------------------------------------------------------ 
Subject ID             Current Trt    Onset              Dur            System Organ Class                                                         
  (Age/Gender/Race)      Period         Resolution         TRD            Preferred Term                                 REL   TRT    
    Treatment Group        Visit          Study Day          Type           Reported Term                                  INT   ACT  
-------------------------
----------------------------------------------------------------------------------- 
           ABA 10        
       1D             GASTROINTESTINAL DISORDERS                         5     0      
  (55/F/C)               ON TRT      
         7H             NAUSEA                                             2     1    
    ABATACEPT              Day 1     
 1          SAE            NAUSEA                                                    
                       
                       ABA 10         
       1D             SKIN AND SUBCUTANEOUS TISSUE DISORDERS             5     0      
                         ON TRT       
         5H             NIGHT SWEATS                                       2     1    
                           Day 1                  1          AE             NIGHT SWEAT                                             
                                   
                       ABA 15         
       54D            GASTROINTESTINAL DISORDERS                         5     1      
                         ON TRT       
          14H            STOMATITIS                                         1     1    
                           Day 58                58          AE             MOUTH SORES                                             
                                   
                       ABA 20         
        6D             GASTROINTESTINAL DISORDERS                         5     1      
                         ON TRT       
          6H             STOMATITIS                                         2     1    
                           Day 167              167          AE             MOUTH SORES                                             
                                   
                       ABA 30         
       4D             GASTROINTESTINAL DISORDERS                         5     0      
                         ON TRT       
          45M            STOMATITIS                                         1     1    
                           Day 218              218          AE             MOUTH SORES                                             
                     
          PLACEBO        
       1D             MUSCULOSKELETAL AND CONNECTIVE TISSUE              5     1      
  (60/M/C)               ON TRT       
         10H          DISORDERS                                            3     5    
    PLACEBO                Day 15                15          AE           BACK PAIN            
                                                                            PAIN IN BACK                                       
 
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED         
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE                                        
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES                                                                                      
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = DRUG DISCONTINUED            
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS                                                
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = SECONDS                                   
 
MedDRA Version: 7.1                                                                                                                 
Program Source: /wwbdm/ndp/prime/msr/devtest/test/sample21.sas                                                    14JAN2005:16:49:00 
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
288 
 
Parameter 
Values 
Template ID 
GS_AE_L_S_001 
Output File Name 
rl-ae-saes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.2.1E 
Title 1 
Adverse Event 
Title 2 
Serious Adverse Events 
Title 3 
Enrolled Subjects - Stage 1 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AE_L_S_001 
Output File Name 
rl-ae-saes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.2.2E 
Title 1 
Adverse Event 
Title 2 
Serious Adverse Events 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
289 
Title 3 
Enrolled Subjects - Stage 2 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
4.6.4 
Adverse Events Leading to Discontinuation of Study Therapy 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-aediscs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.3.1A 
Title 1 
Adverse Event Summary 
Title 2 
Adverse Events Leading to Discontinuation of Study Medication 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-aediscs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
290 
Table No. 
Table S.6.3.2A 
Title 1 
Adverse Event Summary 
Title 2 
Adverse Events Leading to Discontinuation of Study Medication 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-aediscs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.3.3A 
Title 1 
Adverse Event Summary 
Title 2 
Adverse Events Leading to Discontinuation of Study Medication 
Title 3 
Treated Subjects - Stage 1 and 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-aediscconts1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.6.3.1B 
Title 1 
Adverse Event Summary 
Title 2 
Adverse Events Leading to Discontinuation of Study Medication After Switch to Continuation Dose 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
291 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-aediscconts2.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.3.2B 
Title 1 
Adverse Event Summary 
Title 2 
Adverse Events Leading to Discontinuation of Study Medication After Switch to Continuation Dose 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
292 
Template GS_AE_L_X_001: Adverse Event Listing (by Treatment Group) 
Protocol: IM101031                                       Confidential                                                  Page 1 of 95 
                                                           Adverse Event 
                                                        All Treated Subjects 
 
Treatment Group: ABATACEPT 
------------------------------------------------------------------------------------------------------------------------------------ 
                       Current Trt    Onset              Dur            System Organ Class                                                         
Subject ID               Period         Resolution         TRD            Preferred Term                                 REL   TRT    
  (Age/Gender/Race)        Visit          Study Day          Type           Reported Term                                  INT   ACT  
-------------------------
----------------------------------------------------------------------------------- 
          ABA 10         
       1D             GASTROINTESTINAL DISORDERS                         5     0      
  (55/F/C)               ON TRT       
         7H             NAUSEA                                             2     1    
                           Day 1      
1          SAE            NAUSEA                                                  
                                     
                       ABA 10         
       1D             SKIN AND SUBCUTANEOUS TISSUE DISORDERS             5     0      
                         ON TRT       
         5H             NIGHT SWEATS                                       2     1    
                           Day 1      
1          AE             NIGHT SWEAT                                             
                                    
                       ABA 15         
       54D            GASTROINTESTINAL DISORDERS                         5     1      
                         ON TRT       
         14H            STOMATITIS                                         1     1    
                           Day 58                58          AE             MOUTH SORES                                             
                                    
                       ABA 20         
       6D             GASTROINTESTINAL DISORDERS                         5     1      
                         ON TRT       
         6H             STOMATITIS                                         2     1    
                           Day 167              167          AE             MOUTH SORES                                             
                                    
                       ABA 30         
       4D             GASTROINTESTINAL DISORDERS                         5     0      
                         ON TRT       
          45M            STOMATITIS                                         1     1    
                           Day 218              218          AE             MOUTH SORES                                             
                                   
                       ABA 30         
       15D            SKIN AND SUBCUTANEOUS TISSUE DISORDERS             5     1      
                         ON TRT       
          1H             INGROWN HAIR                                       2     1    
                           Day 297              297          AE             INGROWN HAIR FOLLICLE                                   
                        
          ABA 10         
       1D             MUSCULOSKELETAL AND CONNECTIVE TISSUE              5     1      
  (60/M/C)               ON TRT       
         10H          DISORDERS                                            3     5    
                           Day 15                15          AE           BACK PAIN 
                                                                            PAIN IN BACK                                       
                         
                                          
------------------------------------------------------------------------------------------------------------------------------------ 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED         
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE                                        
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES                                                                                      
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = DRUG DISCONTINUED            
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS                                             
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = SECONDS                                   
MedDRA Version: 7.1                                                                                                                
Program Source: /wwbdm/ndp/prime/msr/devtest/test/sample21.sas                                                    14JAN2005:16:49:00 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
293 
 
Parameter 
Values 
Template ID 
GS_AE_L_X_001 
Output File Name 
rl-ae-discs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.3.1C 
Title 1 
Adverse Event 
Title 2 
Adverse Events Leading to Discontinuation of Study Medication 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AE_L_X_001 
Output File Name 
rl-ae-discs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.3.2C 
Title 1 
Adverse Event 
Title 2 
Adverse Events Leading to Discontinuation of Study Medication 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
294 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
4.6.5 
Other Significant Adverse Events 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-nsae5pcts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.5.1A 
Title 1 
Adverse Event Summary 
Title 2 
Non-Serious Adverse Events Occurring in at Least 5 Percent of Treated Subjects 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
Programming notes 
Apply the 5% cut to preferred terms only, not “TOTAL SUBJECTS WITH AN EVENT” and SOCs.  
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-nsae5pcts2.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
295 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.5.2A 
Title 1 
Adverse Event Summary 
Title 2 
Non-Serious Adverse Events Occurring in at Least 5 Percent of Treated Subjects 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
Programming notes 
Apply the 5% cut to preferred terms only, not “TOTAL SUBJECTS WITH AN EVENT” and SOCs.  
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-grade1to4s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.5.1B 
Title 1 
Adverse Event Summary 
Title 2 
Grade 1 to 4 Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-grade1to4s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.5.2B 
Title 1 
Adverse Event Summary 
Title 2 
Grade 1 to 4 Adverse Events 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
296 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-grade2to4s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.5.1C 
Title 1 
Adverse Event Summary 
Title 2 
Grade 2 to 4 Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-grade2to4s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.5.2C 
Title 1 
Adverse Event Summary 
Title 2 
Grade 2 to 4 Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
297 
Output File Name 
rt-ae-grade3to4s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.5.1D 
Title 1 
Adverse Event Summary 
Title 2 
Grade 3 to 4 Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-grade3to4s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.5.2D 
Title 1 
Adverse Event Summary 
Title 2 
Grade 3 to 4 Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-grade3to4s12.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.5.3D 
Title 1 
Adverse Event Summary 
Title 2 
Grade 3 to 4 Adverse Events 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
298 
Title 3 
Treated Subjects - Stage 1 and 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relateds1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.5.1E 
Title 1 
Adverse Event Summary 
Title 2 
Grade 1 to 4 Related Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relateds2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.5.2E 
Title 1 
Adverse Event Summary 
Title 2 
Grade 1 to 4 Related Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
299 
Output File Name 
rt-ae-relgrade2to4s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.5.1F 
Title 1 
Adverse Event Summary 
Title 2 
Grade 2 to 4 Related Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relgrade2to4s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.5.2F 
Title 1 
Adverse Event Summary 
Title 2 
Grade 2 to 4 Related Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relgrade2to4s12.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.5.3F 
Title 1 
Adverse Event Summary 
Title 2 
Grade 2 to 4 Related Adverse Events 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
300 
Title 3 
Treated Subjects - Stage 1 and 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relgrade3to4s1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.5.1G 
Title 1 
Adverse Event Summary 
Title 2 
Grade 3 to 4 Related Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-relgrade3to4s2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.5.2G 
Title 1 
Adverse Event Summary 
Title 2 
Grade 3 to 4 Related Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AEL_X_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
301 
Output File Name 
rl-ae-lists1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 6.5.1 
Title 1 
Adverse Event 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AEL_X_001 
Output File Name 
rl-ae-lists2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 6.5.2 
Title 1 
Adverse Event 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
302 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-cdcaes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.4.1A 
Title 1 
Adverse Event Summary 
Title 2 
CDC Class C AIDS Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-cdcaes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.4.2A 
Title 1 
Adverse Event Summary 
Title 2 
CDC Class C AIDS Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
303 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-cdcaes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.4.3A 
Title 1 
Adverse Event Summary 
Title 2 
CDC Class C AIDS Events 
Title 3 
Treated Subjects - Stage 1 and 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AEL_X_001 
Output File Name 
rl-ae-cdcaes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.4.1B 
Title 1 
Adverse Event 
Title 2 
CDC Class C AIDS Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
304 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AEL_X_001 
Output File Name 
rl-ae-cdcaes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.4.2B 
Title 1 
Adverse Event 
Title 2 
CDC Class C AIDS Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-giaes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.4.1C 
Title 1 
Adverse Event Summary 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
305 
Title 2 
Gastrointestinal Events of Special Interest 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-giaes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.4.2C 
Title 1 
Adverse Event Summary 
Title 2 
Gastrointestinal Events of Special Interest 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_X_001 
Output File Name 
rt-ae-giaes12.lst 
Purpose 
WK96S2 
Table No. 
Table S.6.4.3C 
Title 1 
Adverse Event Summary 
Title 2 
Gastrointestinal Events of Special Interest 
Title 3 
Treated Subjects - Stage 1 and 2 
Footnote 1 
MedDRA Version x.x 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
306 
Template ID 
GS_AE_L_X_001 
Output File Name 
rl-ae-giaes1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.4.1D 
Title 1 
Adverse Event 
Title 2 
Gastrointestinal Events of Special Interest 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AE_L_X_001 
Output File Name 
rl-ae-giaes2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.4.2D 
Title 1 
Adverse Event 
Title 2 
Gastrointestinal Events of Special Interest 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
307 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
4.6.6 
Multiple Adverse Events 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
308 
Template GS_AE_T_M_001: Exposure Adjusted Adverse Events Summary by SOC and Preferred Term 
Protocol: TA123456                                                                                                      Page 1 of 20 
                                                   Exposure Adjusted Adverse Event Summary 
                                             Including Multiple Occurrences of Unique Events  
                                                           All Treated Subjects 
 
------------------------------------------------------------------------------------------------------------------------------------
-- 
                                                      TRT A                        TRT B                         TOTAL         
                                                     (N=477)                      (N=472)                       (N=949)        
                                                  (P-Y = 218.9)                (P-Y = 218.3)                 (P-Y = 437.2)     
                                             ----------------------        ---------------------          --------------------- 
System Organ Class                            Event       Rate:             Event      Rate:               Event      Rate: 
  Preferred Term                              Count   (IR/100 P-Y)          Count   (IR/100 P-Y)           Count   (IR/100 P-Y)     
------------------------------------------------------------------------------------------------------------------------------------
-- 
                                                                                                                           
TOTAL EVENTS                                   6138       2804.0             6128       2807.3             12266        5611.6 
                                                                                                                      
INFECTIONS AND INFESTATIONS                     616        281.4              566        259.3              1182         271.7    
  URINARY TRACT INFECTION                       179         81.8              179         82.0               358          81.8 
  CYTOMEGALOVIRUS INFECTION                      39         17.8               40         18.3                79          18.1  
  UPPER RESPIRATORY TRACT                        27         12.3               26         11.9                53          11.2    
  INFECTION                                                                                             
  NASOPHARYNGITIS                                26         11.9               18          8.3                44          10.2    
  ORAL CANDIDIASIS                               23         10.5               14          6.4                37           8.9 
  BRONCHITIS                                     23         10.5               13          6.0                36           8.5 
  GASTROENTERITIS                                14          6.4               11          5.0                25           5.4 
  HERPES ZOSTER                                  14          6.4                7          3.2                21           4.6    
  SINUSITIS                                      12          5.5                4          1.8                16           3.9   
  INFLUENZA                                      11          5.0               13          2.0                24           3.5  
  HERPES SIMPLEX                                  9          4.1                7          3.2                16           3.3 
  UROSEPSIS                                       5          2.3                2          0.9                 7           1.2  
 
------------------------------------------------------------------------------------------------------------------------------------ 
P-Y = person-years of exposure 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
 
MedDRA Version: 13.0                                                                                                                 
Program Source: /gbs/prod/clin/programs/im/103/maa-renal/emea150/scs/rpt/rt-adae-ae-inc2-m36-v01.sas              02MAR2011:11:04:59 
 
Parameter 
Values 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjusts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
309 
Table No. 
Table S.6.6.1A 
Title 1 
Exposure Adjusted Adverse Events Summary 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
P-Y = person-years of exposure 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
Footnote 3 
MedDRA Version: x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjusts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.6.2A 
Title 1 
Exposure Adjusted Adverse Events Summary 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
P-Y = person-years of exposure 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
Footnote 3 
MedDRA Version: x.x 
 
Parameter 
Values 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjsaes1eu.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.6.1B 
Title 1 
Exposure Adjusted Adverse Events Summary 
Title 2 
Including Multiple Occurrences of Unique Adverse Events 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
310 
Title 3 
Treated Subjects - Stage 1 
Title 4 
Serious Adverse Events 
Footnote 1 
P-Y = person-years of exposure 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
Footnote 3 
MedDRA Version: x.x 
Programming notes 
Subset SAEs then collapse using multiple events macro. 
 
Parameter 
Values 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjsaes2eu.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.6.2B 
Title 1 
Exposure Adjusted Adverse Events Summary 
Title 2 
Including Multiple Occurrences of Unique Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Title 4 
Serious Adverse Events 
Footnote 1 
P-Y = person-years of exposure 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
Footnote 3 
MedDRA Version: x.x 
Programming notes 
Subset SAEs then collapse using multiple events macro. 
 
Parameter 
Values 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjrelsaes1eu.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
311 
Table No. 
Table S.6.6.1C 
Title 1 
Exposure Adjusted Adverse Events Summary 
Title 2 
Including Multiple Occurrences of Unique Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Title 4 
Drug Related Serious Adverse Events 
Footnote 1 
P-Y = person-years of exposure 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
Footnote 3 
MedDRA Version: x.x 
Programming notes 
Subset SAEs then collapse using multiple events macro. 
 
Parameter 
Values 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjrelsaes2eu.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.6.2C 
Title 1 
Exposure Adjusted Adverse Events Summary 
Title 2 
Including Multiple Occurrences of Unique Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Title 4 
Drug Related Serious Adverse Events 
Footnote 1 
P-Y = person-years of exposure 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
Footnote 3 
MedDRA Version: x.x 
Programming notes 
Subset SAEs then collapse using multiple events macro. 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
312 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjnsae5pcts1eu.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.6.6.1D 
Title 1 
Exposure Adjusted Adverse Event Summary  
Title 2 
Including Multiple Occurrences of Unique Adverse Events 
Title 3 
Treated Subjects - Stage 1 
Title 4 
Non-Serious Adverse Events Using a Global Cutoff of 5 Percent  
Footnote 1 
P-Y = person-years of exposure. Only events occurring in at least 5% of treated subjects in any group are displayed. 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 
Footnote 3 
MedDRA Version: x.x 
Programming notes 
Display perferred terms with frequency ≥ 5% of treated subjects per rt-ae-nsae5pct.lst. Do not apply the 5% cut to “TOTAL 
EVENTS” and SOCs 
Subset NSAEs then collapse using multiple events macro. 
 
Parameter 
Values 
Template ID 
GS_AE_T_M_001 
Output File Name 
rt-ae-expadjnsae5pcts2eu.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.6.6.2D 
Title 1 
Exposure Adjusted Adverse Event Summary 
Title 2 
Including Multiple Occurrences of Unique Adverse Events 
Title 3 
Treated Subjects - Stage 2 
Title 4 
Non-Serious Adverse Events Using a Global Cutoff of 5 Percent  
Footnote 1 
P-Y = person-years of exposure. Only events occurring in at least 5% of treated subjects in any group are displayed. 
Footnote 2 
Incidence rate per 100 person-years of exposure (IR/100 P-Y) = event count * 100 /person-years of exposure 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
313 
Footnote 3 
MedDRA Version: x.x 
Programming notes 
Display perferred terms with frequency ≥ 5% of treated subjects per rt-ae-nsae5pct.lst. Do not apply the 5% cut to “TOTAL 
EVENTS” and SOCs 
Subset NSAEs then collapse using multiple events macro. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
314 
Template GS_AE_L_U_002: Unique Adverse Event Listing 
Protocol: IM101031                                                                                                                                 
Page 1 of 95 
                                                           Adverse Event                                                                           
                                                           Unique Events 
                                                        All Treated Subjects                                                                       
Treatment Group: ABATACEPT 
------------------------------------------------------------------------------------------------------------------------------------ 
                       Current Trt    Onset              Dur                                                                                       
Subject ID               Period         Resolution         TRD          System Organ Class                               REL   TRT    
 (Age/Gender/Race)         Visit          Study Day          Type         Preferred Term                                   INT   ACT  
--------------------------
----------------------------------------------------------------------------------- 
          ABA 10        
       1D             GASTROINTESTINAL DISORDERS                         5     0      
  (55/F/C)               ON TRT      
         7H             NAUSEA                                             2     1    
                           Day 1     
1          SAE                                                                
                       
                       ABA 10        
       1D             SKIN AND SUBCUTANEOUS TISSUE DISORDERS             5     0      
                         ON TRT      
         5H             NIGHT SWEATS                                       2     1    
                           Day 1     
1          AE                                                          
                                   
                       ABA 15        
       54D            GASTROINTESTINAL DISORDERS                         5     1      
                         ON TRT      
         14H            STOMATITIS                                         1     1    
                           Day 58                58          AE              
                                   
                       ABA 20         
       6D             GASTROINTESTINAL DISORDERS                         5     1      
                         ON TRT       
          6H             STOMATITIS                                         2     1    
                           Day 167              167          AE                                                          
                                   
                       ABA 30         
       4D             GASTROINTESTINAL DISORDERS                         5     0      
                         ON TRT       
         45M            STOMATITIS                                         1     1    
                           Day 218              218          AE                                                          
                     
          PLACEBO        
       1D             MUSCULOSKELETAL AND CONNECTIVE TISSUE              5     1      
  (60/M/C)               ON TRT       
         10H          DISORDERS                                            3     5    
                           Day 15                15          AE           BACK PAIN            
                                                                                                                   
------------------------------------------------------------------------------------------------------------------------------------ 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED         
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE                                        
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES                                                                                      
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = DRUG DISCONTINUED            
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS                                                
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = SECONDS                                   
 
MedDRA Version: 7.1                                                                                                                 
Program Source: /wwbdm/ndp/prime/msr/devtest/test/sample21.sas                                                    14JAN2005:16:49:00 
 
Parameter 
Values 
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
315 
Template ID 
GS_AE_L_U_002 
Output File Name 
rl-ae-uniques1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 6.6.1 
Title 1 
Adverse Event 
Title 2 
Unique Events 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
Parameter 
Values 
Template ID 
GS_AE_L_U_002 
Output File Name 
rl-ae-uniques2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 6.6.2 
Title 1 
Adverse Event 
Title 2 
Unique Events 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
REL (RELATIONSHIP):       5 = NOT RELATED  6 = RELATED 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
316 
Footnote 2 
INT (INTENSITY):          1 = MILD       2 = MODERATE      3 = SEVERE          4 = VERY SEVERE 
Footnote 3 
TRT (TREATMENT REQUIRED): 0 = NO         1 = YES     
Footnote 4 
ACT (ACTION):             1 = NONE       2 = DOSE REDUCED  3 = DOSE INCREASED  4 = DRUG INTERRUPTED  5 = 
DRUG DISCONTINUED          
Footnote 5 
DUR (DURATION OF EVENT):  D = DAYS       H = HOURS         M = MINUTES         S = SECONDS   
Footnote 6 
TRD (TIME RELATIVE TO MOST RECENT DOSE): D = DAYS          H = HOURS           M = MINUTES           S = 
SECONDS 
Footnote 7 
MedDRA Version XX.X 
 
4.6.7 
Clinical Laboratory Evaluations 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
317 
Template SS_LB_T_001: Laboratory Test Worst Abnormalities Table by Baseline 
Protocol: AI438XXX 
                                                                                                   Page 1 of X 
Laboratory Test Summary of <Toxicity Grade Description> Abnormalities 
<Title 2> 
 
                                    -----------------------------------------------------------------------------------------  
                                                                        Number With Abnormality/Number With Measurement (%) 
                                                                     -------------------------------------------------------- 
                                                                           Group 1                      Group 2 
                                    <Lab Type>           Baseline          N = XXX                      N = XXX 
                                    ----------------------------------------------------------------------------------------- 
 
                                    <TEST 1>             TOTAL          XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         NORMAL         XXX/XXX (XXX.X)              XXX/XXX (XXX.X)    
                                                         GRADE 1        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         GRADE 2        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         GRADE 3        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         GRADE 4        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         NOT REPORTED   XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
 
                                    ... <ADDITIONAL TESTS> 
 
                                    <TEST X>             TOTAL          XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         NORMAL         XXX/XXX (XXX.X)              XXX/XXX (XXX.X)    
                                                         GRADE 1        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         GRADE 2        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         GRADE 3        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         GRADE 4        XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
                                                         NOT REPORTED   XXX/XXX (XXX.X)              XXX/XXX (XXX.X) 
 
... <ADDITIONAL LAB TYPES AND TESTS ON SEPARATE PAGES>                                                        
                                     
                                     
              
 
------------------------------------------------------------------------------------------------------------------------------------ 
Toxicity Scale: DAIDS Version 1.0 
<Footnote 2> 
<Footnote 3>  
Program Source: <TBD>                                                                                             DDMMMYYYY:HR:MM:SS 
 
 
Parameter 
Values 
Template ID 
SS_LB_T_001 
Output File Name 
rt-lb-toxs1.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
318 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.1.1A 
Title 1 
Laboratory Test Results Summary of Worst Toxicity Grade 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
Parameter 
Values 
Template ID 
SS_LB_T_001 
Output File Name 
rt-lb-toxs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.1.2A 
Title 1 
Laboratory Test Results Summary of Worst Toxicity Grade 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
Parameter 
Values 
Template ID 
SS_LB_T_001 
Output File Name 
rt-lb-g34toxs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.1.1B 
Title 1 
Laboratory Test Results  
Title 2 
Summary of Grade 3-4 Toxicity 
Title 3 
Treated Subjects - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
319 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
Parameter 
Values 
Template ID 
SS_LB_T_001 
Output File Name 
rt-lb-g34toxs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.1.2B 
Title 1 
Laboratory Test Results  
Title 2 
Summary of Grade 3-4 Toxicity 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
Parameter 
Values 
Template ID 
SS_LB_T_001 
Output File Name 
rt-lb-g34toxs12.lst 
Purpose 
WK96S2 
Table No. 
Table S.7.1.3B 
Title 1 
Laboratory Test Results  
Title 2 
Summary of Grade 3-4 Toxicity 
Title 3 
Treated Subjects - Stage 1 and 2 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
320 
Template SS_LB_T_002: Laboratory Test Treatment Emergent Abnormalities Table 
Protocol: AI438XXX 
                                                                                                   Page 1 of X 
Laboratory Test Summary of Treatment Emergent Abnormalities 
<Title 2> 
 
     -------------------------------------------------------------------------------------------------------------------------------  
                                                                     Number With Abnormality/Number With Measurement (%) 
                                            ----------------------------------------------------------------------------------------  
                                                                              Group 1                                
                                                                              N = XXX                              
                                            ---------------------------------------------------------------------------------------- 
                                                   Increased to      Increased to    Increased to      Increased to    Increased to         
    <Lab Type>                Baseline      n      Grade 1           Grade 2         Grade 3           Grade 4         Any Grade     
    -------------------------------------------------------------------------------------------------------------------------------- 
                
    <TEST 1>                  TOTAL         XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X) 
                              NORMAL        XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)                 
                              GRADE 1 TO 4  XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X) 
                              NOT REPORTED  XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X) 
 
               ... <ADDITIONAL TESTS> 
 
    <TEST X>                  TOTAL         XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X) 
                              NORMAL        XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)                 
                              GRADE 1 TO 4  XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X) 
                              NOT REPORTED  XXX    XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)       XXX (XXX.X)     XXX (XXX.X)          
 
<... ADDITIONAL TREATMENT GROUPS AND LAB TYPES ON SEPARATE PAGES>                
                
 
                     
 
------------------------------------------------------------------------------------------------------------------------------------ 
Toxicity Scale: DAIDS Version 1.0 
<Footnote 2> 
<Footnote 3> 
Program Source: <TBD>                                                                                             DDMMMYYYY:HR:MM:SS 
 
Parameter 
Values 
Template ID 
SS_LB_T_001 
Output File Name 
rt-lb-etoxs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.1.1C 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
321 
Title 1 
Laboratory Test Results Summary of Treatment-Emergent Abnormalities 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
Parameter 
Values 
Template ID 
SS_LB_T_001 
Output File Name 
rt-lb-etoxs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.1.2C 
Title 1 
Laboratory Test Results Summary of Treatment-Emergent Abnormalities 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Toxicity Scale: DAIDS 
Programming notes 
The laboratory tests to be included in this output are specified in the SAP. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-renals1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.2.1A 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Function Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 1 
Programming notes 
Include creatinine and creatinine clearance as renal tests. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
322 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-renals2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.2.2A 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Function Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 2 
Programming notes 
Include creatinine and creatinine clearance as renal tests. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-renals1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.2.1B 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Function Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 1 
Programming notes 
Include creatinine and creatinine clearance as renal tests. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-renals2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.2.2B 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
323 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Function Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 2 
Programming notes 
Include creatinine and creatinine clearance as renal tests. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-lipidss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.2.1C 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-lipidss2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.2.2C 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
324 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-lipidss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.2.1D 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-lipidss2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.2.2D 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
325 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-pchglipidss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.2.1E 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Percent Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-pchglipidss2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.2.2E 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Percent Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
326 
Output File Name 
rt-zl-pchglipidss1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Table S.7.2.1F 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Percent Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 1 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-pchglipidss2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Table S.7.2.2F 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Fasting Lipid Values and Percent Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 2 
Footnote 1 
Values obtained after the start of serum lipid-reducing agents are excluded from the summary. 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include fasting Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and total:HDL cholesterol ratio 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-tchols1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
327 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.7.2.1A 
Title 1 
Fasting Total Cholesterol (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: Fasting Total Cholesterol Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-tchols2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.7.2.2A 
Title 1 
Fasting Total Cholesterol (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: Fasting Total Cholesterol Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-ldlcs1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.7.2.1B 
Title 1 
Fasting LDL-Cholesterol (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
328 
Layout notes 
Y-axis label: Fasting LDL-Cholesterol Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-ldlcs2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.7.2.2B 
Title 1 
Fasting LDL-Cholesterol (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: Fasting LDL-Cholesterol Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-hdlcs1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.7.2.1C 
Title 1 
Fasting HDL-Cholesterol (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: Fasting HDL-Cholesterol Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
329 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-hdlcs2 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Figure S.7.2.2C 
Title 1 
Fasting HDL-Cholesterol (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: Fasting HDL-Cholesterol Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-trigs1 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Figure S.7.2.1D 
Title 1 
Fasting Total Triglycerides (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: Fasting Triglycerides Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-trigs2 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
330 
Table No. 
Figure S.7.2.2D 
Title 1 
Fasting Total Triglycerides (mg/dL) Mean Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: Fasting Triglycerides Mean Percent Change from Baseline (SE) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
331 
Template SS_LB_L_001: Laboratory Test Results Listing With Toxicity Grades 
Protocol: AI468XXX 
                                                                                                   Page 1 of X 
 
Treatment Group: XXXXXXXX 
             ------------------------------------------------------------------------------------------- 
                                  Current Trt  Lab Date 
             Subject ID             Period       Study     <Test 1>          <Test X> 
               (Age/Gender/Race)      Visit      Day       (<Units)>   ...   (<Units>) 
             ------------------------------------------------------------------------------------------- 
 
            
 XXXXXXX      DDMMMYYYY    XX.X L             XXX.X (X)  
               (AAA/G/R)            XXXXXXX          XXX  
                                      XXXXXXX 
                                       
                                  ... <ADDITIONAL PERIODS AND VISITS> 
 
                                  XXXXXXX      DDMMMYYYY    XX.X H             XXX.X (XE)  
                                    XXXXXXX          XXX 
                                      XXXXXXX 
             
             ... <ADDITIONAL SUBJECTS>        
 
 
                 
 
              
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Normal range flag: L = low, H = high 
Toxicity Scale: DAIDS Version 1.0(Toxicity Grade; E = Emergent on treatment) 
Program Source: <TBD>                                                                                             DDMMMYYYY:HR:MM:SS               
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
332 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-hems1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1A 
Title 1 
Hematology - SI Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Hematology:
 
  White Blood Cells (WBC); Neutrophils + Bands, absolute; Red Blood Cells (RBC); Hematocrit; Hemoglobin; 
Platelets 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-hems2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2A 
Title 1 
Hematology - SI Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Hematology:
 
  White Blood Cells (WBC); Neutrophils + Bands, absolute; Red Blood Cells (RBC); Hematocrit; Hemoglobin; 
Platelets 
Parameter 
Values 
Template ID 
SS_LB_L_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
333 
Output File Name 
rl-lb-lfts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1B 
Title 1 
Liver Function Tests - SI Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Liver Function Tests:
 
 Alanine Aminotransferase (ALT); Aspartate Aminotransferase (AST); Total Protein; Albumin; Alkaline 
Phosphatase; Total Bilirubin; Direct Bilirubin; Indirect Bilirubin 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-lfts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2B 
Title 1 
Liver Function Tests - SI Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Liver Function Tests:
 
 Alanine Aminotransferase (ALT); Aspartate Aminotransferase (AST); Total Protein; Albumin; Alkaline 
Phosphatase; Total Bilirubin; Direct Bilirubin; Indirect Bilirubin 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-enzs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
334 
Table No. 
Appendix 7.1.1C 
Title 1 
Enzymes - SI Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Enzymes:
 
 Amylase; Creatinine Kinase (CK); Lipase 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-enzs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2C 
Title 1 
Enzymes - SI Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Enzymes:
 
 Amylase; Creatinine Kinase (CK); Lipase 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-rfts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1D 
Title 1 
Renal Function Tests - SI Units 
Title 2 
Treated Subjects - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
335 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Renal Function Tests:
 
 Blood Urea Nitrogen (BUN); Creatinine; Creatinine Clearance; Uric Acid; Estimated Glomerular Filtration 
Rate (eGFR) using Cockcroft-Gault 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-rfts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2D 
Title 1 
Renal Function Tests - SI Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Renal Function Tests:
 
 Blood Urea Nitrogen (BUN); Creatinine; Creatinine Clearance; Uric Acid; Estimated Glomerular Filtration 
Rate (eGFR) using Cockcroft-Gault 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-elcs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1E 
Title 1 
Electrolytes - SI Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
336 
Layout notes 
Electrolytes:
 
  Bicarbonate, serum; Calcium, serum; Chloride, serum; Potassium, serum; Sodium, serum 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-elcs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2E 
Title 1 
Electrolytes - SI Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Electrolytes:
 
  Bicarbonate, serum; Calcium, serum; Chloride, serum; Potassium, serum; Sodium, serum 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-flgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1F 
Title 1 
Fasting Lipids and Glucose - SI Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Fasting Lipids: Total Cholesterol; LDL Cholesterol; HDL Cholesterol; Triglycerides; Total:HDL Cholesterol 
Fasting Glucose:
 
  Glucose, serum 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
337 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-lb-flgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2F 
Title 1 
Fasting Lipids and Glucose - SI Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Fasting Lipids: Total Cholesterol; LDL Cholesterol; HDL Cholesterol; Triglycerides; Total:HDL Cholesterol 
Fasting Glucose:
 
  Glucose, serum 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-hems1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1G 
Title 1 
Hematology - US Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Hematology:
 
  White Blood Cells (WBC); Neutrophils + Bands, absolute; Red Blood Cells (RBC); Hematocrit; Hemoglobin; 
Platelets 
Parameter 
Values 
Template ID 
SS_LB_L_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
338 
Output File Name 
rl-zl-hems2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2G 
Title 1 
Hematology - US Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Hematology:
 
  White Blood Cells (WBC); Neutrophils + Bands, absolute; Red Blood Cells (RBC); Hematocrit; Hemoglobin; 
Platelets 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-lfts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1H 
Title 1 
Liver Function Tests - US Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Liver Function Tests:
 
 Alanine Aminotransferase (ALT); Aspartate Aminotransferase (AST); Total Protein; Albumin; Alkaline 
Phosphatase; Total Bilirubin; Direct Bilirubin; Indirect Bilirubin 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-lfts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
339 
Table No. 
Appendix 7.1.2H 
Title 1 
Liver Function Tests - US Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Liver Function Tests:
 
 Alanine Aminotransferase (ALT); Aspartate Aminotransferase (AST); Total Protein; Albumin; Alkaline 
Phosphatase; Total Bilirubin; Direct Bilirubin; Indirect Bilirubin 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-enzs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1I 
Title 1 
Enzymes - US Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Enzymes:
 
 Amylase; Creatinine Kinase (CK); Lipase 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-enzs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2I 
Title 1 
Enzymes - US Units 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
340 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Enzymes:
 
 Amylase; Creatinine Kinase (CK); Lipase 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-rfts1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1J 
Title 1 
Renal Function Tests - US Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Renal Function Tests:
 
 Blood Urea Nitrogen (BUN); Creatinine; Creatinine Clearance; Uric Acid; Estimated Glomerular Filtration 
Rate (eGFR) using Cockcroft-Gault 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-rfts2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2J 
Title 1 
Renal Function Tests - US Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
341 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Renal Function Tests:
 
 Blood Urea Nitrogen (BUN); Creatinine; Creatinine Clearance; Uric Acid; Estimated Glomerular Filtration 
Rate (eGFR) using Cockcroft-Gault 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-elcs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1K 
Title 1 
Electrolytes - US Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Electrolytes:
 
  Bicarbonate, serum; Calcium, serum; Chloride, serum; Potassium, serum; Sodium, serum 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-elcs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2K 
Title 1 
Electrolytes - US Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Electrolytes:
 
  Bicarbonate, serum; Calcium, serum; Chloride, serum; Potassium, serum; Sodium, serum 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
342 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-flgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1L 
Title 1 
Fasting Lipids and Glucose - US Units 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Fasting Lipids: Total Cholesterol; LDL Cholesterol; HDL Cholesterol; Total:HDL Cholesterol Ratio; Triglycerides 
Fasting Glucose:
 
  Glucose, serum 
Parameter 
Values 
Template ID 
SS_LB_L_001 
Output File Name 
rl-zl-flgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2L 
Title 1 
Fasting Lipids and Glucose - US Units 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Normal range flag: L = low, H = high 
Footnote 2 
Toxicity Scale: DAIDS Version 1.0 (Toxicity Grade; E = Emergent on treatment) 
Layout notes 
Fasting Lipids: Total Cholesterol; LDL Cholesterol; HDL Cholesterol; Total:HDL Cholesterol Ratio; Triglycerides 
Fasting Glucose:
 
  Glucose, serum 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
343 
Template GS_LB_L_S_008: Differences in Categorization of SI and US units 
Protocol: AI463022                                              Draft                                                    Page 1 of 1 
Differences in Categorization of SI and US Laboratory Test Results 
Treated Subjects 
 
Lab Test: Glucose (SI units: mmol/L, US Std Units: mg/dL) 
----------------------------------------------------------------------------------------------------------------------------------- 
           
 
 
 
 
                SI Unit                                   US Standard Unit  
                                             ----------------------------------------      ------------------------------------- 
Subject ID                                        Standard  Normal Range                     Standard   Normal Range                 
  (Age/Gender/Race)  Period        Lab Date       Lab       ----------------                 Lab        ---------------- 
    Treatment Group     Visit        Study Day    Result    Low   High  Flag  Toxicity       Result     Low   High   Flag   Toxicity   
-----------------------
---------------------------------------------------------------------------------------- 
           BASELINE  
        2.1    4.0   5.0   L     GRADE 0          37.8     52.0   65.0  L      GRADE 1 
  (59/F/O)                  A00            -28                                                          
    ENTECAVIR                      
    
                     ON TREATMENT 
        3.1    4.0   5.0   L     GRADE 1          45.8     52.0   65.0  L      GRADE 2 
                            B01              1 
 
            
 
       ON TREATMENT 
        4.1    4.0   5.0         GRADE 1          53.1     52.0   65.0         GRADE 2 
  (43/F/C)                  B02             14                                                          
    PLACEBO              
                     ON TREATMENT 
        5.6    4.0   5.0         GRADE 2          66.6     39.0   65.0  H      GRADE 3 
                            B03             27 
                               
------------------------------------------------------------------------------------------------------------------------------------ 
NORMAL RANGE FLAG: L = LOW     H = HIGH     + = NO NORMAL RANGES 
Toxicity Scale   : Descriptive text of toxicity scale 
 
Parameter 
Values 
Template ID 
GS_LB_L_S_008 
Output File Name 
rl-lb-diffunits1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1M 
Title 1 
Differences in Categorization of SI and US Laboratory Test Results 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
NORMAL RANGE FLAG: L = LOW     H = HIGH     + = NO NORMAL RANGES 
Footnote 2 
Toxicity Scale   : DAIDS 
 
PPD
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
344 
Parameter 
Values 
Template ID 
GS_LB_L_S_008 
Output File Name 
rl-lb-diffunits2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.1.2M 
Title 1 
Differences in Categorization of SI and US Laboratory Test Results 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
NORMAL RANGE FLAG: L = LOW     H = HIGH     + = NO NORMAL RANGES 
Footnote 2 
Toxicity Scale   : DAIDS 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
345 
Template GS_LB_L_X_006: Pregnancy Listing by Treatment Group 
 
Protocol: TA123456                                              Draft                                                    Page 1 of 2 
Pregnancy Test 
All Treated Female Subjects 
 
Treatment Group: TRT B   
------------------------------------------------------------------------------------------------------------------------------------ 
Subject ID                                     Study 
  (Age/Gender/Race) Period         Test Date   Day      Method         Result       Reason Not done 
----------------------
---------------------------------------------------------------------------------------- 
       X             
     -1    URINE HCG      NEGATIVE 
  (59/F/O)          Y             
     28    SERUM HCG      0 
       X             
     -1    URINE HCG      NEGATIVE 
  (34/F/B)          Y             
     24    URINE HCG      NEGATIVE 
                                  
     46    SERUM HCG      0 
    X             
     -1                                SURGICALLY STERILE 
  (44/F/C)          Y             
      7                                SURGICALLY STERILE 
 
------------------------------------------------------------------------------------------------------------------------------------ 
Program Source: /wwbdm/ndp/prime/gssr/devtest/prg/test/prg_lst.sas                                                07SEP2004:14:35:00 
 
Parameter 
Values 
Template ID 
GS_LB_L_X_006 
Output File Name 
rl-lb-pregs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.1.1N 
Title 1 
Pregnancy Test 
Title 2 
Treated Female Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_LB_L_X_006 
Output File Name 
rl-lb-pregs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
346 
Table No. 
Appendix 7.1.2N 
Title 1 
Pregnancy Test 
Title 2 
Treated Female Subjects - Stage 2 
 
4.6.8 
Electrocardiograms 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
347 
Template SS_EG_T_003 : ECG Summary Table with 95% CI 
Protocol: AI438XXX 
                                                                                                Page 1 of X 
<Domain> Summary of Values and Changes From Baseline Over Time 
<Title 2> 
 
<Parameter> (<Units>) 
Subgroup: XXXXXXXXXX    Level: XXXXXXXXXXXXX 
 
----------------------------------------------------------------------------------------------------------------------------------- 
Period                                            Percentiles                           Change From Baseline                  
  Visit                                    ----------------------  ----------------------------------------------------------------  
    Group          N      Mean      SD       Q1    Median   Q3      N     Mean      SD    95% CI for Mean    Q1     Median    Q3         
-----------------------------------------------------------------------------------------------------------------------------------  
        
PRE-TRT 
  B/L      
    Group 1        XXX    XXX.X   XXX.XX   XXX.X   XXX.X   XXX.X    XXX   XXX.X   XXX.XX  (XXX.XX, XXX.XX)  XXX.X   XXX.X   XXX.X  
    Group 2        XXX    XXX.X   XXX.XX   XXX.X   XXX.X   XXX.X    XXX   XXX.X   XXX.XX  (XXX.XX, XXX.XX)  XXX.X   XXX.X   XXX.X   
 
ON TRT 
  WK XX 
    Group 1        XXX    XXX.X   XXX.XX   XXX.X   XXX.X   XXX.X    XXX   XXX.X   XXX.XX  (XXX.XX, XXX.XX)  XXX.X   XXX.X   XXX.X  
    Group 2        XXX    XXX.X   XXX.XX   XXX.X   XXX.X   XXX.X    XXX   XXX.X   XXX.XX  (XXX.XX, XXX.XX)  XXX.X   XXX.X   XXX.X       
     
... <ADDITIONAL PERIODS AND VISITS>   
                         
 
Parameter 
Values 
Template ID 
SS_EG_T_003 
Output File Name 
rt-eg-sumchgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.3.1A 
Title 1 
Electrocardiogram Summary of Values and Changes from Baseline over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Parameters are specified in SAP, Section 7.6.14. 
 
Parameter 
Values 
Template ID 
SS_EG_T_003 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
348 
Output File Name 
rt-eg-sumchgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.3.2A 
Title 1 
Electrocardiogram Summary of Values and Changes from Baseline over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Parameters are specified in SAP, Section 7.6.14. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
349 
Template SS_EG_T_001 : ECG Change from Baseline Category Summary 
------------------------------------------------------------------------------------------------------------------------------------ 
 
                                 BMS-663068          BMS-663068          BMS-663068          BMS-663068                              
                                 400 mg BID/         800 mg BID/         600 mg QD/          1200 mg QD/         ATV/r/              
ECG Parameter (unit)             RAL/TDF             RAL/TDF             RAL/TDF             RAL/TDF             RAL/TDF             
  Category (%)                   N = 50              N = 49              N = 51              N = 50              N = 51              
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
PR INTERVAL (MSEC)                                                                                                                   
  <0                               4 (  8.0)           8 ( 16.3)           4 (  7.8)           7 ( 14.0)           8 ( 15.7)         
  0 to <20                         33 ( 66.0)          30 ( 61.2)          35 ( 68.6)          33 ( 66.0)          28 ( 54.9)         
  20 to <40                        11 ( 22.0)          11 ( 22.4)          11 ( 21.6)           7 ( 14.0)          13 ( 25.5)         
  40 to <60                         0                   0                   1 (  2.0)           1 (  2.0)           1 (  2.0)         
  60 to <80                         0                   0                   0                   0                   0                 
  >=80                              0                   0                   0                   0                   0                 
  NOT REPORTED                      2 (  4.0)           0                   0                   2 (  4.0)           1 (  2.0)         
                                                                                                                                     
QRS (MSEC)                                                                                                                           
  <0                                4 (  8.0)           6 ( 12.2)           3 (  5.9)           2 (  4.0)           6 ( 11.8)         
  0 to <10                         33 ( 66.0)          32 ( 65.3)          37 ( 72.5)          38 ( 76.0)          29 ( 56.9)         
  10 to <20                         9 ( 18.0)           9 ( 18.4)          10 ( 19.6)           6 ( 12.0)          15 ( 29.4)         
  20 to <30                         2 (  4.0)           2 (  4.1)           1 (  2.0)           2 (  4.0)           0                 
  30 to <40                         0                   0                   0                   0                   0                 
  >=40                              0                   0                   0                   0                   0                 
  NOT REPORTED                      2 (  4.0)           0                   0                   2 (  4.0)           1 (  2.0)         
                                                                                                                                     
QTC [FRIDERICIA] (MSEC)                                                                                                              
  <0                                6 ( 12.0)           6 ( 12.2)           4 (  7.8)           3 (  6.0)           9 ( 17.6)         
  0 to <10                          7 ( 14.0)           8 ( 16.3)          13 ( 25.5)          11 ( 22.0)          13 ( 25.5)         
  10 to <20                        17 ( 34.0)          21 ( 42.9)          18 ( 35.3)          20 ( 40.0)          15 ( 29.4)         
  20 to <30                        11 ( 22.0)           9 ( 18.4)           7 ( 13.7)          10 ( 20.0)           7 ( 13.7)         
  30 to <40                         6 ( 12.0)           2 (  4.1)           4 (  7.8)           1 (  2.0)           5 (  9.8)         
  >=40                              1 (  2.0)           3 (  6.1)           5 (  9.8)           3 (  6.0)           1 (  2.0)         
  NOT REPORTED                      2 (  4.0)           0                   0                   2 (  4.0)           1 (  2.0)         
                                                                                                                                     
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_EG_T_001 
Output File Name 
rt-eg-changecats1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.3.1B 
Title 1 
Electrocardiogram Change from Baseline Category Summary 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
350 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Each subject is counted only once using the longest change observed. 
 
Parameter 
Values 
Template ID 
SS_EG_T_001 
Output File Name 
rt-eg-changecats2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.3.2B 
Title 1 
Electrocardiogram Change from Baseline Category Summary 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Each subject is counted only once using the longest change observed. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
351 
Template SS_EG_T_002: ECG Category Summary 
------------------------------------------------------------------------------------------------------------------------------------ 
 
                                 BMS-663068          BMS-663068          BMS-663068          BMS-663068                              
                                 400 mg BID/         800 mg BID/         600 mg QD/          1200 mg QD/         ATV/r/              
ECG Parameter (unit)             RAL/TDF             RAL/TDF             RAL/TDF             RAL/TDF             RAL/TDF             
  Category (%)                   N = 50              N = 49              N = 51              N = 50              N = 51              
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
PR INTERVAL (MSEC)                                                                                                                   
  <200                             44 ( 88.0)          46 ( 93.9)          46 ( 90.2)          43 ( 86.0)          49 ( 96.1)         
  200 to <220                       4 (  8.0)           1 (  2.0)           5 (  9.8)           5 ( 10.0)           1 (  2.0)         
  220 to <240                       0                   2 (  4.1)           0                   0                   0                 
  240 to <260                       0                   0                   0                   0                   0                 
  260 to <280                       0                   0                   0                   0                   0                 
  280 to <300                       0                   0                   0                   0                   0                 
  >=300                             0                   0                   0                   0                   0                 
  NOT REPORTED                      2 (  4.0)           0                   0                   2 (  4.0)           1 (  2.0)         
                                                                                                                                     
QRS (MSEC)                                                                                                                           
  <100                             39 ( 78.0)          40 ( 81.6)          38 ( 74.5)          38 ( 76.0)          33 ( 64.7)         
  100 to <110                       8 ( 16.0)           8 ( 16.3)          12 ( 23.5)           5 ( 10.0)          12 ( 23.5)         
  110 to <120                       1 (  2.0)           1 (  2.0)           1 (  2.0)           5 ( 10.0)           5 (  9.8)         
  120 to <130                       0                   0                   0                   0                   0                 
  130 to <140                       0                   0                   0                   0                   0                 
  >=140                             0                   0                   0                   0                   0                 
  NOT REPORTED                      2 (  4.0)           0                   0                   2 (  4.0)           1 (  2.0)         
                                                                                                                                     
QTC [FRIDERICIA] (MSEC)                                                                                                              
  <400                              1 (  2.0)           4 (  8.2)           2 (  3.9)           2 (  4.0)           8 ( 15.7)         
  400 to <425                      17 ( 34.0)          14 ( 28.6)          25 ( 49.0)          29 ( 58.0)          21 ( 41.2)         
  425 to <450                      27 ( 54.0)          25 ( 51.0)          17 ( 33.3)          13 ( 26.0)          16 ( 31.4)         
  450 to <460                       3 (  6.0)           1 (  2.0)           5 (  9.8)           2 (  4.0)           3 (  5.9)         
  460 to <470                       0                   5 ( 10.2)           0                   1 (  2.0)           2 (  3.9)         
  470 to <480                       0                   0                   0                   0                   0                 
  480 to <490                       0                   0                   1 (  2.0)           0                   0                 
  >=490                             0                   0                   1 (  2.0)           1 (  2.0)           0                 
  NOT REPORTED                      2 (  4.0)           0                   0                   2 (  4.0)           1 (  2.0)         
                                                                                                                                     
  
  
  
------------------------------------------------------------------------------------------------------------------------------------ 
 
Parameter 
Values 
Template ID 
SS_EG_T_002 
Output File Name 
rt-eg-cats1.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
352 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.3.1C 
Title 1 
Electrocardiogram Category Summary 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
Each subject is counted only once using the longest interval observed. 
 
Parameter 
Values 
Template ID 
SS_EG_T_002 
Output File Name 
rt-eg-cats2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.3.2C 
Title 1 
Electrocardiogram Category Summary 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
Each subject is counted only once using the longest interval observed. 
 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
353 
Template GS_EG_L_X_001: ECG Listing 
Protocol: CN138112                                              Draft                                                   Page 1 of 11  
                                                          Electrocardiogram 
                                                         All Treated Subjects 
 
Treatment Group: TRT A 
------------------------------------------------------------------------------------------------------------------------------------  
                                                                                             Interval (msec)                           
Subject ID                                                    Study               HR      --------------------                         
  (Age/Gender/Race)       Period       Visit       Date       Day    Time   TRD#  (bpm)   PR   QRS   QT    QTC  Interpretation         
--------------------------------------
------------------------------------------------------------------------  
             SCREENING    Day -1     
    -1  09:50  -30D     66   169   91   402   421  NORMAL 
  (54/M/C)  
             SCREENING    Day -1     
    -1  16:47  -1H     103   180   78   346   405  ABNORMAL 
  (44/F/C)       
             SCREENING    Day -1     
    -1  17:11  -32D     87   200   70   334 
 
  (42/M/C)  
              SCREENING    Day -30    
   -44  09:50  -29D     65   165   92   383   399  NORMAL 
  (55/M/C)                SCREENING    Day -1     
    -1  13:53  -2H      77   173   93   383   434  ABNORMAL 
 
------------------------------------------------------------------------------------------------------------------------------------  
# Time relative to most recent dose 
Program Source: /wwbdm/ndp/prime/gssr/devtest/ecg/test/eg_st.sas                                                  07OCT2004:17:58:00 
 
 
Parameter 
Values 
Template ID 
GS_EG_L_X_001 
Output File Name 
rl-eg-ecgs1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.3.1D 
Title 1 
Electrocardiogram 
Title 2 
Treated Subjects - Stage 1 
Footnote 1 
# Time relative to most recent dose 
 
Parameter 
Values 
PPD
PPD
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
354 
Template ID 
GS_EG_L_X_001 
Output File Name 
rl-eg-ecgs2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.3.2D 
Title 1 
Electrocardiogram 
Title 2 
Treated Subjects - Stage 2 
Footnote 1 
# Time relative to most recent dose 
 
4.6.9 
Vital Signs and Physical Findings 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-vs-sums1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.4.1A 
Title 1 
Vital Sign Summary of Values and Changes from Baseline over Time  
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Parameters are: Sitting Systolic Blood Pressure, Sitting Diastolic Blood Pressure, Sitting Heart Rate (beats/min), Respiration Rate 
(/min) and Temperature (C). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-vs-sums2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.4.2A 
Title 1 
Vital Sign Summary of Values and Changes from Baseline over Time  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
355 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Parameters are: Sitting Systolic Blood Pressure, Sitting Diastolic Blood Pressure, Sitting Heart Rate (beats/min), Respiration Rate 
(/min) and Temperature (C). 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
356 
Template GS_VS_L_X_006: Vital Signs Listing by Treatment Group 
Protocol: IM101031                                               Draft                                                  Page 1 of 11 
Vital Signs 
All Treated Subjects 
 
         Treatment Group: DRUG A 
         ---------------------------------------------------------------------------------------------------------------- 
                                                                                           Blood      Heart        Resp   
         Subject ID                                                       Study            Pressure   Rate   Temp  Rate   
           (Age/Gender/Race)       Period        Visit        Date        Day    Position  (mmHg)     (bpm)  (C)   (/Min) 
         
-----------------------------------------
------------------------------------------------- 
         
              SCREENING     DAY -26     
    -26  SITTING   138 / 90      64  36.2      32 
           (46/M/C)                PHASE I       DAY 1       
      1  SITTING   120 / 65      68  36.2      34 
                                                             
         SITTING   126 / 70      72  36.5      33 
                                                 DAY 13      
     13  SITTING   116 / 82      72  36.7      31 
                                                             
         SITTING   120 / 84      68  36.6      30 
                                   PHASE II      DAY 31      
     31  SITTING   110 / 70      72  36.6      33 
                                                             
         SITTING   122 / 75      80  36.7      32 
                                   PHASE III     DAY 59      
     59  SITTING   118 / 76      68  36.7      31 
                                                             
         SITTING   122 / 68      68  36.7      32 
                                                             
         STANDING  134 / 78      70         
                                                 DAY 87      
     87  SITTING   134 / 84      72  36.9      32 
                                                             
         SITTING   130 / 80      70  36.6      33 
                                                 DAY 122     
    122  SITTING   128 / 86      70  36.9      32 
                                                             
         SITTING   124 / 82      70  37.3      31 
                                                 DAY 142     
    142  SITTING   126 / 86      70  36.7      32 
                                                             
         SITTING   130 / 80      78  36.7      33 
                                                 DAY 167     
    167  SITTING   128 / 84      68  37.2      33 
                                                             
         SITTING   132 / 80      70  36.9      32 
                                                 DAY 199     
    199  SITTING   132 / 84      80  36.5      32 
                                                             
         SITTING   130 / 86      78  36.6      30 
                                   POST ST       DAY 223     
    223  SITTING   128 / 84      76  36.9      32 
         
         
             SCREENING     DAY -1      
    -26  SITTING   138 / 90      64  36.2      32 
           (56/F/C)                                          
      1  SITTING       / 80      68  36.2      34 
                                                             
         SITTING   126 / 70      72  36.5      33 
                                   PHASE I       DAY 7       
     13  SITTING   116 / 82      72  36.7      31 
                                                             
         SITTING   122 / 75      80  36.6      32 
                                   PHASE II      DAY 14      
     31  SITTING   110 / 70      72  36.6      32 
                                   PHASE III     DAY 21      
     87  SITTING   134 / 84      72  37.2      32 
                                                              
         SITTING   130 / 80      70  36.9      33 
 
------------------------------------------------------------------------------------------------------------------------------------  
Program Source: /wwbdm/ndp/prime/gssr/devtest/dem/test/vs_st.sas                                                  07SEP2004:14:35:00 
 
Parameter 
Values 
Template ID 
GS_VS_L_X_006 
PPD
PPD
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
357 
Output File Name 
rl-vs-lists1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.4.1B 
Title 1 
Vital Signs 
Title 2 
Treated Subjects - Stage 1 
 
Parameter 
Values 
Template ID 
GS_VS_L_X_006 
Output File Name 
rl-vs-lists2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.4.2B 
Title 1 
Vital Signs 
Title 2 
Treated Subjects - Stage 2 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-pm-sums1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 7.4.1C 
Title 1 
Physical Measurements Summary of Values and Changes from Baseline over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Parameters are: Weight (kg) and BMI (kg/m2). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
358 
Output File Name 
rt-pm-sums2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 7.4.2C 
Title 1 
Physical Measurements Summary of Values and Changes from Baseline over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Parameters are: Weight (kg) and BMI (kg/m2). 
 
4.6.10 
Other Observations Related to Safety 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-bmrenals1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.7.5.1A 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Biomarker Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 1 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-bmrenals2.lst 
Purpose 
WK96S2 
Table No. 
Table S.7.5.2A 
Title 1 
Laboratory Test Results  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
359 
Title 2 
Summary Statistics for Renal Biomarker Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 2 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-bmrenals1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.7.5.1B 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Biomarker Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 1 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-bmrenals2.lst 
Purpose 
WK96S2 
Table No. 
Table S.7.5.2B 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Biomarker Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 2 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
360 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-pchbmrenals1.lst 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.7.5.1C 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Biomarker Values and Percent Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-pchbmrenals2.lst 
Purpose 
WK96S2 
Table No. 
Table S.7.5.2C 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Biomarker Values and Percent Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-pchbmrenals1.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
361 
Purpose 
WK96S1, WK96S2 
Table No. 
Table S.7.5.1D 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Biomarker Values and Percent Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-pchbmrenals2.lst 
Purpose 
WK96S2 
Table No. 
Table S.7.5.2D 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Renal Biomarker Values and Percent Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include urinary beta-2-microglobilin/creatinine and fractional excretion of phosphorous. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-bmbones1.lst 
Purpose 
WK24S1 
Table No. 
Table S.7.5.1E 
Title 1 
Laboratory Test Results  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
362 
Title 2 
Summary Statistics for Bone Biomarker Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 1 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-bmbones2.lst 
Purpose 
WK24S2 
Table No. 
Table S.7.5.2E 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Bone Biomarker Values and Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 2 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-bmbones1.lst 
Purpose 
WK24S1 
Table No. 
Table S.7.5.1F 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Bone Biomarker Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 1 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
363 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-bmbones2.lst 
Purpose 
WK24S2 
Table No. 
Table S.7.5.2F 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Bone Biomarker Values and Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 2 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-pchbmbones1.lst 
Purpose 
WK24S1 
Table No. 
Table S.7.5.1G 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Bone Biomarker Values and Percent Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-lb-pchbmbones2.lst 
Purpose 
WK24S2 
Table No. 
Table S.7.5.2G 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
364 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Bone Biomarker Values and Percent Change from Baseline - US Units 
Title 3 
Treated Subjects - Stage 2 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-pchbmbones1.lst 
Purpose 
WK24S1 
Table No. 
Table S.7.5.1H 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Bone Biomarker Values and Percent Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 1 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-zl-pchbmbones2.lst 
Purpose 
WK24S2 
Table No. 
Table S.7.5.2H 
Title 1 
Laboratory Test Results  
Title 2 
Summary Statistics for Bone Biomarker Values and Percent Change from Baseline - SI Units 
Title 3 
Treated Subjects - Stage 2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
365 
Layout notes 
Change spanning header to “Percent Change From Baseline”. 
Programming notes 
Include N-terminal Propeptide of Type 1 procollagen (P1NP) and Cross-linked C-telopeptide of Type 1 collagen (CTx). 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-ub2s1 
Purpose 
WK24S1 
Table No. 
Figure S.7.5.1A 
Title 1 
Urinary Beta-2-Microglobulin/Creatinine Median Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: Urinary Beta-2-Microglobulin/Creatinine Median Percent Change from Baseline (IQR) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-ub2s2 
Purpose 
WK24S2 
Table No. 
Figure S.7.5.2A 
Title 1 
Urinary Beta-2-Microglobulin/Creatinine Median Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: Urinary Beta-2-Microglobulin/Creatinine Median Percent Change from Baseline (IQR) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
366 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-feps1 
Purpose 
WK24S1 
Table No. 
Figure S.7.5.1B 
Title 1 
Fractional Excretion of Phosphorous Median Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: Fractional Excretion of Phosphorous Median Change from Baseline (IQR) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-feps2 
Purpose 
WK24S2 
Table No. 
Figure S.7.5.2B 
Title 1 
Fractional Excretion of Phosphorous Median Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: Fractional Excretion of Phosphorous Median Change from Baseline (IQR) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-pchp1nps1 
Purpose 
WK96S1, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
367 
Table No. 
Figure S.7.5.1C 
Title 1 
N-Terminal Propeptide of Type 1 Procollagen Median Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: P1NP Median Percent Change from Baseline (IQR) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-pchp1nps2 
Purpose 
WK96S2 
Table No. 
Figure S.7.5.2C 
Title 1 
N-Terminal Propeptide of Type 1 Procollagen Median Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: P1NP Median Percent Change from Baseline (IQR) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-pchctxs1 
Purpose 
WK96S1, WK96S2 
Table No. 
Figure S.7.5.1D 
Title 1 
Cross-Linked C-Telopeptide of Type 1 Collagen Median Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Y-axis label: CTx Median Percent Change from Baseline (IQR) 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
368 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 
Parameter 
Values 
Template ID 
GS_LB_G_002 
Output File Name 
rg-lb-pchctxs2 
Purpose 
WK96S2 
Table No. 
Figure S.7.5.2D 
Title 1 
Cross-Linked C-Telopeptide of Type 1 Collagen Median Percent Change from Baseline Over Time 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Y-axis label: CTx Median Percent Change from Baseline (IQR) 
X-axis label: Time (Weeks) 
Include horizontal reference line at Y=0. 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
4.7 
Pharmacokinetic Results 
 
Template MS_PK_T_004:  Summary Statistics for PK Parameters 
-------------------------------------------------------------------------------------------------- 
                                                                               TREATMENT 
                                         --------------------------------------------------------- 
                      PARAMETER    UNIT       STATISTIC           A             B              C                              
-------------------------------------------------------------------------------------------------- 
                                                                                                                            
                      Cmax        ng/mL              N           xx            xx             xx                           
                                                  MEAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   S.D.     xxxx.xx       xxxx.xx        xxxx.xx       
                                              GEO.MEAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   %CV           xx            xx             xx 
                                                MEDIAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   MIN      xxxx.xx       xxxx.xx        xxxx.xx                           
                                                   MAX      xxxx.xx       xxxx.xx        xxxx.xx      
 
                      Tmax         h                 N           xx            xx             xx                           
                                                  MEAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   S.D.      xxxx.xx      xxxx.xx       xxxx.xx       
                                              GEO.MEAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   %CV           xx            xx             xx 
                                                MEDIAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   MIN      xxxx.xx       xxxx.xx        xxxx.xx                            
                                                   MAX      xxxx.xx       xxxx.xx        xxxx.xx        
                           
                                                                                                            
                      AUC        ng.h/mL            N           xx            xx             xx                           
                                                  MEAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   S.D.      xxxx.xx      xxxx.xx       xxxx.xx       
                                              GEO.MEAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   %CV           xx            xx             xx 
                                                MEDIAN      xxxx.xx       xxxx.xx        xxxx.xx       
                                                   MIN      xxxx.xx       xxxx.xx        xxxx.xx                            
                                                   MAX      xxxx.xx       xxxx.xx        xxxx.xx                            
 
                     
           
-------------------------------------------------------------------------------------------------- 
 
Parameter 
Values 
Template ID 
MS_PK_T_004 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
370 
Output File Name 
rt-pk-sumbmss1.lst 
Purpose 
WK24S1 
Table No. 
Table S.8.1.1A 
Title 1 
Summary Statistics of BMS-955176 Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
Layout notes 
PK parameters: Cmax, Tmax, Ctau, C0, AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_T_004 
Output File Name 
rt-pk-sumbmss2.lst 
Purpose 
WK24S2 
Table No. 
Table S.8.1.2A 
Title 1 
Summary Statistics of BMS-955176 Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
Layout notes 
PK parameters: Cmax, Tmax, Ctau, C0, AUC(TAU) 
 
 
Parameter 
Values 
Template ID 
MS_PK_T_004 
Output File Name 
rt-pk-sumatvs1.lst 
Purpose 
WK24S1 
Table No. 
Table S.8.1.1B 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
371 
Title 1 
Summary Statistics of ATV Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Layout notes 
PK parameters: Cmax, Tmax, Ctau, C0, AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_T_004 
Output File Name 
rt-pk-sumatvs2.lst 
Purpose 
WK24S2 
Table No. 
Table S.8.1.2B 
Title 1 
Summary Statistics of ATV Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG  
E = TDF + ATV/r + DTG 
Layout notes 
PK parameters: Cmax, Tmax, Ctau, C0, AUC(TAU) 
 
 
Parameter 
Values 
Template ID 
MS_PK_T_004 
Output File Name 
rt-pk-sumdtgs1.lst 
Purpose 
WK24S1 
Table No. 
Table S.8.1.1C 
Title 1 
Summary Statistics of DTG Pharmacokinetic Parameters  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
372 
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Layout notes 
PK parameters: Cmax, Tmax, Ctau, C0, AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_T_004 
Output File Name 
rt-pk-sumdtgs2.lst 
Purpose 
WK24S2 
Table No. 
Table S.8.1.2C 
Title 1 
Summary Statistics of DTG Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Layout notes 
PK parameters: Cmax, Tmax, Ctau, C0, AUC(TAU) 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
373 
Template MS_PK_T_005:  In-text Table for Summary Statistics for PK Parameters 
 
------------------------------------------------------------------------- 
                                        TREATMENT 
PARAMETER             -------------------------------------------------- 
STATISTIC                    A               B               C                  
------------------------------------------------------------------------- 
Cmax (ng/mL)               
Geo.Mean [N]              199 [12]        640 [12]        493 [12] 
(%CV)                       (25)            (21)            (27)    
 
AUC(0-T)(ng.h/mL)          
Geo.Mean [N]              721 [12]        534 [12]        503 [12] 
(%CV)                       (15)            (27)            (23)    
 
AUC(INF)(ng.h/mL)          
Geo.Mean [N]              696 [12]        612 [12]        523 [12] 
(%CV)                       (22)            (23)            (21)    
 
Tmax (h)                   
Median [N]               4.10 [15]       1.75 [16]       4.00 [16] 
(Min - Max)             (3.00 - 6.00)   (1.00 - 5.00)   (3.00 - 8.00) 
 
T-HALF (h)                 
Mean [N]                 9.70 [15]       8.71 [16]       8.90 [16] 
(SD)                      (2.862)         (3.912)         (3.762) 
------------------------------------------------------------------------- 
 
 
Parameter 
Values 
Template ID 
MS_PK_T_005 
Output File Name 
rt-pk-itsumbmss1.lst 
Purpose 
WK24S1 
Table No. 
Table 9.2.1A 
Title 1 
Summary Statistics of BMS-955176 Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
Programming notes 
This is an in-text table 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
374 
Parameter 
Values 
Template ID 
MS_PK_T_005 
Output File Name 
rt-pk-itsumbmss2.lst 
Purpose 
WK24S2 
Table No. 
Table 9.2.2A 
Title 1 
Summary Statistics of BMS-955176 Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
Programming notes 
This is an in-text table 
 
Parameter 
Values 
Template ID 
MS_PK_T_005 
Output File Name 
rt-pk-itsumdtgs1.lst 
Purpose 
WK24S1 
Table No. 
Table 9.3.1A 
Title 1 
Summary Statistics of DTG Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Programming notes 
This is an in-text table 
 
Parameter 
Values 
Template ID 
MS_PK_T_005 
Output File Name 
rt-pk-itsumdtgs2.lst 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
375 
Purpose 
WK24S2 
Table No. 
Table 9.3.2A 
Title 1 
Summary Statistics of DTG Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Programming notes 
This is an in-text table 
 
Parameter 
Values 
Template ID 
MS_PK_T_005 
Output File Name 
rt-pk-itsumatvs1.lst 
Purpose 
WK24S1 
Table No. 
Table 9.4.1A 
Title 1 
Summary Statistics of ATV Pharmacokinetic Parameters  
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Programming notes 
This is an in-text table 
 
Parameter 
Values 
Template ID 
MS_PK_T_005 
Output File Name 
rt-pk-itsumatvs2.lst 
Purpose 
WK24S2 
Table No. 
Table 9.4.2A 
Title 1 
Summary Statistics of ATV Pharmacokinetic Parameters  


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
376 
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Programming notes 
This is an in-text table 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
377 
Template MS_PK_T_006:  Statistical Analysis for PK Parameters 
 
PK Parameter 
------------------------------------------------------------------------------------------------------------------------------- 
                                           On Natural Logarithmic Scale                           on Original Scale 
--------------------------------------------------------------------------       ---------------------------------------------- 
TREATMENT         ADJUSTED STANDARD                                                   ADJUSTED 
AND COMPARISON        MEAN    ERROR    DF        T       Pr > |T|       90% CI       GEO MEAN           90% CI 
---------------  ----------  -----    ---     ------   -----------   --------------   ----------   ---------------- 
      A             X.XXX    X.XXX    X.X     XX.XX      0.XXXX     (X.XXX,X.XXX)      XXXX.XXX   (XXXX.XXX,XXXX.XXX) 
      B             X.XXX    X.XXX    X.X     XX.XX      0.XXXX     (X.XXX,X.XXX)      XXXX.XXX   (XXXX.XXX,XXXX.XXX) 
      B vs A        X.XXX    X.XXX    X.X      X.XX      0.XXXX     (X.XXX,X.XXX)       X.XXX       (X.XXX,X.XXX) 
------------------------------------------------------------------------------------------------------------------------------- 
MODEL INFORMATION 
------------------------------------------------- 
Covariance Structure        - Unstructured 
Subject Effect              - USUBJID 
Estimation Method           - REML 
Residual Variance Method    - None 
Fixed Effects SE Method     - Prasad-Rao-Jeske-Kackar-Harville 
Degrees of Freedom Method   - Kenward-Roger 
Fixed Effects               - TRT SEQ PERIOD USUBJID 
 
Covariance Matrix Block 
------------------------------------- 
Row     Col 1     Col 2     COL 3      
1       X.XXX     X.XXX     X.XXX      
2       X.XXX     X.XXX     X.XXX      
3       X.XXX     X.XXX     X.XXX      
 
 
 
Parameter 
Values 
Template ID 
MS_PK_T_006 
Output File Name 
rt-pk-mixedbmsdtgs1.lst  
Purpose 
WK24S1 
Table No. 
Table  S.8.2.5.1A 
Title 1 
Effect of BMS-955176 on Exposure of DTG 
Title 2 
PK Parameters DTG Cmax, Ctau and AUC(TAU) 
Title 3 
BMS-955176 120 mg QD+ ATV/r + DTG versus TDF + ATV/r + DTG 
Title 4 
Evaluable PK Population - Stage 1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
378 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
 
Parameter 
Values 
Template ID 
MS_PK_T_006 
Output File Name 
rt-pk-mixedbms120dtgs2.lst  
Purpose 
WK24S2 
Table No. 
Table  S.8.2.5.2A 
Title 1 
Effect of BMS-955176 on Exposure of DTG 
Title 2 
PK Parameters DTG Cmax, Ctau and AUC(TAU) 
Title 3 
BMS-955176 120 mg QD+ ATV + DTG versus Historical Data 
Title 4 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
F = Historical Data 
 
Parameter 
Values 
Template ID 
MS_PK_T_006 
Output File Name 
rt-pk-mixedbms180dtgs2.lst  
Purpose 
WK24S2 
Table No. 
Table  S.8.2.5.2B 
Title 1 
Effect of BMS-955176 on Exposure of DTG 
Title 2 
PK Parameters DTG Cmax, Ctau and AUC(TAU) 
Title 3 
BMS-955176 180 mg QD+ ATV + DTG versus Historical Data 
Title 4 
Evaluable PK Population - Stage 2 
Footnote 1 
D = BMS 955176 180 mg QD + ATV + DTG 
F = Historical Data 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
379 
Template MS_PK_T_007:  In-text Table for Statistical Analysis for PK Parameters 
 
------------------------------------------------------------------------------------------        
 PK                    TREATMENT            ADJUSTED 
 PARAMETER             AND COMPARISON       GEOMETRIC MEAN             90% CI 
------------------------------------------------------------------------------------------        
 CMAX(ng/mL)               A                   XX.XX              (XX.XX,XX.XX) 
                           B                   XX.XX              (XX.XX,XX.XX) 
                           B vs A              X.XXX              (X.XXX,X.XXX) 
 
 CTAU(ng/mL)               A                   XX.XX              (XX.XX,XX.XX) 
                           B                   XX.XX              (XX.XX,XX.XX) 
                           B vs A              X.XXX              (X.XXX,X.XXX) 
 
 AUC(TAU)(ng.h/mL)         A                   XX.XX              (XX.XX,XX.XX) 
                           B                   XX.XX              (XX.XX,XX.XX) 
                           B vs A              X.XXX              (X.XXX,X.XXX) 
 
 
------------------------------------------------------------------------------------------        
 
Parameter 
Values 
Template ID 
MS_PK_T_007 
Output File Name 
rt-pk-itmixedbmss1.lst  
Purpose 
WK24S1 
Table No. 
Table  9.3.1.1A 
Title 1 
In-text Table of Effect of BMS-955176 on Exposure of DTG 
Title 2 
PK Parameters DTG Cmax, Ctau and AUC(TAU) 
Title 3 
BMS-955176 120 mg QD+ ATV/r + DTG versus TDF + ATV/r + DTG 
Title 4 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Source: Table S.8.2.5.1A 
Programming notes 
This is an in-text table 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
380 
Parameter 
Values 
Template ID 
MS_PK_T_007 
Output File Name 
rt-pk-itmixedbms120s2.lst  
Purpose 
WK24S2 
Table No. 
Table  9.3.1.2A 
Title 1 
In-text Table of Effect of BMS-955176 on Exposure of DTG 
Title 2 
PK Parameters DTG Cmax, Ctau and AUC(TAU) 
Title 3 
BMS-955176 120 mg QD+ ATV + DTG versus TDF + ATV/r + DTG 
Title 4 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
F = Historical Data 
Footnote 2 
Source: Table S.8.2.5.2A 
Programming notes 
This is an in-text table 
 
Parameter 
Values 
Template ID 
MS_PK_T_007 
Output File Name 
rt-pk-itmixedbms180s2.lst  
Purpose 
WK24S2 
Table No. 
Table  9.3.1.2B 
Title 1 
In-text Table of Effect of BMS-955176 on Exposure of DTG 
Title 2 
PK Parameters DTG Cmax, Ctau and AUC(TAU) 
Title 3 
BMS-955176 180 mg QD+ ATV + DTG versus TDF + ATV/r + DTG 
Title 4 
Evaluable PK Population - Stage 2 
Footnote 1 
D = BMS 955176 180 mg QD + ATV + DTG 
F = Historical Data 
Footnote 2 
Source: Table S.8.2.5.2B 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
381 
Programming notes 
This is an in-text table 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
382 
Template MS_PK_L_005:  Listing for PK Parameters 
 
------------------------------------------------------------------------------------------------------------------------------------ 
                          Study      Cmax      Tmax     Ctau       C0        AUC(TAU)        Exclusion 
  Subject      Treatment    Day     (ng/mL)     (h)  (ng*h/mL)  (ng*h/mL)                    Flag 
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                                                                     
XXXXXXXX-X-X      A           1      xx.xx     xx.xx    xx.xx     xx.xx         xx.xx         3    
                             14      xx.xx     xx.xx    xx.xx     xx.xx         xx.xx              
                                                                                                                                     
XXXXXXXX-X-X      B           1      xx.xx     xx.xx    xx.xx     xx.xx         xx.xx              
                             14      xx.xx     xx.xx    xx.xx     xx.xx         xx.xx              
                                                                                                                                     
------------------------------------------------------------------------------------------------------------------------------------ 
 
 
Parameter 
Values 
Template ID 
MS_PK_L_005 
Output File Name 
rl-pk-listbms01s1.lst 
Purpose 
WK24S1 
Table No. 
Appendix 8.2.5A 
Title 1 
Listing of BMS-955176 Pharmacokinetic Parameters 
Title 2 
PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Note:# Values are excluded from PK Summary Statistics  
Footnote 3 
Exclusion Flag Definitions: 1= All Parameters, 2= CMAX, 3= Tmax, 4= Ctau, 5= C0, 6= AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_L_005 
Output File Name 
rl-pk-listbms01s2.lst 
Purpose 
WK24S2 
Table No. 
Appendix 8.2.5A 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
383 
Title 1 
Listing of BMS-955176 Pharmacokinetic Parameters 
Title 2 
PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Note:# Values are excluded from PK Summary Statistics  
Footnote 3 
Exclusion Flag Definitions: 1= All Parameters, 2= CMAX, 3= Tmax, 4= Ctau, 5= C0, 6= AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_L_005 
Output File Name 
rl-pk-listatv01s1.lst 
Purpose 
WK24S1 
Table No. 
Appendix 8.2.5B 
Title 1 
Listing of ATV Pharmacokinetic Parameters 
Title 2 
PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Note:# Values are excluded from PK Summary Statistics  
Footnote 3 
Exclusion Flag Definitions: 1= All Parameters, 2= CMAX, 3= Tmax, 4= Ctau, 5= C0, 6= AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_L_005 
Output File Name 
rl-pk-listatv01s2.lst 
Purpose 
WK24S2 
Table No. 
Appendix 8.2.5B 
Title 1 
Listing of ATV Pharmacokinetic Parameters 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
384 
Title 2 
PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Note:# Values are excluded from PK Summary Statistics  
Footnote 3 
Exclusion Flag Definitions: 1= All Parameters, 2= CMAX, 3= Tmax, 4= Ctau, 5= C0, 6= AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_L_005 
Output File Name 
rl-pk-listdtg01s1.lst 
Purpose 
WK24S1 
Table No. 
Appendix 8.2.5C 
Title 1 
Listing of DTG Pharmacokinetic Parameters 
Title 2 
PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Note:# Values are excluded from PK Summary Statistics  
Footnote 3 
Exclusion Flag Definitions: 1= All Parameters, 2= CMAX, 3= Tmax, 4= Ctau, 5= C0, 6= AUC(TAU) 
 
Parameter 
Values 
Template ID 
MS_PK_L_005 
Output File Name 
rl-pk-listdtg01s2.lst 
Purpose 
WK24S2 
Table No. 
Appendix 8.2.5C 
Title 1 
Listing of DTG Pharmacokinetic Parameters 
Title 2 
PK Population - Stage 2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
385 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Note:# Values are excluded from PK Summary Statistics  
Footnote 3 
Exclusion Flag Definitions: 1= All Parameters, 2= CMAX, 3= Tmax, 4= Ctau, 5= C0, 6= AUC(TAU) 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
386 
Template MS_PK_L_001:  Listing of Plasma Concentration-Time Data  
------------------------------------------------------------------------------------------------------------------------------------ 
                                                                                          
                                            STUDY                NOMINAL         ACTUAL         CONCENTRATION       EXCLUSION  
                SUBJECT      TREATMENT      DAY                  TIME(h)         TIME(h)               (ng/mL)      FLAG 
------------------------------------------------------------------------------------------------------------------------------------ 
               
                                                                                  
               
     A            14                      0.00           0.00                <LLQ 
                                                                     1.00           1.00               36.39 
                                                                     1.50           1.50              100.02 
                                                                     2.00           2.00              108.94 
                                                                     3.00           3.00               99.00 
                                                                     4.00           4.00               79.14 
                                                                     8.00           8.00               46.23 
                                                                    12.00          12.00               22.94 
                                                                    18.00          18.00               15.75 
                                                                    24.00          24.00               11.73 
                                                                    48.00          48.00                3.30 
                                                                    72.00          72.00                1.12 
                                                                    96.00          96.00                <LLQ 
                                                                   120.00         120.02                <LLQ 
                                                                   144.00         144.00                <LLQ 
 
 
 
------------------------------------------------------------------------------------------------------------------------------------ 
 
 
Parameter 
Values 
Template ID 
MS_PK_L_001 
Output File Name 
rl-pk-cpar1bmss1.lst 
Purpose 
WK24S1 
Table No. 
Appendix 8.2.1A 
Title 1 
Listing of BMS-955176 Plasma Concentration – Time Data 
Title 2 
PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Note: <LLQ = Below Lower Limit of Quantification (xx ng/mL) 
 
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
387 
Parameter 
Values 
Template ID 
MS_PK_L_001 
Output File Name 
rl-pk-cpar1bmss2.lst 
Purpose 
WK24S2 
Table No. 
Appendix 8.2.1A 
Title 1 
Listing of BMS-955176 Plasma Concentration – Time Data 
Title 2 
PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Note: <LLQ = Below Lower Limit of Quantification (xx ng/mL) 
 
Parameter 
Values 
Template ID 
MS_PK_L_001 
Output File Name 
rl-pk-cpar1atvs1.lst 
Purpose 
WK24S1 
Table No. 
Appendix 8.2.1B 
Title 1 
Listing of ATV Plasma Concentration – Time Data 
Title 2 
PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Note: <LLQ = Below Lower Limit of Quantification (xx ng/mL) 
 
Parameter 
Values 
Template ID 
MS_PK_L_001 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
388 
Output File Name 
rl-pk-cpar1atvs2.lst 
Purpose 
WK24S2 
Table No. 
Appendix 8.2.1B 
Title 1 
Listing of ATV Plasma Concentration – Time Data 
Title 2 
PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Note: <LLQ = Below Lower Limit of Quantification (xx ng/mL) 
 
Parameter 
Values 
Template ID 
MS_PK_L_001 
Output File Name 
rl-pk-cpar1dtgs1.lst 
Purpose 
WK24S1 
Table No. 
Appendix 8.2.1C 
Title 1 
Listing of DTG Plasma Concentration – Time Data 
Title 2 
PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Note: <LLQ = Below Lower Limit of Quantification (xx ng/mL) 
 
Parameter 
Values 
Template ID 
MS_PK_L_001 
Output File Name 
rl-pk-cpar1dtgs2.lst 
Purpose 
WK24S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
389 
Table No. 
Appendix 8.2.1C 
Title 1 
Listing of DTG Plasma Concentration – Time Data 
Title 2 
PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Note: <LLQ = Below Lower Limit of Quantification (xx ng/mL) 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
390 
Template MS_PK_G_002:  Individual Plot of Plasma Concentrations vs. Time 
 
 
Subject =
Lin
Saxagliptin Plasma Concentration (ng/mL)
0
3
6
9
12
15
18
21
24
27
30
33
Time (h)
0
2
4
6
8
10
12
14
16
18
20
22
24
Semi-Logarithmic Scale
TRT A
TRT B
Saxagliptin Plasma Concentration (ng/mL)
0.01
0.10
1.00
10.00
100.00
1000.00
Time (h)
0
2
4
6
8
10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
PPD


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
391 
Parameter 
Values 
Template ID 
MS_PK_G_002 
Output File Name 
rg-pk-cpar3bmss1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.3A 
Title 1 
Plots of Individual BMS-955176 Plasma Concentration Profiles vs. Time  
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Notes: LLOQ – xx ng/mL; <LLOQ values were treated as “missing” for calculation of mean values 
Layout notes 
x-axis label: time 
y-axis label: BMS-955176 concentration (ng/mL) 
Programming notes 
1. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
 2. Treatment and/or Study Day overlay, as appropriate 
 3. Add in dotted line for LLOQ value 
 4. Cartesian and semi-log plots for each individual subject on the same page 
 
Parameter 
Values 
Template ID 
MS_PK_G_002 
Output File Name 
rg-pk-cpar3bmss2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.3A 
Title 1 
Plots of Individual BMS-955176 Plasma Concentration Profiles vs. Time  
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
392 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Notes: LLOQ – xx ng/mL; <LLOQ values were treated as “missing” for calculation of mean values 
Layout notes 
x-axis label: time 
y-axis label: BMS-955176 concentration (ng/mL) 
Programming notes 
1. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
 2. Treatment and/or Study Day overlay, as appropriate 
 3. Add in dotted line for LLOQ value 
 4. Cartesian and semi-log plots for each individual subject on the same page 
 
 
Parameter 
Values 
Template ID 
MS_PK_G_002 
Output File Name 
rg-pk-cpar3atvs1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.3B 
Title 1 
Plots of Individual ATV Plasma Concentration Profiles vs. Time  
Title 2 
Evaluable PK Population- Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Notes: LLOQ – xx ng/mL; <LLOQ values were treated as “missing” for calculation of mean values 
Layout notes 
x-axis label: time 
y-axis label: ATV concentration (ng/mL) 
Programming notes 
1. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
393 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
 2. Treatment and/or Study Day overlay, as appropriate 
 3. Add in dotted line for LLOQ value 
 4. Cartesian and semi-log plots for each individual subject on the same page 
 
Parameter 
Values 
Template ID 
MS_PK_G_002 
Output File Name 
rg-pk-cpar3atvs2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.3B 
Title 1 
Plots of Individual ATV Plasma Concentration Profiles vs. Time  
Title 2 
Evaluable PK Population- Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Footnote 2 
Notes: LLOQ – xx ng/mL; <LLOQ values were treated as “missing” for calculation of mean values 
Layout notes 
x-axis label: time 
y-axis label: ATV concentration (ng/mL) 
Programming notes 
1. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
 2. Treatment and/or Study Day overlay, as appropriate 
 3. Add in dotted line for LLOQ value 
 4. Cartesian and semi-log plots for each individual subject on the same page 
 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
394 
Template ID 
MS_PK_G_002 
Output File Name 
rg-pk-cpar3dtgs1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.3C 
Title 1 
Plots of Individual DTG Plasma Concentration Profiles vs. Time  
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Footnote 2 
Notes: LLOQ – xx ng/mL; <LLOQ values were treated as “missing” for calculation of mean values 
Layout notes 
x-axis label: time 
y-axis label: DTG concentration (ng/mL) 
Programming notes 
1. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
 2. Treatment and/or Study Day overlay, as appropriate 
 3. Add in dotted line for LLOQ value 
 4. Cartesian and semi-log plots for each individual subject on the same page 
 
Parameter 
Values 
Template ID 
MS_PK_G_002 
Output File Name 
rg-pk-cpar3dtgs2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.3C 
Title 1 
Plots of Individual DTG Plasma Concentration Profiles vs. Time  
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
395 
E = TDF + ATV/r + DTG 
Footnote 2 
Notes: LLOQ – xx ng/mL; <LLOQ values were treated as “missing” for calculation of mean values 
Layout notes 
x-axis label: time 
y-axis label: DTG concentration (ng/mL) 
Programming notes 
1. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
 2. Treatment and/or Study Day overlay, as appropriate 
 3. Add in dotted line for LLOQ value 
 4. Cartesian and semi-log plots for each individual subject on the same page 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
396 
Template MS_PK_G_001:  Overlay of Individual Matrix Concentration vs. Time  
 
 
Parameter 
Values 
Template ID 
MS_PK_G_001 
Output File Name 
rg-pk-cpar1bmss1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.1A 
Title 1 
Overlay of Individual BMS-955176 Plasma Concentration Profile vs. Time by Treatment 
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
397 
B = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: BMS955176 concentration (ng/mL) 
Programming notes 
1. Treatment and/or Study Day overlay, as appropriate. 
2. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
3. Cartesian and semi-log plots on the same page (sometimes referred to as a spaghetti plot as there are no symbols in the profiles) 
 
Parameter 
Values 
Template ID 
MS_PK_G_001 
Output File Name 
rg-pk-cpar1bmss2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.1A 
Title 1 
Overlay of Individual BMS-955176 Plasma Concentration Profile vs. Time by Treatment 
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: BMS955176 concentration (ng/mL) 
Programming notes 
1. Treatment and/or Study Day overlay, as appropriate. 
2. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
3. Cartesian and semi-log plots on the same page (sometimes referred to as a spaghetti plot as there are no symbols in the profiles) 
 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
398 
Parameter 
Values 
Template ID 
MS_PK_G_001 
Output File Name 
rg-pk-cpar1atvs1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.1B 
Title 1 
Overlay of Individual ATV Plasma Concentration Profile vs. Time by Treatment 
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 60 mg QD + TDF/FTC 
B = BMS 955176 120 mg QD + TDF/FTC 
C = BMS 955176 180 mg QD + TDF/FTC 
D = EFV 600 mg QD + TDF/FTC 
Layout notes 
x-axis label: time 
y-axis label: ATV concentration (ng/mL) 
Programming notes 
1. Treatment and/or Study Day overlay, as appropriate. 
2. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
3. Cartesian and semi-log plots on the same page (sometimes referred to as a spaghetti plot as there are no symbols in the profiles) 
 
Parameter 
Values 
Template ID 
MS_PK_G_001 
Output File Name 
rg-pk-cpar1atvs2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.1B 
Title 1 
Overlay of Individual ATV Plasma Concentration Profile vs. Time by Treatment 
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
399 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: ATV concentration (ng/mL) 
Programming notes 
1. Treatment and/or Study Day overlay, as appropriate. 
2. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
3. Cartesian and semi-log plots on the same page (sometimes referred to as a spaghetti plot as there are no symbols in the profiles) 
 
Parameter 
Values 
Template ID 
MS_PK_G_001 
Output File Name 
rg-pk-cpar1dtgs1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.1A 
Title 1 
Overlay of Individual DTG Plasma Concentration Profile vs. Time by Treatment 
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: DTG concentration (ng/mL) 
Programming notes 
1. Treatment and/or Study Day overlay, as appropriate. 
2. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
3. Cartesian and semi-log plots on the same page (sometimes referred to as a spaghetti plot as there are no symbols in the profiles) 
 
Parameter 
Values 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
400 
Template ID 
MS_PK_G_001 
Output File Name 
rg-pk-cpar1dtgs2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.1A 
Title 1 
Overlay of Individual DTG Plasma Concentration Profile vs. Time by Treatment 
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: DTG concentration (ng/mL) 
Programming notes 
1. Treatment and/or Study Day overlay, as appropriate. 
2. There should be two plots (on same page): 
    a. Cartesian Plot over 24 h or tau (to show Cmax differences) 
    b. Semi-Log Plot over entire time range (to show terminal phase differences 
3. Cartesian and semi-log plots on the same page (sometimes referred to as a spaghetti plot as there are no symbols in the profiles) 
 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
401 
Template MS_PK_G_006:  Mean Plot of Matrix Concentration vs. Time 
 
 
 
 
 
C o n ce n tra tio n  (n g /m
0
150
300
450
600
750
900
1050
1200
Time (h)
0
3
6
9
12
15
18
21
24
Treatments
TRT A
TRT B
TRT C
TRT D
Concentration (ng/mL)
0.1
1.0
10.0
100.0
1000.0
Time (h)
0
3
6
9
12
15
18
21
24


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
402 
Parameter 
Values 
Template ID 
MS_PK_G_006 
Output File Name 
rg-pk-cpar6bmss1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.6A 
Title 1 
Mean (+SD) BMS-955176 Plasma Concentration Profile vs. Time   
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: BMS-955176 concentration (ng/mL) 
Programming notes 
1. Including SD bar  
2. Treatment and/or Study Day overlay, as appropriate 
3. There should be two plots (both on same page): 
     a. Linear plot over 24 h or tau (to show Cmax differences) 
     b. Semi-log plot over entire time range if longer than tau (to show terminal phase differences) 
4. Add in dotted line for LLOQ 
5. in-text figure required (Figure 9.1) 
 
Parameter 
Values 
Template ID 
MS_PK_G_006 
Output File Name 
rg-pk-cpar6bmss2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.6A 
Title 1 
Mean (+SD) BMS-955176 Plasma Concentration Profile vs. Time   
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
403 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: BMS-955176 concentration (ng/mL) 
Programming notes 
1. Including SD bar  
2. Treatment and/or Study Day overlay, as appropriate 
3. There should be two plots (both on same page): 
     a. Linear plot over 24 h or tau (to show Cmax differences) 
     b. Semi-log plot over entire time range if longer than tau (to show terminal phase differences) 
4. Add in dotted line for LLOQ 
5. in-text figure required (Figure 9.1) 
 
Parameter 
Values 
Template ID 
MS_PK_G_006 
Output File Name 
rg-pk-cpar6atvs1.lst 
Purpose 
WK24S1 
Table No. 
Figure S.8.2.6B 
Title 1 
Mean (+SD) ATV Plasma Concentration Profile vs. Time   
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: ATV concentration (ng/mL) 
Programming notes 
1. Including SD bar  
2. Treatment and/or Study Day overlay, as appropriate 
3. There should be two plots (both on same page): 
     a. Linear plot over 24 h or tau (to show Cmax differences) 
     b. Semi-log plot over entire time range if longer than tau (to show terminal phase differences) 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
404 
4. Add in dotted line for LLOQ 
5. in-text figure required (Figure 9.1) 
 
Parameter 
Values 
Template ID 
MS_PK_G_006 
Output File Name 
rg-pk-cpar6atvs2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.6B 
Title 1 
Mean (+SD) ATV Plasma Concentration Profile vs. Time   
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: ATV concentration (ng/mL) 
Programming notes 
1. Including SD bar  
2. Treatment and/or Study Day overlay, as appropriate 
3. There should be two plots (both on same page): 
     a. Linear plot over 24 h or tau (to show Cmax differences) 
     b. Semi-log plot over entire time range if longer than tau (to show terminal phase differences) 
4. Add in dotted line for LLOQ 
5. in-text figure required (Figure 9.1) 
 
Parameter 
Values 
Template ID 
MS_PK_G_006 
Output File Name 
rg-pk-cpar6dtgs1.lst 
Purpose 
WK24S1 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
405 
Table No. 
Figure S.8.2.6C 
Title 1 
Mean (+SD) DTG Plasma Concentration Profile vs. Time   
Title 2 
Evaluable PK Population - Stage 1 
Footnote 1 
A = BMS 955176 120 mg QD + ATV/r + DTG 
B = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: DTG concentration (ng/mL) 
Programming notes 
1. Including SD bar  
2. Treatment and/or Study Day overlay, as appropriate 
3. There should be two plots (both on same page): 
     a. Linear plot over 24 h or tau (to show Cmax differences) 
     b. Semi-log plot over entire time range if longer than tau (to show terminal phase differences) 
4. Add in dotted line for LLOQ 
5. in-text figure required (Figure 9.1) 
 
Parameter 
Values 
Template ID 
MS_PK_G_006 
Output File Name 
rg-pk-cpar6dtgs2.lst 
Purpose 
WK24S2 
Table No. 
Figure S.8.2.6C 
Title 1 
Mean (+SD) DTG Plasma Concentration Profile vs. Time   
Title 2 
Evaluable PK Population - Stage 2 
Footnote 1 
C = BMS 955176 120 mg QD + ATV + DTG 
D = BMS 955176 180 mg QD + ATV + DTG 
E = TDF + ATV/r + DTG 
Layout notes 
x-axis label: time 
y-axis label: DTG concentration (ng/mL) 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
406 
Programming notes 
1. Including SD bar  
2. Treatment and/or Study Day overlay, as appropriate 
3. There should be two plots (both on same page): 
     a. Linear plot over 24 h or tau (to show Cmax differences) 
     b. Semi-log plot over entire time range if longer than tau (to show terminal phase differences) 
4. Add in dotted line for LLOQ 
5. in-text figure required (Figure 9.1) 
 
4.8 
Pharmacodynamic Results 
Not applicable 
 
4.9 
Other Study Results 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-qs-eq5ds1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 10.1.1 
Title 1 
EQ-5D-3L Summary of US and UK Centric Scores and Changes From Baseline Over Time on Treatment 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Parameters: US Centric Score, UK Centric Score 
No units. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-qs-eq5ds2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 


Analysis Data Presentation Plan 
 
Clinical Study Report for AI438-048  
BMS-955176, v.2.0 
 
 
407 
Table No. 
Appendix 10.1.2 
Title 1 
EQ-5D-3L Summary of US and UK Centric Scores and Changes From Baseline Over Time on Treatment 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Parameters: US Centric Score, UK Centric Score 
No units. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-qs-fahis1.lst 
Purpose 
WK24S1, WK48S1, WK96S1, WK96S2 
Table No. 
Appendix 10.2.1 
Title 1 
FAHI Summary of Total Scores Over Time on Treatment 
Title 2 
Treated Subjects - Stage 1 
Layout notes 
Do not show title row “Parameter (Units)”. Do not show changes from baseline. No units. 
 
Parameter 
Values 
Template ID 
SS_VL_T_006 
Output File Name 
rt-qs-fahis2.lst 
Purpose 
WK24S2, WK48S2, WK96S2 
Table No. 
Appendix 10.2.2 
Title 1 
FAHI Summary of Total Scores Over Time on Treatment 
Title 2 
Treated Subjects - Stage 2 
Layout notes 
Do not show title row “Parameter (Units)”. Do not show changes from baseline. No units.