Clinical trial NCT04371380
Conditions: HIV Infections
Keywords: cabotegravir rilpivirine HIV Pharmacokinetics intramuscular injection
Sponsor: ViiV Healthcare
Start date: 2020-09-16; Completion date: 2021-12-26
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase 1, open label study in healthy participants to assess the pharmacokinetics of cabotegravir and rilpivirine in plasma following the administration of a single 600 milligram (mg) and a 900 mg intramuscular (IM) injection respectively, to separate vastus lateralis muscles on each leg. Cabotegravir is an integrase inhibitor being developed in combination with rilpivirine, a non-nucleoside reverse transcriptase inhibitor, for the treatment of human immunodeficiency virus (HIV). The objective is to evaluate pharmacokinetics, tolerability, and safety of cabotegravir long acting plus rilpivirine long acting administered concomitantly as two separate IM injections in the vastus lateralis muscle of adult healthy participants. The screening phase will be of 30 days, oral lead-in (OLI) phase of 28 days, there will be washout period of 10-14 days, followed by an injection phase and follow-up period will be up to 52-weeks. Approximately 15 adult healthy participants will be enrolled.

Detailed description:

Arms: arm 1: Participants will be administered cabotegravir at a dose of 30 mg plus rilpivirine dose of 25 mg once daily with meal on Day 1 to Day 28 in OLI phase. There will be 10 to 14 days wash out period after OLI. This will be followed by an injection phase, wherein participants will receive 600 mg cabotegravir long acting given as one 3 milliliter (mL) IM injection plus 900 mg rilpivirine long acting given as one 3 mL IM injection on Day 1.
Interventions: intervention 1: Cabotegravir Tablets intervention 2: Rilpivirine Tablets intervention 3: Cabotegravir extended release suspension for injection (long-acting) intervention 4: Rilpivirine extended release suspension for injection (long-acting)
Intervention descriptions: intervention 1: Cabotegravir tablets will be white to almost white oval shaped film coated tablets with a unit dose of 30 mg and will be administered orally. intervention 2: Rilpivirine tablets will be off-white, round, biconvex film coated tablets with a unit dose of 25 mg and will be administered orally. intervention 3: Cabotegravir long-acting will be a sterile white to slightly pink suspension containing 200 mg per mL of GSK1265744 as free acid for administration by intramuscular injection. intervention 4: Rilpivirine long-acting will be a sterile white suspension containing 300 mg per mL of rilpivirine as the free base for administration by intramuscular injection.

Protocol documents:
Prot_000.pdf: 
2018N357118_01
CONFIDENTIAL
ViiV Healthcare group of companies
208832
1
TITLE PAGE
Protocol Title: A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics and 
Tolerability of Cabotegravir and Rilpivirine Long-Acting Injections Following 
Intramuscular Administration in the Vastus Lateralis Muscle of Healthy Adult 
Participants
Protocol Number: 208832/01
Compound Number 
GSK1265744, GSK1329758
Study Phase: Phase 1
Short Title: Cabotegravir LA and Rilpivirine LA Thigh PK Study
ViiV Healthcare group of companies
US IND Sponsor Name and Legal Registered Address:
ViiV Healthcare Company
Five Moore Drive
P.O. 13398
Research Triangle Park, NC 27709-3398, USA
Telephone: + 1 919 438 2100
This study is sponsored by ViiV Healthcare.  GlaxoSmithKline is supporting ViiV 
Healthcare in the conduct of this study.  
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual
Regulatory Agency Identifying Number(s):
IND: 109,678
Approval Date: 13-AUG-2020
Copyright 2020 ViiV Healthcare group of companies.  All rights reserved.  Unauthorized 
copying or use of this information is prohibited.


2018N357118_01
CONFIDENTIAL
208832
3
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
DNG Number
Amendment 1
13-AUG-2020
2018N357118_01
Original Protocol
02-MAR-2020
2018N357118_00
Amendment 1: 13-AUG-2020
Overall Rationale for the Amendment:
Revisions were made to the study eligibility criteria and safety assessments to further 
mitigate the potential risks for study conduct during the COVID-19 pandemic.  
Section # and 
Name
Description of Change
Brief Rationale
1.3 Schedule of 
Activities (SOA)
SOA revised to include SARS-
CoV-2 testing at Screening and 
on admission to the Phase I unit 
prior to the oral lead-in phase 
To mitigate risk to study conduct during 
the COVID-19 pandemic
5.1 Inclusion 
Criteria
Participant age range revised so 
that no participants >50 years of 
age are included
To mitigate risk to study conduct during 
the COVID-19 pandemic
5.1 Inclusion 
Criteria
Included a new criterion for 
participants to have two 
consecutive negative tests for 
SARS-CoV-2 at Screening and 
on admission 
To mitigate risk to study conduct during 
the COVID-19 pandemic
5.2 Exclusion 
Criteria
Included two new criteria 
excluding participants having 
signs and symptoms suggestive 
of COVID-19 and participants 
who had contact with a known 
COVID-19 positive person/s 
within 14 days prior to admission
To mitigate risk to study conduct during 
the COVID-19 pandemic
8.1.4. Clinical 
Safety Laboratory 
Assessments
Information on screening for 
SARS-Cov-2 included
To mitigate risk to study conduct during 
the COVID-19 pandemic
8.4 
Pharmacokinetics
One additional PK sampling 
timepoint added (Day 1 12h) and 
modification of sampling window 
for Day 1 8h and Day 2 PK 
during OLI Phase
Since participants remain at the site 
overnight on Day 1 during OLI, 
additional PK timepoints was added to 
improve precision of PK parameter 
estimation
11.8. Appendix 8: 
Permissible 
Investigator(s) should utilise 
WHO Case Definitions to classify 
To mitigate risk to study conduct during 
the COVID-19 pandemic


2018N357118_01
CONFIDENTIAL
208832
4
Section # and 
Name
Description of Change
Brief Rationale
Procedures 
during the 
COVID-19 
Pandemic
12. References
COVID-19 cases [World Health 
Organisation, 2020].
WHO reference included.  
Throughout
Minor editorial and document 
formatting revisions
Minor, therefore have not been 
summarized


2018N357118_01
CONFIDENTIAL
208832
5
TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
PROTOCOL SUMMARY..........................................................................................8
1.1.
Synopsis.......................................................................................................8
1.2.
Schema ......................................................................................................10
1.3.
Schedule of Activities (SoA)........................................................................11
1.3.1.
Screening and Oral Lead-in Phase ..............................................11
1.3.2.
CAB LA + RPV LA Injection Phase and Follow- up......................14
2.
INTRODUCTION....................................................................................................16
2.1.
Study Rationale ..........................................................................................16
2.2.
Background ................................................................................................16
2.3.
Benefit/Risk Assessment ............................................................................17
2.3.1.
Risk Assessment .........................................................................18
2.3.1.1.
Other Clinically Relevant Information..........................23
2.3.2.
Benefit Assessment.....................................................................23
2.3.3.
Overall Benefit: Risk Conclusion..................................................23
3.
OBJECTIVES AND ENDPOINTS...........................................................................24
4.
STUDY DESIGN ....................................................................................................25
4.1.
Overall Design ............................................................................................25
4.1.1.
Screening ....................................................................................26
4.1.2.
Oral Lead-in Phase......................................................................26
4.1.3.
CAB and RPV Injection and PK Sampling....................................26
4.1.4.
Follow-up/Withdrawal Visit...........................................................26
4.2.
Justification for Dose ..................................................................................27
4.2.1.
Oral Dose: ...................................................................................27
4.2.2.
Long Acting Injectable Dose: .......................................................27
4.3.
End of Study Definition ...............................................................................29
5.
STUDY POPULATION...........................................................................................29
5.1.
Inclusion Criteria.........................................................................................29
5.2.
Exclusion Criteria........................................................................................31
5.3.
Lifestyle Considerations..............................................................................33
5.3.1.
Meals and Dietary Restrictions ....................................................33
5.3.2.
Caffeine, Alcohol, and Tobacco ...................................................34
5.3.3.
Activity .........................................................................................34
5.4.
Screen Failures...........................................................................................34
6.
STUDY INTERVENTION........................................................................................34
6.1.
Study Interventions Administered ...............................................................35
6.1.1.
Formulations of CAB and RPV.....................................................35
6.1.1.1.
Cabotegravir Tablets (CAB)........................................35
6.1.1.2.
Rilpivirine Tablets (RPV).............................................35
6.1.1.3.
Cabotegravir Extended Release Suspension 
for Injection (CAB LA).................................................36


2018N357118_01
CONFIDENTIAL
208832
6
6.1.1.4.
Rilpivirine Extended Release Suspension for 
Injection (RPV LA)).....................................................36
6.2.
Preparation/Handling/Storage/Accountability..............................................36
6.2.1.
Dosing Considerations for CAB LA + RPV LA..............................37
6.3.
Study Intervention Compliance ...................................................................37
6.4.
Concomitant Therapy..................................................................................37
6.4.1.
Permitted Medications and Non-Drug Therapies..........................38
6.4.2.
Prohibited Medications and Non-Drug Therapies.........................38
6.5.
Dose Modification .......................................................................................39
6.6.
Intervention after the End of the Study........................................................39
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL.....................................................................39
7.1.
Discontinuation of Study Intervention..........................................................39
7.1.1.
Liver Chemistry Stopping Criteria ................................................40
7.1.2.
QTc Stopping Criteria ..................................................................41
7.2.
Participant Discontinuation/Withdrawal from the Study ...............................42
7.3.
Lost to Follow Up........................................................................................42
8.
STUDY ASSESSMENTS AND PROCEDURES .....................................................43
8.1.
Safety Assessments ...................................................................................43
8.1.1.
Physical Examinations.................................................................43
8.1.2.
Vital Signs....................................................................................44
8.1.3.
Electrocardiograms......................................................................44
8.1.4.
Clinical Safety Laboratory Assessments ......................................44
8.1.5.
Suicidal Ideation and Behavior Risk Monitoring ...........................45
8.2.
Adverse Events and Serious Adverse Events.............................................45
8.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................45
8.2.2.
Method of Detecting AEs and SAEs.............................................46
8.2.3.
Follow-up of AEs and SAEs.........................................................46
8.2.4.
Regulatory Reporting Requirements for SAEs .............................46
8.2.5.
Pregnancy ...................................................................................47
8.3.
Treatment of Overdose...............................................................................47
8.4.
Pharmacokinetics .......................................................................................47
8.5.
Genetics .....................................................................................................49
8.6.
Patient Reported Outcomes........................................................................49
9.
PHARMACOKINETIC METHOD OF ANALYSES...................................................49
10. STATISTICAL CONSIDERATIONS........................................................................50
10.1.
Statistical Hypotheses.................................................................................50
10.2.
Sample Size Determination ........................................................................50
10.3.
Populations for Analyses ............................................................................50
10.4.
Statistical Analyses.....................................................................................50
10.4.1.
General Considerations ...............................................................51
10.4.2.
Primary Endpoint(s).....................................................................51
10.4.3.
Secondary and Safety Endpoint(s) ..............................................52
10.5.
Interim Analyses .........................................................................................52
11. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS...............................................................................................53


2018N357118_01
CONFIDENTIAL
208832
7
11.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................53
11.1.1.
Regulatory and Ethical Considerations ........................................53
11.1.2.
Financial Disclosure.....................................................................53
11.1.3.
Informed Consent Process ..........................................................53
11.1.4.
Data Protection............................................................................54
11.1.5.
Dissemination of Clinical Study Data ...........................................54
11.1.6.
Data Quality Assurance ...............................................................55
11.1.7.
Source Documents ......................................................................56
11.1.8.
Study and Site Start and Closure.................................................56
11.1.9.
Publication Policy.........................................................................56
11.2.
Appendix 2: Clinical Laboratory Tests.........................................................58
11.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................60
11.3.1.
Definition of AE............................................................................60
11.3.2.
Definition of SAE..........................................................................61
11.3.3.
Recording and Follow-Up of AE and SAE....................................62
11.3.4.
Reporting of SAE to GSK.............................................................64
11.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................66
11.4.1.
Definitions:...................................................................................66
11.4.2.
Contraception Guidance: .............................................................67
11.4.3.
Collection of Pregnancy Information: ...........................................68
11.5.
Appendix 5: Genetics..................................................................................69
11.6.
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................70
11.7.
Appendix 7: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Version 2.1, March 2017..............................72
11.8.
Appendix 8: Permissible Procedures during the COVID-19 
Pandemic....................................................................................................73
11.9.
Appendix 9: Abbreviations and Trademarks................................................74
11.10. Appendix 10: Protocol Amendment History.................................................77
12. REFERENCES.......................................................................................................78


2018N357118_01
CONFIDENTIAL
208832
8
1.
PROTOCOL SUMMARY
1.1.
Synopsis
Protocol Title: A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics and 
Tolerability of Cabotegravir and Rilpivirine Long-Acting Injections Following 
Intramuscular Administration in the Vastus Lateralis Muscle of Healthy Adult 
Participants
Short Title: Cabotegravir LA and Rilpivirine LA Thigh PK Study
Rationale: The objective of this study is to evaluate the pharmacokinetics, tolerability, 
and safety of cabotegravir (CAB) long acting (LA) + rilpivirine (RPV) LA administered 
concomitantly as two separate IM injections in the vastus lateralis muscle of adult 
healthy participants.  Data from this study will be used to inform the feasibility of 
administering CAB LA + RPV LA in the vastus lateralis muscle in HIV-infected 
children < 12 years of age and adult populations.   
Objectives and Endpoints:
Objectives
Endpoints
Primary

To describe the PK profiles of 
CAB and RPV following a 
single intramuscular injection 
each of CAB LA + RPV LA 
administered to the lateral thigh 
muscle in adult healthy 
participants 

Maximum observed concentration 
(Cmax) and time of maximum observed 
concentration (tmax) in plasma

Area under the concentration – time curve 
from time zero to last quantifiable time 
point (AUC(0-t)) through the follow-up 
phase

Area under the concentration – time curve 
from time zero to infinity (AUC0-)

Apparent terminal phase half-life (t½) 
and absorption rate constant (KALA))
Safety

To assess safety and tolerability 
of CAB and RPV following 
repeated oral dose and single 
intramuscular injection in the 
lateral thigh of healthy 
participants
Safety and tolerability parameters including 
adverse events (AEs), clinical laboratory 
tests, electrocardiogram (ECG), and vital sign 
assessments


2018N357118_01
CONFIDENTIAL
208832
9
Overall Design:
This is a Phase 1, open label study conducted in healthy participants to assess the PK of 
CAB and RPV in plasma following a single 600 mg (1 x 3 mL) and a 900 mg (1 x 3 mL)
injection each, respectively, administered IM to separate vastus lateralis muscles on each 
leg. 
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participant’s ability to attend clinic visits.  Based on these 
challenges, it may be necessary to adopt additional measures and procedures to protect 
participant safety, and to allow flexibility to allow conduct of the study.  
Number of Participants:
Approximately 15 adult healthy participants will be dosed with injectable study 
interventions. If participants prematurely discontinue the study, for any other reason,
other than an AE, additional replacement participants may be enrolled at the discretion of 
the Sponsor in consultation with the investigator.
Approximately 30% of female participants will be enrolled.
Intervention Groups and Duration:
The study will consist of 

30-day screening period

28-day oral lead-in (OLI) phase at a CAB dose of 30 mg and RPV dose of 25 mg 
once a day with a meal 

10 – 14 days washout period

CAB and RPV injection, administered IM: 600 mg (1 x 3 mL) CAB on left and a 
900 mg (1 x 3 mL) RPV injection on right vastus lateralis muscle 

Sparse PK sampling for up to 29 days in OLI and serial PK sampling for up to 4 
weeks after the injection, per SoA. Participants will return for safety assessments 
and additional PK sampling at Week 8, 12, 24, 36, and 52 post last injection during 
the follow-up phase.
Data Monitoring or other Committee: No


2018N357118_01
CONFIDENTIAL
208832
10
1.2.
Schema


2018N357118_01
CONFIDENTIAL
208832
11
1.3.
Schedule of Activities (SoA)
The timing and number of planned study assessments, including as outlined in the SoA below, including safety and pharmacokinetic or 
other assessments may be altered during the course of the study based on newly available data (e.g., to obtain data closer to the time of 
peak plasma concentrations) and to ensure appropriate monitoring.
Any changes in the timing or addition of time points for any planned study assessments must be documented and approved by the relevant 
study team member and then archived in the Sponsor and site study files but will not constitute a protocol amendment. The IRB/IEC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or amendment of the informed consent form
(ICF). Appendix 8 summarises permissible procedures during the COVID-19 pandemic (Section 11.8). 
1.3.1.
Screening and Oral Lead-in Phase
Study Period
Screening1
Oral Lead-in9
Day 29
Early 
Withdrawal9
Washout Period
Dosing Days 1-28
Visit Window  
Within
30 days
of oral 
lead-in
Day -1
Day 1
Day 2
Day 14
Within 24 
hours of the 
Day 28 last 
dose
EW
10 – 14 days
Informed Consent
X
Demographics
X
Medical / Medication / 
Drug / Alcohol History
X
Inclusion/Exclusion 
Criteria2
X
X
Height, Weight, BMI
X
Physical Exam
X
X
Vital Signs3
X
X
X
X
X
X
12-Lead ECG
X
X
X
Drug / Alcohol Screen3
X
X


2018N357118_01
CONFIDENTIAL
208832
12
Study Period
Screening1
Oral Lead-in9
Day 29
Early 
Withdrawal9
Washout Period
Dosing Days 1-28
Visit Window  
Within
30 days
of oral 
lead-in
Day -1
Day 1
Day 2
Day 14
Within 24 
hours of the 
Day 28 last 
dose
EW
10 – 14 days
Pregnancy Test3
X
X
X
X
Testing for SARS-CoV-24
X
X
Hepatitis B, Hepatitis C 
Screening
X
HIV Test 
X
Urine Dipstick 
X
Hematology with 
differential; Clinical 
Chemistry Tests3
X
X
X
X
X
X
Coagulation Tests 
X
Admit to clinic
X
Dispense Oral lead-in IP
X
Administer oral CAB + 
RPV5
X
X
X
Dispense Medication 
Dosing Diary
X
Drug accountability/ pill 
count/review drug diary
X
X
X
Blood plasma PK 
sampling6
X
X
X
X
X
AE Assessment7
X
X
X
X
X
Concomitant Medication 
Review
X
X
X
X
X
Genetic sample8
X
Discharge from the clinic
X
1.
Screening may occur over more than one visit but within 30 days of the first dose of oral CAB and RPV in the oral lead in phase.


2018N357118_01
CONFIDENTIAL
208832
13
2.
Eligibility criteria must be carefully assessed at the Screening visit and confirmed at the Day 1 Oral lead-in phase visit and re-confirmed prior to injection.
3.
Prior to administering the first oral dose of CAB and RPV, study personnel must verify the following pre-dose assessments to be within normal limits prior to administration: vital 
signs, pregnancy test (negative; Females of Reproductive Potential (FRP) only. The results of the Drug/Alcohol screen, hematology with differential, and clinical chemistry tests on 
Day 1 are not required prior to administering the first oral doses of CAB and RPV but should be drawn prior to CAB and RPV administration.
4.
Two consecutive approved molecular tests (PCR or antigen test) must be conducted on all study participants and separated by >48 hours. Following the second test for SARS-
CoV-2, participants should be quarantined within the unit. Once the second test is negative, the participant can be released into the unit and follow Infection Control practices  
5.
Oral CAB and RPV dosing Days 1 to 28. Day 1, Day 2, and Day 14 doses should be administered in the clinic.  
6.
PK sampling – On Day 1 - 1h, 2h, 3h, 4h, 6h, 8h, and 12h, and Day 2 PK between 22 to 26 h post first oral dose. On Day 14 pre-dose samples. Day 29 PK should occur between 
22 to 26 hours from the last dose on Day 28. Total of 20 PK samples (10 for CAB, 10 for RPV assay) will be collected during oral lead-in phase. Please refer to Section 8.4 for 
permitted PK window for OLI phase.
7.
AE assessment will include a brief, symptom-directed physical exam as needed.
8.
Genetic sample - collect the sample at the earliest convenient time after the first dose in the oral lead in phase on Day 1.
9.
If a participant is withdrawn prior to receiving the CAB LA and/or RPV LA injection, a follow-up/withdrawal visit should be scheduled 10-14 days after the last oral dose of CAB and 
RPV.


	

	

	

)*-*,*
(3# 4 .52 
5'"
6%%.* 
'
5
&(
&,
&3
&7
&89/
&(2
&(7
&(8
&,,
&,/
:-;3<
-;/
-;(,
-;,3
-;1=
-;7,
-".%(
"



	
	
1	
E	
)D	
D2	
'..!'>%%
8		$

J*!
J,!
J	
J	
J	
J	
J	
J	
J	
J	
J	
J '
J '
J '
J '
J '
%99#9
?%"%&,
>
'#&
>
>
>
>
>
>
>
>
(,*)	,
>
>
>
>
>
0
>
>
>
>
%#&@%%"&
>
>
>
>
>
>
>
>
>
>
0%#,
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
??$)?A'0)?,
>
>
>
>
>
>
>
5
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
?	?3
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
B.
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
$% %'> %#7
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
" $  -	
! 
4

-

&*-4
 &

	

 -	 - 
CCI


	

	

	

( '6'$

!
'	
-$

 
!
4
-	! !$F
7.@6 6$
 '

 
BG"'6

-
. 
!
6 ! !
 #   4! '6  ' .6$	4
!
 	 $

F
4

0

6	
!
 
!!4
 
	

" $ -4
 &

4
	
!

-		
F






1. 
!
-
 4
6'!$!

$	' 
/ ! 



* % 1 "5 !$
E 
 	? "-4


		?3C"3 #F
"	 
 G-$
CCI
CCI


2018N357118_01
CONFIDENTIAL
208832
16
2.
INTRODUCTION
2.1.
Study Rationale
Cabotegravir (CAB) is an integrase inhibitor being developed in combination with 
rilpivirine (RPV, TMC278), a non-nucleoside reverse transcriptase inhibitor, for the 
treatment of HIV. CAB is currently in Phase 3 development as monotherapy for the 
prevention of sexually-acquired HIV-1 infection.  CAB and RPV are separately formulated 
as oral tablets for once daily administration and as long-acting (LA) aqueous suspensions 
for parenteral administration monthly or every 2-months.  RPV 25mg oral tablets is 
approved as EDURANT in multiple countries, including the USA, Europe and Canada, for 
use in antiretroviral (ARV) treatment-naïve patients.   
A two-drug long-acting, monthly antiretroviral regimen of CAB + RPV has demonstrated 
good efficacy, tolerability, and long-term safety in HIV-infected adults following oral and 
monthly and every 2-month IM dosing in the gluteus muscle for durations exceeding 3 
years in Phase 2 and Phase 3 studies [LATTE, 2019; LATTE-2, 2018; ATLAS, 2019; 
FLAIR, 2019, ATLAS-2M, 2018]. Review and approval of the CAB + RPV regimen for 
treatment of HIV infection is ongoing.     
Separate early Phase 1 studies of CAB LA and RPV LA evaluated PK and tolerability of 
single and repeat-dose injections in other anatomic locations including abdomen 
(subcutaneous) and IM administration in the ventrogluteal muscle (CAB), gluteus maximus 
muscle (RPV), and deltoid muscle (RPV) in healthy volunteers [HIV Therapy, 2013; 
International AIDS Society, 2013; RPV LA NATAP report, 2008].  Gluteal injections of 
CAB LA + RPV LA were progressed in late-stage studies given better participant
tolerability to injections at this injection site with the anticipated injection dosing volume 
required to achieve desired exposures.  
There remains considerable interest in exploring alternative injection sites either as an 
alternative rotational (e.g. gluteal injection fatigue) or chronic injection site (e.g. gluteal 
implants contraindicating injection or young pediatric populations without sufficient 
gluteal mass for injection).  The vastus lateralis muscle in the thigh has been used as an 
injection location for other drugs (e.g. epinephrine, etc.) and is a common injection site in 
young children (e.g. vaccines). Moreover, self- or partner-injection of CAB LA + RPV LA 
in the thigh muscle may be explored in future studies pending favorable pharmacokinetics, 
safety, and tolerability of CAB LA + RPV LA thigh injections. 
The objective of this study is to evaluate the pharmacokinetics, tolerability, and safety of 
CAB LA + RPV LA administered concomitantly as two separate IM injections in the vastus 
lateralis muscle of adult healthy participants.  Data from this study will be used to inform 
the feasibility of administering CAB LA + RPV LA in the vastus lateralis muscle in HIV-
infected children <12 years of age and adult populations.   
2.2.
Background
The treatment of HIV-1 infection has advanced since the first oral antiretroviral agent 
(AZT) was approved for the treatment of HIV-1 infected individuals in 1987. Newer 


2018N357118_01
CONFIDENTIAL
208832
17
antiretrovirals are more potent, better tolerated and have enabled the formulation of 
multiple regimens that can provide viral suppression with a single tablet once daily. 
Long acting injectable versions of drugs are being developed to enable therapy with 
infrequent dosing schedule. These therapeutic options hold great promise for future 
treatment and represent an emerging paradigm for the treatment of HIV infection. CAB is 
a potent integrase inhibitor that possesses attributes that allow formulation and delivery as 
a long-acting parenteral product. RPV is a diarylpyrimidine derivative and a potent non-
nucleoside reverse transcriptase inhibitor (NNRTI) with in vitro activity against wild type 
HIV-1 and select NNRTI-resistant mutants. A two-drug regimen with CAB LA plus RPV 
LA (CAB + RPV LA) offers many potential advantages over daily oral regimens including 
infrequent dosing that decreases the daily reminder to patients of their HIV status, better 
tolerability, less likely to develop viral resistance due to intermittent compliance with oral 
agents that can lead to sub-therapeutic concentration of antiretroviral medication and 
emergence of resistance, and improved adherence and overall treatment satisfaction in 
virologically suppressed patients. Results to date have demonstrated the efficacy of a two-
drug regimen of CAB + RPV LA as maintenance therapy with several on-going Phase 2 
and 3 studies including LATTE-2, ATLAS, FLAIR, and ATLAS 2M currently underway 
[ATLAS, 2019; FLAIR, 2019]
As of 18-Oct-2018, in the Phase 3 Study 201584, a total of 283 HIV-infected subjects have 
received CAB 30 mg once daily with RPV 25 mg once daily as oral lead-in (OLI) therapy 
prior to initiation of injections. Of these subjects, 278 have received CAB LA + RPV LA 
gluteal injections (dosed every 4 weeks, Q4W) during the Maintenance Phase of the study. 
In Phase 3 Study 201585, a total of 308 HIV-infected subjects entered the Maintenance 
Phase and received CAB 30 mg once daily and RPV 25 mg once daily as OLI therapy prior 
to initiation of gluteal injections. Of the 308 subjects who received OLI, 303 transitioned 
to receive CAB + RPV LA injections (dosed Q4W). Of the 308 subjects that entered the 
Maintenance Phase, 282 successfully completed and 26 subjects withdrew. A pooled 
analysis of the Phase 3 studies demonstrated that monthly injections with CAB + RPV LA 
were non-inferior to daily oral antiretroviral therapy for the key virologic endpoints at week 
48. Low confirmed virologic failure was seen across both treatment arms. Injection site 
reactions in the LA arm were mainly Grade 1 or 2 but with few associated discontinuations.
To date, Phase 2 and Phase 3 studies of CAB LA + RPV LA have utilized the gluteus 
medius injection site in HIV-1 patients.  This study aims to evaluate alternate injection site 
of thigh muscles for CAB LA + RPV LA administered in injection per each thigh muscle, 
at the same visit.   
2.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse effects of CAB and RPV may be found in the [CAB IB 2019;  
GlaxoSmithKline Document Number RH2009/00003/09; RPV IB, 2019].


2018N357118_01
CONFIDENTIAL
208832
18
2.3.1.
Risk Assessment
Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Drug Induced Liver 
Injury (DILI)
A small proportion of participants in the 
CAB program to date (total exposure 
>3100 participants) have developed 
transaminitis (elevated liver 
transaminases characterized by 
predominant alanine aminotransferase 
(ALT) elevation).  In most participants, 
transient transaminitis was explained by 
acute viral hepatitis infection (.  In a 
small number of participants, there was 
not an alternative explanation, 
suggesting a mild form of drug induced 
liver injury (DILI) without hepatic 
dysfunction, which resolved upon 
withdrawal of treatment with CAB. 
All participants with suspected DILI 
identified to date were receiving oral 
CAB.  

Exclusion criteria as described in 
Section 5.2 will prohibit participation 
with significant liver impairment based 
on screening liver chemistry including 
transaminases (ALT and Aspartate 
aminotransferase [AST]) as well on 
prior medical history.

A 4-week oral lead-in Phase is being 
implemented in this study, where all 
participants will receive oral CAB prior 
to the administration of IM CAB to 
assess individual safety and tolerability 
Liver transaminases (ALT and AST) 
will be monitored throughout this study 
(refer to Schedule of Activities) and the 
liver chemistry stopping criteria will be 
adopted as described in Section 7.1.1
of this protocol. 

All instances of liver transaminase 
elevations of Grade 2 and above will 
be followed to resolution. Participants 
withdrawn from the study due to 
meeting liver chemistry stopping 
criteria will be regularly monitored both 
clinically and using liver chemistries to 
determine progress towards resolution 
of the liver event.
Effects in late stage 
pregnancy seen in 
non-clinical studies
In animal reproduction studies, CAB 
when administered to rats at > 30 times 
the systemic exposure at the maximum 
recommended oral human dose 
(MRHD) of 30 mg during organogenesis 
through delivery, had adverse effects on 
labor and delivery that may be related 
to a delay in the onset of parturition, 
resulting in increased fetal mortality 
(stillbirths) and neonatal deaths 
immediately after birth.
The clinical significance of these finding 
in humans is unknown.

As a routine precaution, pregnant 
women are excluded from participation 
in this study and females of 
reproductive potential (FRP) are 
required to adopt highly reliable means 
of contraception during participation 
and throughout the long term follow up 
phase of this study following exposure 
to CAB LA.

FRP are also required to undergo 
regular pregnancy testing throughout 
study conduct to enable early 
discontinuation of CAB LA if 
pregnancy is identified.


2018N357118_01
CONFIDENTIAL
208832
19
Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Potential effects in 
women exposed to 
dolutegravir during 
conception and early 
pregnancy
A preliminary analysis of an ongoing 
birth outcome surveillance study in 
Botswana involving women exposed to 
dolutegravir (DTG) a different molecule 
in the same integrase class of 
medications as CAB, identified four 
cases (as of May 2018) of neural tube 
defects in 426 infants born to mothers 
who were exposed to DTG-containing 
regimens from the time of conception. 
In the same study, no infant born to a 
woman who started DTG during 
pregnancy had a neural tube defect, out 
of 2,824 women. A causal relationship 
of these events to the use of DTG has 
not been established. The incidence of 
neural tube defects in the general 
population ranges from 0.5-1 case per 
1,000 live births. As neural tube defects 
occur within the first 4 weeks of fetal 
development (at which time the neural 
tubes are sealed) this potential risk 
would concern women exposed to DTG 
at the time of conception and in early 
pregnancy.
The clinical relevance of either of these 
findings in relation to CAB use is 
unknown

As a routine precaution, pregnant 
women are excluded from participation 
in clinical trials of CAB at this time and 
females of reproductive potential 
(FRP) are required to adopt highly 
reliable means of contraception during 
participation and throughout long term 
follow up phases of studies after 
exposure to CAB and RPV LA.

Females of reproductive potential also 
undergo regular pregnancy testing 
throughout study conduct to enable 
early discontinuation of study drugs 
once pregnancy is identified. However, 
it should be noted that CAB 
concentration could remain for 
prolonged periods despite 
discontinuation of CAB LA.
Drug-Drug 
Interactions (DDIs)
For a complete listing of permitted and 
prohibited concurrent medications for 
CAB, CAB LA, RPV and RPV LA, refer 
to Section 6.4.

All participants will be informed of 
prohibited medications throughout the 
study and updates provided as needed 
via the informed consent.
Injection Site 
Reactions (ISR)
There are extensive safety and 
tolerability data, including ISRs
following IM administration of CAB LA 
and RPV LA. Please refer to each IB 
for additional information [CAB IB 
GlaxoSmithKline Document Number 
RH2009/00003/09, RPV IB, 2019]

Administration advice to minimize risk 
of poor administration technique giving 
rise to injection site reactions. Advice 
on care, monitoring, natural course, 
and treatment of ISRs given in study 
documentation 

Advice to participants on care of 
injection site on day/days immediately 
post administration, use of analgesia, 
compresses where appropriate.

Participants will be closely monitored 
for ISRs particularly for signs of pain, 
tenderness, infections, erythema, 
swelling, induration, or nodules 
(granulomas or cysts) throughout the 
study. 

Complications of ISRs such as 
infections (abscess, cellulitis) and 


2018N357118_01
CONFIDENTIAL
208832
20
Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
collections of fluid requiring drainage 
will be monitored 

Significant ISRs may be photographed 
and referred to a dermatologist for 
specialist advice.
Rash
Some observations of rash with oral 
RPV have been reported in clinical 
studies executed to date (the majority 
are mild). 
Severe skin and hypersensitivity 
reactions have been reported during the 
post-marketing experience with oral 
RPV-containing regimens, , including 
cases of Drug Reaction with 
Eosinophilia and Systemic Symptoms 
(DRESS).  While some skin reactions 
were accompanied by constitutional 
symptoms such as fever, other skin 
reactions were associated with organ 
dysfunctions, including elevations in 
hepatic serum biochemistries.

Participants with a Grade 1 or 2 rash 
will be allowed to continue treatment or 
to be rechallenged, depending on the 
clinical judgment of the investigator.

All participants developing a Grade 3 
or 4 rash should discontinue  study 
drugs and be withdrawn from the 
study.

All rash events should be assessed 
with special attention to systemic 
symptoms, laboratory abnormalities, or 
mucosal involvement. Close clinical 
follow-up, including follow-up of 
laboratory abnormalities, and 
appropriate medical intervention, 
including referral to dermatologist as 
appropriate, should be instituted for 
these events; daily follow-up is 
recommended for 5 days from the 
onset of the event to monitor for 
progression of the event. In case of 
cutaneous reaction/rash and/or an 
allergic reaction, the use of cetirizine, 
levocetirizine, loratadine, 
diphenhydramine, topical 
corticosteroids, or antipruritic agents is 
permitted.


2018N357118_01
CONFIDENTIAL
208832
21
Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Inadvertent 
Intravenous Injection 
(Accidental 
Maladministration)
As with any intramuscular injection, it is 
possible that CAB LA and/or RPV LA 
can be inadvertently administered 
intravenously instead of intramuscularly 
possibly resulting in higher than 
expected concentrations of CAB and/or
RPV shortly after injection and lower 
concentrations thereafter. This could be 
due to administrator error, improper 
injection technique and / or improper 
needle length used based on body type.  

Training will be provided to all sites on 
proper injection technique.

Should IM maladministration be 
suspected at any time (e.g., suspected 
under or overdose or inadvertent 
intravenous [IV] dosing), post dose 
ECG monitoring and vital signs or any 
other supportive testing may be 
obtained at the discretion of the 
investigator, and the medical monitor 
notified.

2-hour post dose PK samples will be 
for determination of CAB and RPV 
concentration and possible 
pharmacokinetic correlation with safety 
parameters such as ECG changes. 
Hypersensitivity 
Reactions (HSR)
Hypersensitivity reactions have been 
reported as uncommon occurrences 
with integrase inhibitors (INI), including 
the closely related compound 
dolutegravir, and were characterized by 
rash, constitutional findings, and 
sometimes, organ dysfunction, including
liver injury. 
While there have been no clinical cases 
of hypersensitivity to CAB to date, there 
is a theoretical risk of systemic or 
severe hypersensitivity reactions with or 
without hepatic symptoms associated 
with use of IM CAB. The long 
exposures anticipated after IM CAB 
injection may complicate the 
management of a drug hypersensitivity 
reaction, were it to occur.

The risk of developing a 
hypersensitivity reaction post 
administration of CAB and RPV will be 
minimized by the use of a 4-week oral 
lead-in of oral CAB/RPV to determine 
individual safety and tolerability prior to 
the introduction of IM CAB.

Clinical assessments, laboratory tests 
(including liver transaminases) and 
vital signs will be performed 
throughout this study. Results from 
these assessments may aid early 
detection of HSR. 

Oral CAB will be withdrawn 
immediately for cases with suspected 
HSR during the oral CAB/RPV lead-in 
phase and participants would not 
proceed to the injection phase. Any 
HSR reactions that occur would be 
managed supportively.
New site of 
intramuscular 
injection: vastus 
lateralis
Intramuscular CAB injections into the 
thigh (vastus lateralis) have not 
previously been administered in the 
CAB development program. Similar to 
the ventrogluteal region, the vastus 
lateralis is free of major nerves and 
blood vessels. Therefore, it is expected 
to be a safe site for injections. The 
vastus lateralis is part of a large muscle 
group and can tolerate high volume 
injections of up to 5ml  [Rodger, 2000]
in adults with lesser amounts being 
stipulated in younger participants or in 
those with less developed or atrophied 
muscle beds [Rodger, 2000]

Training of the appropriate technique 
will be provided to staff at the study 
centre and will be described in the 
study manual

During the injection phase further 
enrolment and dosing of participants 
may be stopped if a participant 
develops a ≥Grade 3 related AE 
(including thigh injection site 
complications).


2018N357118_01
CONFIDENTIAL
208832
22
Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Venipuncture
Participants will be required to have 
blood samples taken, which entails, risk 
of bruising, and rarely, infection

Trained personnel will perform 
venipuncture.
Risks of ECG pad 
removal
Some discomfort and rash may occur 
where the ECG pads are applied and 
subsequently.

ECGs will be conducted by 
appropriately trained personnel and 
effort made to minimize contact time 
for application of the pads.
Vasovagal reaction
Receiving injections can cause some 
participants to feel lightheaded or feel 
like they might pass out, or ‘faint’.  This 
reaction, called a ‘vasovagal reaction’, 
can occur with many medical 
procedures and resolves quickly.

The participants are monitored and 
stay in the clinic for 2 hours after the 
injection for additional sampling and 
further observation.


2018N357118_01
CONFIDENTIAL
208832
23
2.3.1.1.
Other Clinically Relevant Information
Additional details concerning safety observations from clinical studies and for which a 
causal association has not been established or which are of minimal clinical significance 
may be found in the Investigator’s Brochures. Refer to ‘Summary of data and guidance for 
the investigator’.
Seizure
Several cases of seizure have occurred during the CAB program. These cases have had 
alternative explanations for their occurrence. Overall, there is not convincing evidence that 
CAB exposure may be causally associated with seizure or with reduction of seizure 
threshold, due to the low frequency of reports, the confounders present in the cases received 
to date and lack of any pre-clinical signal or identified plausible mechanism. However, 
seizure and seizure-like events are considered as AEs of special interest for CAB. 
Participants with an unstable or poorly controlled seizure disorder will be excluded from 
study participation. Report any cases of seizure or seizure like events within 24 hours of 
the event.
2.3.2.
Benefit Assessment
Participants participating in this study will not receive any clinical benefit but will be 
compensated for their time and participation.
Benefit considerations may include satisfaction from knowledge that participants have 
contributed to the process of developing new therapies for HIV.
2.3.3.
Overall Benefit: Risk Conclusion
Review of the cumulative safety data on CAB and RPV have not identified any safety 
signals which are considered to pose an unacceptable risk to healthy participants.
Considering the multiple and overlapping measures that will be taken to minimize risk to 
participants participating in this study, the potential risks identified in association with 
CAB and RPV are justified by the anticipated benefits that may be afforded to participants 
including the satisfaction of contributing to the ongoing continued clinical development of 
CAB and RPV for both the treatment and prevention of HIV infection.


2018N357118_01
CONFIDENTIAL
208832
24
3.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To describe the PK profiles of 
CAB and RPV following a single 
intramuscular injection each of 
CAB LA + RPV LA administered 
to the lateral thigh muscle in adult
healthy participants 

Maximum observed concentration 
(Cmax) and time of maximum 
observed concentration (tmax) in 
plasma

Area under the concentration – time 
curve from time zero to last 
quantifiable time point (AUC(0-t)) 
through the follow-up phase

Area under the concentration – time 
curve from time zero to infinity 
(AUC0-)

Apparent terminal phase half-life (t½) 
and absorption rate constant (KALA))
Safety

To assess safety and tolerability 
of CAB and RPV following 
repeated oral dose and single 
intramuscular injection in the 
lateral thigh of adult healthy 
participants
Safety and tolerability parameters 
including adverse events, clinical 
laboratory tests, ECG, and vital sign 
assessments 


	

	

	

45/
6
68	
9*
"'	$	
"!
9*)*
/	
  	
					3!"B
$)!(##	4..#A
>0C 8..#A
>0C &	
	M					%*		
 			#:
 	(!

0.		#	

-/	 A%C 	"B	!0.#$)	!-5#
	(	


.E 
7 (	

"B$)&	 		%*, 4..#A
>0C"B 	!
8..#A
>0C $)&	 #
 	

	3#!-8%	3#!7
(		!		&		:(	!!			
3#J		/
--7045-&	#
	!(	:
>	
5 	( 		(&		
		:%!				!		
	 								!
	(		#:
>	0.I!!		(			:
CCI


2018N357118_01
CONFIDENTIAL
208832
26
4.1.1.
Screening
All participants will undergo a screening visit within 30 days of the first dose of the oral 
lead-in phase. Participants may be rescreened once. Participants who are enrolled into the 
trial and subsequently withdrawn from the study, for any reason, may not be re-screened. 
Participants may continue to the oral lead-in phase as soon as all eligibility requirements 
have been met.
4.1.2.
Oral Lead-in Phase
Participants that are eligible to participate will be admitted to the clinic on Day 1 of the 
OLI phase and receive their first oral dose of CAB 30 mg and RPV 25 mg with a standard 
breakfast after the completion of all pre-dose assessments. Participants will undergo sparse
PK sampling of blood as described in Schedule of Activities (SoA). After a pre-dose 24-
hour PK sample collection and laboratory assessments, participants will take their Day 2 
study interventions with a meal at the clinic. Participants will be dispensed a sufficient 
supply of oral CAB + RPV tablets to complete 26 days of once daily dosing at home (with 
exception of the visit days at the clinic) and be counseled to take their dose with a meal at 
about the same time each day, before getting discharged on Day 2. 
On Day 14 of the OLI phase, the participants will return to the clinic. A pre-dose PK sample 
will be collected. In addition, this visit will include assessment of safety, tolerability, and 
participant adherence to study drug. Participants should bring their supply of oral CAB + 
RPV to the Day 14 visit to have drug accountability performed. Participants will receive 
Day 14 dose at the clinic.
Participants will return to the clinic on Day 29, within 24 hours of last dose on Day 28 for 
PK, drug accountability, and all assessments performed as described in the SoA Section
1.3. The participants will begin a wash-out period of 10-14 days, during which no CAB 
and RPV will be administered.
4.1.3.
CAB and RPV Injection and PK Sampling
After the washout period of 10-14 days, participants will return to the clinic and receive an 
intramuscular injection of CAB LA (3 mL; 600 mg) on one lateral thigh and RPV LA (3 
mL; 900 mg) into opposite lateral thigh on Injection Phase Day 1. Participants will remain 
in the research unit for at least 4 hours after the injection for PK sampling and safety 
assessments. Participants will return to clinic for PK sampling and safety assessments for 
4 weeks as outlined in SoA.
4.1.4.
Follow-up/Withdrawal Visit 
Because of the long acting PK profile of CAB LA + RPV LA, every effort should be 
made to bring participants back in through the 52 weeks post injections. Participants, who 
received CAB LA + RPV LA IM injection, will return to clinic for safety and PK 
assessments at Weeks 8, 12, 24, 36, and 52 post IM injections. 


2018N357118_01
CONFIDENTIAL
208832
27
If a participant is withdrawn:

prior to receiving the IM injection, then a follow-up/withdrawal visit should be 
scheduled 10-14 days after the last oral dose of CAB + RPV. 

after receiving IM dose of CAB LA and/or RPV LA injections, every effort 
should be made to bring the participants back in for the 52 weeks of safety and 
PK assessments following the injection(s), because of the long acting PK profile 
of CAB and RPV. 
4.2.
Justification for Dose
4.2.1.
Oral Dose:
The risk of developing a hypersensitivity reaction (HSR), post administration of CAB LA 
and RPV LA is minimized by the use of a 4-week OLI of oral CAB and RPV. In the event 
of a suspected HSR, participants will not receive CAB LA and RPV LA injections. The 
management of participants with HSRs following receipt of drugs with a long half-life may 
be challenging. HSRs have been reported as uncommon occurrences with integrase CAB 
and RPV, and were characterized by rash, constitutional findings, and sometimes, organ 
dysfunction, including liver injury. The time of onset of HSR reactions supports the 
proposed duration of the OLI with the majority of HSRs occurring within the first 28 days 
of exposure to the drugs.
During the OLI phase of this study, oral formulations of CAB + RPV will be co-
administered to assess safety and tolerability in each participant prior to IM dosing with 
CAB LA and RPV LA. The combination of oral RPV 25 mg QD and CAB 10, 30, and 60
mg QD has been used as OLI in HIV-1 infected participants in both Phase IIb studies, the 
pivotal Phase 3 studies (FLAIR and ATLAS), and Phase 3b study ATLAS-2M. 
In these studies, all three oral CAB doses demonstrated similar efficacy at the Week 48 
primary endpoint. However, 30 mg dose was selected as OLI for all CAB LA studies, as it 
delivered higher steady-state exposures than predicted for the monthly or every 2-month 
regimen. CAB 30 mg is also the OLI treatment intended for marketing. Therefore, CAB 
30 mg along with marketed dose of RPV 25 mg (EDURANT) will be used as the OLI 
dosing in this study and will achieve exposures sufficiently high to assess safety and 
tolerability during a short OLI prior to a single IM injection of CAB LA + RPV LA 
formulations.
The PK collected during the OLI phase will be utilized along with the data from LA 
injection phase to precisely estimate PK parameters using a robust population PK (PoPPK) 
model. A window of 10 to 14 days (covering ~7-10 half-lives) will be used for wash-out 
period prior to LA injection accounting for variability in half-life in participants. This 
wash-out period would prevent plasma concentrations after oral administration from being 
mixed with plasma concentrations on Day 1 after LA IM injection. 
4.2.2.
Long Acting Injectable Dose:
This study will evaluate the intramuscular administration of CAB LA (3 mL; 600 mg) and 
RPV LA (3 mL; 900 mg) into the lateral thigh muscle of left leg and right leg respectively.  


2018N357118_01
CONFIDENTIAL
208832
28
The CAB LA + RPV LA Q4W regimen demonstrated noninferiority to oral standard of 
care (SOC) in pivotal Phase 3 studies.  In those studies, gluteal injections were initiated 
with CAB LA 600 mg + RPV LA 900 mg (3mL each) followed by monthly injections of 
CAB LA 400 mg + RPV LA 600 mg (2mL each). An every 2-month dosing regimen of 
CAB LA 600 mg + RPV LA 900 mL is under investigation (3 mL of each drug for all 
injections).  It is anticipated that absorption from the lateral thigh will be similar to gluteal 
and thus the current study will evaluate the intramuscular administration of CAB LA (3 
mL; 600 mg) and RPV LA (3 mL; 900 mg) into the lateral thigh muscle of left leg and 
right leg respectively. Therefore, the terminal slope following the injection (lambda z) is 
expected to be similar in this study to population PK predictions of absorption rate constant 
(KALA) for CAB [overall population: 0.00064 hr-1 (0.0002, 0.0018)] and RPV [0.000145
h-1 (0.00014 – 0.00016)]. In addition, CAB and RPV concentrations for the current study 
are expected to fall within the range of concentrations observed following the first 
injections in the pooled FLAIR and ATLAS studies.
The following table lists the median, 5th, and 95th percentiles of evaluable trough 
concentrations of CAB and RPV following initial gluteal 3 mL injections from ATLAS 
and FLAIR studies. Furthermore, exposure parameters are anticipated to fall within the 
range of the model predictions following a single 3 mL gluteal IM injection as shown in 
Table 2. 
Table 1
Observed Trough Concentrations Following First IM Injection in 
FLAIR and ATLAS Studies, Pooled Data
VISIT
ANALYTE
5th
50th
95th 
WEEK 4
CAB
0.4521
1.57
3.5
WEEK 4
RPV
17.4
39.45
88.275
Table 2
Model Predicted Exposure Parameters of CAB and RPV Following A 
Single IM Injection in Gluteus Medius
Parameter
Units
CAB
RPV
Median (90% PI)
Median (90% PI)
KALA
/h
0.00064
(0.0002, 0.0018)
0.000146 
(0.000145, 0.000164)
Half-Life
Weeks
6.5 (2.3, 20.9)
28.1 ( 25.1 - 28.4)
Tmax
days
8 (5, 15)
4.0 (3.0 - 31.0)
Cmax
g/mL
2.13 (0.69, 5.80)
56.0 (21.2 - 151)
CWk4
g/mL
1.56 (0.63, 2.96)
34.6 (17.5 - 69.3)
CWk8
g/mL
0.91 (0.43, 1.57)
20.3 ( 10.4 - 38.3)
CWk12
g/mL
0.58 (0.18, 1.03)
13.5 (6.75 - 25.6)


2018N357118_01
CONFIDENTIAL
208832
29
Parameter
Units
CAB
RPV
Median (90% PI)
Median (90% PI)
CWk24
g/mL
0.18 (0.025, 0.45)
6.98 ( 3.33 - 13.6)
CWk36
g/mL
0.05 (0.025, 0.26)
4.88 ( 2.26 - 9.68)
CWk48
g/mL
0.025 (0.025, 0.16)
3.58 ( 1.66 - 7.15)
CWk52
g/mL
0.025 (0.025, 0.14)
3.24 ( 1.50 - 6.49)
AUC0-Wk4
g*h/mL
1216 (422, 2857)
28354 (10674 - 67476)
AUC0-Wk8
g*h/mL
2080 (811, 4132)
47419 (21949 - 99140)
AUC0-Wk12
g*h/mL
2601 (1133, 4763)
58909 (29731 - 116809)
AUC0-Wk24
g*h/mL
3271 (1788, 5461)
78560 (43502 - 144786)
AUC0-Wk36
g*h/mL
3519 (2082, 5738)
91349 (51528 - 164003)
AUC0-Wk48
g*h/mL
3634 (2215, 5852)
100079 (56879 -
178154)
AUC0-Wk52
g*h/mL
3655 (2240, 5868)
102380 (58332 -
182124)
4.3.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all 
phases of the study including the follow up visit Week 52.
The end of the study is defined as the date of the last visit of the last participant in the 
study.
5.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria 
apply:
Age
1.
Participant must be 18 to 50 years of age inclusive, at the time of signing the 
informed consent.


2018N357118_01
CONFIDENTIAL
208832
30
Type of Participant and Disease Characteristics
2.
Participants who are overtly healthy as determined by medical evaluation including 
medical history, physical examination, laboratory tests, and cardiac monitoring. 
3.
A participant with a clinical abnormality or laboratory parameter(s) which is/are not
specifically listed in the inclusion or exclusion criteria, outside the reference range
may be included only if the investigator in consultation with the Medical Monitor 
agree and document that the finding is unlikely to introduce additional risk and will 
not interfere with the study procedures. A single repeat of a procedure or laboratory
parameter is allowed to determine eligibility.
4.
Participants who are negative on two consecutive tests for SARS-CoV-2, performed 
at Screening and on Day -1 of admission to the Phase I unit, using an approved 
molecular test (PCR or antigen test).
Weight
5.
Body weight ≥ 40 kg and body mass index (BMI) within the range 18 to 35 kg/m2
(inclusive).
Sex
6.
Male or female. Contraceptive use by men or women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies.
a.
Male Participants:
Male participants are eligible to participate if they agree to the following during the 
intervention period and for at least 52 weeks after the last dose of study intervention: 

Refrain from donating sperm
Plus either:

Be abstinent from heterosexual or homosexual intercourse as their preferred and 
usual lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent 
OR

Must agree to use contraception/barrier as detailed below
o
Agree to use a male condom (and should also be advised of the benefit 
for a female partner to use a highly effective method of contraception 
as a condom may break or leak) when having sexual intercourse with a 
woman of childbearing potential who is not currently pregnant
o
Agree to use male condom when engaging in any activity that allows 
for passage of ejaculate to another person


2018N357118_01
CONFIDENTIAL
208832
31
b. Female Participants: 

A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies:
o
Is not a woman of childbearing potential (WOCBP) 
OR
b.
Is a WOCBP and using a contraceptive method that is highly effective, with a failure 
rate of <1%, as described in Appendix 4 during the intervention period and for at 
least 52 weeks after the last dose of study intervention. The investigator should 
evaluate the effectiveness of the contraceptive method in relationship to the first dose 
of study intervention.
o
A WOCBP must have a negative highly sensitive (Appendix 2) pregnancy test 
(urine or serum as required by local regulations) within 30 days of the first dose 
of study intervention.
o
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a 
serum pregnancy test is required. In such cases, the participant must be excluded 
from participation if the serum pregnancy result is positive.

Additional requirements for pregnancy testing during and after study intervention are 
located in Appendix 2.

The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy
Informed Consent
7.
Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1.
Signs and symptoms which in the opinion of the investigator are suggestive of 
COVID-19 (i.e. fever, cough etc) within 14 days of inpatient admission
2.
Contact with known COVID-19 positive person/s in the 14 days prior to inpatient 
admission
3.
History or presence of/significant history of or current cardiovascular, respiratory, 
hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric 
disorders capable of significantly altering the absorption, metabolism, or elimination 
of drugs; constituting a risk when taking the study intervention or interfering with the 
interpretation of data


2018N357118_01
CONFIDENTIAL
208832
32
4.
Abnormal blood pressure as determined by the investigator.
5.
Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).
6.
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%). 
7.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones)
8.
History of ongoing or clinically relevant seizure disorder within the previous 2 years, 
including participants who have required treatment for seizures within this time 
period. A prior history of seizure, with a seizure free period of at least 2 years, off 
anti-epileptics, may be considered for enrolment if the investigator believes the risk 
of seizure recurrence is low. All cases of prior seizure history should be discussed 
with the medical monitor prior to enrolment.
9.
QTc >450 msec for male participants and >470 msec for female participants
NOTES:

The QTc is the QT interval corrected for heart rate according to Bazett’s 
formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine-
read or manually over-read.

The specific formula that will be used to determine eligibility and 
discontinuation for an individual participant should be determined prior to 
initiation of the study. In other words, several different formulae cannot be used 
to calculate the QTc for an individual participant and then the lowest QTc value 
used to include or discontinue the participant from the trial.
10. A participant, who has an underlying skin disease or disorder (i.e. infection, 
inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, 
urticaria). 
11. A participant, who is considered to have insufficient musculature to allow safe 
administration of CAB or RPV in the opinion of the investigator will be excluded.
Prior/Concomitant Therapy
12. Unable to refrain from the use of prescription or non-prescription drugs, including
vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days 
(or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is 
longer) prior to the first dose of study medication to the completion of the follow-up 
visit unless in the opinion of the Investigator and ViiV Medical Monitor the 
medication will not interfere with the study procedures or compromise participant
safety. The use of any concurrent prohibited medications as outlined in Section 6.4.2.
Prior/Concurrent Clinical Study Experience
13. Participation in the study would result in loss of blood or blood products in excess of 
500 mL within 56 days. 
14. Exposure to more than four new chemical entities within 12 months prior to the first 
dosing day.


2018N357118_01
CONFIDENTIAL
208832
33
15. Participant has participated in a clinical trial and has received an investigational 
product within the following time period prior to the first dosing day in the current 
study: 30 days, 5 half-lives or twice the duration of the biological effect of the 
investigational product (whichever is longer).
Diagnostic assessments
16. Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months 
prior to first dose of study intervention.
17. Positive Hepatitis C antibody test result at screening or within 3 months prior to first 
dose of study intervention.
NOTE:  Participants with positive Hepatitis C antibody due to prior resolved disease can 
be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
18. Positive Hepatitis C RNA test result at screening or within 3 months prior to first 
dose of study intervention.
NOTE: Test is optional and participants with negative Hepatitis C antibody test are not 
required to also undergo Hepatitis C RNA testing.
19. Presence of the Hepatitis B core antibody (HBcAb) should also lead to exclusion 
from the study even if HBsAg is negative.
Other Exclusions
20. Positive pre-study drug/alcohol screen
21. Positive human immunodeficiency virus (HIV) antibody test
22. Regular use of known drugs of abuse
23. Regular alcohol consumption within 6 months prior to the study defined as: 

An average weekly intake of >14 units for males or >7 units for females.  One 
unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 
ml) of wine or 1 (25 ml) measure of spirits. 
24. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or 
nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 
months prior to screening.
25. Participant, who has a tattoo or other dermatological condition overlying the thigh 
region which may interfere with interpretation of injection site reactions.
26. History of sensitivity to any of the study medications, or components thereof or a 
history of drug or other allergy that, in the opinion of the investigator or Medical 
Monitor, contraindicates their participation.
5.3.
Lifestyle Considerations
5.3.1.
Meals and Dietary Restrictions
An overnight fast is preferred prior to screening laboratory assessments; however, a 
minimum of a 6 hour fast is acceptable. Otherwise, food and drink can be given ad libitum 


2018N357118_01
CONFIDENTIAL
208832
34
throughout the course of the trial. At visits where participants will be in the clinic for 
multiple hours, meals will be provided by the study site (in the form of a boxed lunch or 
card for use at the site cafeteria). 
Refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice,
pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices during the oral lead in phase 
through Day 29 PK collection. 
5.3.2.
Caffeine, Alcohol, and Tobacco
Participants will abstain from alcohol for 48 hours prior to initiating oral dosing and prior 
to the injections. Participants will abstain from alcohol for 48 hours prior to the collection 
of the pharmacokinetic sampling and clinical laboratory tests.
5.3.3.
Activity
Participants will abstain from strenuous exercise for 48 hours before each blood 
collection for clinical laboratory tests, and also the first 4 hours after injection. During 
this time, participants may participate in light recreational activities (e.g., watching 
television, reading).
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently enrolled. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, any protocol deviations and any serious adverse events 
(SAEs).
Individuals who do not meet the criteria for participation in this study (screen failure) may 
be rescreened. Rescreened participants should be assigned a new participant number.
6.
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol.
Investigational product (IP) in this protocol refers to the investigational study drugs Oral 
CAB, CAB LA, Oral RPV, and RPV LA. CAB and RPV products will be supplied by 
GlaxoSmithKline/ViiV Healthcare and Janssen Pharmaceuticals, respectively.


2018N357118_01
CONFIDENTIAL
208832
35
Dosing and Administration
CAB + RPV Oral Lead-In Phase
Day 1 to Day 
28
Take one tablet of CAB 30 mg +  RPV 25 mg once daily with a meal
CAB LA + RPV LA Injection Phase
Injection Day 
1

Receive CAB LA 600 mg given as 1 X 3 mL IM injection

Receive RPV LA 900 mg given as 1 X 3 mL IM injection 
6.1.
Study Interventions Administered
6.1.1.
Formulations of CAB and RPV
6.1.1.1.
Cabotegravir Tablets (CAB)
CAB is manufactured by GlaxoSmithKline and is formulated as white to almost white oval 
shaped film coated 30 mg tablets for oral administration, packaged in high density 
polyethylene (HDPE) bottles with desiccant and child-resistant closure that include an 
induction seal. CAB tablets will be packaged in bottles of 30 tablets. Participants must keep 
all IP in its original pack container. GSK/ViiV will notify sites if and when data are 
available to support the use of pill boxes. The recommended storage conditions, and expiry 
date where required, are stated on the product label.
CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline 
cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-
coating. The white film-coating contains hypromellose, titanium dioxide and polyethylene 
glycol.
6.1.1.2.
Rilpivirine Tablets (RPV)
RPV is provided by Janssen Research & Development, LLC, a division of Janssen 
Pharmaceuticals, as 25 mg tablets that are off-white, round, biconvex, film-coated and 
debossed on one side with “TMC” and the other side with “25”. RPV is manufactured by 
Janssen-Cilag S.p.A, Latina, Italy. RPV will be provided as a globally marketed product 
which includes approvals in the US and the European Union. RPV will be overlabeled and 
packaged in bottles of 30 tablets. The recommended storage conditions, and expiry date 
where required, are stated on the product label.
Each tablet contains 27.5 mg of rilpivirine hydrochloride, which is equivalent to 25 mg of 
RPV. Each tablet also contains the inactive ingredients croscarmellose sodium, lactose 
monohydrate, magnesium stearate, polysorbate 20, povidone K30 and silicified 


2018N357118_01
CONFIDENTIAL
208832
36
microcrystalline cellulose. The tablet coating contains hypromellose 2910 6 mPa.s, lactose 
monohydrate, PEG 3000, titanium dioxide and triacetin.
6.1.1.3.
Cabotegravir Extended Release Suspension for Injection (CAB LA)
CAB LA (GSK1265744 LA) is manufactured by GlaxoSmithKline and is a sterile white to 
slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for 
administration by intramuscular (IM) injection. The product is packaged in a glass vial 
with a 13 mm stopper and aluminum seal. Each vial is for single-dose use containing a 
withdrawable volume of 2.0 mL (400 mg) and does not require dilution prior to 
administration. The recommended storage conditions, and expiry date where required, are 
stated on the product label.
CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, 
mannitol, and water for injection.
6.1.1.4.
Rilpivirine Extended Release Suspension for Injection (RPV LA))
RPV LA (TMC278, GSK1329758, also named JNJ-16150108-AAA), 300 mg/mL 
Extended Release Suspension for Injection (G001), is provided by Janssen Research & 
Development, LLC, a division of Janssen Pharmaceuticals, as a sterile white suspension 
containing 300 mg/mL of RPV as the free base. The route of administration is by 
intramuscular (IM) injection. RPV LA is packaged in a single use 4 mL glass vial with a 
13 mm stopper and aluminum seal. Each vial contains a nominal fill of 2.0 mL (600 mg) 
and does not require dilution prior to administration. The recommended storage conditions, 
and expiry date where required, are stated on the product label.
RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate 
monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for 
injection.
6.2.
Preparation/Handling/Storage/Accountability
The investigator or designee must confirm appropriate temperature conditions have been
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention.
Only participants enrolled in the study will receive study intervention and only authorized 
site staff may supply or administer study intervention. All study interventions must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area 
in accordance with the labeled storage conditions with access limited to the investigator 
and authorized site staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records).
Further guidance and information for the final disposition of unused study intervention are 
provided in the Study Reference Manual (SRM). 


2018N357118_01
CONFIDENTIAL
208832
37

Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff.  Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or 
GSK/ViiV study contact.

Precaution will be taken to avoid direct contact with the study intervention.  A Material 
Safety Data Sheet (MSDS) describing occupational hazards and recommended 
handling precautions will be provided to the investigator. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or GSK/ViiV study 
contact.
6.2.1.
Dosing Considerations for CAB LA + RPV LA
Vials of CAB LA and RPV LA are each supplied as a suspension and need no further 
dilution or reconstitution. Since RPV LA requires refrigeration, sites should allow the 
vial(s) to come to approximately room temperature prior to injecting. The vials should be 
gently inverted a few times to re-suspend sediments and allow bubbles to subside, and then 
use a syringe or provided vial adapter to withdraw the required volume of suspension for 
IM injection.
All injections must be given intramuscularly in the thigh muscle, each injection on one 
thigh. The time and location of injection will be captured in the case report form (CRF).  
Additional injections instructions can be found in the SRM.
6.3.
Study Intervention Compliance

When participants are dosed at the site, they will receive study intervention directly 
from the investigator or designee, under medical supervision.  The date and time of 
each dose administered in the clinic will be recorded in the source documents.  The 
dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering 
the study intervention.  Study site personnel will examine each participant’s mouth to 
ensure that the study intervention was ingested.

When participants self-administer study intervention(s) at home, compliance with 
CAB + RPV dosing will be assessed through querying the participant during the site 
visits and documented in the source documents and CRF. IP accountability will be 
evaluated using pill counts of unused IP (CAB and RPV tablets). 

A record of the number of CAB + RPV tablets dispensed to and taken by each 
participant must be maintained and reconciled with study intervention and 
compliance records. Intervention start and stop dates, including dates for intervention 
delays and/or dose reductions will also be recorded in the CRF.
6.4.
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements or other specific categories of interest) that the 


2018N357118_01
CONFIDENTIAL
208832
38
participant is receiving at the time of enrollment or receives during the study must be 
recorded along with:

reason for use

dates of administration including start and end dates

dosage information including dose and frequency
The Medical Monitor should be contacted if there are any questions regarding concomitant 
or prior therapy.
6.4.1.
Permitted Medications and Non-Drug Therapies
Participants must abstain from taking prescription drugs within 7 days (or 14 days if the 
drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start 
of study intervention until completion of the follow-up visit, unless, in the opinion of the 
investigator and sponsor, the medication will not interfere with the study. 
Participants must abstain from taking non-prescription drugs (including vitamins and 
dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme 
inducer) or 5 half-lives (whichever is longer) before the start of study intervention until
the last PK sample collected on Week 8, unless, in the opinion of the investigator and 
sponsor, the medication will not interfere with the study.
Paracetamol/Acetaminophen at doses of 2 grams/day is permitted for use any time during 
the study. Other concomitant medication may be considered on a case-by-case basis by the 
investigator in consultation with the Medical Monitor if required.
Oral CAB and RPV only:

Antacid products containing divalent cations (e.g., aluminum, calcium and magnesium) 
must be taken at least 2 hours before or at least 4 hours after oral CAB and RPV

H2 antagonists must be taken at least 12 hours before or at least 4 hours after oral RPV 
oral RPV should not be co-administered with proton pump inhibitors, such as 
esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
6.4.2.
Prohibited Medications and Non-Drug Therapies
For participants receiving either formulation of CAB and RPV, the following 
medications could significantly decrease the levels of CAB and/or RPV due to enzyme 
induction and therefore must not be administered concurrently:

Carbamazepine

Oxcarbazepine

Phenobarbital 

Phenytoin

Rifabutin

Rifampicin/ rifampin, rifapentine


2018N357118_01
CONFIDENTIAL
208832
39

Rifapentine

St. John’s wort (Hypericum perforatum)
In addition, participants must discontinue the following (or change to an allowable 
alternative) while receiving treatment with oral RPV:

proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, 
pantoprazole, rabeprazole;

systemic dexamethasone (more than a single dose).

anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances 
in which prohibited therapies are administered.
6.5.
Dose Modification
No dose reductions, modifications, or changes in the frequency of any components of each 
regimen will be allowed during the study beyond what is allowed within the 
protocol. Protocol waivers or exemptions are not allowed. Therefore, adherence to the 
study design requirements is essential and required for study conduct. 
6.6.
Intervention after the End of the Study
Participants will not receive any additional treatment from GSK/ViiV Healthcare after 
completion of the study because only healthy participants are eligible for study 
participation.
7.
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
7.1.
Discontinuation of Study Intervention
Participants may voluntarily withdraw from the study at any time and for any reason. Site 
investigators and study staff may withdraw participants before their scheduled termination 
visit for safety, behavioral, or administrative reasons, or if the participants are unable or 
unwilling to comply with study procedures. The reasons for withdrawals will be recorded 
in the participants’ study records. If a participant withdraws from the study, he/she may 
request destruction of any samples taken, and the investigator must document this in the 
site study records.
During the oral lead-in period, early withdrawal on medical grounds will occur if the 
participant develops a Grade 3 or higher AE that is judged by the investigator to be related 
directly to the study product (see Appendix 3 and Appendix 4) for definitions and grading 
of severity of adverse events), or a participant develops a grade 3 or higher clinical 
significant laboratory abnormality (see Division of AIDS [DAIDS] table Appendix 7 for 
grading) or any AE that is deemed clinically significant by the investigator and is judged 
by the investigator to be related directly to the study product.
For liver-related stopping criteria, please refer to Section 7.1.1.


2018N357118_01
CONFIDENTIAL
208832
40
If a participant receives the injections, they will be followed 52-weeks post the final 
injection per protocol for appropriate procedures, including blood plasma PK sampling, 
and safety evaluations, and will not be removed from the study for medical reasons, unless 
they refuse to continue participation.
During the oral lead in phase additional pre-specified reasons for discontinuing a 
participant from the study (or, at minimum, discontinuing administration of study product
and continuing safety evaluations) include:

Pregnancy (please see Section 8.2.5)

Protocol deviation

Non-compliance

Participant withdraws consent

Participant lost to follow-up

Investigator discretion

Sponsor discontinues study
7.1.1.
Liver Chemistry Stopping Criteria
Study intervention will be discontinued for a participant if liver chemistry stopping 
criteria are met:


2018N357118_01
CONFIDENTIAL
208832
41
Phase I Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm
Abbreviations: ALT = alanine transaminase; INR = international normalized ratio; SAE = serious adverse 
event; ULN = upper limit of normal.
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology (in alignment with the FDA 
premarketing clinical liver safety guidance). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf
Discontinuation of study treatment for abnormal liver tests should be considered by the 
investigator when a participant meets one of the conditions outlined or if the investigator 
believes that it is in the best interest of the participant.
Refer to Appendix 6 for required Liver Safety Actions and Follow up Assessments. 
7.1.2.
QTc Stopping Criteria
A participant that meets the bulleted criterion below will be withdrawn from the study.

QTc > 500 msec

QTc increase from baseline > 60 msec

The same QT correction formula must be used for each individual participant to 
determine eligibility for and discontinuation from the study.  This formula may not be 
changed or substituted once the participant has been enrolled.

For example, if a participant is eligible for the protocol based on QTcB, then 
QTcB must be used for discontinuation of this individual participant as well.

Once the QT correction formula has been chosen for a participant’s eligibility, the 
same formula must continue to be used for that participant for all QTc data being 
collected for data analysis.  Safety ECGs and other non-protocol specified ECGs 
are an exception.  


2018N357118_01
CONFIDENTIAL
208832
42

The QTc should be based on the average of triplicate QTc values ECG readings
obtained over a brief (e.g., 5-10 minute) recording period.  
7.2.
Participant Discontinuation/Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance or administrative reasons. This is expected to be uncommon.

At the time of discontinuing from the study, if possible, an early withdrawal visit 
should be conducted. See SoA for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be 
completed.

The participant will be permanently discontinued both from the study intervention and 
from the study at that time.

If the participant withdraws consent for disclosure of future information, the sponsor 
may retain and continue to use any data collected before such a withdrawal of consent.

If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site study 
records.
7.3.
Lost to Follow Up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record.

Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 
1.


2018N357118_01
CONFIDENTIAL
208832
43
8.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA. 
If these assessments are scheduled for the same nominal time, THEN the assessments
should occur in the following order:
o
12-lead ECG
o
vital signs
o
blood draws.
Note: The timing of the assessments should allow the blood draw to occur at the exact 
nominal time

Protocol waivers or exemptions are not allowed 

Safety concerns should be discussed with the sponsor immediately upon occurrence 
or awareness to determine if the participant should continue or discontinue study 
intervention.

Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record reasons 
for screening failure, as applicable. 

Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA.

The maximum amount of blood collected from each participant over the duration 
of the study, including any extra assessments that may be required, will not exceed 
500 mL.

Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples.
8.1.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
8.1.1.
Physical Examinations

A complete physical examination will include, at a minimum, assessments of the skin, 
cardiovascular, respiratory, gastrointestinal and neurological systems. Height and 
weight will also be measured and recorded.

A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen).


2018N357118_01
CONFIDENTIAL
208832
44

Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
8.1.2.
Vital Signs

Vital signs will be measured in a semi-supine position after 5 minutes rest and will 
include temperature, systolic and diastolic blood pressure, and pulse.
8.1.3.
Electrocardiograms

Triplicate 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using 
an ECG machine that automatically calculates the heart rate and measures PR, QRS, 
QT, and QTc intervals. Refer to Section 7 for QTc withdrawal criteria and additional 
QTc readings that may be necessary.

At each time point at which triplicate ECGs are required, 3 individual ECG tracings 
should be obtained as closely as possible in succession, but no more than 2 minutes 
apart. The full set of triplicates should be completed in less than 4 minutes. 12-lead 
ECGs will be performed with the subject in a supine position having rested in this 
position for at least 5 minutes beforehand.
8.1.4.
Clinical Safety Laboratory Assessments

Refer to Appendix 2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency. 

The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
CRF. The laboratory reports must be filed with the source documents. Clinically 
significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected 
for the participant's condition.

All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 7 days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered significantly abnormal by the investigator or medical monitor. 

If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the sponsor 
notified.

All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA.

Screening for SARS-CoV-2: Study participants will be monitored at Screening 
and daily while inpatients for COVID-19 symptoms.  Investigator(s) should 
utilise the World Health Organisation (WHO)_Case Definitions to classify 
COVID-19 cases [World Health Organisation, 2020].  While outpatients, 
participants should report to the unit any symptoms suggestive of COVID-19.  
All participants who experience symptoms suggestive of COVID-19 should be 


2018N357118_01
CONFIDENTIAL
208832
45
isolated in the unit or at home and tested for SARS-CoV-2 using an approved 
molecular test (PCR or antigen test).  If a participant tests positive or becomes 
symptomatic with suspected/confirmed COVID-19 while on-unit, then the 
remaining participants in that cohort on the unit should be discharged).  The 
investigator should consider any participant testing positive for SARS-CoV-2 
being discontinued from study drug if COVID-19 symptoms are moderate to 
severe. Appropriate contact tracing for all participants testing positive will be 
performed within the unit.  This should be done in accordance with local 
legislation and guidelines. Appropriate follow up should be implemented for 
participants who discontinue the study due to COVID-19.
8.1.5.
Suicidal Ideation and Behavior Risk Monitoring

Participants will be monitored appropriately and observed closely for suicidal ideation 
and behavior or any other unusual changes in behavior. It is recommended that the 
investigator consider mental health consultation or referral for participants who 
experience signs of suicidal ideation or behavior. Participants presenting with new 
onset/treatment emergent depression should be advised to contact the investigator 
immediately if symptoms of severe acute depression (including suicidal 
ideation/attempts) develop, because medical intervention and discontinuation of the 
study medication may be required.
8.2.
Adverse Events and Serious Adverse Events
The definitions of an AE or SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, 
documenting, and reporting events that meet the definition of an AE or SAE and 
remain responsible for following up AEs that are serious, considered related to the 
study intervention or the study, or that caused the participant to discontinue the 
study (see Section 7). 
8.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information

All SAEs will be collected from the start of intervention until the follow-up Week 
52 visit at the time points specified in the SoA (Section 1.3). However, any SAEs 
assessed as related to study participation (e.g., study intervention, protocol-
mandated procedures, invasive tests, or change in existing therapy) or related to a 
GSK/ViiV product will be recorded from the time a participant consents to 
participate in the study.

All AEs will be collected from the start of intervention until the follow-up Week 
52 visit  at the time points specified in the SoA (Section 1.3).


2018N357118_01
CONFIDENTIAL
208832
46

Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the CRF not the AE section.

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in Appendix 
3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.

Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor.
8.2.2.
Method of Detecting AEs and SAEs

The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 3.

Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence. 
8.2.3.
Follow-up of AEs and SAEs

After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is given in 
Appendix 3.
8.2.4.
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the sponsor of a SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met. 

The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators.

For all studies except those utilizing medical devices investigator safety reports must 
be prepared for suspected unexpected serious adverse reactions (SUSAR) according 
to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary.


2018N357118_01
CONFIDENTIAL
208832
47

An investigator who receives an investigator safety report describing a SAE or other 
specific safety information e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements.
8.2.5.
Pregnancy

Details of all pregnancies in female participants and female partners of male 
participants will be collected after the start of study intervention and until 52-week
post injections. 

If a pregnancy is reported, the investigator should inform GSK/ViiV within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 
4.

Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE.
8.3.
Treatment of Overdose
For the oral lead in phase of this study, any dose of CAB > 30 mg and/or RPV > 25mg 
within a 24-hour time period will be considered an overdose. 
For the injection phase of the study, any dose of CAB LA > 600 mg and/or RPV LA > 
900 mg will be considered an overdose.
GSK/ViiV does not recommend specific treatment other than supportive care for an 
overdose.
The investigator will use clinical judgement to treat any overdose.
In the event of an overdose, the investigator should:
1.
Contact the Medical Monitor immediately.
2.
Closely monitor the participant for AE/SAE and laboratory abnormalities until CAB 
and/or RPV can no longer be detected systemically. 
3.
Document the quantity of the excess dose as well as the duration of the overdosing in 
the CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant.
8.4.
Pharmacokinetics
Blood samples of CAB (~ 2 mL each) and RPV (~ 2mL each) will be collected for 
measurement of plasma concentrations of CAB and RPV, respectively, as specified in the 
SoA.

Samples may be collected at additional time points during the study if warranted 
and agreed upon between the investigator and the sponsor. The timing of sampling 
may be altered during the course of the study based on newly available data (e.g., 


2018N357118_01
CONFIDENTIAL
208832
48
to obtain data closer to the time of peak plasma concentrations) to ensure 
appropriate monitoring.

Instructions for the collection and handling of biological samples will be provided 
by the sponsor. The actual date and time (24-hour clock time) of each sample will 
be recorded.

Samples will be used to evaluate the PK of CAB and RPV. Genetic analyses will 
not be performed on these plasma samples. 
Plasma analysis for CAB concentration determination will be performed under the control 
of GlaxoSmithKline, the details of which will be included in the Study Reference Manual 
(SRM). Concentrations of CAB will be determined in plasma samples using the currently 
approved bioanalytical methodology. Raw data will be archived at the bioanalytical site 
(detailed in the SRM). 
Plasma RPV analysis will be performed under the control of Janssen R&D. 
Concentrations of RPV will be determined in plasma samples using the currently 
approved bioanalytical methodology.  Raw data will be archived at the bioanalytical site. 
Permitted sampling window for the OLI Phase: 
Plasma PK Assessment
Permitted Sampling Window
Day 1 (1 h)
15min
Day 1 (2 h)
15min
Day 1 (3 h)
30 min
Day 1 (4 h)
15min
Day 1 (6 h)
30 min
Day 1 (8 h)
1h
Day 1 (12 h)
1h
Day 2 (24 h)
2h
Day 14
1 day
Day 29 
22-26h from Day 28 dose
Permitted sampling window for injection phase is provided in SoA. 


	

	

	
C
C*?*
!
4	!9;(			!(	
				#			!	:
:  (   (  	  	 #		 		  
		:
% 	 		 ! 9; 	> !	  			 #		  	  	
	F		 ! 	 : #	 !	 	 ( 	 	F	   
					(		#	:
9	  		 ! 	  	  	 ! #		 		
		!	$*:
C*@*
 #.
	$					(		#	:
!(		$*:
E*
 #&:
&
	$"
"
 	 		 ! " # *	# @  A"*C ( 	
		!	3!	"B$):
3!	"B$)		(		#
		(J;A)	4:0#	C:#
#				"$'(		!:' 	 	
CCI


2018N357118_01
CONFIDENTIAL
208832
50
time data, the following pharmacokinetic parameters will be determined, as data permit: 
AUC(0-), AUC(0-t), Cmax, tmax, half-life (t½), and absorption rate constant (KALA).
Plasma CAB and RPV concentration data will be presented in graphical and/or tabular 
form and will be descriptively summarized. 
Details of PK analyses will be provided in the report and analysis plan (RAP) separately. 
10.
STATISTICAL CONSIDERATIONS
10.1.
Statistical Hypotheses
The primary objective of this study is to evaluate the pharmacokinetics of CAB and RPV 
following a single intramuscular administration of each in the lateral thigh of healthy adult 
participants. No formal statistical hypotheses are to be tested. Where appropriate, an 
estimation approach will be taken and point estimates and confidence intervals will be 
constructed. 
10.2.
Sample Size Determination
There was no formal calculation of power or sample size for this study. Approximately 15
participants will receive CAB LA + RPV LA IM injections and provide informative safety 
and pharmacokinetic data based on feasibility considerations.
10.3.
Populations for Analyses
The following populations are defined:
Population
Description
Enrolled
All participants who sign the ICF.
Safety
All participants who take at least 1 dose of study drug.
Pharmacokinetic
Concentration
All participants who undergo plasma PK sampling and have 
evaluable PK assay results. This population will be used for the 
concentration listing.
Pharmacokinetic 
Parameter
All participants who undergo plasma PK sampling and have 
evaluable PK parameters estimated. This population will be used 
for PK parameter listing, plotting of the concentration-time data 
and PK parameter summary.
10.4.
Statistical Analyses
The statistical analysis plan will be finalized prior to Database Release (DBR) and it will 
include a more technical and detailed description of the statistical analyses described in 


2018N357118_01
CONFIDENTIAL
208832
51
this section. This section is a summary of the planned statistical analyses of the most 
important endpoints including primary and key secondary endpoints.
10.4.1.
General Considerations
Final analysis will be performed after the completion of the study and final datasets 
authorization. Data will be listed and summarized according to GSK reporting standards, 
where applicable. 
Unless stated otherwise, descriptive summaries will include n, mean, standard deviation 
(SD), median, minimum, and maximum for continuous variables, whereas n and percent 
will be used as summary statistics for categorical variables. For PK data, coefficient of 
variation (%CV), geometric mean with associated 95% confidence interval (CI), and the 
between- participant CV (%CVb) for the log-transformed PK parameters will also be 
provided as appropriate. 
Baseline or pre-dose assessment is the last available assessment prior to time of the first 
dose unless it is specified otherwise. If there are multiple assessments collected on the same 
scheduled time, the average of these assessments will be used. For tabulated safety 
summaries, only the scheduled assessments will be included in the summary tables.
Version 9.4 or higher of the SAS system will be used to analyze the data as well as to 
generate tables, figures, and listings. Complete details will be documented in the RAP.
10.4.2.
Primary Endpoint(s)
Descriptive statistics and/or graphics will be created to describe the primary endpoints of 
interest. Concentrations will be determined directly from concentration-time data from 
each matrix.  Data will be presented in tabular and or graphical format and summarized 
descriptively according to GSK’s Integrated Data Standards Library (IDSL) standards. No 
formal statistical testing will be conducted.
Pharmacokinetic analyses will be the responsibility of Clinical Pharmacokinetics Modeling 
& Simulation Department within GSK. Plasma CAB and RPV concentration-time data will 
be analyzed by non-compartmental methods with WinNonlin Professional 5.2 or higher, 
Phoenix (Pharsight Corporation) or comparable software. Calculations will be based on the 
actual sampling times recorded during the study. 
The following pharmacokinetic parameters will be determined, as data permits, for the PK 
profile of CAB LA + RPV LA:

maximum observed concentration (Cmax)

time of maximum observed concentration (tmax) 

area under the concentration-time curve from time zero to last quantifiable time 
point (AUC(0-t)) 

area under the concentration-time curve from time zero to infinity (AUC(0-))

apparent terminal phase half-life (t½) 

absorption rate constant (KALA)


2018N357118_01
CONFIDENTIAL
208832
52
10.4.3.
Secondary and Safety Endpoint(s)
All secondary and safety analyses will be performed on the Safety Population. AEs will be 
summarized using MedDRA preferred terms. All AEs, drug-related AEs, SAEs, liver-
related AEs and AEs leading to permanent discontinuation of study drug or withdrawal 
will be summarized or listed. AEs and drug-related AEs will also be summarized by 
maximum toxicity grade (based on DAIDS categories). Laboratory data, vital signs and 
ECG data (absolute values and change from Baseline) will be summarized by visit. Liver 
chemistry abnormalities will be summarized or listed.  Details will be documented in the 
RAP.
10.5.
Interim Analyses
There is no planned formal interim analysis.  All preliminary safety, tolerability and 
available pharmacokinetic data may be reviewed internally at any time point.  Depending 
on feasibility, evaluation of PK data may be performed at time points such as Week 4 and 
Week 12 post injection for preparatory PK modelling.


2018N357118_01
CONFIDENTIAL
208832
53
11.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
11.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
11.1.1.
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with:

Consensus of ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines

Applicable ICH Good Clinical Practice (GCP) Guidelines

Applicable laws and regulations

The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated. 

Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 

The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC

Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures
Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies 
(if applicable), and all other applicable local regulations.
11.1.2.
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.
11.1.3.
Informed Consent Process

The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study. 


2018N357118_01
CONFIDENTIAL
208832
54

Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
Health Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must also 
sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 

A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative. 
Participants who are rescreened are required to sign a new ICF.
GSK/ViiV (alone or working with others) may use participant’s coded study data and 
samples and other information to carry out this study; understand the results of this study; 
learn more about the study intervention and the injection site; publish the results of these 
research efforts; work with government agencies or insurers to have the study intervention 
approved for medical use or approved for payment coverage. 
11.1.4.
Data Protection

Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable 
will not be transferred. 

The participant must be informed that his/her personal study-related data will be used 
by the sponsor in accordance with local data protection law. The level of disclosure 
must also be explained to the participant who will be required to give consent for their 
data to be used as described in the informed consent. 

The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities.
11.1.5.
Dissemination of Clinical Study Data

Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report.  The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a GSK/ViiV site or other 
mutually-agreeable location.

GSK/ViiV will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study 
participants, as appropriate.


2018N357118_01
CONFIDENTIAL
208832
55

The procedures and timing for public disclosure of the protocol and results summary 
and for development of a manuscript for publication for this study will be in 
accordance with GSK Policy.

GSK/ViiV intends to make anonymized participant-level data from this trial available 
to external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure the data 
provided by trial participants are used to maximum effect in the creation of knowledge 
and understanding
11.1.6.
Data Quality Assurance

All participant data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee electronically (e.g., laboratory data). The
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 

The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 

The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 

Monitoring details describing strategy (e.g., risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-
Based Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan.

The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 

The sponsor assumes accountability for actions delegated to other individuals (e.g., 
Contract Research Organizations).

Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 

Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 15 years from the issue of the final Clinical 
Study Report (CSR)/ equivalent summary unless local regulations or institutional 
policies require a longer retention period. No records may be destroyed during the
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 


2018N357118_01
CONFIDENTIAL
208832
56
11.1.7.
Source Documents

Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site.

Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available.

Definition of what constitutes source data can be found in Monitoring Plan. 
11.1.8.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the first site open and will be the study start date.
GSK/ViiV or its designee reserves the right to close the study site or terminate the study at 
any time for any reason at the sole discretion of GSK//ViiV. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but 
are not limited to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The Investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up, if required.
11.1.9.
Publication Policy

The results of this study may be published or presented at scientific meetings. If this 
is foreseen, the investigator agrees to submit all manuscripts or abstracts to the 
sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.


2018N357118_01
CONFIDENTIAL
208832
57

The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual 
site data. In this case, a coordinating investigator will be designated by mutual 
agreement.

Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.


2018N357118_01
CONFIDENTIAL
208832
58
11.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 3 will be performed by the local laboratory. 

Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol.

Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations.

Pregnancy Testing 

Refer to Section 5.1 Inclusion Criteria for screening pregnancy criteria.

Pregnancy testing (urine or serum as required by local regulations) should be 
conducted per SoA.

Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the 
absence of pregnancy at any time during the participant's participation in the 
study.
Table 3
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments1
Parameters
Hematology
Platelet Count
RBC Indices:
Mean Corpuscular 
Volume
Mean Corpuscular 
Hemoglobin
%Reticulocytes
White Blood Cell count 
with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Red blood cell (RBC)
Count
Hemoglobin
Hematocrit
Clinical 
Chemistry2
Blood Urea 
Nitrogen
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase
(SGOT)
Total and direct 
bilirubin
Creatinine
Sodium
Alanine 
Aminotransferase
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase
(SGPT)
Total Protein
Glucose fasting
Calcium
Alkaline 
phosphatase
Coagulation 
tests
Prothrombin Time
Partial Thromboplastin 
Time
International 
Normalized Ratio


2018N357118_01
CONFIDENTIAL
208832
59
Laboratory 
Assessments1
Parameters
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood, ketones by dipstick

Microscopic examination (if blood or protein is abnormal)
Other 
Screening 
Tests

HIV: HIV 1-2 antibody/antigen (Ab/Ag) testing

Hepatitis B screen: Hepatits B surface antigen (HBsAg) 

Hepatitis B surface antibody(HBsAb), and Hepatitis core antibody 
(HBcAb)

Hepatitis C (Hep C antibody)

Alcohol screen and drugs of abuse screen (to include at minimum: 
amphetamines, barbiturates, cocaine, opiates, cannabinoids and 
benzodiazepines)

Urine (or serum) human Chorionic Gonadotropin Pregnancy test (as 
needed for women of child bearing potential)4
The results of each test must be entered into the CRF.
NOTES:
1.
An overnight fast is preferred prior to screening laboratory assessments; however, a minimum of a 6 hour fast 
is acceptable.  
2.
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1 and Appendix 7 All events of ALT 3 × upper limit of normal (ULN) 
and bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized ratio (INR) >1.5, if 
INR measured, which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis).
3.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC.


2018N357118_01
CONFIDENTIAL
208832
60
11.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
11.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease).
Note: Clinically significant laboratory abnormalities captured as AEs should be graded 
as per the clinical AE grade criteria, rather than by laboratory grade to be graded by the 
central laboratory or central statistical analysis group using DAIDS laboratory grading 
criteria as per 

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfill the definition of an AE or SAE. Also, 
"lack of efficacy" or "failure of expected pharmacological action" constitutes an 
AE or SAE.


2018N357118_01
CONFIDENTIAL
208832
61
Events NOT Meeting the AE Definition 

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
11.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
o
Results in death
o
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant 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 prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been detained 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious.

Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.


2018N357118_01
CONFIDENTIAL
208832
62
Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g. sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
Is a congenital anomaly/birth defect
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.
Is associated with liver injury and impaired liver function defined as: 

ALT ≥ 3xULN and total bilirubin* ≥ 2xULN (>35% direct), or 

ALT ≥ 3xULN and INR** > 1.5. 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick.  If fractionation is unavailable and 
ALT ≥ 3xULN and total bilirubin  ≥ 2xULN, then the event is still to be reported as an 
SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants.  If INR measurement is obtained, the value is to 
be recorded on the SAE form.
11.3.3.
Recording and Follow-Up of AE and SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.


2018N357118_01
CONFIDENTIAL
208832
63

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories per Appendix 7: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AE and SAE can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 


2018N357118_01
CONFIDENTIAL
208832
64
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE and SAE

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information.
11.3.4.
Reporting of SAE to GSK
SAE Reporting to GSK/ViiV via Electronic Data Collection Tool

The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and verification 
of the relationship of each SAE to IP/study participation (causality) within 72 
hours of SAE entry into the eCRF.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the medical monitor/SAE coordinator by telephone.


2018N357118_01
CONFIDENTIAL
208832
65

Contacts for SAE reporting can be found in SRM.
SAE Reporting to GSK/ViiV via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the medical monitor or the SAE coordinator.

In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames.

Contacts for SAE reporting can be found in SRM.


2018N357118_01
CONFIDENTIAL
208832
66
11.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information
11.4.1.
Definitions:
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered.
Women in the following categories are not considered WOCBP
1.
Premenarchal
2.
Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry.
Note: Documentation can come from the site personnel’s: review of the 
participant’s medical records, medical examination, or medical history interview.
3.
Postmenopausal female

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. 

A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). 
However, in the absence of 12 months of amenorrhea, confirmation with 
more than one FSH measurement is required. 

Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before 
study enrollment.


2018N357118_01
CONFIDENTIAL
208832
67
11.4.2.
Contraception Guidance:

CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:

Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per 
year when used consistently and correctly.

Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)c

Bilateral tubal occlusion

Vasectomized partner

Note: Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days.

Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly.

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc

oral

intravaginal

transdermal

injectable

Progestogen-only hormone contraception associated with inhibition of ovulationc

oral

injectable

Sexual abstinence

Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
a.
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies.
b.
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly.
c.
If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of action.
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Male 
condom and female condom should not be used together (due to risk of failure with friction)


2018N357118_01
CONFIDENTIAL
208832
68
11.4.3.
Collection of Pregnancy Information:
Male participants with partners who become pregnant

Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while participating in this study. This applies 
only to male participants who receive CAB + RPV.

After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy. 

The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK.

Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure. 
Female Participants who become pregnant

Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study. 

The initial information will be recorded on the appropriate form and submitted to 
GSK within 24 hours of learning of a participant's pregnancy. 

Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which will 
be forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  

Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure. 

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 

A spontaneous abortion (occurring at < 22 weeks gestational age) or still birth 
(occurring at > 22 weeks gestational age) is always considered to be an SAE and will 
be reported as such. 

Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study intervention by the investigator, will be reported to 
GSK as described in Appendix 3. While the investigator is not obligated to actively 
seek this information in former study participants, he or she may learn of an SAE 
through spontaneous reporting. 
Any female participant who becomes pregnant in OLI phase. will discontinue study 
intervention if participant gets pregnant and will not receive IM injections. 
If participant gets pregnant after receiving CAB LA and RPV LA, the participant should 
be followed up through 52 weeks post injections. 


2018N357118_01
CONFIDENTIAL
208832
69
11.5.
Appendix 5: Genetics
USE/ANALYSIS OF DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and IRB/IEC allow, a blood sample will be collected for DNA 
analysis

DNA samples will be used for research related to CAB and/or RPV. They may also 
be used to develop tests/assays including diagnostic tests related to CAB and/or RPV 
and other medicines used to treat or prevent HIV infection. Genetic research may 
consist of the analysis of one or more candidate genes or the analysis of genetic 
markers throughout the genome (as appropriate)

Additional analyses of DNA samples may be conducted if it is hypothesized that this 
may help further understand the clinical data. 

The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to CAB and/or RPV or study interventions of this class. The 
results of genetic analyses may be reported in the clinical study report or in a 
separate study summary.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained while research on CAB and/or RPV (or study 
interventions of this class) or and other medicines used to treat or prevent HIV 
infection continues but no longer than 15 years after the last participant last visit or 
other period as per local requirements.


2018N357118_01
CONFIDENTIAL
208832
70
11.6.
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments 
Phase 1 liver chemistry stopping criteria have been designed to assure participant safety 
and to evaluate liver event etiology 
Phase 1 liver chemistry stopping criteria and required follow up assessments
Liver Chemistry Stopping Criteria 
ALT-absolute
ALT≥3xULN
If ALT≥3xULN AND bilirubin1,2 2xULN (>35% direct bilirubin) or 
international normalized ratio (INR) >1.5, Report as an SAE.
See additional Actions and Follow Up Assessments listed below
Required Actions and Follow up Assessments 
Actions
Follow Up Assessments

Immediately discontinue study intervention

Report the event to GSK within 24 hours

Complete the liver event CRF, and 
complete an SAE data collection tool if the 
event also meets the criteria for an SAE2

Perform liver event follow up assessments 

Monitor the participant until liver 
chemistries resolve, stabilize, or return to 
within baseline (see MONITORING below)
MONITORING:
If ALT≥3xULN AND bilirubin 2xULN or INR 
>1.5

Repeat liver chemistries (include ALT, 
aspartate transaminase [AST], alkaline
phosphatase, bilirubin and INR) and 
perform liver event follow up assessments 
within 24 hours

Monitor participant twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline

A specialist or hepatology consultation is 
recommended

Viral hepatitis serology3

Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend

Obtain blood sample for pharmacokinetic 
(PK) analysis, obtained CAB + RPV of 
last dose4 

Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH).

Fractionate bilirubin, if total 
bilirubin2xULN

Obtain complete blood count with 
differential to assess eosinophilia

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications.

Record alcohol use on the liver event 
alcohol intake CRF


2018N357118_01
CONFIDENTIAL
208832
71
Liver Chemistry Stopping Criteria 
If ALT≥3xULN AND bilirubin < 2xULN and 
INR ≤1.5:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) 
and perform liver event follow up 
assessments within 24-72 hours

Monitor participant weekly until liver 
chemistries resolve, stabilize or return to 
within baseline
If ALT≥3xULN AND bilirubin 2xULN or 
INR >1.5:

Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins.

Serum acetaminophen adduct high 
performance liquid chromatography 
(HPLC) assay (quantifies potential 
acetaminophen contribution to liver injury 
in participants with definite or likely 
acetaminophen use in the preceding 
week) [James, 2009]. NOTE: not 
required in China.

Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy CRF forms.
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT 3xULN and bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary bilirubin on 
dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
2.
All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, which 
may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving anticoagulants
3.
Includes: Hepatitis A immunoglobulin (IgM) antibody; HBsAg and HBcAb; Hepatitis C RNA; Cytomegalovirus IgM 
antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile antibody or 
monospot testing) and Hepatitis E IgM antibody 
4.
PK sample may not be required for participants known to be receiving placebo or non-GSK comparator 
interventions.  Record the date/time of the PK blood sample draw and the date/time of the last dose of study 
intervention prior to PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the 
participant’s best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot 
be collected in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and 
shipping are in the SRM. 
References
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA,et al. 
Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen Overdose 
and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784.


2018N357118_01
CONFIDENTIAL
208832
72
11.7.
Appendix 7: Division of AIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events Version 2.1, March 
2017
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (“DAIDS AE Grading Table”) is a descriptive terminology which can be utilized
for Adverse Event (AE) reporting.  A grading (severity) scale is provided for each AE 
term. 
The table can be found at: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse 
Events (Corrected Version 2.1 - July 2017)
Reference
U.S. Department of Health and Human Services, National Institutes of Health, National 
Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 
2.1. [March 2017]. Available from:
https://rsc.tech-res.com/docs/default-source/safety/daids-ae-grading-table-mar2017.pdf


2018N357118_01
CONFIDENTIAL
208832
73
11.8.
Appendix 8: Permissible Procedures during the COVID-19 
Pandemic
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participant’s ability to attend clinic visits.  Based on these 
challenges, it may be necessary to adopt additional measures and procedures to protect 
participant safety, and to allow flexibility to allow conduct of the study. 
Permissible changes to procedures during the COVID-19 pandemic if deemed necessary 
by the investigator are outlined below. The investigator should discuss with the medical 
monitor the rationale if any of these changes are required for a participant. For further 
details refer to the Study Reference Manual (SRM).

Participants previously deemed eligible during the screening period unable to attend 
within the allowable screening window due to COVID-19 may be rescreened. 

Oral CAB dosing Days 1 to 28. All doses except Day 1 and Day 14 may be 
administered at home if participants are unable to attend due to COVID-19.  

AE assessments during the oral lead in may be conducted by telephone at home if 
participants are unable to attend due to COVID-19.  

Duration of admission to the clinic may be extended if deemed necessary by the 
investigator due to the COVID-19 pandemic.

The 10 to 14-day washout period after the oral lead in may be extended if deemed 
necessary by the investigator due to the COVID-19 pandemic.

If a participant has suspected COVID-19, or tests positive for COVID-19, or has 
potential COVID19 exposure while enrolled in the study, the Investigator must assess 
the impact of this disease/situation on the benefit/risk for the participant(s) to 
continue in the study, as well as if the participant has met protocol withdrawal 
criteria. Any adverse events related to the COVID-19 infection should continue to be 
evaluated as to whether they meet SAE criteria as defined in Section 11.3.2., and if 
so, reported in line with the SAE reporting requirements (Section 11.3.4). 
Investigator(s) should utilise WHO Case Definitions to classify COVID-19 cases 
[World Health Organisation, 2020].  The Sponsor recognises that COVID-19 case 
definitions may evolve during the study period, the most recent edition should be 
consulted for each case.  For all AEs or SAEs related to COVID-19, details should 
also be entered into the specific COVID-19 eCRF.  The study site should contact the 
study Medical Monitor for questions related to definitions and reporting, and 
decisions around impact to study drug continuation in the setting of clinically defined 
mild COVID-19 infection.


2018N357118_01
CONFIDENTIAL
208832
74
11.9.
Appendix 9: Abbreviations and Trademarks
AC
Active control
AE
Adverse Event
ALT
Alanine aminotransferase (SGPT)
AST
Aspartate aminotransferase (SGOT)
AUC
Area under concentration-time curve
AUC(0-)
Area under the concentration-time curve over one dosing 
interval
AUC(0-24)
Area under the concentration-time curve over 24 hours
hCG
Human Chorionic Gonadotropin
BMI
Body mass index
BUN
Blood urea nitrogen
Cmax
Maximum observed concentration 
Cmin
Minimum observed concentration
Cτ
Last observed quantifiable concentration
CONSORT
Consolidated Standards of Reporting Trials
CPK
Creatine phosphokinase
CPMS
Clinical Pharmacokinetics Modelling & Simulation
CRF
Case Report Form
CV
Coefficient of variance
DILI
Drug Induced Liver Injury
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
FDA
Food and Drug Administration
FPFV
First participant First Visit
FSH
Follicle Stimulating Hormone
GCP
Good Clinical Practice
GCSP
Global Clinical Safety and Pharmacovigilence
GLP
Good Laboratory Practice
GSK
GlaxoSmithKline
HBsAg
Hepatitis B surface antigen
hCG
Human chorionic gonadotropin
HDPE
High density polyethylene
HIV
Human Immunodeficiency Virus
HSR
Hypersensitivity Reactions
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for 
Human Use
IDMC
Independent Data Monitoring Committee
IDSL
Integrated Data Standards Library
IEC
Independent Ethics Committee
IM
Intramuscular
IND
Investigational New Drug


2018N357118_01
CONFIDENTIAL
208832
75
IP
Investigational Product
IRB
Institutional Review Board
ISRs
Injection Site Reactions 
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
z
Terminal phase rate constant
L
Liter
LA
Long Acting
LFTs
Liver function tests
µg
Microgram
µL
Microliter
MCH
Mean corpuscular hemoglobin
MCHC
Mean corpuscular hemoglobin concentration
MCV
Mean corpuscular volume
MedDRA
Medical Dictionary for Regulatory Activities
Mg
Milligrams
mL
Milliliter
MSDS
Material Safety Data Sheet
msec
Milliseconds
NNRTI
Non-nucleoside reverse transcriptase inhibitor
OLI
Oral Lead In
PCR
Polymerase chain reaction
PD
Pharmacodynamic
PGx
Pharmacogenetics
PK
Pharmacokinetic
PoPPK
Population PK
QC
Quality control
QD
Once daily
QTcB
QT duration corrected for heart rate by Bazett’s formula
QTcF
QT duration corrected for heart rate by Fridericia’s 
formula
RAP
Reporting and Analysis Plan
RBC
Red blood cells
RNA
Ribonucleic acid
RPV
Rilpivirine
SAE
Serious adverse event(s)
SARS-CoV2/ COVID-19
Severe acute respiratory syndrome coronavirus 2
SAS
Statistical Analysis Software
SC
Subcutaneous
SD
Standard deviation
SGOT
Serum glutamic-oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transaminase
SoA
Schedule of Activities
SOP
Standard Operating Procedure
SRM
Study Reference Manual
STR
Study Team safety & PK Review


2018N357118_01
CONFIDENTIAL
208832
76
SUSAR
Suspected, Unexpected, Serious Adverse drug Reaction
t½
Terminal phase half-life
τ
Dosing interval
tmax
Time of occurrence of Cmax
UGT
UDP glucuronosyltransferase
ULN
Upper limit of normal
VSLC
ViiV Safety and Labelling Committee
US
United States
WBC
White blood cells
WOCBP
Woman of Childbearing Potential
Trademark Information
Trademarks of ViiV Healthcare
Trademarks not owned by the ViiV 
Healthcare
None
EDURANT


2018N357118_01
CONFIDENTIAL
208832
77
11.10.
Appendix 10: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC).
DOCUMENT HISTORY
Document
Date
DNG Number
Amendment 1
13-AUG-2020
2018N357118_01
Original Protocol
02-MAR-2020
2018N357118_00


2018N357118_01
CONFIDENTIAL
208832
78
12.
REFERENCES
ATLAS-2M: press release https://viivhealthcare.com/en-gb/media/press-
releases/2018/viiv-healthcare-reports-positive-48-week-results-for-first-pivotal-phase-iii-
study-for-novel-long-acting-injectable-hiv-treatment-regimen/
Chevat C, Viala-Dante M, et al. Development and psychometric validation of a self-
administered questionnaire assessing the acceptance of influenza vaccination: the 
Vaccinees' Perception of Injection (VAPI©) questionnaire. Health Qual Life Outcomes. 
2009; 7: 21.
Edurant Prescribing Information, June 2019.
Ford S, Margolis D, Chen S, Gould E, Spreen W. Plasma and tissue GSK1265744 
pharmacokinetics following long-acting parenteral administration in healthy male and 
female subjects. Published at: International Workshop on Clinical Pharmacology of HIV 
Therapy 2013 - 14th Annual; April 22-24, 2013; Amsterdam, The Netherlands.
GlaxoSmithKline Document Number RH2009/00003/09: GSK1265744 (Cabotegravir) 
Clinical Investigator's Brochure, Version 09, December 2019.
Margolis D, Sutton K, Vente J, LeBlanc R et al. Long-Term Efficacy, Safety and 
Durability of CAB and RPV as Two Drug Oral Maintenance Therapy – LATTE Week 
312 Result –IDWeek 2019 
Margolis DA, Gonzalez Garcia J, Stellbrink H-J, et al. Safety, efficacy and durability of 
long-acting CAB and RPV as two drug IM maintenance therapy for HIV-1 infection:  
LATTE-2 week 160 results. Presented at: HIV Drug Therapy Glasgow 2018
NATAP report: R Verloes, G vanÔt Klooster, L Baert, F van Velsen,M-P Bouche, K 
Spittaels, J Leempoels, P Williams, G Kraus, P Wigerinck: TMC278 long acting - a 
parenteral nanosuspension formulation that provides sustained clinically relevant plasma 
concentrations in HIV-negative volunteers XVII International AIDS Conference, Mexico 
City August 2008 
Orkin C, Arasteh K, Hernandez-Mora MG, et al. Long-acting cabotegravir + rilpivirine as 
maintenance therapy: FLAIR week 48 results. Published at: Conference on Retroviruses 
and Opportunistic Infections - 26th Annual; March 4-7, 2019; Seattle, WA.
Rilpivirine Clinical Investigator Brochure [RPV IB], Edition Version 12 (18-Jul-2019).
Rodger MA, King L. Drawing up and administering intramuscular injections: a review of 
the literature. J Adv Nurs. 2000;31(3):574-582.
Spreen W, Williams P, Ford SF, et al. Repeat dose co-administration of GSK1265744 
and TMC278 long-acting parenteral nanosuspensions: pharmacokinetics, safety, and 
tolerability in healthy subjects. Published at: International AIDS Society 2013 - 7th 
Conference on HIV Pathogenesis, Treatment & Prevention; Jun 30-July 3, 2013: Kuala 
Lumur, Malaysia.


2018N357118_01
CONFIDENTIAL
208832
79
Swindells S, Andrade-Villanueva J-F, Richmond G, et al. Long-acting cabotegravir + 
rilpivirine as maintenance therapy: ATLAS week 48 results. Published at: Conference on 
Retroviruses and Opportunistic Infections - 26th Annual; March 4-7, 2019; Seattle, WA.
World Health OrganisationMarch 2020: Global surveillance for COVID-19 caused by 
human infection with COVID-19 virus. Interim guidance. Available at:
https://www.who.int/publications-detail/global-surveillance-for-human-infection-with-
novel-coronavirus-(2019-ncov). Accessed 18 June 2020.

SAP_001.pdf: 
 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
208832 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: A Phase 1, Open-Label Study to Evaluate the 
Pharmacokinetics and Tolerability of Cabotegravir and 
Rilpivirine Long-Acting Injections Following 
Intramuscular Administration in the Vastus Lateralis 
Muscle of Healthy Adult Participants 
Compound Number  
: GSK1265744  
Effective Date  
: 07-MAY-2021 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 208832 
• 
This RAP is intended to describe the safety, pharmacokinetics, and tolerability 
analyses required for the study  
• 
This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable. 
 



&21),'(17,$/

7KH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV




5$3$XWKRUV
$XWKRU
'DWH
/HDG


0$<
6WDWLVWLFLDQ+,9*6.&OLQLFDO6WDWLVWLFV
&R$XWKRUV
0$<

3ULQFLSDO3URJUDPPHU+,9*6.&OLQLFDO3URJUDPPLQJ

5$37HDP5HYLHZ&RQILUPDWLRQV0HWKRG(PDLO
5HYLHZHU
'DWH

0$<
&OLQLFDO'HYHORSPHQW0DQDJHU5	'*&6'*6.

0$<
3ULQFLSDO&OLQLFDO'DWD0DQDJHU*&'2*6.&OLQLFDO'DWD
0DQDJHPHQW

0$<
0DQDJHU&OLQLFDO3KDUPDFRORJ\*6.&306

0$<
5HVHDUFK	'HYHORSPHQW9LL9
+HDOWKFDUH

&OLQLFDO6WDWLVWLFV	&OLQLFDO3URJUDPPLQJ/LQH$SSURYDOV0HWKRG3KDUPD70)
H6LJQDWXUH
$SSURYHU
'DWH

0$<
6WDWLVWLFV/HDGHU+,9*6.&OLQLFDO6WDWLVWLFV

0$<
3URJUDPPLQJ'LUHFWRU+,9*6.&OLQLFDO3URJUDPPLQJ

&RS\ULJKWWKH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV$OOULJKWVUHVHUYHG
8QDXWKRULVHGFRS\LQJRUXVHRIWKLVLQIRUPDWLRQLVSURKLELWHG

PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD



&21),'(17,$/






7$%/(2)&217(176
3$*(
 
5(3257,1*	$1$/<6,63/$16<1236,6 
 
5HYLVLRQ&KURQRORJ\ 
 
6800$5<2).(<35272&2/,1)250$7,21 
 
&KDQJHVWRWKH3URWRFRO'HILQHG6WDWLVWLFDO$QDO\VLV3ODQ 
 
6WXG\2EMHFWLYHVDQG(QGSRLQWV 
 
6WXG\'HVLJQ 
 
6WDWLVWLFDO+\SRWKHVHV 
 
+\SRWKHVHV 
 
3/$11('$1$/<6(6 
 
,QWHULP$QDO\VHV 
 
)LQDO$QDO\VHV 
 
$1$/<6,63238/$7,216 
 
3URWRFRO'HYLDWLRQV 
 
&216,'(5$7,216)25'$7$$1$/<6(6$1''$7$+$1'/,1*
&219(17,216 
 
7UHDWPHQWDQG2WKHU6XE*URXS'HVFULSWLRQVIRU'DWD'LVSOD\V 
 
%DVHOLQH'HILQLWLRQV 
 
2WKHU&RQVLGHUDWLRQVIRU'DWD$QDO\VHVDQG'DWD+DQGOLQJ
&RQYHQWLRQV 
 
2WKHU&RQVLGHUDWLRQV 
 
678'<3238/$7,21 
 
6XEMHFW'LVSRVLWLRQ 
 
'HPRJUDSKLFDQG%DVHOLQH&KDUDFWHULVWLFV 
 
0HGLFDO+LVWRU\DQG&RQFRPLWDQW0HGLFDWLRQV 
 
6$)(7<$1$/<6(6 
 
([WHQWRI([SRVXUHDQG7UHDWPHQW&RPSOLDQFH 
 
$GYHUVH(YHQWV 
 
,QMHFWLRQ6LWH5HDFWLRQ$GYHUVH(YHQWV 
 
$GYHUVH(YHQWVRI6SHFLDO,QWHUHVW$(6,V 
 
3UHJQDQFLHVDVDSSOLFDEOH 
 
&OLQLFDO/DERUDWRU\(YDOXDWLRQV 
 
2WKHU6DIHW\$QDO\VHV 
 
3+$50$&2.,1(7,&$1$/<6(6 
 
'UXJ&RQFHQWUDWLRQ0HDVXUHV 
 
'HULYLQJDQG6XPPDUL]LQJ3KDUPDFRNLQHWLF3DUDPHWHUV 
 
6WDWLVWLFDO$QDO\VHV 
 
6WUDWHJ\IRU,QWHUFXUUHQW(YHQWV±&RYLG&RPSOLFDWLRQV 
 
+($/7+287&20(6$1$/<6(6 
 
 
 
 
CCI


 
CONFIDENTIAL 
 
 
 
208832 
4 
 
10. REFERENCES ....................................................................................................... 22 
11. APPENDICIES ....................................................................................................... 23 
11.1. 
Appendix 1: Schedule of Activities .............................................................. 23 
11.1.1. 
Screening and Oral Lead-in Phase .............................................. 23 
11.1.2. 
CAB LA + RPV LA Injection Phase and Follow- up ...................... 25 
11.2. 
Appendix 2: Assessment Windows ............................................................. 27 
11.2.1. 
Definitions of Assessment Windows ............................................ 27 
11.3. 
Appendix 3: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 29 
11.3.1. 
Study Phases .............................................................................. 29 
11.3.2. 
Treatment Emergent Flag for Adverse Events ............................. 30 
11.4. 
Appendix 4: Data Display Standards and Handling Conventions ................ 31 
11.4.1. 
Reporting Process ....................................................................... 31 
11.4.2. 
Reporting Standards .................................................................... 31 
11.4.3. 
Reporting Standards for Pharmacokinetic Data ........................... 32 
11.4.4. 
Reporting Standards for Liver Safety Data ................................... 32 
11.4.4.1. Liver Stopping/Monitoring Criteria ............................... 32 
11.4.4.2. Hepatobiliary Abnormality Criteria .............................. 33 
11.5. 
Appendix 5: Derived and Transformed Data ............................................... 34 
11.5.1. 
General ........................................................................................ 34 
11.5.2. 
Study Population .......................................................................... 35 
11.5.3. 
Safety .......................................................................................... 36 
11.5.4. 
Pharmacokinetic .......................................................................... 37 
11.5.5. 
Health Outcomes ......................................................................... 37 
11.6. 
Appendix 6: Reporting Standards for Missing Data ..................................... 39 
11.6.1. 
Premature Withdrawals ................................................................ 39 
11.6.2. 
Handling of Missing Data ............................................................. 39 
11.6.2.1. Handling of Missing and Partial Dates ........................ 39 
11.7. 
Appendix 7: Values of Potential Clinical Importance ................................... 41 
11.7.1. 
Laboratory Values ........................................................................ 41 
11.7.2. 
ECG ............................................................................................. 42 
11.8. 
Appendix 8: Abbreviations & Trademarks ................................................... 43 
11.8.1. 
Abbreviations ............................................................................... 43 
11.8.2. 
Trademarks ................................................................................. 44 
11.9. 
Appendix 9: List of Data Displays ............................................................... 45 
11.9.1. 
Data Display Numbering .............................................................. 45 
11.9.2. 
Deliverables ................................................................................. 45 
11.9.3. 
Study Population Tables .............................................................. 46 
11.9.4. 
Safety Tables ............................................................................... 47 
11.9.5. 
Safety Figures ............................................................................. 52 
11.9.6. 
Pharmacokinetic Tables ............................................................... 52 
11.9.7. 
Pharmacokinetic Figures ............................................................. 53 
11.9.8. 
Health Outcomes Tables ............................................................. 54 
11.9.9. 
ICH Listings ................................................................................. 55 
11.9.10. Non-ICH Listings .......................................................................... 58 
11.9.11. Mock Displays ............................................................................. 60 
11.10. Appendix 10: AESI Identification ................................................................. 68 
11.10.1. Hepatotoxicity .............................................................................. 68 
11.10.2. Seizures ...................................................................................... 72 
11.10.3. Torsade de pointes/QT prolongation ............................................ 75 
11.10.4. COVID-19 Adverse Events .......................................................... 76 


 
CONFIDENTIAL 
 
 
 
208832 
5 
 
1. 
REPORTING & ANALYSIS PLAN SYNOPSIS 
Overview 
Key Elements of the RAP 
Purpose 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses 
to be included in the Clinical Pharmacology Study Report for Protocol 208832. 
Protocol 
This RAP is based on the original protocol (Dated 02-MAR-2020) of study  
GSK1265744/208832 (GSK Document No.: 2018N357118_00) and its protocol 
amendment 1 (Dated 13-AUG-2020; GSK Document No.: 2018N357118_01) 
Primary 
Objective  
To describe the PK profiles of CAB and RPV following a single intramuscular 
injection each of CAB LA + RPV LA administered to the lateral thigh muscle in 
adult healthy participants 
Primary 
Endpoint 
• 
Maximum observed concentration (Cmax) and time of maximum observed 
concentration (tmax) in plasma 
• 
Area under the concentration – time curve from time zero to last 
quantifiable time point (AUC0-t) through the follow-up phase 
• 
Area under the concentration – time curve from time zero to infinity 
(AUC0-) 
• 
Apparent terminal phase half-life (t½) and absorption rate constant (KA LA) 
Study 
Design 
This is a Phase 1, open label study conducted in healthy participants to assess the 
PK of CAB and RPV in plasma following a single 600 mg (1 x 3 mL) and a 900 
mg (1 x 3 mL) injection each, respectively, administered IM to separate vastus 
lateralis muscles on each leg. The study will consist of a 30-day screening phase, 
a 28-day oral lead-in (OLI) phase at a CAB dose of 30 mg and RPV dose of 25 
mg once a day with a meal, followed by a 10-14 day washout phase. Single 
doses of CAB and RPV will then be injected, administered IM: 600 mg (1 x 3 
mL) CAB on left and a 900 mg (1 x 3 mL) RPV injection on right vastus 
lateralis muscles. Sparse PK sampling for up to 29 days in OLI and serial PK 
sampling for up to 4 weeks after the injection, per SoA. Participants will return 
for safety assessments and additional PK sampling at Week 8, 12, 24, 36, and 52 
post last injection during the follow-up phase. 
Planned 
Analyses 
All the derived PK parameters will be listed and summarized by treatment and 
study phase. For each of these PK parameters the following descriptive summary 
statistics will be calculated: n, arithmetic mean with associated 95% CI, standard 
deviation, median, minimum, and maximum. The mean & geometric mean with 
associated 95% CIs, standard deviations, and geometric coefficient of variation 
(CVb(%)) will be calculated for all parameters except ttmax.  
Analysis 
Populations 
Enrolled Population, Safety Population, Pharmacokinetic Concentration 
Population and Pharmacokinetic Parameter Population 
Hypothesis 
No formal hypothesis will be tested in this study  
Primary 
Analyses 
Primary endpoints include CAB and RPV PK parameters Cmax, AUC0-t, AUC0-, 
t1/2, and KA LA as calculated from injection phase concentration-time data.  
Descriptive statistics and graphics will be created to describe the primary PK 
endpoints of interest. 
 
1.1. 
Revision Chronology 
Revision Chronology: 
ID: 35421_2099331 
31-AUG-2020 
Critical Components 


 
CONFIDENTIAL 
 
 
 
208832 
6 
 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
Cabotegravir (CAB) is an integrase inhibitor being developed in combination with 
rilpivirine (RPV, TMC278), a non-nucleoside reverse transcriptase inhibitor, for the 
treatment of HIV. CAB is currently in Phase 3 development as monotherapy for the 
prevention of sexually-acquired HIV-1 infection.  CAB and RPV are separately formulated 
as oral tablets for once daily administration and as long-acting (LA) aqueous suspensions 
for parenteral administration monthly or every 2-months.  RPV 25mg oral tablets is 
approved as EDURANT in multiple countries, including the USA, Europe and Canada, for 
use in antiretroviral (ARV) treatment-naïve patients.    
 
A two-drug long-acting, monthly antiretroviral regimen of CAB + RPV has demonstrated 
good efficacy, tolerability, and long-term safety in HIV-infected adults following oral and 
monthly and every 2-month IM dosing in the gluteus muscle for durations exceeding 3 
years in Phase 2 and Phase 3 studies [LATTE; LATTE-2; ATLAS, 2019; FLAIR, 2019, 
ATLAS-2M]. Review and approval of the CAB + RPV regimen for treatment of HIV 
infection is ongoing.      
Separate early Phase 1 studies of CAB LA and RPV LA evaluated PK and tolerability of 
single and repeat-dose injections in other anatomic locations including abdomen 
(subcutaneous) and IM administration in the ventrogluteal muscle (CAB), gluteus 
maximus muscle (RPV), and deltoid muscle (RPV) in healthy volunteers [HIV Therapy 
2013; International AIDS Society 2013; RPV LA NATAP report].  Gluteal injections of 
CAB LA + RPV LA were progressed in late-stage studies given better participant 
tolerability to injections at this injection site with the anticipated injection dosing volume 
required to achieve desired exposures.   
There remains considerable interest in exploring alternative injection sites either as an 
alternative rotational (e.g. gluteal injection fatigue) or chronic injection site (e.g. gluteal 
implants contraindicating injection or young pediatric populations without sufficient 
gluteal mass for injection).  The vastus lateralis muscle in the thigh has been used as an 
injection location for other drugs (e.g. epinephrine, etc.) and is a common injection site in 
young children (e.g. vaccines). Moreover, self- or partner-injection of CAB LA + RPV LA 
in the thigh muscle may be explored in future studies pending favorable pharmacokinetics, 
safety, and tolerability of CAB LA + RPV LA thigh injections.  
The objective of this study is to evaluate the pharmacokinetics, tolerability, and safety of 
CAB LA + RPV LA administered concomitantly as two separate IM injections in the 
vastus lateralis muscle of adult healthy participants.  Data from this study will be used to 
inform the feasibility of administering CAB LA + RPV LA in the vastus lateralis muscle 
in HIV-infected children <12 years of age and adult populations.   
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
In consideration of the recent, global Covid-19 pandemic, and in accordance with recent 
GSK clinical guidance, sensitivity analyses summarizing disposition and select safety 
results will be displayed alongside primary results. This stands as an addition to the 
originally planned statistical analysis specified in the protocol dated 02-MAR-2020 and 



&21),'(17,$/






SURWRFRODPHQGPHQWGDWHG$8*$VHFRQGDGGLWLRQZLOOEHWKHFDOFXODWLRQRI
3.SDUDPHWHUVLQWKH2/,SKDVHDORQJVLGHWKH3.SDUDPHWHUVRIWKH,QMHFWLRQSKDVHDV
QRWHGLQWKHSULPDU\REMHFWLYH7KLUGO\WKHSURWRFROFDOOVIRUWKHVKRUWYHUVLRQ
TXHVWLRQQDLUHWREHLPSOHPHQWHGZKLOHWKLV5$3SODQVIRUWKHIXOOYHUVLRQDGPLQLVWHUHG
VHSDUDWHO\IRUHDFKWKLJKLQRUGHUWRFROOHFWFOLQLFDOO\PHDQLQJIXOLQIRUPDWLRQRQWKH
IXWXUHXVHRIWKLJKLQMHFWLRQVLQWKHSHGLDWULFSRSXODWLRQ)LQDOO\OLVWLQJVDUHVSHFLILHGWR
EHLQFOXVLYHRIDOOVFUHHQHGVXEMHFWV
&KDQJHVIURPWKHRULJLQDOO\SODQQHGVWDWLVWLFDODQDO\VLVVSHFLILHGLQWKHSURWRFRODQGLWV
DPHQGPHQWDUHRXWOLQHGLQ7DEOH
7DEOH
&KDQJHVWR3URWRFRO'HILQHG$QDO\VLV3ODQ
Protocol 
Reporting & Analysis Plan 
Rationale 
x
Study objectives and endpoints 
listed without consideration of the 
Covid-19 pandemic 
x
Disposition and select safety 
results will be repeated with 
consideration to subjects’ 
relation to Covid-19. 
x
The Covid-19 pandemic 
has spurred the need to 
assess whether the 
impact creates substantial 
impact on study results. 
x
PK parameters only calculated 
for Injection phase 
x
Applicable PK parameters will 
also be calculated in the OLI 
phase as data permits 
x
OLI PK parameters are of 
interest in addition to 
Injection parameters 
x
Short version of 
 
questionnaire recorded 
x
Full version of the 
 
questionnaire recorded 
separately for each injection 
x
Information found in the 
full version is considered 
clinically meaningful to 
plan for further thigh 
injections in children. 
x
PK Listings are subset by 
population relevant to the data 
x
All listing data will be shown 
for all screened subjects 
x
To more feasibly serve as 
a reference for subjects 
not meeting population 
requirements 


6WXG\2EMHFWLYHVDQG(QGSRLQWV
7DEOH
6WXG\2EMHFWLYHVDQG(QGSRLQWV
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
x
7RGHVFULEHWKH3.SURILOHVRI&$%
DQG539IROORZLQJDVLQJOH
LQWUDPXVFXODULQMHFWLRQHDFKRI&$%
/$539/$DGPLQLVWHUHGWRWKH
ODWHUDOWKLJKPXVFOHLQDGXOWKHDOWK\
SDUWLFLSDQWV.  
 
x
0D[LPXPREVHUYHGFRQFHQWUDWLRQ&PD[DQG
WLPHRIPD[LPXPREVHUYHGFRQFHQWUDWLRQWPD[
LQSODVPD
x
$UHDXQGHUWKHFRQFHQWUDWLRQ±WLPHFXUYHIURP
WLPH]HURWRODVWTXDQWLILDEOHWLPHSRLQW$8&W
WKURXJKWKHIROORZXSSKDVH
x
$UHDXQGHUWKHFRQFHQWUDWLRQ±WLPHFXUYHIURP
WLPH]HURWRLQILQLW\$8&f
x
$SSDUHQWWHUPLQDOSKDVHKDOIOLIHWòDQG
DEVRUSWLRQUDWHFRQVWDQW.$ LA 


CCI
CCI
CCI



&21),'(17,$/






Safety Objectives 
Safety Endpoints 
x
7RDVVHVVVDIHW\DQGWROHUDELOLW\RI
&$%DQG539IROORZLQJUHSHDWHGRUDO
GRVHDQGVLQJOHLQWUDPXVFXODULQMHFWLRQ
LQWKHODWHUDOWKLJKRIKHDOWK\
SDUWLFLSDQWV
x
6DIHW\DQGWROHUDELOLW\SDUDPHWHUVLQFOXGLQJ
DGYHUVHHYHQWV$(VFOLQLFDOODERUDWRU\WHVWV
HOHFWURFDUGLRJUDP(&*DQGYLWDOVLJQ
DVVHVVPHQWV
Secondary Objectives 
Secondary Endpoints 
x
7RDVVHVVOLYHUVDIHW\DQGWROHUDELOLW\
RI&$%DQG539IROORZLQJUHSHDWHG
RUDOGRVHDQGVLQJOHLQWUDPXVFXODU
LQMHFWLRQLQWKHODWHUDOWKLJKRIDGXOW
KHDOWK\SDUWLFLSDQWV
x
7ROHUDELOLW\SDUDPHWHUVOLYHUUHODWHGDGYHUVH
HYHQWVDQGOLYHUFKHPLVWU\DEQRUPDOLWLHV
Exploratory Objectives 
Exploratory Endpoints 

6WXG\'HVLJQ
7KLVLVDSKDVHRSHQODEHOVWXG\LQKHDOWK\SDUWLFLSDQWVWRDVVHVVWKH3.RI&$%DQG
539LQSODVPDIROORZLQJDVLQJOHPJ[P/DQGDPJ[P/LQMHFWLRQ
HDFKUHVSHFWLYHO\DGPLQLVWHUHG,0WRVHSDUDWHYDVWXVODWHUDOLVPXVFOHVRQHDFKOHJ
7KHVWXG\ZLOOFRQVLVWRI
x GD\VFUHHQLQJSHULRG
x GD\RUDOOHDGLQ2/,SKDVHDWD&$%GRVHRIPJDQG539GRVHRIPJ
RQFHDGD\ZLWKDPHDO
x ±GD\VZDVKRXWSHULRG
x &$%DQG539LQMHFWLRQDGPLQLVWHUHG,0PJ[P/&$%RQOHIWDQGD
PJ[P/539LQMHFWLRQRQULJKWYDVWXVODWHUDOLVPXVFOH
x 6SDUVH3.VDPSOLQJIRUXSWRGD\VLQ2/,DQGVHULDO3.VDPSOLQJIRUXSWR
ZHHNVDIWHUWKHLQMHFWLRQSHU6R$3DUWLFLSDQWVZLOOUHWXUQIRUVDIHW\DVVHVVPHQWV
DQGDGGLWLRQDO3.VDPSOLQJDW:HHNDQGSRVWODVWLQMHFWLRQGXULQJ
WKHIROORZXSSKDVH

$SSUR[LPDWHO\DGXOWKHDOWK\SDUWLFLSDQWVZLOOEHGRVHGZLWKLQMHFWDEOHVWXG\
LQWHUYHQWLRQV,ISDUWLFLSDQWVSUHPDWXUHO\GLVFRQWLQXHWKHVWXG\IRUDQ\RWKHUUHDVRQ
CCI


 
CONFIDENTIAL 
 
 
 
208832 
9 
 
other than an AE, additional replacement participants may be enrolled at the discretion of 
the Sponsor in consultation with the investigator. The study design is defined in Table 3. 
Table 3 
Study Design 
Screening 
Oral  
Lead-in  
Washout 
CAB Injection and Compartmental PK 
Sampling 
Safety/ 
Blood Plasma Sampling 
Within 30 days 
of Oral Lead-in 
Oral CAB 30 mg 
tablet + Oral 
RPV 25 mg 
tablet once daily  
x 28 days 
 
No drug 
administered 10 - 
14 days 
 
Single 600 mg CAB LA IM dose into lateral 
thigh + single 900 mg RPV LA IM dose into 
opposite lateral thigh 
 
Serial blood plasma sampling up to 4 
weeks post-injection 
Follow-up safety 
assessments and blood 
plasma PK sampling will 
occur at 8, 12, 24, 36, and 
52 Weeks post-dose 
 
Figure 1 
Study Schematic 
 
Injection Day 1: CAB LA 600mg IM (3mL) + RPV LA 900mg IM (3mL) Lateral thigh 
2.4. 
Statistical Hypotheses 
2.4.1. 
Hypotheses 
The primary objective of this study is to describe the PK profiles of CAB and RPV 
following a single intramuscular injection each of CAB LA + RPV LA administered to 
the lateral thigh muscle. No formal statistical hypotheses are to be tested. Where 
appropriate, an estimation approach will be taken, and point estimates and confidence 
intervals will be constructed. There will be no formal comparison. 
3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
There will be no formal interim analysis. All preliminary safety, tolerability and available 
pharmacokinetic data may be reviewed internally at any time point.  Depending on 
feasibility, evaluation of PK data may be performed at time points such as Week 4 and 
Week 12 post injection for preliminary PK analysis.    


 
CONFIDENTIAL 
 
 
 
208832 
10 
 
3.2. 
Final Analyses 
Final analysis will be performed after all subjects have completed the study and final 
database freeze (DBF) has been declared by Data Management. Data will be listed and 
summarized according to GSK reporting standards, where applicable. 
Statistical data analyses will be performed by, or under the direct auspices of, Clinical 
Statistics and Programming, GlaxoSmithKline utilizing SAS version 9.4 or higher. PK 
analysis of the plasma CAB and RPV concentration-time data will be conducted using 
non-compartmental methods with WinNonlin (Version 6.3 or higher).  
All the derived PK parameters will be listed and summarized by treatment and study 
phase. For each of these PK parameters the following descriptive summary statistics will 
be calculated: n, arithmetic mean with associated 95% CI, standard deviation, median, 
minimum, and maximum. The mean & geometric mean with associated 95% CIs, 
standard deviations, and geometric coefficient of variation (CVb(%)) will also be 
calculated for all parameters except tmax. 
Safety and health outcome data will be presented in tabular and/or graphical format and 
summarized descriptively according to GSK’s Integrated Data Standards Library (IDSL) 
standards. 
4. 
ANALYSIS POPULATIONS 
As a convention, listing data will be displayed for all screened subjects. 
Table 4 
Study Populations 
Population 
Definition / Criteria 
Analyses Evaluated 
Enrolled 
• 
All participants who sign the ICF. 
• 
Note screening failures (who never passed screening 
even if rescreened) and participants screened but 
never enrolled into the study are excluded from the 
Enrolled population as they did not enter the study. 
• 
Study Population 
Safety 
• 
All participants who take at least 1 dose of study drug. 
• 
Study Population 
• 
Safety 
Pharmacokinetic 
Concentration 
(PC) 
• 
All participants who undergo plasma PK sampling and 
have evaluable PK assay results from either oral or 
injection dosing 
• 
Concentration 
summaries  
• 
Individual plotting 
of concentration-
time data 
Pharmacokinetic 
Parameter 
(PP) 
• 
All participants who undergo plasma PK sampling and 
have evaluable PK parameters estimated.  
• 
Note: PK samples that may be affected by protocol 
deviations will be reviewed by the study team to 
determine whether or not the sample will be excluded. 
• 
PK parameter 
summaries 
• 
Mean/median plots 
and summary 
tables 
Refer to Appendix 9: List of Data Displays which details the population used for each display. 
 


 
CONFIDENTIAL 
 
 
 
208832 
11 
 
4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, excluded medications, conduct of the trial, participant management, or 
participant assessment) will be summarized with frequencies and proportions by study 
phase and overall.  
Protocol deviations will be tracked by the study team throughout the conduct of the 
study. 
o Data will be reviewed prior to freezing the database to ensure all significant 
deviations and deviations which may lead to exclusion from the analysis 
populations are captured and categorized on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
All protocol deviations will be listed. A separate listing of all inclusion/exclusion criteria 
deviations will also be provided. This listing will be based on data as recorded on the 
inclusion/exclusion page of the electronic case report form (eCRF). 
 
 


 
CONFIDENTIAL 
 
 
 
208832 
12 
 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Treatment and Other Sub-Group Descriptions for Data 
Displays 
Data display treatment descriptors with actual treatment dose will be defined as displayed 
in Table 5. Safety events in the washout phase will be counted with events in the Oral 
lead-in phase. Safety events in the Follow-up phase will be counted separately from the 
Injection phase. 
 
Table 5 
Study Treatment 
 
Treatment Group Descriptions 
Phase 
Analysis 
Data Set 
Final Data Display (i.e. HARP / other) 
Code 
Treatment 
Description 
Treatment 
Description-
Footnote 
Column Header 
Oral Lead-in 
PK 
A 
Oral CAB 30mg 
tablet once daily x 
4 weeks lead-in 
Oral CAB 
30mg=Cabotegravi
r 30mg PO 4 
weeks lead-in 
Oral CAB 30mg 
B 
Oral RPV 25mg 
tablet once daily x 
4 weeks lead-in 
Oral RPV 25mg= 
Rilpivirine 25mg 
PO 4 weeks lead-
in. 
Oral RPV 25mg 
Safety 
AB 
Oral CAB 30mg + 
RPV 25mg tablets 
once daily x 4 
weeks lead-in 
Oral CAB 30mg + 
Oral RPV 25mg 
=Cabotegravir 
30mg + Rilpivirine 
25mg PO 4 weeks 
lead-in 
Oral CAB 30mg + 
Oral RPV 25mg 
Injection, 
Follow-up 
PK, Safety 
(ISRs), HO 
C 
Single 600mg CAB 
LA IM dose 
IM CAB 
600mg=Cabotegra
vir IM 600mg 
single dose. 
IM CAB 600mg – 
Injection Phase; 
IM CAB 600mg – 
Follow-up Phase 
D 
Single 900mg RPV 
LA IM dose 
IM RPV 
900mg=Rilpivirine 
IM 900mg single 
dose. 
IM RPV 900mg – 
Injection Phase; 
IM RPV 900mg – 
Follow-up Phase 
Safety 
CD 
Single 600mg CAB 
+ single 900mg 
RPV LA IM dose 
IM CAB 600mg + 
IM RPV 900mg = 
Cabotegravir IM 
600mg + Rilpivirine 
IM 900mg single 
dose. 
IM CAB 600mg + 
IM RPV 900mg – 
Injection Phase; 
IM CAB 600mg + 
IM RPV 900mg – 
Follow-up Phase 



&21),'(17,$/







%DVHOLQH'HILQLWLRQV
)RUVDIHW\SDUDPHWHUVWKHEDVHOLQHRUSUHGRVHYDOXHZLOOEHWKHODWHVWDVVHVVPHQWSULRUWR
WKHWLPHRIVWXG\GUXJDGPLQLVWUDWLRQLQHDFKSKDVHZLWKDQRQPLVVLQJYDOXHLQFOXGLQJ
WKRVHIURPXQVFKHGXOHGYLVLWV,IWLPHLVQRWFROOHFWHG'D\DVVHVVPHQWVDUHDVVXPHGWR
EHWDNHQSULRUWRILUVWGRVHDQGFRQVLGHUHGIRUXVHDVEDVHOLQH,IWKHUHDUHPXOWLSOH
DVVHVVPHQWVFROOHFWHGRQWKHVDPHVFKHGXOHGWLPHWKHDYHUDJHRIWKHVHDVVHVVPHQWVZLOO
EHXVHG7DEOHLQGLFDWHVWKHEDVHOLQHGD\WREHXVHGLQWKHDQDO\VLV
7DEOH
%DVHOLQH3DUDPHWHU6SHFLILFDWLRQV
Phase 
Parameter 
Study Assessments Considered as 
Baseline 
Baseline Used in Data 
Display 
Oral Lead-in Phase 
Laboratory results, 
Vital Sign results, 
ECG results1 
OLI Baseline = last non-missing pre-dose 
assessment collected <= Date of first OLI 
dose 
OLI Day 1 
Injection Phase 
Laboratory results, 
Vital Sign results 
(pre-dose), ECG 
results1 (pre-dose), 
 scores 
Injection Phase Baseline = assessment 
collected on the date of CAB + RPV 
injection 
Injection Day 1 
Follow-up Phase 
Laboratory results, 
Vital Sign results 
(pre-dose), ECG 
results1 (pre-dose) 
Follow-up Phase Baseline = assessment 
collected on the date of CAB + RPV 
injection 
Injection Day 1 
1.
Average of the triplicate assessments for quantitative assessments will be used as the baseline. 
,IWLPHLVQRWFROOHFWHG'D\DVVHVVPHQWVDUHDVVXPHGWREHWDNHQSULRUWRILUVWGRVHRI
WKHUHVSHFWLYHSKDVH8QOHVVRWKHUZLVHVWDWHGLIEDVHOLQHGDWDLVPLVVLQJQRGHULYDWLRQ
ZLOOEHSHUIRUPHGDQGEDVHOLQHZLOOEHVHWWRPLVVLQJ

2WKHU&RQVLGHUDWLRQVIRU'DWD$QDO\VHVDQG'DWD+DQGOLQJ
&RQYHQWLRQV

2WKHU&RQVLGHUDWLRQV
2WKHUFRQVLGHUDWLRQVIRUGDWDDQDO\VHVLQFOXGLQJLQIRUPDWLRQUHJDUGLQJSUHPDWXUH
ZLWKGUDZDOXQVFKHGXOHGDVVHVVPHQWVGHULYHGDQGWUDQVIRUPHGGDWDDQGGDWDKDQGOLQJ
FRQYHQWLRQVDUHRXWOLQHGLQWKHDSSHQGLFHV
Section 
Component 
11.1 
Appendix 1: Schedule of Activities 
11.2 
Appendix 2: Assessment Windows 
11.3 
Appendix 3: Study Phases and Treatment Emergent Adverse Events 
11.4 
Appendix 4: Data Display Standards and Handling Conventions 
11.5 
Appendix 5: Derived and Transformed Data 
11.6 
Appendix 6: Reporting Standards for Missing Data 
CCI


 
CONFIDENTIAL 
 
 
 
208832 
14 
 
Section 
Component 
11.7 
Appendix 7: Values of Potential Clinical Importance 
11.8 
Appendix 8: Abbreviations & Trademarks 
11.9 
Appendix 9: List of Data Displays 
11.10 
Appendix 10: AESI Identification 
 


 
CONFIDENTIAL 
 
 
 
208832 
15 
 
6. 
STUDY POPULATION 
The study population analyses will be based on both the Enrolled and Safety populations, 
unless otherwise specified. 
Study population analyses include analyses of study populations, subjects’ disposition, 
important protocol deviations, demographic and baseline characteristics, and prior and 
concomitant medications. Outputs will be based on GSK Core Data Standards.  Details of 
the planned displays are presented in Appendix 9: List of Data Displays. 
6.1. 
Subject Disposition 
A summary table will be generated to provide the count of subjects included in each 
analysis population for the study (see Section 4 for definition of analysis populations). 
The End of Study Record will be summarized by study phase and overall. Counts for the 
all discontinuation categories will be repeated considering subjects who discontinued to a 
Covid-19 related incident.  
A disposition listing will include whether subjects prematurely withdrew from the study, 
the reason for premature discontinuation along with the start and end date of 
investigational product (IP) dosing and the date of completion or premature 
discontinuation from the study. An additional listing showing subjects who discontinued 
to Covid-19 considerations will be included. 
6.2. 
Demographic and Baseline Characteristics 
Demographic data include date of birth, sex, race, and ethnicity. Demographic data and 
baseline characteristics (i.e. height, weight, and BMI) will be summarized for the Safety 
Population.  Race will be further summarized separately from the other demographic 
characteristics. All demographic data will be listed by subject.  
6.3. 
Medical History and Concomitant Medications 
Medical history events will be summarized and listed. Concurrent medication verbatim 
text will be coded and classified by the Anatomical Therapeutic Chemical Classification 
level 1 (ATC Level 1) code and the preferred term using the GSK coding system, GSK 
DRUG. Concomitant medications will then be summarized by ATC classification, study 
phase, and overall. Coding of concurrent medications will be the responsibility of the 
GSK coding group. 
7. 
SAFETY ANALYSES 
Safety data will be summarised and listed by, or under the direct auspices of, Clinical 
Statistics, GlaxoSmithKline. The safety summaries will be based on the Safety 
population, unless otherwise specified and shown for the Oral Lead-in, Injection, and 
Follow-up phases where applicable. 
Safety endpoints include: 


 
CONFIDENTIAL 
 
 
 
208832 
16 
 
• Safety and tolerability parameters including adverse events, clinical laboratory 
tests, ECG, and vital sign assessments 
• Tolerability parameters (liver related adverse events) and liver chemistry 
abnormalities 
For continuous safety parameters, the Injection phase Baseline will also serve as Follow-
up phase Baseline. No formal statistical analysis of the safety data will be conducted. The 
precise format and content of Safety tables and listings are shown in Appendix 9 of the 
RAP. 
7.1. 
Extent of Exposure and Treatment Compliance 
Overall CAB & RPV exposure will be presented with descriptive statistics (i.e. n, mean, 
SD, median, minimum, and maximum) by study phase and treatment. Treatment will be 
determined by the laterality of the injection. CAB will be administered on a subject’s left 
thigh while RPV will be administered on a subject’s right thigh. Parameters displayed 
will include number of days of oral exposure, oral compliance percentage, and injection 
status. Details on oral compliance percentage calculation are included in Appendix 5. 
A by-subject listing of data on subject exposure will be generated including dose date and 
time, unit, formulation, route, frequency and location.  
7.2. 
Adverse Events 
Adverse event verbatim text will be coded and classified by system organ class (body 
system) and preferred term using a standardized GSK coding system: Medical Dictionary 
for Regulatory Activities (MedDRA, v23.0 or higher). AE data will be summarized with 
frequencies and percent by study phase and overall. The relationship of AE system organ 
class, preferred term, and verbatim text will be listed. Treatment emergent AEs, drug-
related AEs, serious adverse events (SAEs) including fatal AEs, and AEs leading to drug 
withdrawal or study discontinuation will be summarized by study phase and overall. AEs 
and drug-related AEs will also be summarized by maximum toxicity grade (based on 
Division of AIDS (DAIDS) categories). All AEs will be listed by subject and AE start 
date. 
Adverse events related to Covid-19 will also be summarized by SOC, PT, and maximum 
toxicity. Subjects with Covid-19 tests performed as well as Covid-19 diagnoses will also 
be summarized. Summaries of serious Covid-19 AEs and Covid-19 AEs leading to study 
discontinuation or drug withdrawal will also be presented in accordance with Covid-19 
safety assessment guidance. Covid-19 AEs will also be presented by sex and pandemic 
course (during and post-) if applicable.  
7.3. 
Injection Site Reaction Adverse Events 
Injection site reaction adverse event data will also be summarized by treatment and 
overall. Tables will include subject and event-level summaries. ISR treatment will be 
determined by the laterality of the assessment (left vs. right). All ISR AEs will be shown 
in a separate listing from overall adverse events. 


 
CONFIDENTIAL 
 
 
 
208832 
17 
 
7.4. 
Adverse Events of Special Interest (AESIs) 
AESIs will be summarized for Hepatotoxicity and Seizures. QT Prolongation events will 
be listed. A comprehensive list of MedDRA terms based on clinical review will be used 
to identify each type of event for Adverse Events of Special Interest (AESI). [Changes to 
the MedDRA dictionary may occur between the start of the study and the time of 
reporting and/or emerging data from on-going studies may highlight additional adverse 
events of special interest, therefore the list of terms to be used for each event of interest 
and the specific events of interest will be based on the safety review team (SRT) 
agreements in place at the time of reporting.] The details of the current planned grouping, 
including Standardized MedDRA Query (SMQ) values (as applicable), and planned 
displays are provided in Appendix 10: AESI Identification and Appendix 9: List of Data 
Displays. 
7.5. 
Pregnancies (as applicable) 
If any female subjects become pregnant during the study, a listing of such subjects will be 
provided. 
7.6. 
Clinical Laboratory Evaluations 
Worst grade post-baseline for hematology, clinical chemistry, and urinalysis data will be 
summarized by study phase.  Summaries of change from baseline in hematology and 
clinical chemistry by study phase and visit will be created. If any laboratory test results 
are outside of the reference range, they will be flagged with high/low and/or toxicity 
grade in the listing. Standardized units will be used for clinical laboratory summary tables 
and listings. 
Hematology, clinical chemistry, drug, infectious disease, coagulation and urinalysis data 
will be listed by subject, study phase, visit, and collection date. 
7.7. 
Other Safety Analyses 
Vital sign data (temperature, systolic and diastolic blood pressure, and pulse rate) will be 
summarized by study phase, visit, and planned time. Absolute values and change from 
baseline values will be shown. Injection phase Baseline will also serve as Follow-up 
phase Baseline. Vitals signs will be listed by subject, study phase, visit, planned time, and 
actual date and time.  
Electrocardiogram (ECG) data including values and findings will be summarized by 
study phase, visit, and timepoint. Absolute values and change from baseline will be 
shown for PR, QRS, QT, QTcB, and QTcF results. Baseline will be calculated as the 
mean of triplicate readings recorded prior to first dose in each study phase. 
All ECG data including clinical interpretation will be listed by subject, study phase, visit 
and record date. Clinically significant ECG abnormalities will be flagged and listed 
separately, and corresponding values will be provided.  
Liver related adverse events and chemistry abnormalities will be summarized separately 
by study phase. See Appendix 10 for a list of Hepatotoxicity AEs and Appendix 7 for 
Chemistry values of Potential Clinical Importance. 


 
CONFIDENTIAL 
 
 
 
208832 
18 
 
8. 
PHARMACOKINETIC ANALYSES 
The reconciliation of the PK Case Report Form (CRF) and SMS2000 data will be 
performed by, or under the direct auspices of, Clinical Pharmacology Sciences and Study 
Operations (CPSSO), GlaxoSmithKline. 
The merge of PK concentration data and CRF data will be performed by, or under the 
direct auspices of, Clinical Statistics (Programmer), GlaxoSmithKline. 
Derivation of pharmacokinetic parameters will be performed by, or under the direct 
auspices of, Clinical Pharmacology Modelling and Simulation (CPMS), 
GlaxoSmithKline. 
Statistical analysis of pharmacokinetic parameters will be performed by, or under the 
direct auspices of, Clinical Statistics (Statistician), GlaxoSmithKline.  
Concentration and PK parameter data will be reported for specified Pharmacokinetic 
populations in the OLI and Injection phases.  
8.1. 
Drug Concentration Measures 
Plasma CAB and RPV concentration values will be summarized with descriptive statistics 
by study phase, treatment, visit, and planned timepoint for the PK Concentration 
Population (PC). These concentration values will be determined directly from 
concentration-time data from each analyte. Descriptive statistics including the n, mean with 
associated 95% CI, standard deviation, median, minimum, maximum, geometric mean 
with associated 95% CI, standard deviation of logarithmically transformed data, 5th/95th 
percentiles and the geometric coefficient of variation (CVb(%))).  
Individual concentration-time profiles and median/mean profiles from each analyte in 
each study phase will be plotted for the PK Concentration (PC) Population.  Each of the 
figures will contain one plot on the untransformed scale (i.e. a linear plot) and one plot on 
the log transformed scale (i.e. semi-log plot).  Actual assessment times will be used in the 
individual concentration-time plots. Nominal times will be used for the purposes of 
summarization and in mean and median plots. See Appendix 4: Data Display Standards 
& Handling Conventions. for details on pharmacokinetic figure and table displays. 


 
CONFIDENTIAL 
 
 
 
208832 
19 
 
8.2. 
Deriving and Summarizing Pharmacokinetic Parameters 
Pharmacokinetic parameters will be derived by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin 6.3 or higher (Pharsight, Inc., Cary, NC). All calculations of non-
compartmental PK parameters will be based on actual sampling times. Pharmacokinetic 
parameters listed will be determined from the plasma concentration-time data, as data 
permits. The following PK parameters will be derived and displayed for the PP 
Population as data permits: 
Table 7 
Derived PK Parameters 
Parameter 
Parameter Description 
OLI Phase 
Injection Phase 
Cmax 
Maximum observed concentration 
Day 1 
Overall 
tmax 
Time of occurrence of Cmax 
Day 1 
Overall 
AUC0-∞ 
Area under the concentration time curve from 
time zero to infinity 
Day 1-2 
Overall 
AUC0-t 
Area under the concentration time curve from 
time zero to last quantifiable time point 
Day 1-2 
Overall 
t1/2 
Terminal phase half-life 
Day 1-2 
Overall 
KA LA 
Absorption rate constant, Long-acting 
NA 
Overall 
z 
Terminal phase rate constant 
Day 1-2 
NA 
C24 
Concentration at OLI Phase 24-hour timepoint 
Day 2 
NA 
C 
Trough concentrations (C) at OLI Phase Day 29 
Day 29 
NA 
NOTES: NA: Not Applicable 
• 
Additional parameters may be included as required. 
 
 
Primary Pharmacokinetic endpoints include the following PK parameters from Injection 
Phase:  
• Maximum observed concentration (Cmax) and time of maximum observed 
concentration (tmax) in plasma 
• Area under the concentration – time curve from time zero to last quantifiable time 
point (AUC0-t) through the follow-up phase 
• Area under the concentration – time curve from time zero to infinity (AUC0-) 
• Apparent terminal phase half-life (t½) and absorption rate constant (KALA)) 
PK parameters such as Cmax and AUC should be reported in g/mL and g*h/mL for 
CAB and in ng/mL and ng*h/mL for RPV. Other PK parameters such as tmax and t1/2 
should be reported in hours and KALA and z parameters in /h for both CAB and RPV. 
 
 


 
CONFIDENTIAL 
 
 
 
208832 
20 
 
8.3. 
Statistical Analyses 
All the derived pharmacokinetic parameters will be summarized and listed for the PP 
population by study phase and treatment. For each of these PK parameters, with the 
exception of tmax, the following descriptive summary statistics will be calculated for each 
treatment: n, arithmetic mean with associated 95% CI, standard deviation, median, 
minimum, maximum, geometric mean with associated 95% CI, standard deviation of 
logarithmically transformed data, and the geometric coefficient of variation (CVb(%)). 
For tmax, the n, median, minimum, and maximum summary statistics will be provided. 
 
Data display specifications for derived PK parameter summaries and listings are given in 
Appendix 9 of this RAP 
PK samples collected outside the protocol defined time-windows and/or other protocol 
deviations will be reviewed by the study team to determine whether the sample will be 
excluded from PK analyses. PK reporting will also consider planned Quality Tolerance 
Limit (QTL) outcomes affecting study data quality. Details are found in the QTL Report. 
8.4. 
Strategy for Intercurrent Events – Covid-19 Complications 
While incidents of Covid-19 could be expected to affect subject safety, its effect on CAB 
+ RPV PK concentrations is unknown. Given the small study sample size implying less 
likelihood that a subject acquires Covid-19 through the course of the study, the benefit of 
a sensitivity analysis for subjects that acquire Covid-19 during the course of their PK 
sampling appears minimal. Should more information become available and/or the clinical 
need arise, this RAP may be amended to include Covid-19 PK sensitivity analyses in 
order to further understand any potential interacting effects.



&21),'(17,$/







+($/7+287&20(6$1$/<6(6
+HDOWKRXWFRPHVTXHVWLRQQDLUHGDWDZLOOEHVXPPDULVHGDQGOLVWHGE\RUXQGHUWKHGLUHFW
DXVSLFHVRI&OLQLFDO6WDWLVWLFV*OD[R6PLWK.OLQH7KHKHDOWKRXWFRPHVDQDO\VHVZLOOEH
EDVHGRQWKH6DIHW\SRSXODWLRQXQOHVVRWKHUZLVHVSHFLILHG$OOTXHVWLRQQDLUHGDWDZLOOEH
OLVWHGE\VXEMHFWLWHPWUHDWPHQWDQGWLPHSRLQWDVDSSOLFDEOH
1RIRUPDOVWDWLVWLFDODQDO\VLVRIWKHKHDOWKRXWFRPHVGDWDZLOOEHFRQGXFWHG7KHSUHFLVH
IRUPDWDQGFRQWHQWRIKHDOWKRXWFRPHVWDEOHVDQGOLVWLQJVDUHVKRZQLQ$SSHQGL[RIWKH
5$3
CCI


 
CONFIDENTIAL 
 
 
 
208832 
22 
 
10. 
REFERENCES 
GlaxoSmithKline Document Number 2018N357118_00: A Phase 1, Multicompartment 
Pharmacokinetic Study of Cabotegravir Long-acting in Healthy Adult Volunteers. 
Effective Date: 02-MAR-2020 
 
GlaxoSmithKline Document Number 2018N357118_01: A Phase 1, Multicompartment 
Pharmacokinetic Study of Cabotegravir Long-acting in Healthy Adult Volunteers. 
Effective Date: 13-AUG-2020 
 
GlaxoSmithKline Document: Covid-19 Guidance for Estimands and Estimation. 
 
GlaxoSmithKline Document: Impact of Covid-19 on Assessment of Safety in Clinical 
Trials. 
 


 
CONFIDENTIAL 
208832 
23 
 
11. 
APPENDICIES 
11.1. 
Appendix 1: Schedule of Activities 
11.1.1. 
Screening and Oral Lead-in Phase 
Study Period 
Screening1 
 
Oral Lead-in9 
Day 29 
Early 
Withdrawal9 
Washout Period 
Dosing Days 1-28 
Visit Window   
Within 
30 days 
of oral lead-in 
Day -1 
Day 1 
Day 2 
Day 14 
Within 24 hours 
of the Day 28 last 
dose 
EW 
10 – 14 days 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical / Medication / Drug / 
Alcohol History 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria2 
X 
 
X 
 
 
 
 
 
Height, Weight, BMI 
X 
 
 
 
 
 
 
 
Physical Exam 
X 
 
X 
 
 
 
 
 
Vital Signs3 
X 
 
X 
X 
X 
X 
X 
 
12-Lead ECG 
X 
 
X 
 
 
X 
 
 
Drug / Alcohol Screen3  
X 
 
X 
 
 
 
 
 
Pregnancy Test3 
X 
 
X 
 
X 
X 
 
 
Testing for SARS-CoV-24 
X 
X 
 
 
 
 
 
 
Hepatitis B, Hepatitis C Screening 
X 
 
 
 
 
 
 
 
HIV Test  
X 
 
 
 
 
 
 
 
Urine Dipstick  
X 
 
 
 
 
 
 
 
Hematology with differential; 
Clinical Chemistry Tests3 
X 
 
X 
X 
X 
X 
X 
 
Coagulation Tests  
X 
 
 
 
 
 
 
 
Admit to clinic 
 
X 
 
 
 
 
 
 
Dispense Oral lead-in IP 
 
 
X 
 
 
 
 
 


 
CONFIDENTIAL 
208832 
24 
 
Study Period 
Screening1 
 
Oral Lead-in9 
Day 29 
Early 
Withdrawal9 
Washout Period 
Dosing Days 1-28 
Visit Window   
Within 
30 days 
of oral lead-in 
Day -1 
Day 1 
Day 2 
Day 14 
Within 24 hours 
of the Day 28 last 
dose 
EW 
10 – 14 days 
Administer oral CAB + RPV5 
 
 
X 
X 
X 
 
 
 
Dispense Medication Dosing 
Diary 
 
 
 
X 
 
 
 
 
Drug accountability/ pill 
count/review drug diary 
 
 
 
X 
X 
X 
 
 
Blood plasma PK sampling6 
 
 
X 
X 
X 
X 
X 
 
AE Assessment7 
 
 
X 
X 
X 
X 
X 
 
Concomitant Medication Review 
 
 
X 
X 
X 
X 
X 
 
Genetic sample8 
 
 
X 
 
 
 
 
 
Discharge from the clinic 
 
 
 
X 
 
 
 
 
1. Screening may occur over more than one visit but within 30 days of the first dose of oral CAB and RPV in the oral lead in phase. 
2. Eligibility criteria must be carefully assessed at the Screening visit and confirmed at the Day 1 Oral lead-in phase visit and re-confirmed prior to injection. 
3. Prior to administering the first oral dose of CAB and RPV, study personnel must verify the following pre-dose assessments to be within normal limits prior to administration: vital 
signs, pregnancy test (negative; Females of Reproductive Potential (FRP) only. The results of the Drug/Alcohol screen, hematology with differential, and clinical chemistry tests on 
Day 1 are not required prior to administering the first oral doses of CAB and RPV but should be drawn prior to CAB and RPV administration. 
4. Following the second test for SARS-CoV-2, participants will be advised to self-quarantine until entrance to the unit while awaiting final testing clearance.  
5. Oral CAB and RPV dosing Days 1 to 28. Day 1, Day 2, and Day 14 doses should be administered in the clinic.   
6. PK sampling – On Day 1 - 1h, 2h, 3h, 4h, 6h, 8h, and 12h, and Day 2 PK between 22-26 h from first oral dose. On Day 14 pre-dose samples. Day 29 assessments should occur 
between 22-26 hours from the last dose on Day 28. Total of 20 PK samples (10 for CAB, 10 for RPV assay) will be collected during oral lead-in phase. Please refer to Protocol 
Section 8.4 for permitted PK window for OLI phase. 
7. AE assessment will include a brief, symptom-directed physical exam as needed. 
8. Genetic sample - collect the sample at the earliest convenient time after the first dose in the oral lead in phase on Day 1. 
9. If a participant is withdrawn prior to receiving the CAB LA and/or RPV LA injection, a follow-up/withdrawal visit should be scheduled 10-14 days after the last oral dose of CAB and 
RPV. 



&21),'(17,$/




&$%/$539/$,QMHFWLRQ3KDVHDQG)ROORZXS
 
Injection Phase 
Follow-up 
Procedures 
 
Injection 
Day 1 
Day 2 
Day 4 
Day 5 
Day 7/8 
Day 10 
Day 15 
Day 17 
Day 22 
Day 28 
 (Week 4) 
Week 8 
Week 12 
Week 24 
Week 36 
Week 52 
Withdrawal1 
Pre-
dose2 
1h 
2h 
24h 
72h 
96h 
168h 
 
 
 
 
 
 
 
 
Permitted window for PK 
collection 
Within 1 h prior to 
dosing 
± 15 min 
± 30 min 
± 2 h 
± 2 h 
± 2 h 
± 2 h 
± 2 h 
± 2 h 
± 2 h 
± 2 h 
± 2 h 
± 3 days 
± 3 days 
± 3 days 
± 3 days 
± 3 days 
 
Interim Medical/Medication/ 
Drug / Alcohol History2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test  
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG2  
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
HIV Test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
Testing for SARS-CoV-2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology; Clinical Chemistry 
X 
 
 
 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Vital Signs2 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Administer CAB LA + RPV LA2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X3 
 
X3 
X3 
X3 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X3 
 
 
 
 
 
 
 
 
 
 
 
Injection site reaction 
assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE Assessment4 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medication 
Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood plasma PK Sampling5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI



&21),'(17,$/



 Participants who terminate before week 52 will be asked to return to the site for a withdrawal visit.  
 On Day 1, study personnel must verify the following pre-dose assessments to be within normal limits prior to injection: ECG, vital signs, pregnancy test (negative; FRP only), 
review AE assessment, and concomitant medications. If a clinical abnormality, clinically significant AE, or prohibited medication that precludes injection is observed/recorded, the 
medical monitor must be contacted for further instruction.   
 Participants will be asked to describe the comfort level with the injections received.
 AE assessment will include a brief, symptom-directed physical exam as needed. 
 Total of 34 PK samples (17 each for CAB and RPV) will be collected through CAB LA + RPV LA Injection Phase and Follow-up. 
CCI
CCI



&21),'(17,$/





$SSHQGL[$VVHVVPHQW:LQGRZV
$OODVVHVVPHQWVHYHQWVLQFOXGLQJWKRVHIURPSODQQHGXQVFKHGXOHGDQGZLWKGUDZDO
YLVLWVZLOOEHDVVLJQHGWRDVVHVVPHQWZLQGRZVDQDO\VLVYLVLWVDFFRUGLQJWRDFWXDOGDWHVRI
FROOHFWLRQUDWKHUWKDQWKHQRPLQDOYLVLWODEHOVUHFRUGHGRQWKHH&5)RULQWKHODERUDWRU\
GDWDEDVH$OODVVHVVPHQWGDWDLQFOXGLQJXQVFKHGXOHGGDWDZLOOEHSUHVHQWHGLQOLVWLQJV
)RUSDUDPHWHUVZKLFKDUHQRWVFKHGXOHGWREHDVVHVVHGDWDSDUWLFXODUYLVLWWKHDOO
LQFOXVLYHDVVHVVPHQWZLQGRZVZLOOVWLOOEHXVHGKRZHYHUGDWDGLVSOD\VVXPPDUL]LQJ
PHDVXUHPHQWVE\YLVLWZLOORQO\UHSRUWYLVLWVLQZKLFKWKHSDUDPHWHULVDSODQQHG
FROOHFWLRQDFFRUGLQJWR$SSHQGL[6FKHGXOHRI$FWLYLWLHV
1RWH3ULRUWRYLVLWVORWWLQJDVVHVVPHQWVDUHILUVWDVVLJQHGWRDVWXG\SKDVHDFFRUGLQJWR
7DEOH

'HILQLWLRQVRI$VVHVVPHQW:LQGRZV
7DEOH
$VVHVVPHQW:LQGRZVIRU6FUHHQLQJDQG2/,3KDVH'DWD
Parameter 
Analysis Window 
Target 
Period Day 
Analysis 
Timepoint 
Assessments assigned to Phase=Screening or OLI (per Table 3)  
All  
OLI Phase Day <1 
The day of 
earliest 
record 
Screening 
PK, Vital Signs, Labs, ECG 
OLI Phase Day = 1 
1 
Day 1 
PK, Vital Signs, Labs 
OLI Period Day = 2 
2 
Day 2 
PK 
13 d OLI Phase Day d 15 
14 
Day 14 
Vital Signs, Labs 
3 d OLI Phase Day d 21 
14 
Day 14 
PK 
28 d OLI Phase Day d 30 
29 
Day 29 
Vital Signs, Labs, ECG 
22 d OLI Phase Day  
29 
Day 29 
If none of the above 
Day X, where 
X=OLI Phase day 

7DEOH
$VVHVVPHQW:LQGRZVIRU,QMHFWLRQ	)ROORZXS3KDVH'DWD
Parameter a 
Analysis Window 
Target 
Period 
Day 
Analysis 
Timepoint 
Assessments assigned to Phase=Injection (per Table 3) 
PK, Vital Signs, Labs, ECG, 
 
Injection Phase Day = 1 
1 
Day 1 
PK, Vital Signs, 
 
Injection Phase Day = 2 
2 
Day 2 
PK 
Injection Phase Day = 4 
4 
Day 4 
 
3 d Injection Phase Day d 4 
4 
Day 4 
PK 
Injection Phase Day = 5 
5 
Day 5 
Vital Signs 
3 d Injection Phase Day d 6 
5 
Day 5 
 
5 d Injection Phase Day d 6 
5 
Day 5 
ECG 
2 d Injection Phase Day 
5 
Day 5 
CCI
CCI
CCI
CCI



&21),'(17,$/




Parameter a 
Analysis Window 
Target 
Period 
Day 
Analysis 
Timepoint 
PK 
Injection Phase Day = 7 
7 
Day 7 
PK 
Injection Phase Day = 8 
8 
Day 8 
7 d Injection Phase Day 
8 
Day 8 
Vital Signs 
7 d Injection Phase Day d 9 
8 
Day 8 
Labs 
2 d Injection Phase Day d 10 
8 
Day 8 
PK 
Injection Phase Day = 10 
10 
Day 10 
Vitals 
10 d Injection Phase Day d 12 
10 
Day 10 
PK 
Injection Phase Day = 15 
14 
Day 15 
Vital Signs 
12 d Injection Phase Day d 16 
14 
Day 15 
PK 
Injection Phase Day = 17 
17 
Day 17 
Vital Signs 
17 d Injection Phase Day d 19 
17 
Day 17 
Labs 
11 d Injection Phase Day d 23 
17 
Day 17 
PK 
Injection Phase Day = 22 
22 
Day 22 
Vital Signs 
20 d Injection Phase Day d 25 
22 
Day 22 
PK 
Injection Phase Day = 28 
28 
Week 4 
Vital Signs 
26 d Injection Phase Day 
28 
Week 4 
Labs 
24 d Injection Phase Day  
28 
Week 4 
 
If none of the above  
 
Day X, where 
X=Injection Phase 
Day 
Assessments assigned to Phase=Follow-up (per Table 3) 
Vital Signs, Labs 
(Date of Nominal Follow-up Week 4 
Visit – CAB + RPV Injection Date) +2 
d Injection Phase Day d 70  
56 
Week 8 
PK 
53 d Follow-up Period Day d 59 
56 
Week 8 
Vital Signs, Labs 
71 d Follow-up Period Day d 126  
84 
Week 12 
PK 
81 d Follow-up Period Day d 87 
84 
Week 12 
Vital Signs, Labs 
127 d Follow-up Period Day d 210 
168 
Week 24 
PK 
165 d Follow-up Period Day d 171 
168 
Week 24 
Vital Signs, Labs 
 211 d Follow-up Period Day d 308 
252 
Week 36 
PK 
 249 d Follow-up Period Day d 255 
252 
Week 36 
Vital Signs, Labs, ECG 
309 d Follow-up Period Day 
364 
Week 52 
PK 
361 d Follow-up Period Day d 367 
364 
Week 52 
If none of the above  
Day X, where 
X=Follow-up 
Phase Day 
NOTES: 
x
OLI Day, Injection Day, and Follow-up Day are defined in Section 11.5.1. 
CCI


 
CONFIDENTIAL 
208832 
 
29 
 
11.3. 
Appendix 3: Study Phases and Treatment Emergent 
Adverse Events 
11.3.1. 
Study Phases 
All assessments and events (including those collected as planned, early withdrawal and 
unscheduled visits) will be classified in study phases according to Table 3. 
Assessments/events are assigned to study phases sequentially, starting from the top of 
each table. 
Table 3 
Assignment of Study Phases 
For All Events or Assessments 
Study Period 
Date range 
Screen 
If actual “Time of Day” for the assessment/event is collected: 
Start Date and Time < OLI Treatment Start Date & Time 
If actual “Time of Day” for the assessment/event is not collected: 
Start Date < OLI Treatment Start Date 
OLI Phase 
If actual “Time of Day” for the assessment/event is collected: 
For participants continuing into Injection Phase: 
OLI Treatment Start Date & Time ≤ Start Date & Time < Date & Time of 
CAB + RPV Injection 
 
For participants not continuing into Injection Phase: 
OLI Treatment Start Date & Time ≤ Start Date & Time 
If actual “Time of Day” for the assessment/event is not collected: 
For participants continuing into Injection Phase: 
OLI Treatment Start Date ≤ Start Date < Date of CAB + RPV Injection 
 
For participants not continuing into Injection Phase: 
OLI Treatment Start Date ≤ Start Date 
Injection Phase 
If actual “Time of Day” for the assessment/event is collected: 
Date & Time of CAB + RPV Injection ≤ Start Date & Time and Start Date ≤ 
Date of Nominal Follow-up Week 4 
If actual “Time of Day” for the assessment/event is not collected: 
Date of CAB + RPV Injection ≤ Start Date ≤ Date of Nominal Follow-up 
Week 4 Visit  
Follow-up Phase Date of Nominal Follow-up Week 4 Visit < Start Date 
 
 


 
CONFIDENTIAL 
208832 
 
30 
 
NOTES:  
• 
Date = Date of assessment  
Table 4 
Study Phases for Concomitant Medication 
Concomitant during: 
 
Study Period 
Date range 
Prior  
Medication Taken < OLI Treatment Start Date & Time 
OLI Phase 
For participants continuing into Injection Phase: 
OLI Treatment Start Date & Time ≤ Medication Taken < Injection 
Phase Treatment Start Date & Time 
 
For participants not continuing into Injection Phase: 
OLI Treatment Start Date & Time ≤ Medication Taken 
Injection Phase 
Injection Phase Treatment Start Date & Time  Medication Taken ≤ 
Date of Nominal Follow-up Week 4 Visit  
Follow-Up Phase 
Date of Nominal Follow-up Week 4 Visit < Medication Taken  
NOTES:  
• 
If concomitant medication time is missing, the medication will be assumed to be taken predose, prior to that day’s 
treatment dosing. 
• 
Please refer to Appendix 6: Reporting Standards for Missing Data. for handling of missing and partial dates for 
concomitant medication. Use the rules in this table if concomitant medication date is completely missing. 
11.3.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
AEs will be considered emergent in the OLI, Injection and Follow-up Phases 
according to the classification defined in Table 3. AEs that occur in the Follow-up 
Phase will be considered Treatment Emergent. 


 
CONFIDENTIAL 
208832 
 
31 
 
11.4. 
Appendix 4: Data Display Standards and Handling 
Conventions 
11.4.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software version 9.4 will be used. 
Reporting Area 
HARP Server 
us1salx00259 
HARP Compound 
\ARPROD\GSK1265744\mid213199\internal_01 
\ARPROD\GSK1265744\mid213199\internal_02 
\ARPROD\GSK1265744\mid213199\primary_01 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.1.  
Generation of RTF Files 
• 
RTF files will be generated for all tables in Appendix 9: List of Data Displays. 
11.4.2. 
Reporting Standards 
General 
• 
The current GSK Statistical Display Standards in the GSK Standards Library (IDSL) will be applied for 
reporting, unless otherwise stated (Library Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
Formats 
• 
GSK Statistical Display Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for reporting 
of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the GSK Standard Statistical Display Principles 
but may be adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses and calculation 
of any derived parameters, unless otherwise stated. 
• 
The impact of any important deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to GSK 
Standard Statistical Display Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings.  


 
CONFIDENTIAL 
208832 
 
32 
 
Unscheduled Visits 
• 
Unscheduled visits will be assigned to a study visit using assessment windows defined in Section 11.2.1. 
• However, data summaries will only report visits that are planned assessment time points for each 
parameter (according to the Schedule of Activities in Section 11.1). 
• 
Evaluable assessments at unscheduled visits will be used when categorizing values across 
visits, such as ‘maximum grade during the injection phase’. 
Descriptive Summary Statistics 
Continuous Data 
Refer to GSK Standard Statistical Display Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to GSK Standard Statistical Display Principals 7.01 to 7.13. 
11.4.3. 
Reporting Standards for Pharmacokinetic Data 
Pharmacokinetic Concentration Data 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical Principle 6.06.1. 
For continuous data: 
• 
Not quantifiable values (NQs) at the beginning of a participant profile (i.e. before 
the first incidence of a measurable concentration) are deemed to be zero as it is 
assumed that in this circumstance no drug is yet measurable in the blood. 
• 
For NQs at the end of the participant profile (i.e. after the last incidence of a 
measurable concentration); 
• 
for individual plots and pharmacokinetic analyses these are dropped (set to 
missing) as they do not provide any useful information (and can erroneously 
indicate that absolutely no drug is present) 
• 
for summary statistics, these are set to 0 (to avoid skewing of the summary 
statistics) 
• 
Individual NQs which fall between two measurable concentrations are set to 
missing (individual values of this nature are assumed to be an anomaly).  
• 
If two or more NQ values occur in succession between measurable 
concentrations, the profile will be deemed to have terminated at the last 
measurable concentration prior to these NQs. For the purpose of individual 
participant plots, these NQs will be set to 0, and the subsequent measurable 
concentrations will be retained. For the derivation of pharmacokinetic 
parameters, these NQs and any subsequent measurable concentrations will 
be omitted (set to missing). 
Note: Concentration values will be imputed as per GUI_51487 for descriptive summary 
statistics/analysis and summarized graphical displays only. 
 
 
11.4.4. 
Reporting Standards for Liver Safety Data 
11.4.4.1. 
Liver Stopping/Monitoring Criteria 
Element 
Reporting Detail 
General 
• 
A liver monitoring event occurs when subject meets predefined liver chemistry 
monitoring criteria that trigger increased monitoring of the subject's liver chemistries, 
but no action is taken with study treatment unless liver chemistry stopping criteria are 


 
CONFIDENTIAL 
208832 
 
33 
 
Element 
Reporting Detail 
met. A liver stopping event occurs when subject meets predefined liver chemistry 
stopping criteria, ALT >=3xULN for this study, that trigger discontinuation of study 
treatment and requirement of additional actions and follow up assessments to be 
performed. For subjects with more than one liver stopping or liver monitoring event, 
only data related to the earliest most severe criteria event is included in displays.  
• 
Resolved is defined as ALT <3xULN for 2 consecutive visits or <3xULN for one visit if 
subject discontinued and no data available. Post treatment records are included to 
evaluate resolution of the event. 
 
11.4.4.2. 
Hepatobiliary Abnormality Criteria 
Element 
Reporting Detail 
General 
• 
To include ALT, ALP, Bilirubin, & INR parameters 
ALT >=3xULN and BIL >=2xULN 
• 
If direct bilirubin is available (on the same date as Total 
Bilirubin), then direct bilirubin as a portion of total bilirubin 
must be >=35% when total bilirubin is >=2xULN, in order to 
satisfy the criteria. 
• 
Bilirubin value is on or up to 28 days after ALT value. 
ALT >=3xULN and INR >1.5 
• 
INR value is on or up to 28 days after ALT value. 
ALT >=3xULN and BIL >=2xULN and 
ALP 2 (<1%) <2xULN 
• 
If direct bilirubin is available (on the same date as Total 
Bilirubin), then direct bilirubin as a portion of total bilirubin 
must be >=35% when total bilirubin is >=2xULN, in order to 
satisfy the criteria. 
• 
Bilirubin value is on or up to 28 days after ALT value. 
• 
The ALP value must occur on or up to 28 days after the 
ALT value. 
Hepatocellular injury 
• 
Hepatocellular injury is defined as ((ALT/ALT 
ULN)/(ALP/ALP ULN)) >=5 and ALT >=3xULN. ALT and 
ALP values must occur on the same day. 
Hepatocellular injury and BIL >=2xULN 
• 
Hepatocellular injury is defined as ((ALT/ALT 
ULN)/(ALP/ALP ULN)) >=5 and ALT >=3xULN. ALT and 
ALP values must occur on the same day. 
• 
If direct bilirubin is available (on the same date as Total 
Bilirubin), then direct bilirubin as a portion of total bilirubin 
must be >=35% when total bilirubin is >=2xULN, in order to 
satisfy the criteria. 
• 
Bilirubin value is on or up to 28 days after ALT value. 
BIL >=2xULN 
• 
If direct bilirubin is available (on the same date as Total 
Bilirubin), then direct bilirubin as a portion of total bilirubin 
must be >=35% when total bilirubin is >=2xULN, in order to 
satisfy the criteria. 
AST >3xULN and ALP <2xULN and BIL 
>=2xULN 
• 
ALP and BIL values must occur on or up to 28 days after 
AST value. 
• 
If direct bilirubin is available (on the same date as Total 
Bilirubin), then direct bilirubin as a portion of total bilirubin 
must be >=35% when total bilirubin is >=2xULN, in order to 
satisfy the criteria. 


 
CONFIDENTIAL 
208832 
 
34 
 
Element 
Reporting Detail 
ALT>=X ULN and AST>=X ULN 
• 
AST and ALT values must occur on the same day 
 
11.5. 
Appendix 5: Derived and Transformed Data 
11.5.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
If there are multiple measurements within a time window (per Section 11.2.1), the value closest to the 
target day for that window will be used. If values are the same distance from the target, then the mean of 
the measurements (for quantitative parameters including ECG values) or the worst-case of the 
measurements (for qualitative parameters) will be calculated and used in any derivation of summary 
statistics. 
• 
Only planned assessment timepoints (according to Appendix 2: Schedule of Activities) will be included in 
data displays summarizing measurements by visit. 
• 
Assessments not chosen for use in summary statistics will still appear in the associated listings.  
• 
All applicable valid assessments, irrespective of proximity to the target study day, will be used when 
categorizing values across visits, such as ‘maximum grade during the intervention phase’ or ‘at any time 
post-baseline’, and for any algorithm that has specific rules for which observation to use (e.g. LOCF). 
Change from Baseline 
• 
Post-Dose Visit Value – Baseline 
• 
Unless otherwise specified, the baseline definitions specified in Section 6.2 will be used for derivations for 
endpoints / parameters. 
Study Day 
• 
The Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of AE) will be derived as the 
number of days between the date of the event and the Intervention Phase treatment start date as follows:  
o If date of event ≥ start date of study treatment, then 
▪ 
Study Day = Date of Event - Intervention Phase Treatment Start Date +1 
o If date of event < start date of study treatment, then 
▪ 
Study Day = Date of Event - Intervention Phase Treatment Start Date 
o Note that the start date of each phase is on Study Day 1 and the day before this is Study Day 
-1; i.e., there is no Study Day 0. 


 
CONFIDENTIAL 
208832 
 
35 
 
Phase Day 
• 
Calculated as the number of days from First Dose Date of CAB + RPV for the respective phase (based on 
study period classifications in Table 3): 
 
OLI phase: 
• 
If Assessment Date < First Dose Date of Oral CAB + RPV then  
• 
Phase Day = Assessment Date – First Dose Date of Oral CAB + RPV 
• 
If Assessment Date  First Dose Date of Oral CAB + RPV then  
• 
Phase Day = Assessment Date – First Dose Date of Oral CAB + RPV +1 
 
Injection phase: 
• 
If Assessment Date < Dose Date of Injection CAB + RPV then  
• 
Phase Day = Assessment Date – Dose Date of Injection CAB + RPV 
• 
If Assessment Date  Dose Date of Injection CAB +RPV then  
• 
Phase Day = Assessment Date – Dose Date of Injection CAB + RPV +1 
 
Follow-up phase: 
• 
If Assessment Date < Follow-up Week 4 Visit Date then  
• 
Phase Day = Assessment Date – Follow-up Week 4 Visit Date 
• 
If Assessment Date  Follow-up Week 4 Visit Date then  
• 
Phase Day = Assessment Date – Follow-up Week 4 Visit Date +1 
11.5.2. 
Study Population 
Age 
• 
GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed as follows: 
o Any participant with a missing day will have this imputed as day ‘15’. 
o Any participant with a missing day and month will have this imputed as ‘30th June’. 
• 
Birth date will be presented in listings as ‘YYYY’. 
• 
Completely missing dates of birth will remain as missing, with no imputation applied. Consequently, the age 
of the subject will not be calculated and will remain missing. 
Body Mass Index (BMI) 
• 
Calculated in the CRF as Weight (kg) / [Height (m)2] 
 


 
CONFIDENTIAL 
208832 
 
36 
 
11.5.3. 
Safety 
Exposure 
Compliance 
Compliance for the OLI Phase will be calculated as follows: 
OLI Compliance % = 
# 𝑑𝑎𝑦𝑠 𝑠𝑢𝑏𝑗𝑒𝑐𝑡 𝑡𝑜𝑜𝑘 𝑡ℎ𝑒 𝑠𝑡𝑢𝑑𝑦 𝑑𝑟𝑢𝑔
𝑀𝑖𝑛𝑖𝑚𝑢𝑚 (# 𝑜𝑓 𝑑𝑎𝑦𝑠 𝑠𝑢𝑏𝑗𝑒𝑐𝑡 𝑤𝑎𝑠 𝑒𝑛𝑟𝑜𝑙𝑙𝑒𝑑 𝑖𝑛 𝑡ℎ𝑒 𝑂𝐿𝐼 𝑝𝑒𝑟𝑖𝑜𝑑,28) 
 
Extent of Exposure 
• 
Exposure to CAB+RPV Oral Lead-in = IP (oral lead-in) stop date - IP (oral lead-in) start date +1 
Duration (Days) 
• 
AE Resolution Date – AE Start Date + 1 
Laboratory Parameters 
• 
If a laboratory value which is expected to have a numeric value for summary purposes, has a non-
detectable level reported in the database, where the numeric value is missing, but typically a character 
value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the comment field) is present, 
the number of significant digits in the observed values will be used to determine how much to add or 
subtract in order to impute the corresponding numeric value. If a character value starting with “<=x”, then 
the numeric value will be x. 
o Example 1: 2 Significant Digits = ‘< x ‘becomes x – 0.01 
o Example 2: 1 Significant Digit = ‘> x’ or ‘>=x’ becomes x + 0.1 
Example 3: 0 Significant Digits = ‘< x’ becomes x – 1 
12-Lead Electrocardiograms 
QTcB Interval 
When not entered directly in the eCRF, corrected QT intervals by Bazett’s (QTcB) and Fridericia’s 
(QTcF) formulas will be calculated, in msec, depending on the availability of other measurements. 
If RR interval (in msec) is provided, then missing QTcB and/or QTcF will be derived as 
1000
RR
QT
QTcB =
  
3
1000
RR
QT
QTcF =
 
where uncorrected QT interval is also measured in msec. 
If RR interval is not provided directly and one of QTcB or QTcF has been entered, then RR interval 
can be obtained from the above formulas and used to calculate the other correction method value; 
i.e., 
QT
QTcF
QTcB
3
=
 
 
3
2
QTcB
QT
QTcF

=
 
 
 



&21),'(17,$/





3KDUPDFRNLQHWLF
Pharmacokinetic Parameter Statistics 
x
For the purposes of calculating summary statistics and for statistical analysis, all PK parameters 
with the exception of tmax will be loge transformed. 
x
Geometric coefficient of variation: 
o Untransformed Data: 100 * (SD/Mean). 
o Transformed Data: 100 * (sqrt(exp(SDlog2)-1)) where SDlog indicates the standard deviation of log-
transformed data 

+HDOWK2XWFRPHV


CCI



&21),'(17,$/




CCI



&21),'(17,$/





$SSHQGL[5HSRUWLQJ6WDQGDUGVIRU0LVVLQJ'DWD

3UHPDWXUH:LWKGUDZDOV
Element 
Reporting Detail 
General 
x
Withdrawn participants may be replaced in the study. All subjects who withdraw 
prematurely from the study/study drug will be documented and the reason for their 
withdrawal recorded in the final Clinical Pharmacology Study Report (CPSR).  
x
All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.  
x
Withdrawal visits will be slotted according to  Appendix 2: Assessment Windows 

+DQGOLQJRI0LVVLQJ'DWD
Element 
Reporting Detail 
General 
x
Missing data occurs when any requested data is not provided, leading to blank fields 
on the collection instrument: 
o These data will be indicated by the use of a “blank” in participant listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Outliers 
x
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
 
x
Subjects who were injected that have missing 
 data may have it imputed with 
their last observation carried forward (LOCF) 

+DQGOLQJRI0LVVLQJDQG3DUWLDO'DWHV
Element 
Reporting Detail 
General 
x
Partial dates will be displayed as captured in participant listing displays.  
x
Where necessary, partial dates may be imputed for specific analysis purposes as 
outlined below. 
x
Imputed partial dates will not be used to derive study day, time to onset or duration 
(e.g., time to onset or duration of AEs), or elapsed time variables (e.g., time since 
diagnosis).  
Adverse 
Events 
x
Imputations in the AEs dataset are used for slotting events to the appropriate study 
time periods and for sorting in data listings. 
x
Partial dates for AE recorded in the eCRF will be imputed using the following 
conventions: 
 
Missing start day 
x
If study treatment start date is missing (i.e. participant did not 
start study treatment), then set start date = 1st of month. 
x
Else if study treatment start date is not missing: 
o
If month and year of start date = month and year of study 
treatment start date then 

If stop date contains a full date and stop date is 
earlier than study treatment start date then set start 
date= 1st of month. 
CCI
CCI


 
CONFIDENTIAL 
208832 
 
40 
 
Element 
Reporting Detail 
▪ 
Else set start date = study treatment start date. 
o Else set start date = 1st of month. 
Missing start day 
and month 
• 
If study treatment start date is missing (i.e. participant did not 
start study treatment), then set start date = January 1. 
• 
Else if study treatment start date is not missing: 
o 
If year of start date = year of study treatment start date 
then 
▪ 
If stop date contains a full date and stop date is 
earlier than study treatment start date then set start 
date = January 1. 
▪ 
Else set start date = study treatment start date. 
o Else set start date = January 1. 
Missing stop day  
Last day of the month will be used. 
Missing stop day 
and month 
No Imputation 
Completely missing 
start/end date 
No imputation 
 
• 
Completely missing start or end dates will remain missing, with no imputation applied.  
Concomitant 
Medications 
• 
Partial dates for any concomitant medications recorded in the eCRF will be imputed 
using the following convention: 
 
Missing start day 
• 
If study treatment start date is missing (i.e. participant did not 
start study treatment), then set start date = 1st of month. 
• 
Else if study treatment start date is not missing: 
o 
If month and year of start date = month and year of study 
treatment start date then 
▪ 
If stop date contains a full date and stop date is earlier 
than study treatment start date then set start date= 1st 
of month. 
▪ 
Else set start date = study treatment start date. 
o Else set start date = 1st of month. 
Missing start day 
and month 
• 
If study treatment start date is missing (i.e. participant did not 
start study treatment), then set start date = January 1. 
• 
Else if study treatment start date is not missing: 
o 
If year of start date = year of study treatment start date 
then 
▪ 
If stop date contains a full date and stop date is earlier 
than study treatment start date then set start date = 
January 1. 
▪ 
Else set start date = study treatment start date. 
• 
Else set start date = January 1. 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on the month 
and year)  
Missing end day and 
month 
A '31' will be used for the day and 'Dec' will be used for the month. 
Completely missing 
start/end date 
No imputation 
 
• 
The recorded partial date will be displayed in listings. 
 



&21),'(17,$/





$SSHQGL[9DOXHVRI3RWHQWLDO&OLQLFDO,PSRUWDQFH

/DERUDWRU\9DOXHV
/DERUDWRU\YDOXHVZLOOEHJUDGHGEDVHGRQWKH'LYLVLRQRI$,'67DEOHIRU*UDGLQJWKH
6HYHULW\RI$GXOWDQG3HGLDWULF$GYHUVH(YHQWV9HUVLRQ0DUFKDVVSHFLILHGLQ
WKHSURWRFRO$SSHQGL[DQGVKRZQEHORZ
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.



&21),'(17,$/






(&*
ECG Parameter 
Units 
Clinical Concern Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
<320 
>450 
Absolute PR Interval 
msec 
<120 
>220  
Absolute QRS Interval 
msec 
<70  
>120 
Change from Baseline 
Increase from Baseline QTc 
msec 
 
>60 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.



&21),'(17,$/





$SSHQGL[$EEUHYLDWLRQV	7UDGHPDUNV

$EEUHYLDWLRQV
$'D0
$QDO\VLVGDWDPRGHO
$(
$GYHUVHHYHQW
$/7
DODQLQHDPLQRWUDQVIHUDVH6*37
$67
$VSDUWDWHDPLQRWUDQVIHUDVH6*27
$7&
$QDWRPLFDO7KHUDSHXWLF&KHPLFDO&ODVVLILFDWLRQOHYHO
$8&W
$UHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPH]HURWR
ODVWTXDQWLILDEOHWLPHSRLQW
$8&W
$UHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHRYHURQHGRVLQJ
LQWHUYDO
$8&f
$UHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPH]HURWR
LQILQLW\
$8&
$UHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHRYHUKRXUV
%0,
%RG\PDVVLQGH[
%4/
%HORZWKHTXDQWLILFDWLRQOLPLW
&$%
&DERWHJUDYLU
&',6&
&OLQLFDO'DWD,QWHUFKDQJH6WDQGDUGV&RQVRUWLXP
&,
&RQILGHQFHLQWHUYDO
&PD[
0D[LPXPREVHUYHGFRQFHQWUDWLRQ
&3.
&UHDWLQHSKRVSKRNLQDVH
&306
&OLQLFDO3KDUPDFRNLQHWLF0RGHOOLQJ6LPXODWLRQ
&
&RQFHQWUDWLRQDWKRXUWLPHSRLQW
&W
/DVWREVHUYHGTXDQWLILDEOHFRQFHQWUDWLRQ
&9
&RHIILFLHQWRIYDULDQFH
&9E
*HRPHWULF&RHIILFLHQWRIYDULDWLRQ
(&*
(OHFWURFDUGLRJUDP
*6.
*OD[R6PLWK.OLQH
+,9
+XPDQLPPXQRGHILFLHQF\YLUXV
+2
+HDOWK2XWFRPHV
,'6/
,QWHJUDWHG'DWD6WDQGDUGV/LEUDU\
,0
,QWUDPXVFXODU
,3
,QYHVWLJDWLRQDOSURGXFW
,65
,QMHFWLRQVLWHUHDFWLRQ
.$/$
$EVRUSWLRQUDWHFRQVWDQW/RQJDFWLQJ
O]
7HUPLQDOSKDVHUDWHFRQVWDQW
/$
/RQJDFWLQJ
/2&)
/DVW2EVHUYDWLRQ&DUULHG)RUZDUG
0HG'5$
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
0J
0LOOLJUDPV
P/
0LOOLOLWHU
1157,
1RQQXFOHRVLGHUHYHUVHWUDQVFULSWDVHLQKLELWRU
14
1RQTXDQWLILDEOH
CCI



&21),'(17,$/




2/,
2UDO/HDG,Q
3.
3KDUPDFRNLQHWLFV
47F% 

47GXUDWLRQFRUUHFWHGIRUKHDUWUDWHE\%D]HWW¶VIRUPXOD
47F)
47GXUDWLRQFRUUHFWHGIRUKHDUWUDWHE\)ULGHULFLD¶VIRUPXOD
5$3
5HSRUWLQJDQG$QDO\VLV3ODQ
539
5LOSLYLULQH
6$(
6HULRXVDGYHUVHHYHQWV
6$6
6WDWLVWLFDO$QDO\VLV6RIWZDUH
6'
6WDQGDUGGHYLDWLRQ
6'70
6WXG\'DWD7DEXODWLRQ0RGHO
6R$
6FKHGXOHRI$FWLYLWLHV
623
6WDQGDUGRSHUDWLQJSURFHGXUH
Wò
$SSDUHQWWHUPLQDOSKDVHKDOIOLIH
Ĳ
'RVLQJLQWHUYDO
WPD[
7LPHRIRFFXUUHQFHRI&PD[
8/1
8SSHUOLPLWRIQRUPDO


7UDGHPDUNV
Trademarks of ViiV Healthcare 
 
Trademarks not owned by ViiV 
Healthcare 
NONE 
 
MedDRA 
 
 
SAS 
 
 
Winnonlin 

CCI


 
CONFIDENTIAL 
208832 
 
45 
 
11.9. 
Appendix 9: List of Data Displays 
All data displays will use the term “subject” rather than “participant” in accordance with 
CDSIC and GSK Statistical Display Standards. 
The list of data displays included in this critical component RAP is tentative, to be 
confirmed and modified as appropriate during the development of the full RAP. 
11.9.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.10 
N/A 
Safety 
3.1 to 3.37 
3.38 
Pharmacokinetic 
4.1 to 4.4 
4.5 to 4.10 
Health Outcomes 
6.1 to 6.7 
N/A 
Section 
Listings 
ICH Listings 
1 to 24 
Other Listings 
25 to 38 
 
11.9.2. 
Deliverables 
Delivery  
Description 
Interim 
Informal Interim PK Analyses at Week 4 and Week 12 post injection 
SAC 
Final Statistical Analysis Complete 
 
 


CONFIDENTIAL 
208832 
46 
 
11.9.3. 
Study Population Tables 
Study Population Tables 
No. 
Population 
GSK Standard  
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
Safety 
ES1 
Summary of Subject Disposition for the Subject Conclusion 
Record 
ICH E3, FDAAA, EudraCT 
 
SAC  
1.2. 
Safety 
DISP_T1 
Summary of Subject Disposition at Each Study Phase 
ICH E3 
SAC  
1.3. 
Safety 
DISP_T2 
Summary of Reasons for Withdrawal at Each Study Phase 
 
SAC 
1.4. 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure 
Journal Requirements 
SAC  
Protocol Deviation 
1.5. 
Safety 
DV1 
Summary of Important Protocol Deviations by Study Phase and 
Overall 
ICH E3 
SAC  
Population Analysed 
1.6. 
Enrolled 
SP1 
Summary of Study Populations by Study Phase and Overall  
GSK Statistical Display Standard 
Note: Show n’s at each study phase. 
SAC  
Demographic and Baseline Characteristics 
1.7. 
Safety 
DM1 
Summary of Demographics and Baseline Characteristics 
ICH E3, FDAAA, EudraCT 
Note: To include Age Ranges 
SAC  
1.8. 
Safety 
DM5 
Summary of Race and Racial Combinations 
ICH E3, FDA, FDAAA, EudraCT 
SAC  
Prior and Concomitant Medications 
1.9. 
Safety 
MH1  
Summary of Past Medical Conditions 
ICH E3  
SAC  
1.10. 
Safety 
CM1 
Summary of Concomitant Medications by Study Phase and 
Overall 
ICH E3 
SAC  
 


CONFIDENTIAL 
208832 
47 
 
11.9.4. 
Safety Tables 
Safety: Tables 
No. 
Population 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Exposure and Treatment Compliance 
3.1.  
Safety 
207966/primary_15/
T3.1 
Summary of Exposure to Study Treatment  
ICH E3 
Display treatment in columns. 
Include the following parameters: 
“Exposure (Days-oral lead-in)” 
“Exposure (Weeks-oral lead-in)” 
“Oral Lead-in Compliance %” from 
11.5.3  
“No. of Subjects Receiving Injections” 
“Number of Injections” 
SAC  
Adverse Events (AEs) 
3.2.  
Safety 
AE13 
Adverse Event Overview by Study Phase and Overall 
High level summary to include counts of 
overall AEs, Treatment emergent AEs, 
Serious AEs, AEs leading to 
withdrawal, related AEs, serious related 
AEs, AEs related to Covid-19, AEs 
related to Covid-19 leading to 
withdrawal, fatal AEs 
Repeat for each study phase and 
overall 
SAC  
3.3.  
Safety 
AE1xo 
Summary of All Adverse Events by System Organ Class and 
Preferred Term  
ICH E3 
 
SAC  
3.4.  
Safety 
AE5B 
Summary of All Adverse Events by System Organ Class, 
Preferred Term, and Maximum Grade  
ICH E3 
Repeat for each study phase and 
overall 
SAC  


CONFIDENTIAL 
208832 
48 
 
Safety: Tables 
No. 
Population 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.5.  
Safety 
AE15 
Summary of Common (>=10%) Adverse Events by Overall 
Frequency (Number of Subjects and Occurrences) 
ICH E3 
Note: “Common” AEs will be based on 
the Total column. 
Repeat for each study phase and 
overall 
SAC  
3.6.  
Safety 
AE5B 
Summary of Common (>=10%) Adverse Events by System 
Organ Class, Preferred Term, and Maximum Grade 
ICH E3 
Note: “Common” AEs will be based on 
the Total column. 
Repeat for each study phase and 
overall 
SAC  
3.7.  
Safety 
AE5B 
Summary of Drug-Related Adverse Events by System Organ 
Class, Preferred Term, and Maximum Grade  
ICH E3 
Repeat for each study phase and 
overall 
SAC  
3.8.  
Safety 
AE15 
Summary of Common (>=10%) Non-serious Adverse Events 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences)  
FDAAA, EudraCT 
Note: “Common” AEs will be based on 
the Total column. 
Repeat for each study phase and 
overall 
SAC  
Serious and Other Significant Adverse Events 
3.9.  
Safety 
AE5B 
Summary of Serious Adverse Events by System Organ Class, 
Preferred Term, and Maximum Grade 
ICH E3 
Repeat for each study phase and 
overall 
SAC 
3.10. 
Safety 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Subjects and Occurrences)  
FDAAA, EudraCT 
Repeat for each study phase and 
overall 
SAC  


CONFIDENTIAL 
208832 
49 
 
Safety: Tables 
No. 
Population 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.11. 
Safety 
AE5B 
Summary of Serious, Drug-Related Adverse Events by 
System Organ Class, Preferred Term, and Maximum Grade 
Repeat for each study phase and 
overall 
SAC  
3.12. 
Safety 
AE5B 
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study 
by System Organ Class, Preferred Term, and Maximum 
Grade 
GSK Statistical Display Standard 
Repeat for each study phase and 
overall 
SAC 
3.13. 
Safety 
AE5B 
Summary of All Drug-Related Adverse Events Excluding 
Injection Site Reactions by System Organ Class, Preferred 
Term, and Maximum Grade 
Repeat for each study phase and 
overall 
SAC 
3.14. 
Safety 
PAN1A 
Summary of COVID-19 Assessments for Subjects with 
COVID-19 Adverse Events 
Note: To also include results of Covid-
19 tests performed 
SAC 
3.15. 
Safety 
AE5B 
Summary of Covid-19 Adverse Events by System Organ 
Class, Preferred Term, and Maximum Grade 
Repeat for each study phase and 
overall 
SAC  
3.16. 
Safety 
AE1xo 
Summary of Covid-19 Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study 
by System Organ Class and Preferred Term  
Repeat for each study phase and 
overall 
SAC  
3.17. 
Safety 
AE15 
Summary of Serious Covid-19 Adverse Events by System 
Organ Class, and Preferred Term (Number of Subjects and 
Occurrences)  
Repeat for each study phase and 
overall 
SAC  
3.18. 
Safety 
PAN3A 
Summary of Covid-19 Symptoms for Subjects with COVID-19 
Adverse Events 
Note: data collected from AE_covid-19 
eCRF 
SAC  
3.19. 
Safety 
PAN10A 
Incidence of Covid-19 Adverse Events by Gender and 
Pandemic Course 
Pandemic course = During and Post 
pandemic Post pandemic date to be 
provided upon availability. 
SAC  
 
 


CONFIDENTIAL 
208832 
50 
 
Injection Site Reaction Adverse Events 
3.20. 
Safety 
201584/primary_7/T
3.43 
Summary of Subject-Level Characteristics of Injection Site 
Reaction Adverse Events by Treatment and Overall 
Treatment to be listed in the columns 
SAC  
3.21. 
Safety 
201584/primary_7/T
3.40 
Summary of Injection Site Reaction Adverse Events (Event-
Level Summary) by Treatment and Overall 
Treatment to be listed in the columns 
SAC  
3.22. 
Safety 
201584/primary_7/T
3.46 
Summary of Subject-Level Characteristics of Injection Site 
Reaction Adverse Events by Maximum Grade, Treatment, 
and Overall 
Treatment to be listed in the columns 
SAC  
Adverse Events of Special Interest 
3.23. 
Safety 
201584/primary_07/
T3.134 
Summary of Seizure Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of 
Subjects and Occurrences)  
 
SAC  
3.24. 
Safety 
201584/primary_07/
T3.137 
Summary of Hepatic Safety Profile: Assessment of Risk of 
Hepatotoxicity Adverse Events of Special Interest by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences)  
 
SAC  
Laboratory: Chemistry  
3.25. 
Safety 
LB1 
Summary of Chemistry Changes from Baseline by Study 
Phase and Visit  
ICH E3 
SAC  
3.26. 
Safety 
LB1 
Summary of Chemistry Values by Study Phase and Visit  
ICH E3 
SAC  
3.27. 
Safety 
LB16  
Summary of Chemistry Results by Maximum Grade Increase 
Post-Baseline Relative to Baseline 
ICH E3 
Repeat for each study phase 
SAC  
Laboratory: Hematology 
3.28. 
 Safety 
LB1 
Summary of Hematology Changes from Baseline by Study 
Phase and Visit 
ICH E3 
SAC  
3.29. 
 Safety 
LB1 
Summary of Hematology Values by Study Phase and Visit 
ICH E3 
SAC  
3.30. 
Safety 
LB16  
Summary of Hematology Results by Maximum Grade 
Increase Post-Baseline Relative to Baseline 
ICH E3 
Repeat for each study phase 
SAC  


CONFIDENTIAL 
208832 
51 
 
Laboratory: Urinalysis 
3.31. 
Safety 
UR1 
Summary of Worst-Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline by 
Study Phase 
ICH E3 
Note: Define change categories 
according to actual values expected 
from lab dataset 
Repeat for each study phase and 
overall 
SAC  
Laboratory: Hepatobiliary (Liver) 
3.32. 
 Safety 
LIVER1 
Summary of Liver Monitoring/Stopping Event Reporting by 
Study Phase and Overall 
GSK Statistical Display Standard 
Note: See Appendix 11.4.4 for Criteria 
SAC  
3.33. 
Safety 
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities by Study 
Phase and Overall 
GSK Statistical Display Standard 
Note: See Appendix 11.4.4 for Criteria  
SAC  
ECG 
3.34. 
Safety 
EG2 
Summary of Change from Baseline in ECG Values by Study 
Phase and Visit 
GSK Statistical Display Standard 
SAC  
3.35. 
Safety 
EG2 
Summary of ECG Values by Study Phase and Visit 
GSK Statistical Display Standard 
SAC  
3.36. 
Safety 
EG1 
Summary of ECG Findings by Study Phase and Visit 
GSK Statistical Display Standard 
SAC  
Vital Signs 
3.37. 
Safety 
VS1 
Summary of Change from Baseline in Vital Signs by Study 
Phase and Visit 
ICH E3 
SAC  
 


CONFIDENTIAL 
208832 
52 
 
11.9.5. 
Safety Figures 
Safety Figures 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events 
3.38. 
Safety 
AE10 
Plot of Common (>=10%) Adverse Events by Relative Risk, 
Study Phase, and Overall 
Note: Display a different plot for each 
phase and overall 
SAC  
 
11.9.6. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Pharmacokinetic Parameters 
4.1.  
PK 
Parameter 
PK_01 
Summary of Derived Plasma Cabotegravir PK Parameters by 
Study Phase 
 
Interim, SAC  
4.2.  
PK 
Parameter 
PK_01 
Summary of Derived Plasma Rilpivirine PK Parameters by 
Study Phase 
 
Interim, SAC  
Pharmacokinetic Concentration 
4.3.  
PK 
Concentration 
PK01 
Summary of Plasma Cabotegravir PK Concentration (ug/mL)-
Time Data by Study Phase and Nominal Timepoint 
 
SAC  
4.4.  
PK 
Concentration 
PK01 
Summary of Plasma Rilpivirine PK Concentration (ng/mL)-Time 
Data by Study Phase and Nominal Timepoint 
 
SAC  
 


CONFIDENTIAL 
208832 
53 
 
11.9.7. 
Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Pharmacokinetic Mean/Median Plots 
4.5.  
PK 
Parameter 
PK17 
Mean (SD) Plasma Cabotegravir Concentration-Time Plots 
(Linear and Semi-Log) by Study Phase 
Display oral and LA phases on 
separate pages 
SAC  
4.6.  
PK 
Parameter 
PK17 
Mean (SD) Plasma Rilpivirine Concentration-Time Plots (Linear 
and Semi-Log) by Study Phase 
Display oral and LA phases on 
separate pages 
SAC  
4.7.  
PK 
Parameter 
PK20 
Median (5th and 95th Percentile) Plasma Cabotegravir 
Concentration-Time Plots (Linear and Semi-Log) by Study 
Phase 
Display oral and LA phases on 
separate pages 
SAC  
4.8.  
PK 
Parameter 
PK20 
Median (5th and 95th Percentile) Plasma Rilpivirine 
Concentration-Time Plots (Linear and Semi-Log) by Study 
Phase 
Display oral and LA phases on 
separate pages 
SAC  
Pharmacokinetic Individual Subject Plots 
4.9.  
PK 
Parameter 
PK16a 
Individual Plasma Cabotegravir Concentration-Time Plots 
(Linear and Semi-Log) by Study Phase 
Display oral and LA phases on 
separate pages 
SAC  
4.10. 
PK 
Parameter 
PK16a 
Individual Plasma Rilpivirine Concentration-Time Plots (Linear 
and Semi-Log) by Study Phase 
Display oral and LA phases on 
separate pages 
SAC  
 


&21),'(17,$/




+HDOWK2XWFRPHV7DEOHV
Health Outcomes Tables 
No. 
Population 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Questionnaire Outcomes 
6.1. 
Safety 
201584/primary_07/T6.2 
SAC  
6.2. 
Safety 
201584/primary_07/T6.1 
SAC  
6.3. 
Safety 
201584/primary_07/T6.35 
SAC  
6.4. 
Safety 
201584/primary_07/T6.36 
SAC  
6.5. 
Safety 
201584/primary_07/T6.37 
SAC  
6.6. 
Safety 
201584/primary_07/T6.38 
SAC  
6.7. 
Safety 
201584/primary_07/T6.39 
SAC  


CCI


CONFIDENTIAL 
208832 
55 
 
11.9.9. 
ICH Listings 
ICH: Listings 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
Screened 
ES2 
Listing of Reasons for Study Withdrawal 
ICH E3 
SAC  
2.  
Screened 
SD2 
Listing of Reasons for Study Treatment Discontinuation 
ICH E3 
SAC  
Protocol Deviations 
3.  
Screened 
DV2 
Listing of Protocol Deviations  
ICH E3 
Note: Include flag for important 
deviations (Y/N) and Covid-19 
relatedness (Y/N) 
SAC  
4.  
Screened 
IE3  
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
ICH E3 
SAC  
Populations Analysed 
5.  
Screened 
SP3 
Listing of Subjects Excluded from Any Population 
ICH E3 
SAC  
Demographic and Baseline Characteristics 
6.  
Screened 
DM2 
Listing of Demographic Characteristics 
ICH E3 
Include column indicating inclusion in 
the enrolled (Y/N) and safety 
populations (Y/N) 
SAC  
7.  
Screened 
DM9 
Listing of Race 
ICH E3 
Include column indicating inclusion in 
the enrolled (Y/N) and safety 
populations (Y/N) 
SAC  
Exposure and Treatment Compliance 
8.  
Screened 
EX3  
Listing of Exposure Data 
ICH E3 
SAC  
 
 


CONFIDENTIAL 
208832 
56 
 
Adverse Events 
9.  
Screened 
AECP   
Listing of All Adverse Events 
ICH E3 
Include column indicating Phase 
SAC  
10.  
Screened 
AE7 
Listing of Subject Numbers for Individual Adverse Events 
ICH E3 
Replace the column for treatment with 
Phase 
SAC  
11.  
Screened 
AECP  
Listing of Serious Adverse Events 
ICH E3 
Include column indicating Phase 
Note: Include Fatal vs Non-Fatal 
Designation 
SAC  
12.  
Screened 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event 
ICH E3 
SAC 
13.  
Screened 
AECP  
Listing of Adverse Events Leading to Withdrawal from Study or 
Permanent Discontinuation of Study Treatment 
ICH E3 
Include column indicating Phase 
SAC  
14.  
Screened 
AECP  
Listing of Covid-19 Adverse Events 
ICH E3 
Include column indicating Phase  
Note: Display Covid-19 Adverse 
events and descriptive details 
SAC  
15.  
Screened 
PAN12 
Listing of COVID-19 Assessments and Symptom Assessments 
 
SAC 
16.  
Screened 
PAN5 
Listing of Dates of COVID-19 Pandemic Measures   
Include Pandemic End date if available 
SAC 
All Laboratory 
17.  
Screened 
LB5 
Listing of Continuous Laboratory Data by Lab Category, Study 
Phase, and Visit 
ICH E3 
Note: Include Chemistry and 
Hematology results 
SAC  
18.  
Screened 
LB14 
Listing of Categorical Laboratory Data by Lab Category, Study 
Phase, and Visit 
ICH E3 
Note: Include Urinalysis, Coagulation, 
Drugs, and Infectious Disease results 
SAC 
19.  
Screened 
EG3 
Listing of ECG Values by Study Phase and Visit 
Sort by Phase and Visit 
SAC  
20.  
Screened 
EG5 
Listing of ECG Findings by Study Phase and Visit 
Sort by Phase and Visit 
SAC  
21.  
Screened 
VS4 
Listing of Vital Signs by Study Phase and Visit 
Sort by Phase and Visit 
SAC  


CONFIDENTIAL 
208832 
57 
 
22.  
Screened 
PREG1 
Listing of Subjects Who Became Pregnant During the Study 
 
SAC  
PK 
23.  
Screened 
PK07 
Listing of Plasma Cabotegravir PK Concentration-Time Data by 
study phase 
 
SAC  
24.  
Screened 
PK07 
Listing of Plasma Rilpivirine PK Concentration-Time Data by 
study phase 
 
SAC  
 
 


CONFIDENTIAL 
208832 
58 
 
11.9.10. 
Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
GSK Standard GSK 
Statistical Display 
Standard / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition  
25.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
Journal Guidelines 
SAC  
26.  
Screened 
SD2 
Listing of End of Study Record for Subjects Affected by 
Covid-19 
Covid-19 relatedness as determined 
by Covid related AEs, PDs, missed 
visits, & Disposition 
SAC  
Prior and Concomitant Medications 
27.  
Screened 
MH2 
Listing of Medical History for All Subjects 
 
SAC  
28.  
Screened 
CM3 
Listing of Prior Medications 
GSK Statistical Display Standard 
SAC  
29.  
Screened 
CM3  
Listing of Concomitant Medications by Study Phase 
GSK Statistical Display Standard 
SAC  
Adverse Events 
30.  
Screened 
AE8 
Listing of Injection Site Reaction Adverse Events 
 
SAC  
31.  
Screened 
AE2 
Listing of Relationship Between Adverse Event System 
Organ Classes, Preferred Terms, and Verbatim Text 
GSK Statistical Display Standard 
SAC  
Laboratory Results 
32.  
Screened 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting 
Note: See Appendix 11.4.4 for 
Criteria 
SAC  
33.  
Screened 
LIVER13 
Listing Subjects Meeting Hepatobiliary Lab Abnormality 
Criteria 
Note: See Appendix 11.4.4 for 
Criteria 
SAC  
 
 


&21),'(17,$/



PK 
34.  
Screened 
PK13 
Listing of Derived Plasma Cabotegravir PK Parameters by 
study phase 

SAC  
35.  
Screened 
PK13 
Listing of Derived Plasma Rilpivirine PK Parameters by 
study phase 
 
SAC  
Health Outcome 
36.  
Screened 
HO_01 
Listing of 
 Scores  
 
SAC  
37.  
Screened 
HO_02 
Listing of 
 Questionnaire 
Results at Day 8 
 
SAC  
38.  
Screened 
HO_03 
Listing of 
 from Daily Diary Cards 
 
SAC  

CCI
CCI
CCI


CONFIDENTIAL 
208832 
60 
 
11.9.11. 
Mock Displays 
Protocol: 208832                                                                                Page 1 of 1 
Population: Safety 
                                                 Table DISP_T1 
                             Summary of Subject Disposition at Each Study Phase 
 
 
 
 
Study Phase 
 
Total 
(N=200) 
 
 
 
Oral Lead-in Phase 
ENTERED 
xx (xx.x%) 
 
COMPLETED 
xx (xx.x%) 
 
WITHDRAWN 
xx (xx.x%) 
 
  COVID-19 RELATED[1] 
xx (xx.x%) 
 
 
 
Injection Phase 
ENTERED 
xx (xx.x%) 
 
COMPLETED 
xx (xx.x%) 
 
WITHDRAWN 
xx (xx.x%) 
 
  COVID-19 RELATED[1] 
xx (xx.x%) 
 
 
 
Follow-up Phase 
ENTERED 
xx (xx.x%) 
 
COMPLETED 
xx (xx.x%) 
 
WITHDRAWN 
xx (xx.x%) 
 
  COVID-19 RELATED[1] 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Covid-19 Related Disposition as collected from the Study Impact record 


CONFIDENTIAL 
208832 
61 
 
Protocol: 208832                                                                                                    
Page 1 of 1 
Population: Safety 
Table DISP_T2 
Summary of Reasons for Withdrawal at Each Study Phase 
 
 
 
Primary Reason 
Oral CAB 30mg 
+ Oral RPV 
25mg (N=100) 
IM CAB 600mg 
+ IM RPV 
900mg – 
Injection 
Phase 
(N=100) 
IM CAB 600mg 
+ IM RPV 
900mg – 
Follow-up 
Phase 
(N=100) 
 
Overall 
(N=100) 
  ADVERSE EVENT 
 xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
xx (xx.x%) 
    COVID-19 RELATED[1] 
  x  (xx.x%) 
  x  (xx.x%) 
  x  (xx.x%) 
x  (xx.x%) 
  PROTOCOL DEVIATION 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    COVID-19 RELATED[1] 
  x  (xx.x%) 
  x  (xx.x%) 
  x  (xx.x%) 
x  (xx.x%) 
  SUBJECT REACHED PROTOCOL-DEFINED STOPPING 
CRITERIA 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  STUDY TERMINATED BY SPONSOR  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  LOST TO FOLLOW-UP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  INVESTIGATOR SITE CLOSED 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  PHYSICIAN DECISION 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  WITHDRAWAL BY SUBJECT  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    COVID-19 RELATED[1] 
  x  (xx.x%) 
  x  (xx.x%) 
  x  (xx.x%) 
x  (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 [1] 
Covid-19 Related Disposition as collected from the Study Impact record 
 
 


CONFIDENTIAL 
208832 
62 
 
 
Protocol: 208832 
Page 1 of x 
Population: Pharmacokinetic Parameter  
PK_01 
Summary of Derived Cabotegravir Pharmacokinetic Parameters by Phase 
Parameter 
Summary Statistics 
Oral CAB 30mg 
(N=xx) 
IM CAB 600 mg 
(N=xx) 
AUC0-t(h*g/mL) 
n 
xx 
xx 
Mean (SD) 
Xxx.x (xx.xx) 
Xxx.x (xx.xx) 
95% CI 
(xxx.xx,xxx.xx) 
(xxx.xx,xxx.xx) 
%CV 
xx.x 
xx.x 
Median 
xxx.xx 
xxx.xx 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
Geometric mean 
xxx.xx 
xxx.xx 
95% CI 
(xxx.xxx,xxx.xxx) 
(xxx.xxx,xxx.xxx) 
SD (log) 
xxx.xxx 
xxx.xxx 
Geometric %CV 
xxx.x 
xxx.x 
 
 
 
AUC0-∞(h*g/mL) 
n 
xx 
xx 
Mean (SD) 
Xxx.x (xx.xx) 
Xxx.x (xx.xx) 
 
95% CI 
(xxx.xx,xxx.xx) 
(xxx.xx,xxx.xx) 
%CV 
xx.x 
xx.x 
Median 
xxx.xx 
xxx.xx 
 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
Geometric mean 
xxx.xx 
xxx.xx 
 
95% CI 
(xxx.xxx,xxx.xxx) 
(xxx.xxx,xxx.xxx) 
 
SD (log) 
xxx.xxx 
xxx.xxx 


CONFIDENTIAL 
208832 
63 
 
 
Geometric %CV 
xxx.x 
xxx.x 
 
 
 
 
/Directory/program.sas  01JAN2002 12:01 
 
 
 
Programming notes:  
1) Repeat table for RPV (Oral RPV 25mg, IM RPV 900mg; ng/mL, ng*h/mL) 
2) Repeat for all of the following PK parameters as available: Cmax, tmax, t1/2, KA LA, z, C24, C 
3) For tmax, only the n, median, minimum, and maximum should be provided. 
4) Report the means & median +1 decimal past the maximum length of results within parameter. Report the SD and 95% CI values 
+2 decimals past the maximum length of results within parameter. %CV statistics should be reported to 1 decimal. 
 
 


&21),'(17,$/



Protocol: 208832                                                                
 
 
Page 1 of 1 
Population: Screened 
 
 
HO_01 
Listing of
 Scores 
 
 
  
 
Treatment 
Site Id./  
Unique Subject Id. 
Treatment/ 
Injection Site 
Side 
 
 
Visit 
 
 
Date 
 
 
 
 
 
Treatment A 
 
CAB/Left 
Day 1 
Day 2 
YYYY-MM-DDTHH:MM 
YYYY-MM-DDTHH:MM 
 
 
Day 4 
YYYY-MM-DDTHH:MM 
 
 
 
Day 5 
YYYY-MM-DDTHH:MM 
 
 
 
Day 8 
YYYY-MM-DDTHH:MM 
 
 
 
 
 
 
 
RPV/Right 
Day 1 
YYYY-MM-DDTHH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
USER ID:/PROGRAM PATH/PROGRAM DATE TIME

CCI
PPD
CCI


&21),'(17,$/



Protocol: 208832                                                                
 
 
Page 1 of 1 
Population: Screened 
 
 
HO_02 
Listing of 
 Results at Day 8 
 
Treatment: Treatment A 
Site Id./  
Unique Subject Id. 
 
 
Date/Time of 
Assessment 
 
Treatment/ 
Injection  
Site Side/ 
 
 
 
Domain 
 
Question 
 
 
 
Result 
 
 
 
 
 
 
YYYY-MM-DD/ 
HH:MM 
 
 
 
 
 
CAB/Left 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
YYYY-MM-DD/ 
HH:MM 
 
RPV/Right 
 
 
 
 
 
 
 
CCI
CCI
CCI
PPD


&21),'(17,$/



 
USER ID:/PROGRAM PATH/PROGRAM DATE TIME


CCI


&21),'(17,$/



Protocol: 208832                                                                 
 
 
Page 1 of 1 
Population: Screened 
 
 
HO_03 
Listing of Injection Area Symptoms from Daily Diary Cards 
 
 
 
Treatment 
Site Id./  
Unique Subject Id. 
Treatment/ 
Injection  
Site Side 
Date of 
Assessment/ 
Study Day 
 
Symptoms? 
(Y/N) 
Pain 
(0-3) 
 
Itching 
(0-3) 
 
Other 
Symptoms [1] 
Home 
Treatment [2] 
 
 
 
 
 
 
 
 
Treatment A 
 
CAB/ 
Left 
YYYY-MM-DD/ 
1 
Y 
2 
 
1 
 
BU, SF 
 
AP, Top 
 
 
 
 
 
 
 
 
 
 
 
 
 
YYYY-MM-DD/ 
2 
Y 
0 
 
1 
 
 
 
Top 
 
 
 
 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RPV/ 
Right 
YYYY-MM-DD/ 
1 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] NO=None, BR=Bruising, BU=Bump, D=Discoloration, R=Redness, SF=Skin firmness, SW=Swelling, W=Warm to touch. 
[2] NO=None, AP=Acetaminophen/paracetamol (Tylenol), D=Diphenhydramine (Benadryl), Top=Topical anti-itch cream 
or ointment such as hydrocortisone/diphenhydramine, etc., W=Warm compress (heating pad), C=Cold compress (cold 
pack or ice pack). 
 
 
USER ID:/PROGRAM PATH/PROGRAM DATE TIME


PPD


CONFIDENTIAL 
208832 
 
68 
 
11.10. 
Appendix 10: AESI Identification 
SMQ and PT codes based on MedDRA dictionary version 23.0. 
11.10.1. 
Hepatotoxicity 
SMQ: Hepatic failure, fibrosis and cirrhosis and other liver damage-
related conditions 
SMQ Code: 20000013 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Acquired hepatocerebral degeneration 
10080860 
Acute hepatic failure 
10000804 
Acute on chronic liver failure 
10077305 
Acute yellow liver atrophy 
10070815 
Ascites 
10003445 
Asterixis 
10003547 
Bacterascites 
10068547 
Biliary cirrhosis 
10004659 
Biliary fibrosis 
10004664 
Cardiohepatic syndrome 
10082480 
Cholestatic liver injury 
10067969 
Chronic hepatic failure 
10057573 
Coma hepatic 
10010075 
Cryptogenic cirrhosis 
10063075 
Diabetic hepatopathy 
10071265 
Drug-induced liver injury 
10072268 
Duodenal varices 
10051010 
Gallbladder varices 
10072319 
Gastric variceal injection 
10076237 
Gastric variceal ligation 
10076238 
Gastric varices 
10051012 


CONFIDENTIAL 
208832 
 
69 
 
Gastric varices haemorrhage 
10057572 
Gastrooesophageal variceal haemorrhage prophylaxis 
10066597 
Hepatectomy 
10061997 
Hepatic atrophy 
10019637 
Hepatic calcification 
10065274 
Hepatic cirrhosis 
10019641 
Hepatic encephalopathy 
10019660 
Hepatic encephalopathy prophylaxis 
10066599 
Hepatic failure 
10019663 
Hepatic fibrosis 
10019668 
Hepatic hydrothorax 
10067365 
Hepatic infiltration eosinophilic 
10064668 
Hepatic lesion 
10061998 
Hepatic necrosis 
10019692 
Hepatic steato-fibrosis 
10077215 
Hepatic steatosis 
10019708 
Hepatitis fulminant 
10019772 
Hepatobiliary disease 
10062000 
Hepatocellular foamy cell syndrome 
10053244 
Hepatocellular injury 
10019837 
Hepatopulmonary syndrome 
10052274 
Hepatorenal failure 
10019845 
Hepatorenal syndrome 
10019846 
Hepatotoxicity 
10019851 
Immune-mediated cholangitis 
10083406 
Immune-mediated hepatic disorder 
10083521 
Intestinal varices 
10071502 
Intestinal varices haemorrhage 
10078058 
Liver dialysis 
10076640 


CONFIDENTIAL 
208832 
 
70 
 
Liver disorder 
10024670 
Liver injury 
10067125 
Liver operation 
10062040 
Liver transplant 
10024714 
Lupoid hepatic cirrhosis 
10025129 
Minimal hepatic encephalopathy 
10076204 
Mixed liver injury 
10066758 
Nodular regenerative hyperplasia 
10051081 
Nonalcoholic fatty liver disease 
10082249 
Non-alcoholic steatohepatitis 
10053219 
Non-cirrhotic portal hypertension 
10077259 
Oedema due to hepatic disease 
10049631 
Oesophageal varices haemorrhage 
10030210 
Peripancreatic varices 
10073215 
Portal fibrosis 
10074726 
Portal hypertension 
10036200 
Portal hypertensive colopathy 
10079446 
Portal hypertensive enteropathy 
10068923 
Portal hypertensive gastropathy 
10050897 
Portal vein cavernous transformation 
10073979 
Portal vein dilatation 
10073209 
Portopulmonary hypertension 
10067281 
Primary biliary cholangitis 
10080429 
Regenerative siderotic hepatic nodule 
10080679 
Renal and liver transplant 
10052279 
Retrograde portal vein flow 
10067338 
Reye's syndrome 
10039012 
Reynold's syndrome 
10070953 
Splenic varices 
10067823 


CONFIDENTIAL 
208832 
 
71 
 
Splenic varices haemorrhage 
10068662 
Steatohepatitis 
10076331 
Subacute hepatic failure 
10056956 
Sugiura procedure 
10083010 
Varices oesophageal 
10056091 
Varicose veins of abdominal wall 
10072284 
White nipple sign 
10078438 
SMQ: Hepatitis, non-infectious 
SMQ Code: 20000010 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Acute graft versus host disease in liver 
10066263 
Allergic hepatitis 
10071198 
Alloimmune hepatitis 
10080576 
Autoimmune hepatitis 
10003827 
Chronic graft versus host disease in liver 
10072160 
Chronic hepatitis 
10008909 
Graft versus host disease in liver 
10064676 
Hepatitis 
10019717 
Hepatitis acute 
10019727 
Hepatitis cholestatic 
10019754 
Hepatitis chronic active 
10019755 
Hepatitis chronic persistent 
10019759 
Hepatitis fulminant 
10019772 
Hepatitis toxic 
10019795 
Immune-mediated hepatitis 
10078962 
Ischaemic hepatitis 
10023025 
Lupus hepatitis 
10067737 
Non-alcoholic steatohepatitis 
10053219 


CONFIDENTIAL 
208832 
 
72 
 
Radiation hepatitis 
10051015 
Steatohepatitis 
10076331 
 
11.10.2. 
Seizures 
SMQ: ‘Convulsions’  
SMQ Code: 20000079 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
1p36 deletion syndrome 
10082398 
2-Hydroxyglutaric aciduria 
10078971 
Acquired epileptic aphasia 
10052075 
Acute encephalitis with refractory, repetitive partial seizures 
10076948 
Alcoholic seizure 
10056347 
Alpers disease 
10083857 
Aspartate-glutamate-transporter deficiency 
10079140 
Atonic seizures 
10003628 
Atypical benign partial epilepsy 
10056699 
Automatism epileptic 
10003831 
Autonomic seizure 
10049612 
Baltic myoclonic epilepsy 
10054895 
Benign familial neonatal convulsions 
10067866 
Benign rolandic epilepsy 
10070530 
Biotinidase deficiency 
10071434 
CEC syndrome 
10083749 
CDKL5 deficiency disorder 
10083005 
Change in seizure presentation 
10075606 
Clonic convulsion 
10053398 
Congenital bilateral perisylvian syndrome 
10082716 


CONFIDENTIAL 
208832 
 
73 
 
Convulsion in childhood 
10052391 
Convulsions local 
10010920 
Convulsive threshold lowered 
10010927 
CSWS syndrome 
10078827 
Deja vu 
10012177 
Double cortex syndrome 
10073490 
Dreamy state 
10013634 
Drug withdrawal convulsions 
10013752 
Early infantile epileptic encephalopathy with burst-suppression 
10071545 
Eclampsia 
10014129 
Epilepsy 
10015037 
Epilepsy surgery 
10079824 
Epilepsy with myoclonic-atonic seizures 
10081179 
Epileptic aura 
10015049 
Epileptic psychosis 
10059232 
Febrile convulsion 
10016284 
Febrile infection-related epilepsy syndrome 
10079438 
Focal dyscognitive seizures 
10079424 
Frontal lobe epilepsy 
10049424 
Gelastic seizure 
10082918 
Generalised onset non-motor seizure 
10083376 
Generalised tonic-clonic seizure 
10018100 
Glucose transporter type 1 deficiency syndrome 
10078727 
GM2 gangliosidosis 
10083933 
Grey matter heterotopia 
10082084 
Hemimegalencephaly 
10078100 
Hyperglycaemic seizure 
10071394 
Hypocalcaemic seizure 
10072456 


CONFIDENTIAL 
208832 
 
74 
 
Hypoglycaemic seizure 
10048803 
Hyponatraemic seizure 
10073183 
Idiopathic generalised epilepsy 
10071081 
Infantile spasms 
10021750 
Juvenile myoclonic epilepsy 
10071082 
Lafora's myoclonic epilepsy 
10054030 
Lennox-Gastaut syndrome 
10048816 
Migraine-triggered seizure 
10076676 
Molybdenum cofactor deficiency 
10069687 
Multiple subpial transection 
10079825 
Myoclonic epilepsy 
10054859 
Myoclonic epilepsy and ragged-red fibres 
10069825 
Neonatal epileptic seizure 
10082068 
Neonatal seizure 
10082067 
Partial seizures 
10061334 
Partial seizures with secondary generalisation 
10056209 
Petit mal epilepsy 
10034759 
Polymicrogyria 
10073489 
Post stroke epilepsy 
10076982 
Post stroke seizure 
10076981 
Postictal headache 
10052470 
Postictal paralysis 
10052469 
Postictal psychosis 
10070669 
Postictal state 
10048727 
Post-traumatic epilepsy 
10036312 
Schizencephaly 
10073487 
Seizure 
10039906 
Seizure anoxic 
10039907 
Seizure cluster 
10071350 


CONFIDENTIAL 
208832 
 
75 
 
Seizure like phenomena 
10071048 
Severe myoclonic epilepsy of infancy 
10073677 
Simple partial seizures 
10040703 
Status epilepticus 
10041962 
Sudden unexplained death in epilepsy 
10063894 
Temporal lobe epilepsy 
10043209 
Tonic clonic movements 
10051171 
Tonic convulsion 
10043994 
Tonic posturing 
10075125 
Topectomy 
10073488 
Transient epileptic amnesia 
10081728 
Tuberous sclerosis complex 
10080584 
Uncinate fits 
10045476 
Additional selected preferred terms from HLT “Disturbances in 
consciousness NEC” (Code: 10013509) under SOC “Nervous systems 
disorders” and HLT “Confusion and disorientation” (Code: 10010301) 
under SOC “Psychiatric disorders”. 
 
Preferred Term 
PT Code 
Confusional state 
10010305 
Loss of consciousness 
10024855 
Syncope 
10042772 
Sopor 
10058709 
Stupor 
10042264 
Altered state of consciousness 
10050093 
Depressed level of consciousness 
10012373 
Consciousness fluctuating 
10050093 
 
11.10.3. 
Torsade de pointes/QT prolongation 
Notes: Medical concept of QT prolongation and complications. Only narrow terms from 
SMQ 'Torsade de pointes/QT prolongation' selected plus one additional PT under HLT 
‘ECG investigations'. 


CONFIDENTIAL 
208832 
 
76 
 
SMQ: Torsade de pointes/QT prolongation 
SMQ Code: 20000001 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Electrocardiogram QT interval abnormal 
10063748 
Electrocardiogram QT prolonged 
10014387 
Long QT syndrome 
10024803 
Long QT syndrome congenital 
10057926 
Torsade de pointes 
10044066 
Ventricular tachycardia 
10047302 
Additional preferred terms selected from HLT ' ECG investigations' 
(Code: 10053104) under SOC ‘Investigations’. 
Preferred Term 
PT Code 
Electrocardiogram repolarisation abnormality 
10052464 
 
11.10.4. 
COVID-19 Adverse Events 
COVID-19 adverse events are identified based on MedDRA coded values and/or AE 
referenced in the COVID-19 Coronavirus Infection assessment. The Lowest Level Terms 
(LLTs) and codes, Preferred Terms (PTs), High Level Terms (HLTs), High Level Group 
Terms (HLGTs), and System Organ Classes (SOCs), below are from MedDRA 23.0. In 
case there is a change to the version of MedDRA at time of reporting, the coded values 
based on the MedDRA version at the time of reporting will be used. The additional 
events may also be added based on the blinded review of AE data collected on study prior 
to the database freeze. 
SOC: Infections and infestations 
LLT code LLT 
PT 
HLT 
HLGT 
10084459 Asymptomatic COVID-19 
Asymptomatic 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 


CONFIDENTIAL 
208832 
 
77 
 
LLT code LLT 
PT 
HLT 
HLGT 
10084467 
Asymptomatic SARS-
CoV-2 infection 
Asymptomatic 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10053983 Corona virus infection 
Coronavirus 
infection 
Coronavirus 
infections 
Viral infectious 
disorders 
10051905 Coronavirus infection 
Coronavirus 
infection 
Coronavirus 
infections 
Viral infectious 
disorders 
10084382 
Coronavirus disease 
2019 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10070255 
Coronavirus test positive 
Coronavirus 
test positive 
Virus identification 
and serology 
Microbiology and 
serology 
investigations 
 
 


CONFIDENTIAL 
208832 
 
78 
 
10084460 
COVID-19 treatment 
COVID-19 
treatment 
Antiinfective 
therapies 
Therapeutic 
procedures and 
supportive care 
NEC 
10084639 
SARS-CoV-2 sepsis 
SARS-CoV-2 
sepsis 
Coronavirus 
infections 
Viral infectious 
disorders 
10084271 SARS-CoV-2 test 
positive 
SARS-CoV-2 
test positive 
Virus identification 
and serology 
Microbiology and 
serology 
investigations 
10084640 
SARS CoV-2 viraemia 
SARS CoV-2 
viraemia 
Coronavirus 
infections 
Viral infectious 
disorders 
10084268 COVID-19 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084401 
COVID-19 respiratory 
infection 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084270 
SARS-CoV-2 acute 
respiratory disease 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084272 SARS-CoV-2 infection 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084381 Coronavirus pneumonia 
COVID-19 
pneumonia 
Coronavirus 
infections 
Viral infectious 
disorders 
10084380 COVID-19 pneumonia 
COVID-19 
pneumonia 
Coronavirus 
infections 
Viral infectious 
disorders 
10084383 
Novel COVID-19-
infected pneumonia 
COVID-19 
pneumonia 
Coronavirus 
infections 
Viral infectious 
disorders 
10084451 Suspected COVID-19 
Suspected 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084452 
Suspected SARS-CoV-2 
infection 
Suspected 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084461 SARS-CoV-2 carrier 
SARS-CoV-2 
carrier 
Infectious 
disorders carrier 
Ancillary infectious 
topics