Clinical trial NCT02751424
Conditions: Infections, Bacterial
Keywords: Multidrug-resistant Gram negative bacterial infection Safety Pharmacokinetic
Sponsor: GlaxoSmithKline
Start date: 2016-06-13; Completion date: 2017-02-02
Enrollment: 62 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A phase I, first-time-in-human (FTIH), randomized, double-blind, placebo controlled, dose-escalation study is conducted to determine the safety, tolerability, and pharmacokinetic (PK) profile of GSK3342830 after administration of single intravenous (IV) infusion in Part 1 and repeat IV infusion in Part 2 in healthy subjects. Part 1 will investigate escalating single IV doses of GSK3342830. Part 2, will investigate escalating repeat IV doses of GSK3342830 with repeat dosing for 15 days as follows: a single IV infusion on Day 1, TID (three times a day) IV infusions on Days 2 through 14 (approximately every 8 hours), and a single IV infusion on Day 15. The planned starting GSK3342830 dose in Part 1 is 250 milligram (mg) administered as a single IV infusion. The dose is planned to increase in subsequent cohorts to 500, 1000, 2000, 4000, and less than or equal to (≤) 6000 mg. Part 1 will be divided into 6 cohorts (A-F) and each cohort will enroll 10 subjects (6 in active and 2 in placebo). Dose escalation will be conducted only if it is supported by the preliminary safety, tolerability, and PK results from the preceding dose levels in the study. The repeat dose escalation component (Part 2) of this study will be planned to be initiated after completion and evaluation of the all single dose cohorts up to and including 4000 mg.

Detailed description:

Arms: arm 1: Enrolled subject will receive single escalation dose of GSK3342830. The escalating doses will be evaluated in six cohorts as A- 250 mg, B-500 mg, C-1000 mg, D-2000 mg, E-4000 mg, and F-=\<6000 mg. In each cohort 6 subjects will receive GSK3342830 in form of infusion for 1 h, therefore approximately 36 subjects will receive GSK3342830. Dose escalation will be based on evaluation of the preceding dose levels in the study. arm 2: Enrolled subject will receive single escalation dose of placebo. In each cohort, 2 subjects will receive placebo in form of infusion for 1 h, therefore approximately 12 subjects will receive placebo. arm 3: Enrolled subject will receive repeat escalating dose of GSK3342830. GSK3342830 as a single IV infusion will be administered on Day 1, TID (8 hours apart) IV infusions on Days 2 through 14, and a single IV infusion on Day 15. The escalating doses will be evaluated in three cohorts as G-1000 mg, H-2000 and I-4000 mg. In each cohort 8 subjects will receive GSK3342830 in form of infusion for 1 h, therefore approximately 24 subjects will receive GSK3342830. The starting dose and maximum dose may change based on clinical safety and PK findings in Part 1 or earlier doses in Part 2 respectively. arm 4: Enrolled subject will receive repeat escalation dose of placebo. Placebo as a single IV infusion will be administered on Day 1, TID (8 hours apart) IV infusions on Days 2 through 14, and a single IV infusion on Day 15. In each cohort, 2 subjects will receive placebo in form of infusion for 1 h, therefore approximately 6 subjects will receive placebo.
Interventions: intervention 1: GSK3342830 intervention 2: Placebo
Intervention descriptions: intervention 1: A pyrogen free lyophilized formulation, white to yellowish brown powder containing 1000 mg of GSK3342830A (as free base) per vial. The reconstituted solution looks like a clear, colorless to yellow or brownish yellow liquid, free from visible particulate matter will be administered as IV infusion over 1 hour. intervention 2: A clear and colorless solution containing 0.9% sodium chloride. It will administered as IV infusion over 1 hour.

Protocol documents:
Prot_000.pdf: 
2015N257523_01
CONFIDENTIAL
The GlaxoSmithKline group of companies
204847
1
TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
A Phase I, Randomized, Double-Blind (Sponsor Unblinded), 
Single-Center, Placebo-Controlled, Three-Part Study to Evaluate 
the Safety, Tolerability, and Pharmacokinetics of Ascending 
Single and Repeat Intravenous Doses of GSK3342830 in 
Healthy Adult Subjects
Compound Number:
GSK3342830
Development Phase:
I
Effective Date:
01-NOV-2016
Protocol Amendment Number:  1
Author (s):
GSK: 
 (Clinical Statistics), 
(Infectious Disease Medicines
Development),
(Preclinical Safety Assessment), 
 (Bioanalysis),
(Clinical Pharmacology Modeling and Simulation), 
(PCPS Therapy
Area Delivery)
PPD: 
(Global Product Development),
 (Biostatistician), 
(Regulatory Affairs), 
 (Pharmacokineticist), 
(Medical 
Writer)
Copyright 2016 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


2015N257523_01
CONFIDENTIAL
The GlaxoSmithKline group of companies
204847
2
Revision Chronology
GlaxoSmithKline 
Document Number
Date
Version
2015N257523_00
2016-FEB-18
Original
2015N257523_01
2016-NOV-01
Amendment No. 1
The purpose of this amendment is to add 1 cohort to this study. This cohort will consist of 
Japanese subjects who will receive a single IV dose of GSK3342830. Testing 
GSK3342830 in this specific population will provide pharmacokinetic data and enable 
future pivotal Phase III studies in the respective country.


PPD
PPD


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4
MEDICAL MONITOR/SPONSOR INFORMATION PAGE
Medical Monitor/SAE Contact Information: 
Role
Name
Day Time Phone 
Number and 
email address
After-hours 
Phone/Cell/
Pager Number
Fax Number
Site Address
Primary 
Medical 
Monitor and 
SAE Contact 
Information
 
MD 
 
Safety fax 
number: 
 
PPD
Level 8, Pavilion KL
168, Jalan Bukit Bintang
55100 Kuala Lumpur
Malaysia
Secondary 
Medical 
Monitor
 
MD
GlaxoSmithKline
1250 South Collegeville 
Road
Collegeville, PA 19426, 
USA
Secondary 
GSK Medical 
Monitor
 
 MD
 
(Office)
 
(Cell)
GlaxoSmithKline
1250 South Collegeville 
Road
Collegeville, PA 19426, 
USA
Sponsor Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline Affiliate 
Company (or designee). If applicable, the details of the alternative Sponsor and contact 
person in the territory will be provided to the relevant regulatory authority as part of the 
clinical trial application.
Regulatory Agency Identifying Number:
PPD
PPD
PPD
PPD
PPD
PP
D
PP
D
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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5
INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol number 204847
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
Investigator Name:
Investigator Address:
Investigator Phone Number:
Investigator Signature
Date


2015N257523_01
CONFIDENTIAL
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6
TABLE OF CONTENTS
PAGE
1.
PROTOCOL SYNOPSIS FOR STUDY 204847........................................................9
2.
INTRODUCTION....................................................................................................13
2.1.
Study Rationale ..........................................................................................14
2.2.
Brief Background ........................................................................................14
3.
OBJECTIVES AND ENDPOINTS...........................................................................15
4.
STUDY DESIGN ....................................................................................................17
4.1.
Overall Design ............................................................................................17
4.2.
Treatment Arms and Duration.....................................................................19
4.3.
Type and Number of Subjects.....................................................................22
4.4.
Design Justification.....................................................................................23
4.5.
Dose Justification........................................................................................23
4.6.
Benefit:Risk Assessment ............................................................................27
4.6.1.
Risk Assessment .........................................................................28
4.6.2.
Benefit Assessment.....................................................................33
4.6.3.
Overall Benefit:Risk Conclusion...................................................33
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA .............33
5.1.
Inclusion Criteria.........................................................................................33
5.2.
Exclusion Criteria........................................................................................35
5.3.
Screening/Baseline/Run-in Failures............................................................37
5.4.
Withdrawal/Stopping Criteria.......................................................................37
5.4.1.
Liver Chemistry Stopping Criteria ................................................38
5.4.1.1.
Study Treatment Restart or Rechallenge....................38
5.4.2.
Hematological Stopping Criteria...................................................38
5.4.3.
Renal Stopping Criteria................................................................38
5.4.4.
QTc Stopping Criteria ..................................................................38
5.4.5.
Vital Signs Stopping Criteria ........................................................39
5.4.6.
Other Safety Dose Adjustment/Stopping Criteria .........................39
5.4.7.
Additional Safety Stopping Criteria...............................................40
5.4.8.
Pharmacokinetic Dose Adjustment/Stopping Criteria ...................41
5.5.
Subject and Study Completion....................................................................41
6.
STUDY TREATMENT ............................................................................................41
6.1.
Investigational Product and Other Study Treatment....................................41
6.2.
Treatment Assignment................................................................................42
6.3.
Planned Dose Adjustments.........................................................................42
6.4.
Blinding.......................................................................................................44
6.5.
Packaging and Labeling..............................................................................44
6.6.
Preparation/Handling/Storage/Accountability..............................................45
6.7.
Compliance with Study Treatment Administration.......................................45
6.8.
Treatment of Study Treatment Overdose....................................................45
6.9.
Treatment after the End of the Study ..........................................................46
6.10.
Lifestyle and/or Dietary Restrictions............................................................46
6.10.1.
Meals and Dietary Restrictions ....................................................46
6.10.2.
Caffeine, Alcohol, and Tobacco ...................................................46


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7
6.10.3.
Activity .........................................................................................47
6.11.
Concomitant Medications and Non-Drug Therapies....................................47
6.11.1.
Permitted Medications and Non-Drug Therapies..........................47
6.11.2.
Prohibited Medications and Non-Drug Therapies.........................47
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................47
7.1.
Time and Events Tables .............................................................................49
7.2.
Screening and Critical Baseline Assessments ............................................55
7.3.
Safety .........................................................................................................55
7.3.1.
Adverse Events and Serious Adverse Events..............................55
7.3.1.1.
Time Period and Frequency for Collecting AE 
and SAE Information ..................................................55
7.3.1.2.
Method of Detecting AEs and SAEs ...........................56
7.3.1.3.
Follow-up of AEs and SAEs........................................56
7.3.1.4.
Regulatory Reporting Requirements for SAEs............56
7.3.2.
Pregnancy ...................................................................................57
7.3.3.
Physical Examinations.................................................................57
7.3.4.
Vital Signs....................................................................................57
7.3.5.
Electrocardiograms......................................................................57
7.3.6.
Continuous Cardiac Monitoring....................................................57
7.3.7.
Clinical Safety Laboratory Assessments ......................................57
7.4.
Pharmacokinetics .......................................................................................59
7.4.1.
Blood Sample Collection..............................................................59
7.4.2.
Urine Sample Collection ..............................................................59
7.4.3.
Sample Analysis ..........................................................................60
7.5.
Genetics .....................................................................................................60
8.
DATA MANAGEMENT ...........................................................................................60
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................61
9.1.
Hypotheses.................................................................................................61
9.2.
Sample Size Considerations.......................................................................61
9.2.1.
Sample Size Assumptions ...........................................................61
9.2.2.
Sample Size Sensitivity................................................................61
9.2.3.
Sample Size Re-estimation or Adjustment...................................62
9.3.
Data Analysis Considerations .....................................................................62
9.3.1.
Analysis Populations....................................................................62
9.3.2.
Interim Analysis ...........................................................................62
9.4.
Key Elements of Analysis Plan ...................................................................63
9.4.1.
Primary Analyses.........................................................................63
9.4.2.
Secondary Analyses ....................................................................64
9.4.3.
Exploratory Analyses ...................................................................66
10. STUDY GOVERNANCE CONSIDERATIONS........................................................67
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............67
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................67
10.3.
Quality Control (Study Monitoring) ..............................................................68
10.4.
Quality Assurance.......................................................................................68
10.5.
Study and Site Closure ...............................................................................68
10.6.
Records Retention......................................................................................69


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8
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................70
11. REFERENCES.......................................................................................................71
12. APPENDICES........................................................................................................73
12.1.
Appendix 1: Abbreviations and Trademarks................................................73
12.2.
Appendix 2: Liver Chemistry Stopping Criteria............................................75
12.3.
Appendix 3: Liver Safety Required Actions and Follow-up 
Assessments ..............................................................................................76
12.4.
Appendix 4: Genetic Research ...................................................................78
12.5.
Appendix 5: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events...............................................81
12.5.1.
Definition of Adverse Events........................................................81
12.5.2.
Definition of Serious Adverse Events...........................................82
12.5.3.
Definition of Cardiovascular Events .............................................83
12.5.4.
Recording of AEs and SAEs ........................................................84
12.5.5.
Evaluating AEs and SAEs............................................................84
12.5.6.
Reporting of SAEs to GSK...........................................................85
12.6.
Appendix 6: DMID Adult Toxicity Tables for AE Assessment ......................87
12.7.
Appendix 7: Allergic Reactions Including Anaphylaxis ................................94
12.8.
Appendix 8: Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential and Collection of 
Pregnancy Information................................................................................96
12.8.1.
Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential.........................96
12.8.2.
Contraceptive Requirements for Male Subjects with 
Female Partners of Reproductive Potential..................................96
12.8.3.
Collection of Pregnancy Information ............................................97
12.9.
Appendix 9: Additional Details on the in vivo Efficacy Calculations 
and Animal to Human Scaling.....................................................................99
12.10. Appendix 10: Clostridium difficile Testing Procedure and Algorithm..........101
12.11. Appendix 11: Chronic Kidney Disease Epidemiology Collaboration 
Formula ....................................................................................................102
12.12. Appendix 12: Country-Specific Requirements...........................................103
12.13. Appendix 13: Protocol Changes................................................................104


2015N257523_01
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204847
9
1.
PROTOCOL SYNOPSIS FOR STUDY 204847
Rationale
This study represents the first administration of GSK3342830 in humans. It will be 
conducted to define the safety, tolerability, and pharmacokinetics of GSK3342830 after 
administration of single and repeat IV doses in healthy adult subjects, and after 
administration of a single IV dose in healthy adult Japanese subjects.
Objectives/Endpoints
Objectives
Endpoints
Part 1
Primary

To investigate the safety and tolerability of 
GSK3342830 after administration of single IV doses 
in healthy adult subjects

Clinical safety data from adverse events (AEs), 
clinical laboratory tests, vital signs (blood pressure, 
heart rate, temperature, and respiration rate), and 
12-lead electrocardiogram (ECG) readings
Secondary

To determine the pharmacokinetics of GSK3342830 
after administration of single IV doses in healthy 
adult subjects

Plasma and urine concentrations and 
pharmacokinetic (PK) endpoints include AUC(0-t), 
AUC(0-), Cmax, Tmax, CL, Vss, t1/2, Feu(t1-t2), 
Ae, and CLr of GSK3342830, as data permit

To assess dose proportionality of GSK3342830 after 
administration of single IV doses in healthy adult 
subjects

Pharmacokinetic endpoints include AUC(0-t), 
AUC(0-), and Cmax of GSK3342830 after 
administration of single IV doses for the assessment 
of dose proportionality, as data permit
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
and Cmax) of GSK3342830 with safety findings after 
administration of single IV doses in healthy adult 
subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine
Part 2
Primary

To investigate the safety and tolerability of 
GSK3342830 after administration of repeat IV doses 
in healthy adult subjects

Clinical safety data from AEs, clinical laboratory 
tests, vital signs (blood pressure, heart rate, 
temperature, and respiration rate), and 12-lead ECG 
readings
Secondary

To determine the pharmacokinetics of GSK3342830 
after administration of repeat IV doses in healthy 
adult subjects

Plasma and urine concentrations and PK endpoints 
include AUC(0-t) and AUC(0-) on Day 1 only, 
AUC(0-), Cmax, Tmax, CL, Vss, t1/2, C, 
Feu(t1-t2), Ae, and CLr of GSK3342830, as data 
permit


2015N257523_01
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Objectives
Endpoints

To assess dose proportionality of GSK3342830 after 
administration of repeat IV doses in healthy adult 
subjects

Pharmacokinetic endpoints include AUC(0-) and 
Cmax of GSK3342830 after administration of repeat 
IV doses for the assessment of dose proportionality, 
as data permit

To examine the extent of accumulation, time 
invariance, and achievement of steady-state of 
GSK3342830 after administration of repeat IV doses 
in healthy adult subjects

Observed accumulation ratio (Ro) based on AUC 
and Cmax of GSK3342830 after administration of 
repeat IV doses, as data permit

Steady-state ratio (Rss) of GSK3342830 to assess 
time invariance, as data permit

Trough plasma concentrations at the end of the 
dosing interval (C) to assess the achievement of 
steady-state of GSK3342830 after administration of 
repeat IV doses, as data permit
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
AUC[0-], and Cmax) of GSK3342830 with safety 
findings and evaluate urine discoloration after 
administration of repeat IV doses in healthy adult 
subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine
Part 3
Primary

To investigate the safety and tolerability of 
GSK3342830 after administration of a single IV dose 
in healthy adult Japanese subjects

Clinical safety data from AEs, clinical laboratory 
tests, vital signs (blood pressure, heart rate, 
temperature, and respiration rate), and 12-lead ECG 
readings
Secondary

To determine the pharmacokinetics of GSK3342830 
after administration of a single IV dose in healthy 
adult Japanese subjects

Plasma and urine concentrations and PK endpoints 
include AUC(0-t), AUC(0-), Cmax, Tmax, CL, Vss, 
t1/2, Feu(t1-t2), Ae, and CLr of GSK3342830, as 
data permit
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
and Cmax) of GSK3342830 with safety findings after 
administration of a single IV dose in healthy adult 
Japanese subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine


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Overall Design
This is a Phase I, first-time-in-human (FTIH), randomized, double-blind (sponsor 
unblinded), single-center, placebo-controlled, dose-escalation study to determine the 
safety, tolerability, and pharmacokinetic (PK) profile of GSK3342830 after 
administration of single (Part 1) and repeat (Part 2) IV doses in healthy adult subjects, 
and a single IV dose in healthy adult Japanese subjects (Part 3).
For Parts 1 and 2, on Day 1, before study drug administration, subjects who meet the 
criteria for study entry will be assigned to the current dose level cohort and randomized 
to receive GSK3342830 or placebo. For Part 3, on Day 1, before study drug 
administration, subjects who meet the criteria for study entry will be randomized to 
receive GSK3342830 or placebo. All doses of GSK3342830 or placebo are planned to be 
administered as a 1-hour infusion.
Dose escalation will be conducted only if it is supported by the preliminary safety, 
tolerability, and PK results from the preceding dose levels in the study. This is the first 
administration of GSK3342830 in humans; therefore, as preliminary safety, tolerability, 
and PK results are reviewed internally at GSK and with the clinical study site, study 
design adjustments may be made based on emerging data from each dose cohort.
The repeat dose escalation component (Part 2) of this study is planned to be initiated after 
completion and evaluation of the all single dose cohorts up to and including 4000 mg. 
Initiation of Part 2 will be based on the evaluation of preliminary safety, tolerability, and 
PK data from the single dose escalation (Part 1) cohorts once safety at an exposure that 
exceeds the daily exposure predicted for the Part 2 planned starting dose of 1000 mg TID 
is demonstrated, which is predicted to occur at the 4000 mg single dose.
The single dose administration in Japanese subjects (Part 3) is planned to be conducted in 
parallel with Part 2. The dose for the Part 3 cohort will be based on preliminary safety 
and tolerability results of doses determined to be safe and well tolerated in subjects of 
non-Japanese heritage after completion of the single escalation dose cohorts (Part 1).
Treatment Arms and Duration
Part 1: Single Dose Escalation in Healthy Adult Subjects
The planned starting GSK3342830 dose in Part 1 is 250 mg administered as a single IV 
infusion. The dose is planned to increase in subsequent cohorts to 500, 1000, 2000, 4000, 
and 6000 mg. As a safety precaution, all Part 1 dose cohorts will be split into 
2 sub-cohorts for sentinel dosing. In each cohort, the first 2 subjects will receive either 
GSK3342830 or placebo (1 active/1 placebo). Dosing in the remaining 6 subjects 
(5 active/1 placebo) in that cohort will occur at least 24 hours later based on the safety 
results from the first sub-cohort. Doses are planned to escalate in a sequential fashion 
contingent on the safety, tolerability, and PK profile of approximately 4 subjects who 
received active treatment in the previous cohort. Dose escalations or reductions will 
progress with modifications based on the safety, tolerability, and preliminary PK data 
from the preceding cohorts.


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In Part 1, subjects will remain confined to the clinical unit from admission on Day –1 
until after all scheduled safety and PK assessments have been completed on Day 3. The 
duration of study (from Screening to the Follow-up visit) for each subject will be up to 
approximately 43 days.
Part 2: Repeat Dose Escalation in Healthy Adult Subjects
The planned starting GSK3342830 dose in Part 2 is 1000 mg administered as a single IV 
infusion on Day 1, TID IV infusions on Days 2 through 14, and a single IV infusion on 
Day 15. The dose is planned to increase in subsequent cohorts to 2000 and 4000 mg 
following the same dosing schedule as the 1000 mg dose cohort. The starting dose and 
maximum dose may be changed based on clinical safety and PK findings in Part 1 or 
earlier doses in Part 2 and consideration of the area under the concentration-time 
curve (AUC) from time zero to 24 hours after dosing (AUC[0-24]) and maximum plasma 
concentration (Cmax) exposures based on the no observed adverse effect level (NOAEL).
Doses are planned to escalate in a sequential fashion contingent on the preliminary safety, 
tolerability, and PK data from Part 1 and at least 14 days of repeat dosing in 
approximately 5 subjects who received active treatment in the previous cohort in Part 2. 
The dosing frequency, duration of dosing, and decision to dose in the next dose level may 
be changed based on the safety, tolerability, or PK findings in Part 1 or earlier doses in 
Part 2.
In Part 2, subjects will remain confined to the clinical unit from admission on Day –1 
until after all scheduled safety assessments have been completed on Day 16. The duration 
of study (from Screening to the Follow-up visit) for each subject will be up to 
approximately 56 days.
Part 3: Single Dose in Healthy Adult Japanese Subjects
The planned GSK3342830 dose in Part 3 will be either 250, 500, 1000, 2000, 4000, or 
6000 mg based on preliminary safety and tolerability results of doses determined to be 
safe and well tolerated in subjects of non-Japanese heritage after completion of the single 
escalation dose cohorts (Part 1). The dose in Part 3 will be administered as a single IV 
infusion on Day 1.
In Part 3, subjects will remain confined to the clinical unit from admission on Day –1 
until after all scheduled safety and PK assessments have been completed on Day 3. The 
duration of study (from Screening to the Follow-up visit) for each subject will be up to 
approximately 43 days.
Type and Number of Subjects
For Part 1, approximately 48 healthy adult subjects will be enrolled with approximately 
8 subjects in each of the 6 planned cohorts. In each Part 1 cohort, approximately 
6 subjects will be assigned to active treatment and approximately 2 subjects will be 
assigned to placebo. For Part 2, approximately 30 healthy adult subjects will be enrolled 
with approximately 10 subjects in each of the 3 planned cohorts. For Part 3, 
approximately 10 healthy adult Japanese subjects will be enrolled. In each Part 2 cohort 


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and the Part 3 cohort, approximately 8 subjects will be randomized to receive active 
treatment and approximately 2 subjects will be randomized to receive placebo. Additional 
subjects/cohorts may be enrolled to allow for evaluation of additional dose levels. 
Subjects may only be randomized to one cohort and may only participate in one part of 
the study.
Analysis
Safety endpoints will include monitoring adverse events (AEs), clinical laboratory test 
results (chemistry [including liver function parameters], hematology, and urinalysis), 
vital signs (blood pressure, heart rate, respiratory rate, and body temperature), and 
12-lead electrocardiogram (ECG) readings.
All safety data will be presented in the data listings. Subject demographics, medical 
history, and prior and concomitant medications will be summarized for each dose level 
using descriptive statistics. For continuous variables, these summaries will include 
number of subjects, mean, median, standard deviation, minimum, and maximum. For 
categorical variables, the summaries will include frequencies and corresponding 
percentages. No inferential hypothesis testing will be performed on the safety variables.
Plasma and urine concentrations of GSK3342830 will be analyzed by non-compartmental 
methods to determine the following PK parameters: AUC from time zero to the last 
quantifiable concentration after dosing (AUC[0-t]), AUC extrapolated from time zero to 
infinity (AUC[0-]; estimated for single dose and on Day 1 for repeat dose), AUC over 
the dosing interval (AUC[0-]), total systemic clearance (CL), Cmax, trough 
concentration (C), terminal elimination half-life (t1/2), time to Cmax (Tmax), 
steady-state volume of distribution (Vss), amount excreted in urine (Ae), renal 
clearance (CLr), and urinary excretion ratio relative to dose (Feu[t1-t2]).
Plasma GSK3342830 concentration data will be listed and summarized by time point for 
each dose level using descriptive statistics (number of subjects, mean, median, standard 
deviation, minimum, maximum, and coefficient of variation). Urine GSK3342830 
concentration and volume data will be listed for each collection interval. Mean, median, 
and individual plasma concentration versus time profiles will be presented graphically on 
linear and semi-logarithmic scales.
For dose proportionality, accumulation, time invariance, and assessment of steady-state, 
an estimation approach will be taken, and point estimates and confidence intervals (CIs) 
will be constructed.
2.
INTRODUCTION
GSK3342830 is a novel catechol-cephem antibiotic that is being developed by 
GlaxoSmithKline (GSK) for the treatment of infections caused by Gram-negative 
bacteria including multidrug-resistant isolates. GSK3342830 has demonstrated potent in 
vitro activity against Enterobacteriaceae including resistant strains of Klebsiella 
pneumoniae, Escherichia coli, and non-fermenting bacteria including Pseudomonas 
aeruginosa and Acinetobacter baumannii, as well as efficacy in a range of murine 


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bacterial infection models including septicemia, respiratory tract infection, urinary tract 
infection, and abscess. GSK3342830 has a predicted efficacious dose of 1 to 2 grams 
TID.
2.1.
Study Rationale
This study represents the first administration of GSK3342830 in humans. It will be 
conducted to define the safety, tolerability, and pharmacokinetics of GSK3342830 after 
administration of single and repeat IV doses in healthy adult subjects, and after 
administration of a single IV dose in healthy adult Japanese subjects.
2.2.
Brief Background
The number of infections and deaths caused by drug-resistant strains of 
Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii is 
increasing and the current antibacterial pipeline for novel therapeutics is especially 
ill-equipped to treat these infections. GSK3342830 contains a catechol group on the 
3-position side chain that facilitates entry into the bacterial cell via iron uptake 
mechanisms, and it shows antibacterial activity by inhibiting synthesis of cell walls. As 
such, GSK3342830 has the potential to meet the current and future threat of 
multidrug-resistant Gram-negative infections and to treat patients where no current 
treatment options exist.
GSK3342830 is a β-lactam-containing antibiotic with two differentiating enhancements 
expected to be of clinical significance. First, the multiple-decorated β-lactam core of 
GSK3342830 is demonstrated to significantly improve stability to β-lactamase resistance 
mechanisms. Second, it has been engineered to utilize the bacterial iron transport system 
and enhance penetration into Gram-negative bacteria through the addition of a catechol 
group on the 3-position side chain that acts as a siderophore mimetic. This siderophore 
moiety binds iron outside the bacteria, is subsequently imported through the bacterial iron 
transport system, and thereby enhances delivery of the cephalosporin into the periplasmic 
space of the bacteria where it is available to bind to penicillin binding proteins and inhibit 
cell wall synthesis.
Although the strategy of incorporation of catechol subunits as siderophore mimetics has 
been widely exploited, the early studies identified compounds with preclinical toxicology
issues and recent efforts have investigated compounds with potency and spectrum of 
activity issues. These issues have prevented -lactams with this functionality from 
successfully advancing to market. GSK3342830 incorporates chemical characteristics 
within the molecule that enhance stability against multiple classes of β-lactamases and 
differentiate its activity from commercially available molecules, including ceftazidime 
and the carbapenems.
Based on the results of preclinical studies of GSK3342830 as well as clinical adverse 
events (AEs) previously associated with cephalosporin antibiotics and antibiotics in 
general, the following areas of interest have been identified for safety monitoring in the 
early clinical development program for GSK3342830: potential effects on heart rate, 
blood pressure, and body temperature; potential effects on the respiratory cycle; injection 


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site reactions, potential effects on kidney function, chromaturia and colored stool, and 
hematologic findings; and potential interactions with 5-hydroxytryptamine, 
serotonin (5-HT)-3 receptors. All of these effects showed evidence of reversibility after a 
1-month recovery period and were considered non-adverse, except for the injection site 
reactions, which were considered adverse. In 4-week Good Laboratory Practice (GLP) 
studies, local irritation and inflammation occurred at the two higher doses (1000 and 
2000 mg/kg/day) tested and irritation occurred at the 50 and 100 mg/mL doses in rat and 
monkey, respectively. It is uncertain whether these local effects were due to the 
GSK3342830 itself or to the high osmolalities (≥740 mOsm) of the dosing formulations, 
or both. The results of these studies suggest that limiting the concentrations to no greater 
than 25 mg/mL is expected to reduce or eliminate the irritation potential in clinical 
formulations.
The findings for GSK3342830 in the toxicology and safety pharmacology studies support 
the proposed clinical trial. The only adverse findings were irritation and injury at the 
injection sites that were believed to be due to the high concentrations (50 - 200 mg/mL) 
and/or osmolalities (740 - 2164 mOsm) of the formulations (Stranz, 2002). Use of lower 
concentrations should avoid this issue in the clinic. The other findings in the 4-week GLP 
studies were non-adverse, secondary to the local irritation, or were of slight severity. 
Hemodynamic findings in monkey and respiratory findings in rat were relatively slight, 
have acceptable safety margins at clinically predicted doses and, if required, are able to 
be monitored.
Refer to GSK3342830 Investigator’s Brochure (IB) [GSK Document 
Number 2015N255155_00] for complete information regarding GSK3342830.
Details of the required monitoring including the specific plan to monitor for and manage 
likely AEs or adverse reactions, and individual subject withdrawal/stopping criteria and 
the procedures and responsibilities for modifying or stopping the trial, if necessary, are 
specified in Section 4.6 and Section 5.4, respectively.
3.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Part 1
Primary

To investigate the safety and tolerability of 
GSK3342830 after administration of single IV doses 
in healthy adult subjects

Clinical safety data from adverse events (AEs), 
clinical laboratory tests, vital signs (blood pressure, 
heart rate, temperature, and respiration rate), and 
12-lead electrocardiogram (ECG) readings
Secondary

To determine the pharmacokinetics of GSK3342830 
after administration of single IV doses in healthy 
adult subjects

Plasma and urine concentrations and 
pharmacokinetic (PK) endpoints include AUC(0-t), 
AUC(0-), Cmax, Tmax, CL, Vss, t1/2, Feu(t1-t2), 
Ae, and CLr of GSK3342830, as data permit

To assess dose proportionality of GSK3342830 after 
administration of single IV doses in healthy adult 
subjects

Pharmacokinetic endpoints include AUC(0-t), 
AUC(0-), and Cmax of GSK3342830 after 
administration of single IV doses for the assessment 
of dose proportionality, as data permit


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Objectives
Endpoints
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
and Cmax) of GSK3342830 with safety findings after 
administration of single IV doses in healthy adult 
subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine
Part 2
Primary

To investigate the safety and tolerability of 
GSK3342830 after administration of repeat IV doses 
in healthy adult subjects

Clinical safety data from AEs, clinical laboratory 
tests, vital signs (blood pressure, heart rate, 
temperature, and respiration rate), and 12-lead ECG 
readings
Secondary

To determine the pharmacokinetics of GSK3342830 
after administration of repeat IV doses in healthy 
adult subjects

Plasma and urine concentrations and PK endpoints 
include AUC(0-t) and AUC(0-) on Day 1 only, 
AUC(0-), Cmax, Tmax, CL, Vss, t1/2, C, 
Feu(t1-t2), Ae, and CLr of GSK3342830, as data 
permit

To assess dose proportionality of GSK3342830 after 
administration of repeat IV doses in healthy adult 
subjects

Pharmacokinetic endpoints include AUC(0-) and 
Cmax of GSK3342830 after administration of repeat 
IV doses for the assessment of dose proportionality, 
as data permit

To examine the extent of accumulation, time 
invariance, and achievement of steady-state of 
GSK3342830 after administration of repeat IV doses 
in healthy adult subjects

Observed accumulation ratio (Ro) based on AUC 
and Cmax of GSK3342830 after administration of 
repeat IV doses, as data permit

Steady-state ratio (Rss) of GSK3342830 to assess 
time invariance, as data permit

Trough plasma concentrations at the end of the 
dosing interval (C) to assess the achievement of 
steady-state of GSK3342830 after administration of 
repeat IV doses, as data permit
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
AUC[0-], and Cmax) of GSK3342830 with safety 
findings and evaluate urine discoloration after 
administration of repeat IV doses in healthy adult 
subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine


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Objectives
Endpoints
Part 3
Primary

To investigate the safety and tolerability of 
GSK3342830 after administration of a single IV dose 
in healthy adult Japanese subjects

Clinical safety data from AEs, clinical laboratory 
tests, vital signs (blood pressure, heart rate, 
temperature, and respiration rate), and 12-lead ECG 
readings
Secondary

To determine the pharmacokinetics of GSK3342830 
after administration of a single IV dose in healthy 
adult Japanese subjects

Plasma and urine concentrations and PK endpoints 
include AUC(0-t), AUC(0-), Cmax, Tmax, CL, Vss, 
t1/2, Feu(t1-t2), Ae, and CLr of GSK3342830, as 
data permit
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
and Cmax) of GSK3342830 with safety findings after 
administration of a single IV dose in healthy adult 
Japanese subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine
4.
STUDY DESIGN
4.1.
Overall Design
This is a Phase I, first-time-in-human (FTIH), randomized, double-blind (sponsor 
unblinded), single-center, placebo-controlled, dose-escalation study to determine the 
safety, tolerability, and pharmacokinetic (PK) profile of GSK3342830 after 
administration of single (Part 1) and repeat (Part 2) IV doses in healthy adult subjects, 
and after administration of a single IV dose in healthy adult Japanese subjects (Part 3). 
Part 1 will investigate escalating single IV doses of GSK3342830. Part 2 will investigate 
escalating repeat IV doses of GSK3342830 with repeat dosing for 14 days and multiple 
dosing per day for 13 days as follows: a single IV infusion on Day 1, TID IV infusions on 
Days 2 through 14 (approximately every 8 hours), and a single IV infusion on Day 15. 
Part 3 will investigate a single IV dose of GSK3342830 in Japanese subjects.
For Parts 1 and 2, on Day 1, before study drug administration, subjects who meet the 
criteria for study entry will be assigned to the current dose level cohort and randomized 
to receive GSK3342830 or placebo. For Part 3, on Day 1, before study drug 
administration, subjects who meet the criteria for study entry will be randomized to 
receive GSK3342830 or placebo. All doses of GSK3342830 or placebo are planned to be 
administered as a 1-hour infusion.
This is the first administration of GSK3342830 in humans; therefore, the study design 
may change based on emerging data from each cohort. As preliminary safety, tolerability, 


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and PK results are reviewed internally at GSK and with the clinical study site, the 
following adjustments may be made to the proposed study design:

The proposed dose levels, dosing frequency, infusion duration, and/or infusion 
volume of GSK3342830 may be adjusted during the course of Part 1 and/or Part 2 
of the study.

The duration of repeat dose administration planned for Part 2 may be adjusted.

Cohorts may be added to or removed from either study Part 1 or Part 2 depending 
on findings from previous cohorts.

Pharmacokinetic sampling and/or study assessment schedules may be changed.
This study will aim to explore the safety, tolerability, and pharmacokinetics of a wide 
range of exposures in healthy adult subjects. The exposures observed in animal 
toxicology studies will be used to guide dose escalation. Systemic exposures as measured 
by AUC in the human subjects in this study may exceed the systemic no observed
adverse effect level (NOAEL) animal exposures from 4-week GLP toxicology studies as 
long as the doses administered in the study are safe and well tolerated. This approach is 
based on the following considerations:

In the 4-week GLP studies, there was no dose-limiting organ toxicity in the 
animals (rats and monkeys) with exposures up to 2000 mg/kg/day, the highest 
dose tested.

This study will incorporate a risk mitigation strategy (see Section 4.6.1).

In the 4-week GLP studies, all observed systemic findings in the animals were 
mild to moderate and readily monitored in the clinic.

Bayesian predictive probabilities of area under the concentration-time 
curve (AUC) from time zero to 24 hours after dosing (AUC[0-24]) and maximum 
plasma concentration (Cmax) meeting criteria defined in Section 9.3.2, along with 
safety data will be used to drive decision making for dose escalation. The dose 
will be escalated only if it is supported by the safety, tolerability, and preliminary 
PK results from the preceding dose levels in the study. 

The planned maximum duration of repeat dosing in the study is 14 days.
As the efficacious exposure levels of GSK3342830 are uncertain, this approach provides 
the best chance of success in reaching therapeutic levels and establishing a sufficient 
margin of safety.
Planned Cmax exposures in humans will not exceed the Cmax exposure of the NOAEL 
as determined by the preclinical safety studies.
The repeat dose escalation component (Part 2) of this study is planned to be initiated after 
completion and evaluation of all single dose cohorts up to and including 4000 mg. 
Initiation of Part 2 will be based on the evaluation of preliminary safety, tolerability, and 
PK data from the single dose escalation (Part 1) cohorts once safety at an exposure that 


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exceeds the daily exposure predicted for the Part 2 planned starting dose of 1000 mg TID 
is demonstrated, which is predicted to occur at the 4000 mg single dose.
The single dose administration in Japanese subjects component (Part 3) of this study is 
planned to be conducted in parallel with Part 2. The dose for the Part 3 cohort will be 
based on preliminary safety and tolerability results of doses determined to be safe and 
well tolerated in subjects of non-Japanese heritage after completion of the single 
escalation dose cohorts (Part 1).
The relationship between dose and plasma GSK3342830 exposure will be determined as 
part of dose escalation as described in Section 9.3.2.
4.2.
Treatment Arms and Duration
Part 1: Single Dose Escalation in Healthy Adult Subjects
Part 1 is planned to include 6 dose level cohorts. Additional doses (1 per cohort) may be 
evaluated to further understand the study drug. The planned starting GSK3342830 dose 
in Part 1 is 250 mg administered as a single IV infusion. The dose is planned to increase 
in subsequent cohorts to 500, 1000, 2000, 4000, and 6000 mg IV as shown in Figure 1.
Doses >6000 mg may be administered if the predicted Cmax exposures will not exceed 
the NOAEL.
On Day 1, before study drug administration, subjects will be randomized to treatment 
with either GSK3342830 or placebo in a 3:1 ratio. As a safety precaution, all Part 1 
cohorts will be split into 2 sub-cohorts for sentinel dosing. In each cohort, the first 
2 subjects will receive either GSK3342830 or placebo (1 active/1 placebo). Dosing in the 
remaining 6 subjects (5 active/1 placebo) in that cohort will occur at least 24 hours later 
based on the safety results from the first sub-cohort. Study assessments will be performed 
as indicated in the Time and Events Tables (Section 7.1).
Doses are planned to escalate in a sequential fashion contingent on the safety, tolerability, 
and PK profile of approximately 4 subjects who received active treatment in the previous 
cohort. The evaluated subjects should be followed for a minimum of 48 hours after 
dosing. Dose escalations or reductions will progress with modifications based on the 
preliminary safety, tolerability, and PK data from the preceding cohorts.
Figure 1
Part 1 Single Dose Escalation Study Design Schematic
Note: Figure shows illustration of the planned doses, which may be switched, changed, or cancelled based on 
preliminary safety, tolerability, and pharmacokinetic data from preceding cohorts.


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The AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) 
and Cmax observed in the human subjects in this study at each single dose will be 
compared with the systemic NOAEL animal exposure values in order to determine the 
magnitude of dose escalation.
The dose escalation strategy is based on the following 2 principles:

Bigger dose escalation steps will be allowed at lower systemic exposures as the 
expected risk of AEs at these exposures is low. The magnitude of dose escalation 
steps will be progressively restricted at higher exposures.

Once a certain dose is reached, the magnitude of dose escalation steps will be 
restricted regardless of systemic exposure.
The following algorithm will be used for dose escalation in Part 1:
For each dose level, the human AUC and Cmax values after a single dose will be 
calculated as percentage of the NOAEL animal exposures. The next dose level will then 
be determined as described in Table 1.
Table 1
Single Dose Escalation Scheme
Human exposure at current 
dose as percentage of rat 
NOAEL
Dose escalation to next dose will 
be no higher than
Predicted human exposure at 
next dose as percentage of 
NOAEL will be no higher than1,2
≤2%
10-fold
N/A
>2 and ≤5%
8-fold
30%
>5 and ≤15%
6-fold
60%
>15 and ≤30%
4-fold
90%
>30%
3-fold
N/A
N/A = not applicable, NOAEL = no observed adverse effect level.
NOTES:
1. The relationship between dose and plasma GSK3342830 exposure, and associated variability will be characterized 
by a power model once data are available from 3 dose levels. Prior to that, prediction of the human exposure at the 
next dose will be based on population pharmacokinetic (PK) modeling (if feasible) or on the assumption of 
dose-exposure proportionality. If prior PK results show less than proportional increase in exposure with increasing 
dose, the prediction will be based on the assumption that the fold exposure increase to fold dose increase ratio will 
be the same with the current dose escalation as it was with the previous one. If prior PK results show more than 
proportional increase in exposure with dose, subsequent dose escalations will not be higher than 3-fold.
2. Human exposure may exceed the NOAEL exposures based on acceptable safety and tolerability data. Initial 
exposure targets will be based on NOAEL exposures.
Both conditions (dose escalation to the next dose level and predicted human exposure at 
next dose as percentage of NOAEL) will be met when determining a dose escalation step 
based on Table 1 (i.e., the condition allowing a smaller dose escalation step will limit the 
maximum dose escalation).

Once the dose is ≥500 mg, any further dose escalation will be no higher than 
3-fold irrespective of the observed exposures.

The targeted mean AUC and Cmax in Part 1 are NOAEL exposures for 
AUC(0-24) (2875 hμg/mL) and Cmax (2270 μg/mL). Human exposure may 


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exceed the NOAEL exposures based on acceptable safety and tolerability data. 
Initial exposure targets will be based on NOAEL exposures.
In Part 1, subjects will remain confined to the clinical unit from admission on Day –1 
until all scheduled safety and PK assessments have been completed on Day 3. The 
duration of study (from Screening to the Follow-up visit) for each subject will be up to 
approximately 43 days.
Part 2: Repeat Dose Escalation in Healthy Subjects
Part 2 is planned to include a sequential panel of up to 3 dose level cohorts. Additional 
repeat dose cohorts may be evaluated to further assess the safety, tolerability, and 
pharmacokinetics of GSK3342830. The planned starting GSK3342830 dose in Part 2 is 
1000 mg administered as a single IV infusion on Day 1, TID IV infusions on Days 2, 3, 
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and a single IV infusion on Day 15. The dose is 
planned to increase in subsequent cohorts to 2000 and 4000 mg TID as shown in 
Figure 2. The starting dose and maximum dose may be changed based on clinical safety 
and PK findings in Part 1 or earlier doses in Part 2 and consideration of the AUC(0-24) 
and Cmax exposures based on the NOAEL.
On Day 1, before study drug administration, subjects will be randomized to treatment 
with either GSK3342830 or placebo in a 4:1 ratio. Study assessments will be performed 
as indicated in the Time and Events Tables (Section 7.1).
Doses are planned to escalate in a sequential fashion based on the preliminary safety, 
tolerability, and PK data from Part 1 and at least 14 days of repeat dosing in 
approximately 5 subjects who received active treatment in the previous cohort in Part 2. 
The evaluated subjects should be followed for a minimum of 24 hours after dosing on 
Day 15. The dosing frequency, duration of dosing, and decision to dose in the next dose 
level may be changed based on the safety, tolerability, or PK findings in Part 1 or earlier 
doses in Part 2.
Figure 2
Part 2 Repeat Dose Escalation Study Design Schematic
Note: Figure shows illustration of the planned doses, which may be switched, changed, or cancelled based on 
preliminary safety, tolerability, and pharmacokinetic data from preceding cohorts.


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The following rules will guide dose selection in Part 2:

The starting daily dose in Part 2 will be selected such that its predicted 
AUC(0-24) and Cmax on the last day of dosing (i.e., account for any drug 
accumulation) is no higher than the exposure of a dose that has been found to be 
safe and well tolerated in Part 1.

Subsequent doses in Part 2 may be selected using the previously described criteria 
for the Part 2 starting dose. Alternatively, a dose may be selected even if it does 
not meet these criteria provided it is no more than 4-fold higher than a previous 
dose that has been found to be safe and well tolerated upon repeat dosing in 
Part 2.

The targeted mean AUC(0-24) and Cmax in Part 2 are the NOAEL exposures 
(AUC[0-24] of 2875 hμg/mL and Cmax of 2270 μg/mL). Human exposure may 
exceed the NOAEL animal exposures based on acceptable safety and tolerability 
data. Initial exposure targets will be based on NOAEL exposures.
In Part 2, subjects will remain confined to the clinical unit from admission on Day –1 
until after all scheduled safety assessments have been completed on Day 16. The duration 
of study (from Screening to the Follow-up visit) for each subject will be up to 
approximately 56 days.
Part 3: Single Dose in Healthy Adult Japanese Subjects
Part 3 is planned to include 1 cohort (Cohort J). The planned GSK3342830 dose in Part 3
will be either 250, 500, 1000, 2000, 4000, or 6000 mg based on preliminary safety and 
tolerability results of doses determined to be safe and well tolerated in subjects of 
non-Japanese heritage after completion of the single escalation dose cohorts (Part 1). The 
dose in Part 3 will be administered as a single IV infusion on Day 1.
On Day 1, before study drug administration, subjects will be randomized to treatment 
with either GSK3342830 or placebo in a 4:1 ratio. Study assessments will be performed 
as indicated in the Time and Events Tables (Section 7.1).
In Part 3, subjects will remain confined to the clinical unit from admission on Day –1 
until all scheduled safety and PK assessments have been completed on Day 3. The 
duration of study (from Screening to the Follow-up visit) for each subject will be up to 
approximately 43 days.
4.3.
Type and Number of Subjects
For Part 1, approximately 48 healthy adult subjects will be enrolled with approximately 
8 subjects in each of the 6 planned cohorts. In each Part 1 cohort, approximately 
6 subjects will be assigned to active treatment and approximately 2 subjects will be 
assigned to placebo. For Part 2, approximately 30 healthy adult subjects will be enrolled 
with approximately 10 subjects in each of the 3 planned cohorts. For Part 3, 
approximately 10 healthy adult Japanese subjects will be enrolled. In each Part 2 cohort 
and the Part 3 cohort, approximately 8 subjects will be randomized to receive active 
treatment and approximately 2 subjects will be randomized to receive placebo.


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Additional subjects/cohorts may be enrolled to allow for evaluation of additional dose 
levels.
Decisions regarding replacement of subjects prematurely discontinued from study drug in 
any cohort will be made by the investigator and the GSK medical monitor on a 
case-by-case basis. Subjects may only be randomized to one cohort and may only 
participate in one part of the study.
4.4.
Design Justification
The design of this FTIH study is consistent with global regulatory guidelines for protocol 
design including subject selection, estimation of starting dose, precautions that are 
applied within and between dosing cohorts, dose escalation scheme, risk mitigation, and 
stopping rules [EMEA, 2007 and DHHS, 2005].
Scheduled assessments of subjective symptoms, and objective clinical laboratory tests, 
vital signs, and 12-lead electrocardiograms (ECGs) will be obtained to monitor subject 
safety. In order to further mitigate the risks to subjects who participate in this study, 
subjects will be specifically monitored for findings observed in animal species with 
GSK3342830, findings identified with similar catechol cephalosporin compounds, as 
well as known risks common to cephalosporin antibiotics. These potential risks and their 
mitigations are presented in Section 4.6.1.
Part 2 of this study is planned to include 14 days of repeat dosing based on the following 
2 factors: 

An objective of this study is to establish the safety and tolerability of the 
medication for a dosing duration that will be clinically relevant in future efficacy 
studies of acute bacterial infection. Most acute bacterial infections for which 
GSK3342830 may be developed will need to permit up to 14 days of treatment. 

Non-adverse hematologic changes were observed in the 4-week preclinical safety 
studies after 14 days of dosing. In this FTIH study, 14 days of dosing will provide 
additional reassurance of hematologic safety specifically for future subjects with 
acute bacterial infection requiring up to 14 days of therapy.
4.5.
Dose Justification
Dose selection of GSK3342830 for this FTIH study was based on NOAEL data from 
animal toxicology studies, predicted pharmacokinetics for humans using PK data from 
preclinical species, and a targeted therapeutic exposure based on efficacy data from a rat 
pneumonia model. GSK3342830 is a catechol cephalosporin antibiotic that utilizes the 
bacterial iron transport system to facilitate transport into bacteria and disrupts the 
synthesis of the peptidoglycan layer of bacterial cell walls. This is not a human target; 
therefore, the minimum anticipated biological effect level in humans for GSK3342830 
was not determined.


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As described in the following sub-sections,

While the maximum recommended starting dose is 1935 mg, the proposed 
starting dose is 250 mg, which is predicted to have AUC(0-t) and Cmax values 
45-fold and 83-fold lower than the NOAEL values, respectively.

The predicted dose to achieve the therapeutic exposure target ranges from 500 to 
2000 mg, which is predicted to have AUC(0-t) values 5.6- to 22-fold lower and 
Cmax values 10- to 42-fold lower than the NOAEL values after administration of 
single doses, and AUC(0-24) values 1.9- to 7.5-fold lower and Cmax values 
10- to 42-fold lower than the NOAEL values after administration of repeat doses.

The anticipated maximum 6000 mg single dose will provide an AUC exposure of 
1933 hμg/mL (predicted AUC encompassing 95% of the simulated population) 
with a safety margin of 1.48-fold and a Cmax of 849 μg/mL (predicted Cmax 
encompassing 95% of the simulated population) with a safety margin of 
2.67-fold. 

The anticipated maximum 4000 mg TID dose will provide an AUC exposure of 
3846 hμg/mL (predicted AUC[0-24] encompassing 95% of the simulated 
population) that may exceed the systemic NOAEL AUC(0-24) exposure of 
2875 hμg/mL (safety margin of 0.93-fold) and a Cmax of 569 μg/mL (predicted 
Cmax encompassing 95% of the simulated population) with a safety margin of 
3.98-fold.

Based on a concentration limitation of 25 mg/mL, IV solution volumes between 
100 to 250 mL would support single doses of 2500 to 6000 mg (IV formulation 
work is ongoing. Formulation instructions will be available in the Pharmacy 
Manual before the start of the study).

Importantly, dose escalation decisions will be based on observed exposure, safety, 
and tolerability data for GSK3342830 from the previous dose level.
Data Used for Dose Justification
No observed adverse effect level (NOAEL)
The primary AEs in the 4-week GLP toxicology studies were those at the infusion site.
The NOAEL dose in both the rat and monkey for these local infusion site effects (ulcer, 
perivascular/vascular inflammation, thrombus) was 500 mg/kg; the formulation 
concentration at this dose was 25 mg/mL for rats and 50 mg/mL for monkeys. These 
local effects were considered secondary to the high concentrations and resultant high 
osmolalities of the formulations at doses higher than 500 mg/kg/day. The concentration 
of the clinical formulation will be limited to no greater than 25 mg/mL (the 
concentrations at the NOAEL dose for rats), which should preclude these local irritation 
effects. Based on a concentration limitation of 25 mg/mL, IV solution volumes between 
100 to 250 mL would support single doses of 2500 to 6000 mg (IV formulation work is 
ongoing. Formulation instructions will be available in the Pharmacy Manual before the 
start of the study) as shown in Table 2.


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Table 2
Single IV Infusion Doses, Concentrations, and Osmolality1
Dose (mg)
Concentration (mg/mL)
for a 100 mL infusion
Concentration (mg/mL)
for a 250 mL infusion
Final osmolality2
(mOsm/kg)
250
2.5
302
500
5
314
1000
10
339
2000
20
388
4000
16
388
6000
24
407
NOTES:
1. Theoretically calculated osmolality values.
2. Based on 100 mL (250 to 2000 mg doses) and 250 mL (4000 and 6000 mg doses) infusion volumes.
Given that the infusion site reactions can be addressed by formulation, the 2000 mg/kg 
dose and exposures were selected to define the exposure limits. Slight decreases (10 to 
20%) in red blood cell count, hemoglobin, and hematocrit, accompanied by an increase in 
reticulocytes, as well as other clinical pathology changes considered non-adverse were 
observed at 2000 mg/kg/day in male and female monkeys; these were considered 
secondary to the severe and ongoing inflammation induced by the infusion site effects. 
The hematological findings showed evidence of reversibility by week 4 of dose 
administration and showed recovery by 4 weeks post dosing. In summary, the 
hematologic findings were mild, reversible, and able to be monitored in the clinic. The 
NOAELs of 2000 mg/kg in the rat and monkey with NOAEL exposures of 
2875 hμg/mL (rat) and 2270 μg/mL (monkey) for AUC(0-t) and Cmax, respectively, 
were selected to define the exposure limits.
Scaling to human exposure
GSK3342830 is structurally similar to another catechol cephalosporin compound with 
generally comparable in vivo PK profiles in preclinical species. Scaling using the dedrick 
monkey method was proven to accurately predict the human clearance and volume of 
distribution for the former compound (observed values within 20% of predicted values). 
Thus, the dedrick method, along with a single-point allometry method, was selected to 
predict human clearance and volume of distribution for GSK3342830. Both methods 
showed similar predicted human clearance values of approximately 0.82 mL/min/kg 
(single-point allometry) and 0.93 mL/min/kg (dedrick monkey), while predicted volume 
of distribution was 0.121 L/kg (dedrick monkey).
In vivo efficacy models
A major objective of this study is to establish safety across a clinically relevant dose 
range to enable a future Phase II efficacy study. In vivo efficacy models predict target 
therapeutic AUC(0-t) exposures of 112 to 467 hμg/mL after administration of single 
doses and AUC(0-24) values of 336 to 1401 hμg/mL after TID dose administration. 
Scaling of animal exposure to humans predicts GSK3342830 will achieve these 
exposures at doses between 500 to 2000 mg. Additional details on the in vivo efficacy 
calculations and animal to human scaling is available in Appendix 9.


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Maximum Recommended Starting Dose
The systemic NOAEL dose level of 2000 mg/kg in the rat (most sensitive species) was 
converted to the human equivalent dose based on body surface area using the US Food 
and Drug Administration (FDA) Guidance for estimation of the maximum safe starting 
dose [DHHS, 2005]. After applying an uncertainty safety factor of 10 (the guideline 
default) to the human equivalent dose, the maximum recommended starting dose is 
1935 mg.

The proposed starting dose is 250 mg which is predicted to have AUC(0-t) and 
Cmax values 45-fold and 83-fold lower than the NOAEL values, respectively.

Assuming an IV solution volume between 100 to 250 mL, the drug concentration 
of 1 to 2.5 mg/mL is well below the lower concentration limitation of 25 mg/mL.
Dose Predicted to Achieve the Therapeutic Exposure Target
Doses of 500 to 2000 mg are predicted to achieve the target therapeutic exposure (total 
AUC[0-t] values of 112 to 467 hμg/mL after administration of single doses and 
AUC[0-24] values of 336 to 1401 hμg/mL after administration of repeat TID doses). 
Comparisons of the therapeutic doses with the NOAELs from the 2000 mg/kg exposures 
suggest the following safety margins:

AUC(0-t) values 5.6- to 22-fold lower and Cmax values 10- to 42-fold lower than 
the NOAEL values after administration of single doses.

AUC(0-24) values 1.9- to 7.5-fold lower and Cmax values 10- to 42-fold lower 
than the NOAEL values after administration of repeat doses.
Predicted Maximum Dose Exposure Margins: Single Dose Escalation Cohorts
Based on the systemic NOAEL AUC(0-24) exposure of 2875 hμg/mL and Cmax 
exposure of 2270 μg/mL, the anticipated maximum 6000 mg single dose will provide:

An AUC exposure of 1933 hμg/mL (predicted AUC encompassing 95% of the 
simulated population [Table 8, Appendix 9]) with a safety margin of 1.48-fold. 

A Cmax of 849 μg/mL (predicted Cmax encompassing 95% of the simulated 
population [Table 8, Appendix 9]) with a safety margin of 2.67-fold.


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Predicted Maximum Dose Exposure Margins: Repeat Dose Escalation Cohorts
Given the evolving PK and pharmacodynamic data currently being generated through 
in vivo preclinical models, doses above 2000 mg TID may be required to adequately treat 
certain challenging bacteria in the clinic. With this in mind, the tolerability of repeat 
doses up to 4000 mg TID will be tested. Based on the systemic NOAEL AUC(0-24) 
exposure of 2875 hμg/mL and Cmax exposure of 2270 μg/mL, the anticipated 4000 mg 
TID dose will provide:

An AUC exposure of 3846 hμg/mL (predicted AUC[0-24] encompassing 95% of 
the simulated population [Table 9, Appendix 9]) that may exceed the systemic 
NOAEL AUC(0-24) exposure of 2875 hμg/mL. 
o
As described previously, dose escalation would be predicated on safety and 
PK data observed at the preceding dose (2000 mg TID) administered for 
14 days with at least 24 hours post-dose observation.

A Cmax of 569 μg/mL (predicted Cmax encompassing 95% of the simulated 
population [Table 9, Appendix 9]) with a safety margin of 3.98-fold.
4.6.
Benefit:Risk Assessment
Summaries of findings from non-clinical studies conducted with GSK3342830 can be 
found in the IB [GSK Document Number 2015N255155_00].
Section 4.6.1 outlines the risk assessment and mitigation strategy for this study.


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4.6.1.
Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (GSK3342830) 
Death in preliminary monkey 
cardiovascular study
Preliminary monkey cardiovascular study:
No effect on corrected QT (QTc)
1 death
1/3 animals, single dose escalation design with 1-week 
washout; 4th dose at 1000 mg/kg
Animal died at 2.5 hours post-dose
No clear etiology
No similar findings in definitive cardiovascular study
26 animals now dosed at and above 1000 mg/kg and at longer 
durations (4 weeks) without major adverse findings
Conduct study in inpatient clinical unit for first time in 
human (FTIH)
Normal vital signs on study entry
Frequent vital signs over the dosing interval
QTc <450 msec
12-lead electrocardiograms (ECGs) across the initial exposure
Telemetry monitoring for Parts 1 and 3 and initial doses in 
Part 2
Blood pressure (BP), heart rate, and 
body temperature changes in 
monkey cardiovascular study
Blood pressure:
Maximum excursion of 29 mm Hg at 1000 mg/kg
Heart rate:
Maximum excursion of 16 beats per minute at 1000 mg/kg
Body temperature:
0.5C decrease at 1000 mg/kg
Conduct study in inpatient clinical unit for FTIH
Starting dose free Cmax margin: approximately 26×
Cmax at highest planned dose (6000 mg) similar to (1.1×) 
Cmax of the no observed effect level (NOEL) dose (250 mg/kg)
Normal vital signs on study entry
Frequent vital signs over the dosing interval
12-lead ECGs across the exposures
Telemetry monitoring for Parts 1 and 3 and initial doses in 
Part 2
Blood pressure and heart rate stopping criteria:
Systolic BP >160 mm Hg for >1 hour
Diastolic BP >100 mm Hg for >1 hour
Heart rate >120 beats per minute for >1 hour


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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Renal findings
Kidney: hyaline droplets in proximal tubules, weight increase 
in both species
Hyaline droplets associates with absorption and secretion of the 
cephem antibiotics in lysosome
No degenerative changes
Probably mixture of drug and protein (stimulation of lysosomal 
turnover)
Accompanied by increases in urinary N-acetyl--D-
glucosaminidase (exploratory biomarker of lysosomal enzyme) 
at all doses and slight change in urinary albumin at 2000 mg/kg 
(relevance unclear)
Inclusion/Exclusion
Healthy subjects
Serum creatinine greater than the upper limit of normal 
(ULN)
Estimated glomerular filtration rate (eGFR) 
<90 mL/min/1.73 m2 as calculated by the Chronic Kidney 
Disease Epidemiology Collaboration formula
Albumin to creatinine ratio (ACR) 0.03 mg/mg
Urinalysis negative for blood/protein
Monitor:
Serum blood urea nitrogen, creatinine, eGFR, electrolytes, 
urinalysis
ACR during the study
Criteria to pause Part 1 progression or interrupt Part 2 
dosing
Creatinine change >0.3 mg/dL without alternative cause
New blood in urinalysis confirmed by microscopy without 
alternative cause
ACR 0.03 mg/mg
Injection site reactions
Local irritation
Gross: discoloration, hardening, wound, thrombosis
Histology: ulcer, perivascular/vascular inflammation, thrombus 
(1000/2000 mg/kg/day; rats and monkeys)
Considered due to high osmolality of the dosing formulations
Reduced osmolality preparation
Monitor injection site including proximal limb for vascular 
change


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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Hematologic findings
Red Blood Cell (RBC) related changes
Decreases in RBC count, hemoglobin (Hgb), hematocrit (Hct; 
2000 mg/kg/day in males and females)
Peaked at Week 2 (–10% to –20% versus pre-dosing values)
Accompanied by increase in reticulocytes
RBC findings considered secondary to:
Ongoing inflammation from infusion site reactions (above)
Contribution from high osmolality infusion
Hemolysis, iron depletion (catechol) or other direct mechanism 
of drug not considered present
Evidence of recovery by end of follow-up
Other hematologic findings

Findings considered secondary to ongoing inflammation at 
the infusion site

Increases in neutrophils and concomitant decreases in 
lymphocyte %

Decreased fibrinogen

Prolongation of activated partial thromboplastin time

Decreases in albumin and albumin/globulin ratio

Increase in total protein (due to globulin increase)

development of iliac lymph node germinal center

Findings were reversible in follow-up
Reduced osmolality infusions
Normal white blood cell (WBC) count, Hgb, Hct, and platelets 
on study entry
Follow for signs or symptoms of anemia
Follow regular clinical labs (WBC, Hgb, Hct, reticulocyte count, 
and platelets)
Stopping criteria
Hemoglobin 9.9 g/dL (99 g/L)
White blood cell 1999/mm3 (1.910 × 109/L)
Platelets 99.999 × 109/L
Increased tidal volume in rat 
respiratory study
Only at high dose (2000 mg/kg)
22.9% at 30 minutes after completion of infusion
Changes considered to be minimal
Magnitude within the range of physiological changes
No changes were seen in minute volume
Not statistically significant
May reflect high individual variability
Conduct study in inpatient Phase I clinical unit
Frequent vital sign capture during study
6000 mg maximum dose maintains 2.1× margin relative to the 
NOEL of 1000 mg/kg


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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Serotonin (5-HT)-3 in vitro binding 
assay
“Moderately” positive with 39% effect at 100 mmol (78 g/mL)
High dose Cmax will reach similar concentration
No clear in vivo correlation from toxicology studies
Possible BP effect in monkey cardiovascular study
Poor central nervous system penetration (approximately 3% 
blood)
Precautions c/w those indicated to mitigate the BP effect seen 
in monkey cardiovascular study
Enroll healthy subjects not on medications to avoid additive 
arrythmogenic potential
Other 
Neurologic findings (seizures)
Known risk (seizures) for some -lactams and cephalosporins
Seen pre-clinically with lead compound
No adverse findings to 2000 mg/kg/ day × 4 weeks in rats or 
monkeys
Central nervous system administration study in rats negative
Specifically assess for negative history of seizures in past 
medical history at screening
Close monitoring during infusion in an acute care setting
Rash/Dermatologic toxicity
Rash is a common adverse event (AE) of -lactam antibiotics. 
Range of manifestations and severity from mild morbilliform drug 
eruption to hives, Erythema multiforme (EM), Stevens-Johnson 
syndrome (SJS) and toxic epidermal necrolysis (TEN) in rare 
cases 
Exclude individuals with history of rash to penicillins or 
cephalosporins
Exclude individuals with history of EM/SJS/TEN to any 
medication
Close monitoring
Discontinuation criteria
Any rash of Grade 3 or greater severity
Any rash characterized by:
Hives
Concomitant fever or other symptoms suggesting 
systemic manifestations
Blistering
Ocular or genital involvement
Access to standard interventions (antihistamines, steroids if 
indicated, intensive care unit/burn unit care in worst case)
Anaphylaxis/hypersensitivity
Common to all -lactam antibiotics
Approximately 10% cross reaction between cephalosporins and 
penicillins
Guinea pig immunotoxicity model negative

Conduct study in inpatient Phase I clinical unit

“Crash” cart availability

Exclude subjects with history of penicillin allergy


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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Clostridium difficile (C. difficile) 
colitis
A general risk with all antibiotics
Cephalosporins generally considered moderate to high risk 
presumably due to broad effects on gut microbiome
No anaerobic activity may reduce propensity for C. difficile
overgrowth

Exclude subjects with a history of C. difficile colitis

Site chosen with experience in antibiotics studies

Importance of infection control procedures will be raised with 
the site
Liver findings
No adverse findings to 2000 mg/kg/day × 4 weeks in rats or 
monkeys
Increase in liver weight (monkey)
Mechanisms unclear
No corresponding alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) or histopathological change

Normal liver biomarkers on study entry with negative history 
of liver disease in past medical history

Frequent assessment of symptoms suggesting liver injury 
(nausea, vomiting, abdominal pain, etc.)

Frequent assessment of liver injury biomarkers (ALT, AST, 
total bilirubin, direct bilirubin, alkaline phosphatase)

Defined GSK liver stopping criteria
Catechol side chain binds free iron
Catechol side chain binds free iron (part of the monoamine 
oxidase)

Normal Hgb and Hct on study entry

Monitor Hgb and Hct with stopping criteria as above

Monitor iron binding studies (serum iron, ferritin, total iron 
binding capacity, reticulocytes)
Candidiasis (vaginal, oral thrush)
A common AE of exposure to broad spectrum antibiotics

Monitor clinically

Discontinue GSK 830 may be needed for treatment

Treat with topical antifungal medication as needed


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4.6.2.
Benefit Assessment
This Phase I study is being conducted in healthy subjects; therefore, there is no direct 
clinical benefit to study subjects. Participation in this study may contribute to the process 
of developing new therapies in an area of unmet need.
4.6.3.
Overall Benefit:Risk Conclusion
The risk of AEs is minimized for the population being investigated in the proposed study 
by careful selection of subjects for the study and the extent of safety monitoring 
incorporated into the study.
5.
SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, AEs, and other 
pertinent information on the GSK investigational product or other study treatment that 
may impact subject eligibility is provided in the IB [GSK Document 
Number 2015N255155_00].
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability, or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
A single repeat for clinical laboratory tests that meet the exclusion criteria may be 
conducted to confirm the value before the subject is excluded from the study.
5.1.
Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
AGE
1. Between 18 and 55 years of age, inclusive, at the time of signing the informed 
consent.
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 
2. Healthy as determined by a responsible and experienced physician, based on a 
medical evaluation including medical history, physical examination, laboratory tests 
and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter 
outside the reference range for the population being studied may be included only if 
the investigator feels and documents that the finding is unlikely to introduce 
additional risk factors and will not interfere with the study procedures.
3. Additional inclusion criteria for Japanese subjects (Part 3 only):

The subject is a non-naturalized Japanese citizen and holds a Japanese passport.

The subject has 2 Japanese parents and 4 Japanese grandparents who are 
non-naturalized Japanese citizens, as confirmed by interview.


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
The subject has been living outside of Japan for less than 10 years, as confirmed 
by interview.
WEIGHT
4. Body weight >50 kg (110 lb) for men and >40 kg (99 lb) for women and body mass 
index within the range of 18.5 to 30 kg/m2, inclusive.
SEX
5. Male or Female
Males:
Male subjects with female partners of child-bearing potential must agree to use one of 
the highly effective contraception requirements listed in Appendix 8 from the time of 
first dose of study drug until completion of the Follow-up visit.
Females:
A female subject is eligible to participate if she is not pregnant (as confirmed by a 
negative serum human chorionic gonadotropin [hCG] test), not lactating, and 
considered to be of non-reproductive potential.
Non-reproductive potential is defined as:

Pre-menopausal females with one of the following:

Documented tubal ligation

Documented hysteroscopic tubal occlusion procedure with follow-up 
confirmation of bilateral tubal occlusion 

Hysterectomy

Documented bilateral oophorectomy

Postmenopausal defined as 12 months of spontaneous amenorrhea and in 
questionable cases a blood sample with simultaneous follicle-stimulating hormone 
(FSH) and estradiol levels consistent with menopause (refer to laboratory 
reference ranges for confirmatory levels).

Females on hormone replacement therapy (HRT) and whose menopausal status is 
in doubt will be required to use one of the highly effective contraception methods 
listed in Appendix 8 if they wish to continue their HRT during the study. 
Otherwise, they must discontinue HRT to allow confirmation of post-menopausal 
status before study enrolment.
INFORMED CONSENT
6. Capable of giving signed informed consent as described in Section 10.2, which 
includes compliance with the requirements and restrictions listed in the consent form 
and in this protocol.


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5.2.
Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER 
FUNCTION AND QTc INTERVAL) 
1. Alanine aminotransferase (ALT) not within normal limits; bilirubin >1.5× upper limit 
of normal (ULN; isolated bilirubin >1.5× ULN is acceptable if bilirubin is 
fractionated and direct bilirubin is <35%).
2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones).
3. Corrected QT (QTc) >450 msec.
4. Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, 
metabolic, renal, hepatic, or gastrointestinal condition or history of such a condition 
that, in the opinion of the investigator, may place the subject at an unacceptable risk 
as a participant in this trial or may interfere with the absorption, distribution, 
metabolism, or excretion of drugs.
5. Use of a systemic antibiotic within 30 days of screening.
6. Ongoing febrile illness.
7. Confirmed history of Clostridium difficile diarrhea (see Appendix 10: Clostridium 
difficile Testing Procedure and Algorithm).
CONCOMITANT MEDICATIONS
8. 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) 
before the first dose of study treatment, unless in the opinion of the Investigator and 
the GSK medical monitor, the medication will not interfere with the study procedures 
or compromise subject safety.
RELEVANT HABITS
9. History of regular alcohol consumption within 6 months of screening defined as an 
average weekly intake of >21 units (or an average daily intake of >3 units) for males 
or an average weekly intake of >14 units (or an average daily intake >2 units) for 
females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 
30 mL of spirits, or 100 mL of wine.
10. Urinary cotinine level indicative of smoking or history or regular use of tobacco- or 
nicotine-containing products within 3 months before screening.


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CONTRAINDICATIONS 
11. History of hypersensitivity attributed to -lactam antibiotics (including cephalosporin,
carbapenem, or penicillin antibiotics) or other drugs, a history of multiple antibiotic 
intolerances, or a history of serious adverse drug reactions.
12. Sensitivityto poison ivy or other catechol-related hypersensitivity (e.g., mango 
allergy).
13. History of sensitivity to heparin or heparin-induced thrombocytopenia.
14. History of latex allergy.
15. History of sensitivity to any of the study treatments or components thereof, or a 
history of drug or other allergy that, in the opinion of the investigator or medical 
monitor, contraindicates participation in this study.
DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
16. Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at 
screening or within 3 months before the first dosing day in this study. 
17. Serum creatinine >ULN.
18. Glomerular filtration rate <90 mL/min/1.73m2 as calculated by the Chronic Kidney 
Disease Epidemiology Collaboration formula (See Appendix 11).
19. Albumin to creatinine ratio (ACR) >0.03 mg/mg. In the event of an ACR above this 
threshold, eligibility may be confirmed by a second measurement.
20. Urinalysis positive for blood without other cause identified.
21. A positive pre-study drug or alcohol screen.
22. A positive test for human immunodeficiency virus antibody at or before screening.
23. Where participation in the study would result in donation of blood or blood products 
in excess of 500 mL within a 56-day period.
24. The subject has participated in a clinical trial and has received an investigational 
product within the following time period before the first dosing day in this study: 
30 days, 5 half-lives or twice the duration of the biological effect of the 
investigational product (whichever is longer).
25. Exposure to more than 4 new chemical entities within 12 months before the first 
dosing day in this study.
26. Exclusion criteria for screening and baseline 12-lead ECG (a single repeat is allowed 
for eligibility determination):
Males
Females
Heart rate
<40 and >100 beats per minute
<50 and >100 beats per minute
PR interval
<120 and >220 msec
QRS duration
<70 and >120 msec
QTcB or QTcF interval
>450 msec
QTcB = corrected QT interval using Bazett’s formula, QTcF = corrected QT interval using Fridericia’s formula.
a) Evidence of previous myocardial infarction (does not include ST segment changes 
associated with repolarization).
b) Subject has bundle branch block.
c) Any conduction abnormality (including but not specific to left or right complete 
bundle branch block, AV block [2nd degree or higher], Wolf-Parkinson-White 


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syndrome), sinus pauses more than 3 seconds, non-sustained or sustained 
ventricular tachycardia (3 consecutive ventricular ectopic beats), or any 
significant arrhythmia that, in the opinion of the investigator and the GSK 
medical monitor, will interfere with the safety of the individual subject.
5.3.
Screening/Baseline/Run-in Failures
Screen failures are defined as subjects who consent to participate in the clinical trial but 
are never subsequently randomized. In order to ensure transparent reporting of screen 
failure subjects, meet the Consolidated Standards of Reporting Trials publishing 
requirements, and respond to queries from Regulatory authorities, a minimal set of screen 
failure information is required including demography, screen failure details, eligibility 
criteria, and serious adverse events (SAEs; see Section 7.3.1.4).
5.4.
Withdrawal/Stopping Criteria
The following actions must be taken in relation to a subject who fails to attend the 
clinical unit for a required study visit:

The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible.

The site must counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study.

In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where 
possible, 3 telephone calls and if necessary a certified letter to the subject’s last 
known mailing address or local equivalent methods). These contact attempts 
should be documented in the subject’s medical record.

Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “lost to 
follow up”.
A subject may withdraw from study treatment at any time at his/her own request, or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, or 
administrative reasons. If a subject withdraws from the study, he/she may request 
destruction of any samples taken, and the investigator must document this in the site 
study records.
This protocol defines several clinical laboratory values, 12-lead ECG values, vital sign 
values, and additional safety criteria that, if observed and confirmed, mandate cessation 
of drug dosing and further evaluations. Any laboratory result that meets the stopping 
criteria should be repeated once to confirm the value before the subject is withdrawn 
from the study.


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5.4.1.
Liver Chemistry Stopping Criteria
Liver chemistry stopping and increased monitoring criteria have been designed to ensure 
subject safety and evaluate liver event etiology in alignment with the FDA guidance, 
“Drug-Induced Liver Injury: Premarketing Clinical Evaluation,” [DHHS, 2009].
Study treatment will be discontinued for a subject who meets the following criterion:

ALT 3 × ULN (Appendix 2)
Refer to Appendix 3, Liver Safety Required Actions and Follow-up Assessments, for 
details of the required assessments if a subject meets the above criterion.
5.4.1.1.
Study Treatment Restart or Rechallenge
Study treatment restart or rechallenge after liver chemistry stopping criteria are met by 
any subject participating in this study is not allowed.
5.4.2.
Hematological Stopping Criteria
Study treatment will be discontinued for a subject who meets any of the following 
criteria:

Hemoglobin ≤9.9 g/dL (99 g/L)

White blood cells ≤1999/mm3 (1.910 × 109/L)

Platelets ≤99.999 × 109/L
5.4.3.
Renal Stopping Criteria
Study treatment will be discontinued for a subject who meets any of the following 
criteria:

Persistent (confirmed on recheck) elevation of serum creatinine (>0.3 mg/dL) 
without an alternative cause identified

Albumin to creatinine ratio 0.03 mg/mg

New blood in urinalysis confirmed by microscopy without an alternative cause 
identified
5.4.4.
QTc Stopping Criteria
The same QT correction formula must be used for each individual subject to determine 
eligibility for and discontinuation from the study. This formula may not be changed or 
substituted once the subject has been enrolled.

For example, if a subject is eligible for the protocol based on corrected QT interval 
using Bazett’s formula (QTcB), then QTcB must be used for discontinuation of this 
individual subject as well.


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Once the QT correction formula has been chosen for a subject’s eligibility, the same 
formula must continue to be used for that subject for all QTc data being collected for 
data analysis. Safety ECGs and other non-protocol specified ECGs are an exception.
The QTc should be based on single or averaged QTc values of triplicate ECGs obtained 
over a brief (e.g., 5 to 10 minute) recording period.
Study treatment will be discontinued for a subject who meets either of the following 
criteria:

QTc >500 msec OR uncorrected QT >600 msec

Change from baseline QTc of >60 msec
Withdrawal of subjects will be based on an average QTc value of triplicate ECGs. If an 
ECG demonstrates a prolonged QT interval, then 2 more ECGs will be obtained over a 
brief period of time (e.g., 5 to 10 minute) and then the averaged QTc values of the 
3 ECGs will be used to determine whether the subject should be discontinued from the 
study.
5.4.5.
Vital Signs Stopping Criteria
Study treatment will be discontinued for a subject who meets any of the following 
criteria:

Systolic blood pressure (BP) >160 mm Hg for >1 hour

Diastolic BP >100 mm Hg for >1 hour

Heart rate >120 beats per minute for >1 hour
Vital signs should be taken with the subject in a semi-supine position, having rested in 
this position for at least 5 minutes. Repeat measurements should be taken within 
5 minutes with the subject in the same physical position.
5.4.6.
Other Safety Dose Adjustment/Stopping Criteria
For an individual study participant, additional stopping criteria include, but are not 
limited to: 

Severe signs or symptoms, or significant changes in any of the safety assessments, 
that put the safety of the individual at risk (e.g., ECG, vital signs, laboratory tests, 
etc.), as judged by the investigator in consultation with the medical monitor if 
necessary


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5.4.7.
Additional Safety Stopping Criteria
Individual subjects, dosed with GSK3342830 who have experienced the following should 
be considered for potential discontinuation in consultation with the GSK medical 
monitor:

Any Grade 4 AE

Grade 3 gastrointestinal AE (see Appendix 6)
o
If a subject has 3 or more unformed stools in a 24-hour time frame, see 
Appendix 10 to determine if samples should be collected for Clostridium 
difficile testing.

Grade 3 renal or urinalysis finding (see Appendix 6)

Severe hypersensitivity

Anaphylaxis (see Appendix 7)

Subjects with a systolic BP of <90 mm Hg or a change in systolic BP from 
baseline of 30 mm Hg with symptoms. Vital signs should be taken with the 
subject in a semi-supine position, having rested in this position for at least 
5 minutes and findings are confirmed upon repeat measurements taken within 
5 minutes with the subject in the same physical position.
Data will be reviewed by the investigator and sponsor for consideration of potential study 
stopping if:

Two (2) or more subjects, within a dose level, receiving GSK3342830 experience 
a Grade 3 renal or urinary AE that is deemed possibly or probably related to study 
drug by the investigator.

Two (2) or more subjects, within a dose level, receiving GSK3342830 experience
Grade 3 hypersensitivity related AE that is deemed possibly or probably related to 
study drug by the investigator.

Two (2) or more subjects, within a dose level, receiving GSK3342830 experience 
a Grade 3 AE of rash that is deemed possibly or probably related to study drug by 
the investigator.

Two (2) or more subjects, within a dose level, receiving GSK3342830 experience 
a Grade 3 vital sign (heart rate or BP) abnormality that is considered an AE and is 
deemed possibly or probably related to study drug by the investigator. Vital signs 
should be taken with the subject in a semi-supine position, having rested in this 
position for at least 5 minutes and findings are confirmed upon repeat 
measurements taken within 5 minutes with the subject in the same physical 
position.

One (1) or more subjects receiving GSK3342830 experience anaphylaxis that is 
deemed possibly or probably related to study drug by the investigator.


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The grading for AEs is based on the US National Institute of Allergy and Infectious 
Diseases Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table 
(see Appendix 6).
5.4.8.
Pharmacokinetic Dose Adjustment/Stopping Criteria
The exposures observed in animal toxicology studies will be used to guide dose 
escalation. Systemic exposures in the human subjects in this study may exceed the 
systemic NOAEL animal exposures from 4-week GLP toxicology studies as long as the 
doses administered in the study are safe and well tolerated. 
For Part 1, the need to dose escalate will be evaluated if no meaningful increase in 
exposure is observed with an increase in dose (i.e., a plateau in exposures is reached).
5.5.
Subject and Study Completion
A completed subject is one who has completed all phases of the study including the 
Follow-up visit.
The end of the study is defined as the last subject’s last visit.
6.
STUDY TREATMENT
6.1.
Investigational Product and Other Study Treatment
The term ‘study treatment’ is used throughout the protocol to describe any combination 
of products received by the subject as per the protocol design. Study treatment may 
therefore refer to the individual study treatments or the combination of those study 
treatments.
Study Treatment
Product name:
GSK3342830
Placebo
Formulation description:
A lyophilized formulation 
aseptically manufactured as a 
pyrogen-free, white to yellowish 
brown powder containing 
1000 mg of GSK3342830A (as 
free base) per vial
A clear and colorless solution 
containing 0.9% sodium
chloride
Dosage form:
Lyophile
IV solution
Unit dose 
strengths/Dosage levels:
Unit dose strength:1000 mg/vial 
as free base equivalent
Dosage levels:
Part 1: 250, 500, 1000, 2000, 
4000, and 6000 mg
Part 2: 1000, 2000, and 
4000 mg
Part 3: 250, 500, 1000, 2000, 
4000, or 6000 mg
Not applicable
Route of Administration:
IV infusion over 1 hour
IV infusion over 1 hour


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Study Treatment
Product name:
GSK3342830
Placebo
Dosing instructions:
Parts 1 and 3: Single IV 
infusion.
Part 2: Single IV infusion on 
Day 1, TID IV infusions 
(approximately every 8 hours) 
on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 
11, 12, 13, and 14, and a single 
IV infusion on Day 15. 
Instructions for the preparation 
of the IV drug are included in 
the Pharmacy Manual.
Parts 1 and 3: Single IV 
infusion.
Part 2: Single IV infusion on 
Day 1, TID IV infusions 
(approximately every 8 hours) 
on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 
11, 12, 13, and 14, and a single 
IV infusion on Day 15. 
Instructions for the preparation 
of the IV drug are included in 
the Pharmacy Manual.
Physical description:
The lyophilized powder cake 
has a white to yellowish brown 
color.
The reconstituted solution is a 
clear, colorless to yellow or 
brownish yellow liquid, free from 
visible particulate matter.
A clear colorless solution
6.2.
Treatment Assignment
Eligible subjects will be assigned to study treatment in accordance with the 
randomization schedule generated by PPD, before the start of the study, using validated 
internal software. Within each cohort, subjects will be randomly assigned to receive 
either GSK3342830 or placebo in a ratio of 3:1 in Part 1 and 4:1 in Part 2.
Each subject scheduled to receive study treatment will receive a treatment allocation 
number when randomized. The treatment number will indicate if the subject is to receive 
the scheduled dose of GSK3342830 or placebo. 
6.3.
Planned Dose Adjustments

This protocol allows some alteration from the currently outlined dosing schedule. 
The maximum daily dose is planned to not exceed 6000 mg in Parts 1 and 3, and 
4000 mg in Part 2.

The decision to proceed to the next dose level of GSK3342830 will be made by 
the GSK study team and the investigator based on preliminary safety, tolerability, 
and PK data obtained in approximately 4 subjects for Part 1 and approximately 
5 subjects for Part 2 that received active study treatment in the prior dose level. 
The actual doses to be administered may be adjusted based on the preliminary 
safety, tolerability, and PK data at previous dose levels; these dose adjustments 
may involve either an increase or a decrease in the planned dose. A schematic of 
the planned study design is presented in Figure 3.


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
The dosing schedule may also be adjusted to expand a dosing cohort to further 
evaluate safety and PK findings at a given dose level, or to add cohorts to evaluate 
additional dose levels. The study procedures for these additional subject(s) or 
cohort(s) will be the same as those described for other study subjects.

If AEs, which are of severe intensity or greater and are consistent across subjects 
in a given dose level, or if unacceptable pharmacological effects, reasonably 
attributable in the opinion of the investigator to dosing with GSK3342830, are 
observed in 2 or more subjects in a dose level, further dose escalation will be 
temporarily halted and no further subject in subsequent cohorts will be dosed until 
a full safety review of the study has taken place. Relevant reporting and 
discussion with the medical monitor, relevant GSK personnel, and with the Ethics 
Committee will then take place before any resumption of dosing.

If the same SAE occurs in more than 1 subject, further dose escalation will be 
temporarily halted and no further subject in subsequent cohorts will be dosed until 
a full safety review of the data has taken place.

The previously mentioned criteria will apply even if measured PK parameters are 
below the PK stopping criteria, and every effort will be made to take a blood 
sample at the time of the event for PK analysis in the presence of any of the above 
events.
Figure 3
Planned Study Schematic


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6.4.
Blinding
This will be a double-blind (sponsor unblinded) study. The subjects will be completely 
blinded and the site staff will be blinded to subject-specific treatment assignment. The 
GSK study team will be unblinded at the aggregate level for decision making throughout 
the study (e.g. to support dose escalations and use of Bayesian predictive techniques). 
Where possible, the GSK/clinical research organization personnel will not have access to 
subject-specific treatment assignment so as to not potentially introduce bias in 
discussions with the study site. The pharmacokineticists, statisticians, programmers, and 
data managers, however, will need access to subject randomization during the course of 
the single dose escalation and repeat dose escalation portions of the study for analysis 
purposes to support dose adjustments and escalations. Other GSK staff may be included 
in discussions around dose adjustments and progression if it is deemed necessary and 
relevant by the above mentioned GSK study team members.
During dosing of a specific cohort, the investigator or treating physician may unblind a 
subject’s treatment assignment only in the case of an emergency, when knowledge of the 
study treatment is essential for the appropriate clinical management or welfare of the 
subject. Whenever possible, the investigator must first discuss options with the GSK 
medical monitor or appropriate GSK study personnel before unblinding the subject’s 
treatment assignment. If this is impractical, the investigator must notify GSK as soon as 
possible, but without revealing the treatment assignment of the unblinded subject, unless 
that information is important for the safety of subjects currently in the study. The date 
and reason for the unblinding must be recorded in the electronic data capture system. In 
this situation, the subject will be withdrawn from further treatment if the subject’s 
treatment code is unblinded by the investigator or treating physician. The primary reason 
for discontinuation (the event or condition which led to the unblinding) will be recorded 
in the electronic data capture system. GSK’s Global Clinical Safety and 
Pharmacovigilance staff may unblind the treatment assignment for any subject with an 
SAE. If the SAE requires that an expedited regulatory report be sent to 1 or more 
regulatory agencies, a copy of the report, identifying the subject’s treatment assignment, 
may be sent to the investigator in accordance with local regulations and/or GSK policy.
During the dose escalation safety review, the GSK clinical team and the investigator will 
review safety data in a blinded aggregate form. In the event of concern over a potential 
safety signal, the GSK clinical team and the investigator may review unblinded treatment 
assignments for the purposes of safety review and dose selection without study 
interruption. If a safety signal is determined to indicate findings in subjects who received 
GSK3342830, the findings will be escalated for assessment by the GSK safety team and 
actions taken as appropriate including review of study for possible halting of further 
dosing.
6.5.
Packaging and Labeling
The contents of the label will be in accordance with all applicable regulatory 
requirements.


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6.6.
Preparation/Handling/Storage/Accountability
A description of the methods and materials required for preparation of GSK3342830 
infusion and placebo infusion will be detailed in a Pharmacy Manual which will be 
accompanied by a Quality Agreement.

Only subjects enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study 
treatments must be stored in a secure environmentally controlled and monitored 
(manual or automated) area in accordance with the labelled 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 treatment accountability, reconciliation, and 
record maintenance (i.e. receipt, reconciliation and final disposition records).

Further guidance and information for final disposition of unused study treatment 
are provided in the Pharmacy Manual.

Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff.

A Material Safety Data Sheet or equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request 
from GSK.
6.7.
Compliance with Study Treatment Administration
When the individual dose for a subject is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second member of the study site staff. 
Subjects will be dosed at the clinical unit and receive study treatment directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinical unit will be recorded in the source documents. The dose of 
study treatment and study subject identification will be confirmed at the time of dosing 
by a member of the study site staff other than the person administering the study 
treatment.
GSK3342830 and placebo will be administered intravenously to subjects at the site. 
Administration will be documented in the source documents and recorded in the 
electronic case report form (eCRF).
6.8.
Treatment of Study Treatment Overdose
GSK3342830 will be administered at the clinical unit, thus limiting the risk of overdose. 
In the unlikely event that an overdose with GSK3342830 should occur, the investigator 
must notify the sponsor promptly. There is no specific antidote for overdose with 
GSK3342830. In the event of a suspected overdose, it is recommended that the 
appropriate supportive clinical care should be instituted, as dictated by the subject’s 
clinical status.


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GSK does not recommend specific treatment for an overdose.
In the event of a suspected overdose the investigator should:
1. Contact the medical monitor
2. Closely monitor the subjects for AEs/SAEs and laboratory abnormalities until 
GSK3342830 can no longer be detected systemically (at least 1 day)
3. Obtain a plasma sample for PK analysis within 1 day from the date of the last 
dose of study treatment if requested by the medical monitor (determined on a 
case-by-case basis)
4. Document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF
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 subject.
6.9.
Treatment after the End of the Study
Subjects will not receive any additional treatment from GSK after completion of the 
study because only healthy adult subjects are eligible for study participation.
6.10.
Lifestyle and/or Dietary Restrictions
6.10.1.
Meals and Dietary Restrictions
Standardized meals will be provided while the subject is confined to the clinical unit. At 
all mealtimes, food will be served only after completion of protocol-specified procedures.
Subjects will refrain from consumption of red wine, Seville oranges, grapefruit, or 
grapefruit juice (and/or pummelos, exotic citrus fruits, grapefruit hybrids, or fruit juices) 
from 7 days before the first dose of study drug until after the final dose.
Water will be allowed ad libitum except for 1 hour before the start of infusion and 1 hour 
after the end of infusion.
Subjects will fast from food and drink (except water) for at least 10 hours before dosing 
on Day 1 (Parts 1, 2, and 3) and Day 15 (Part 2 only). Meals at all other times will be 
provided at times that will not interfere with fasting required for clinical laboratory 
testing.
These fasting requirements may be removed or modified at the discretion of the sponsor 
in consultation with the investigator.
6.10.2.
Caffeine, Alcohol, and Tobacco
Subjects will abstain from ingesting caffeine- or xanthine-containing products (e.g., 
coffee, tea, cola drinks and chocolate) for 24 hours before the start of dosing on Day 1 
until collection of the final PK sample.


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Subjects will abstain from alcohol for 24 hours before the start of dosing on Day 1 until 
collection of the final PK sample.
Use of tobacco products is not allowed from 3 months before screening until after the 
final Follow-up visit.
6.10.3.
Activity
Subjects will abstain from strenuous exercise during the course of the study through the 
Follow-up visit. Subjects may participate in light recreational activities during the study 
(e.g., watch television, read).
6.11.
Concomitant Medications and Non-Drug Therapies
6.11.1.
Permitted Medications and Non-Drug Therapies
Paracetamol or Acetaminophen at doses of ≤2 grams/day and HRT are permitted for use 
during the study. Other concomitant medication may be considered on a case-by-case 
basis by the investigator in consultation with the medical monitor.
6.11.2.
Prohibited Medications and Non-Drug Therapies
Subjects must refrain from the use of prescription or non-prescription drugs, including 
vitamins and 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) 
before the first dose of study drug, unless in the opinion of the investigator and GSK 
medical monitor, the medication will not interfere with the study procedures or 
compromise subject safety.
7.
STUDY ASSESSMENTS AND PROCEDURES
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the Time and Events Tables (Section 7.1) are essential and required for study 
conduct.
This section lists the procedures and parameters of each planned study assessment. The 
exact timing of each assessment is listed in the Time and Events Tables (Section 7.1).
The following points must be noted:

If assessments are scheduled for the same nominal time, THEN the assessments 
should occur in the following order:
1. 12-lead ECG
2. vital signs
3. blood draws


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
Note: The timing of the assessments should allow the blood draw to occur at the 
exact nominal time.

The timing and number of planned study assessments, including safety and PK 
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) to ensure appropriate monitoring.

The change in timing or addition of time points for any planned study assessments 
must be documented in a Note to File, which is approved by the relevant GSK 
study team member and then archived in the study sponsor and site study files; 
but, this will not constitute a protocol amendment.

The Institutional Review Board (IRB)/Independent Ethics Committee (IEC) will 
be informed of any safety issues that require alteration of the safety monitoring 
scheme or amendment of the informed consent form.

No more than 500 mL of blood will be collected over the duration of the study, 
including any extra assessments that may be required.


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7.1.
Time and Events Tables
Table 3
Time and Events Table: Screening and Day –1; Single and Repeat Dose Escalation (Part 1 and Part 2) and Single 
Dose (Part 3)
Procedure
Screening (up to 
30 days before Day 1)
Day –1
Notes
Informed consent
X
Inclusion and exclusion criteria
X
X
Demography
X
Medical history (includes substance usage and family 
history of premature cardiovascular disease)
X
X
Substances: drugs, alcohol, tobacco and caffeine.
Past and current medical conditions including 
cardiovascular medical history
X
X
Safety and Laboratory Assessments
SAE review
X
X
Serious AEs will be collected from the signing of informed consent.
Concomitant medication review
X
X
Full physical examination including height and weight
X
Brief physical examination
X
Vital signs (BP, HR, oral temperature, respiration rate)
X
X
12-lead electrocardiogram
X
X
Continuous cardiac monitoring
X
Continuous dual-lead telemetry will be initiated on Day –1 at least 8 hours before study 
drug administration on Day 1.
Urine cotinine and drug and breath alcohol screens
X
X
-hCG pregnancy test/estradiol/FSH
X
X
Pregnancy test (if female of child-bearing age; serum at screening and urine at Day –1); 
estradiol and FSH at screening as appropriate. Only women of non-child-bearing 
potential may participate.
Human immunodeficiency virus antibody, hepatitis B 
surface antigen, and hepatitis C antibody screen
X
Clinical chemistry (including liver chemistries), 
hematology, and urinalysis 
X
X
The albumin to creatinine ratio will be determined at Screening using the first morning 
void urine as described in Section 7.3.7. An aliquot of the urine sample will be collected 
for NGAL and KIM-1 at Day –1. These samples may be analyzed after the end of the 
study if a clinical signal is detected. Instructions for collection and storage of these urine 
samples are included in the Study Reference Manual. Hematology assessments on 
Day –1 will also include total iron, total binding iron capacity, ferritin, haptoglobin, 
ceruloplasmin and reticulocytes.


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Procedure
Screening (up to 
30 days before Day 1)
Day –1
Notes
Table is continued on the next page.
Blood collection for additional iron tests
X
In Part 2 only. Samples will be collected for potential analysis of some or all of the 
additional iron tests at the end of the study if a clinical signal is detected.
Genetic sample
X
Collect a pharmacogenomics sample only if the subject has a signed consent specific for 
this purpose. The pharmacogenomics sample can be collected anytime, but Day –1 is 
recommended. Informed consent for optional sub-studies (e.g., genetics research) must 
be obtained before collecting a sample.
Admission to clinical unit
X
-hCG = beta human chorionic gonadotropin, BP = blood pressure, FSH = follicle-stimulating hormone, HR = heart rate, KIM-1 = kidney injury molecule 1, NGAL = neutrophil 
gelatinase-associated lipocalin, SAE = serious adverse event.


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Table 4
Time and Events Table: Part 1 - Single Dose Escalation and Part 3 - Single Dose
Procedure
Day 1
Day 2
Day 3
Hours relative to treatment administration
Pre-dose
0
0.5
1
1.25
1.5
2
3
3.5
4
4.5
5
6
8
10
12
16
24
36
48
Randomization
X
12-lead ECG1
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BP, HR, oral temperature, 
respiration rate)
X
X
X
X
X
X
X
X
X
X
X
Fasting clinical chemistry, 
hematology, and urinalysis2
X
Treatment administration3
X
Blood collection for pharmacokinetics4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine collection for pharmacokinetics5
X-- ---------X---------------------------------------------------------------------------X-----------------------------------X-----------------X-----------------X----------------X
Continuous cardiac monitoring6
X-------------------------------------------------------------Continuous review-----------------------------------------------------------------------------------------
AE review
X--------------------------------------------------------Continuous review-----------------------------------------------------------------------------
SAE review
X-------------------------------------------------------------Continuous review-----------------------------------------------------------------------------------------
Concomitant medication review
X-------------------------------------------------------------Continuous review-----------------------------------------------------------------------------------------
Discharge from inpatient unit7
X
AE = adverse event, BP = blood pressure, ECG = electrocardiogram, HR = heart rate, SAE = serious adverse event.
NOTES:
1. Triplicate 12-lead ECGs to be obtained at least 5 minutes apart within 1 hour before dosing. Single ECGs will be obtained at all other time points.
2. An aliquot of the urine sample will be collected for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1). These samples may be analyzed after the 
end of the study if a clinical signal is detected. Instructions for collection and storage of these urine samples are included in the Study Reference Manual. The albumin to creatinine 
ratio will be determined using the first morning void urine on Day 2.
3. GSK3342830 or placebo will be administered as a single IV infusion in the morning on Day 1. The planned infusion duration time is 1 hour.
4. Pharmacokinetic blood samples will be collected for GSK3342830 and potential metabolites. At the end of the study the saved blood samples from a predicted 
therapeutically-relevant dose level and higher dose level for plasma PK analysis of parent and the highest dose level completed for metabolite profile, will be transferred to a GSK 
specified laboratory. Details of PK sample collection and storage will be provided in the Study Reference Manual.
5. Pooled urine samples will be collected over the following time intervals: pre-dose (within a 24-hour period before dosing, may begin on Day –1) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, 
and 24 to 48 hours post-dose. Two aliquots of urine samples for baseline analysis may be collected from any time after admission to just before dosing on Day 1. At the end of the 
study, the saved urine samples from a predicted therapeutically-relevant dose level and higher dose level for urinary PK analysis of parent and the highest dose level completed for 
potential metabolite profile, will be transferred to a GSK specified laboratory. Urine will be collected in opaque bottles to maintain blind of blinded study site personnel. Details of 
urine sample collection and storage will be provided in the Study Reference Manual.
6. Continuous dual-lead telemetry will be initiated on Day –1 at least 8 hours before treatment administration on Day 1 and will continue until 48 hours post dose.
7. Subjects will be discharged from the clinical unit after the 48-hour post-dose assessments are complete.


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Table 5
Time and Events Table: Part 2 - Repeat Dose Escalation
Procedure
Study Day
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Randomization
X
12-lead ECG1
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BP, HR, oral temperature, 
respiration rate)2
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting clinical chemistry, hematology, 
and urinalysis tests3
X
X
X
X
Treatment administration4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood collection for pharmacokinetics5
X
X
X
X
X
X
X
Urine collection for pharmacokinetics6
X
X
X
X
Continuous cardiac monitoring7
XContinuous review
AE review
X--------------------------------------------- ---------------------Continuous review------------------------------------------------------------------------------------
SAE review
X-------------------------------------------------------------------Continuous review------------------------------------------------------------------------------------
Concomitant medication review
X-------------------------------------------------------------------Continuous review------------------------------------------------------------------------------------
Discharge from inpatient unit8
X
AE = adverse event, BP = blood pressure, ECG = electrocardiogram, HR = heart rate, SAE = serious adverse event.
NOTES:
1. Triplicate 12-lead ECGs will be obtained at least 5 minutes apart within 1 hour before the start of infusion (pre-dose) on Day 1. Single ECGs will be obtained at 0.5, 1, 1.5, 2, 3, 4, 6, 
and 12 hours after the start of infusion on Day 1 and Day 15, within 1 hour before the start of the morning infusion on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the 
morning on Day 16.
2. Vital signs will be measured within 1 hour before the start of infusion (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 12 hours after the start of infusion on Days 1 and 15, within 1 hour 
before the start of the morning infusion and on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the morning on Day 16.
3. An aliquot of the urine sample will be collected for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1). These samples may be analyzed after the 
end of the study if a clinical signal is detected. Instructions for collection and storage of these urine samples are included in the Study Reference Manual. Hematology assessments 
on Days 5 and 15 will also include total iron, total iron binding capacity, ferritin, haptoglobin, ceruloplasmin and reticulocytes. The albumin to creatinine ratio will be determined using 
the first morning void urine on Days 5 and 15. Urinalysis assessments before dosing on Day 15 will also include urine color.
4. GSK3342830 or placebo will be administered as a single IV infusion in the morning on Day 1, TID IV infusions (approximately every 8 hours) on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 
13, and 14, and as a single IV infusion in the morning on Day 15. The planned infusion duration time is 1 hour.
5. Pharmacokinetic samples for GSK3342830 and potential metabolites will be collected on Day 1 at the following time points: pre-dose (within 15 minutes before dosing) and 0.5, 1 
(end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hours after the start of infusion. Single pre-dose trough samples will be taken on the mornings of Days 3, 
6, 9, 12, and 13. Serial samples will be collected on Day 15 at the following time points: pre-dose (within 15 minutes before dosing) and 0.5, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 
3.5, 4, 4.5, 5, 6, and 8 hours after the start of infusion. At the end of the study, the saved blood samples from a predicted therapeutically-relevant dose level and higher dose level for 
plasma PK analysis of parent and from the highest dose level completed for potential metabolite profile will be transferred to a GSK specified laboratory. Details of PK sample 


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collection and storage will be provided in the Study Reference Manual.
6. Pooled urine samples will be collected on Day 1 and Day 15 over the following time intervals: pre-dose (within a 24-hour period before dosing, may begin on Day –1) and 0 to 8 and 
8 to 24 hours post-dose. Two aliquots of urine samples for baseline analysis may be collected from any time after admission to just before dosing on Day 1. At the end of the study, 
the saved urine samples from a predicted therapeutically-relevant dose level and higher dose level for urinary PK analysis of parent and from the highest dose level completed for 
potential metabolite profile, will be transferred to a GSK specified laboratory. Urine will be collected in opaque bottles to maintain blind of blinded study site personnel. Details of 
urine sample collection and storage will be provided in the Study Reference Manual.
7. Continuous dual-lead telemetry will be initiated on Day –1 at least 8 hours before treatment administration on Day 1 and will continue until 48 hours post dose.
8. Subjects will be discharged from the clinical unit after the Day 16 assessments are complete.


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Table 6
Time and Events Table: Follow-up Visit; Single and Repeat Dose Escalation (Part 1 and Part 2) and Single Dose 
(Part 3)
Procedure
Follow-up Visit (7 to 10 days post last dose or early termination)
Adverse event/serious adverse event review
X
Concomitant medication review
X
Brief physical examination
X
12-lead electrocardiogram
X
Vital signs
X
Urine -human chorionic gonadotropin pregnancy test (women of child-bearing age)
X
Clinical chemistry, hematology, and urinalysis tests1
X
NOTE:
1. An aliquot of the urine sample will be collected for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1). These samples may be analyzed after the 
end of the study if a clinical signal is detected. Instructions for collection and storage of these urine samples are included in the Study Reference Manual. Hematology assessments 
will also include total iron, total iron binding capacity, ferritin, haptoglobin, ceruloplasmin and reticulocytes. The albumin to creatinine ratio will be determined using the first morning 
void urine as described in Section 7.3.7.


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7.2.
Screening and Critical Baseline Assessments
Cardiovascular medical history, family history, and risk factors (as detailed in the eCRF) 
will be assessed at screening.
The following demographic parameters will be captured: year of birth, sex, race, and 
ethnicity.
Medical and medication history will be assessed as related to the inclusion/exclusion 
criteria listed in Section 5.
Procedures conducted as part of the subject’s routine clinical management (e.g., blood 
count) and obtained before signing of informed consent may be utilized for screening or 
baseline purposes provided the procedure meets the protocol-defined criteria and has 
been performed in the time frame of the study.
7.3.
Safety
Planned time points for all safety assessments are listed in the Time and Events Tables 
(Section 7.1). Additional time points for safety tests such as vital signs, physical 
examinations, and laboratory safety tests may be added during the course of the study 
based on newly available data to ensure appropriate safety monitoring.
7.3.1.
Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 5.
The investigator and their designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. 
7.3.1.1.
Time Period and Frequency for Collecting AE and SAE Information

Any SAEs assessed as related to study participation (e.g., protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK 
product will be recorded from the time a subject consents to participate in the 
study up to and including any follow-up contact. 

Serious AEs will be collected from the signing of informed consent and AEs will 
be collected from the start of treatment until the follow-up contact (see 
Section 7.3.1.3) as indicated in the Time and Events Tables (Section 7.1).

Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent may be recorded on the Medical History/Current 
Medical Conditions section of the eCRF.

All SAEs will be recorded and reported to GSK within 24 hours, as indicated in 
Appendix 5.

Investigators are not obligated to actively seek AEs or SAEs in former study 
subjects. However, if the investigator learns of any SAE, including a death, at any 
time after a subject has been discharged from the study, and he/she considers the 


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event reasonably related to the study treatment or study participation, the 
investigator must promptly notify GSK.
NOTE: The method of recording, evaluating, and assessing causality of AEs and SAEs 
plus procedures for completing and transmitting SAE reports to GSK are provided in 
Appendix 5 and Appendix 6.
7.3.1.2.
Method of Detecting AEs and SAEs
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrence. Appropriate questions include:
“How are you feeling?”
“Have you had any (other) medical problems since your last visit/contact?”
“Have you taken any new medicines, other than those provided in this study, since 
your last visit/contact?”
7.3.1.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts. All SAEs, and non-serious AEs of special interest 
(as defined in Section 4.6.1) will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the subject is lost to follow-up 
(as defined in Section 5.4). Further information on follow-up procedures is given in 
Appendix 5.
7.3.1.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to GSK or designee of SAEs related to study 
treatment (even for non-interventional post-marketing studies) is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a 
product under clinical investigation are met.
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation. GSK will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/ IEC and investigators.
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.


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7.3.2.
Pregnancy
Details of all pregnancies in female subjects and female partners of male subjects will be 
collected after the start of dosing and until the Follow-up visit (7 to 10 days post-last 
dose).
If a pregnancy is reported then the investigator should inform GSK within 2 weeks of 
learning of the pregnancy and should follow the procedures outlined in Appendix 8.
7.3.3.
Physical Examinations
A complete physical examination will include, at a minimum, assessments of the head, 
eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular system, 
gastrointestinal system, abdomen (liver and spleen), lymph nodes, and extremities. 
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, gastrointestinal system, and abdomen (liver and spleen).
7.3.4.
Vital Signs
Vital signs should be taken with the subject in a semi-supine position, having rested in 
this position for at least 5 minutes and will include temperature, systolic and diastolic BP, 
pulse rate, and respiratory rate. Refer to Section 5.4.5 for vital sign stopping criteria.
7.3.5.
Electrocardiograms
Triplicate 12-lead ECGs will be obtained at least 5 minutes apart for the time points that 
are within 1 hour before dosing. Single 12-lead ECGs will be obtained at all other time 
points during the study. All 12-lead ECGs will be obtained using an ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 
Refer to Section 5.4.4 for QTc stopping criteria.
7.3.6.
Continuous Cardiac Monitoring
Continuous dual-lead telemetry will be initiated on Day –1 at least 8 hours before study 
drug administration on Day 1 and will continue until 48 hours post dose.
7.3.7.
Clinical Safety Laboratory Assessments
All protocol required safety laboratory assessments, as defined in Table 7, must be 
conducted in accordance with the Laboratory Manual, and Protocol Time and Events 
Tables (Section 7.1). Laboratory requisition forms must be completed and samples must 
be clearly labelled with the subject number, protocol number, site/center number, and 
visit date. Details for the preparation and shipment of samples will be provided by the 
laboratory and are detailed in the Study Reference Manual (SRM). Reference ranges for 
all safety parameters will be provided to the site by the laboratory responsible for the 
assessments.


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If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in subject management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification) the results must be recorded in the eCRF.
Refer to the SRM for appropriate processing and handling of samples to avoid duplicate 
and/or additional blood draws.
Hematology, clinical chemistry, urinalysis, and additional parameters to be tested are 
listed in Table 7.
Table 7
Protocol Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
Total iron1
RBC Indices:
WBC count with Differential:
RBC Count
TIBC1
MCV
Neutrophils
Hemoglobin
Ferritin1
MCH
Lymphocytes
Hematocrit
MCHC
Monocytes
Reticulocytes1
Eosinophils
Basophils
Additional Iron 
Tests2
Transferrin 
(apotransferrin)
Ceruloplasmin
Haptoglobin/Hemopexin
Clinical 
Chemistry3
Blood urea 
nitrogen
Potassium
AST 
Total and direct 
bilirubin
Creatinine
Sodium
ALT 
Total protein
Glucose
Calcium
Alkaline phosphatase
Albumin
Bicarbonate
Chloride
Uric acid
Urinalysis

Specific gravity

pH, glucose, protein, blood and ketones by dipstick

ACR4

Microscopic examination (if blood or protein is abnormal)

NGAL5

KIM-15

Urine color6
Other 
Screening Tests

Human immunodeficiency virus

Hepatitis B surface antigen

Hepatitis C antibody

Follicle-stimulating hormone and estradiol (as appropriate)

Alcohol, cotinine, and drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, cannabinoids and benzodiazepines)

-human chorionic gonadotropin pregnancy test (if female of child-bearing 
age; serum at screening and urine at Day –1 and follow-up) 
ACR = albumin to creatinine ratio, ALT = alanine aminotransferase, AST = aspartate aminotransferase, KIM-1 = kidney 
injury molecule 1, MCH = mean corpuscular hemoglobin, MCHC = mean corpuscular hemoglobin concentration, 
MCV = mean corpuscular volume, NGAL = Neutrophil gelatinase-associated lipocalin, RBC = red blood cell, 
TIBC = total iron binding capacity, WBC = white blood cell
Footnotes are on the next page.


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NOTES:
1. In Parts 1 and 3, analyzed on Day –1 and at Follow-up visit. In Part 2, analyzed on Day –1, Day 5, Day 15, and at 
Follow-up visit.
2. Blood samples will be collected on Day –1, predose (at least 1 hour before dosing) on Days 5, and 15, and at 
Follow-up visit..
3. Details of Liver Chemistry Stopping Criteria and Required Actions and Follow-Up Assessments after liver stopping or 
monitoring event are given in Section 5.4.1, Appendix 2, and Appendix 3.
4. The ACR on urine albumin and creatinine will be determined using the first morning void urine at Screening and 
Follow-up visit for all subjects in both parts of the study. In addition, the ACR will be determined on Day 2 in Parts 1 
and 3, and Days 5 and 15 in Part 2. Screening ACR may be performed on urine during the screening visit. Subjects 
should be provided a sterile urine transport container and instructions on how to collect a first void urine at home for 
screening. In the event a subject fails by ACR, the subject should be contacted to bring back first void urine for 
recheck. For the Follow-up visit, subjects must be provided a sterile urine transport container on discharge from the 
clinical unit and instructed to bring back the first morning void urine on the day of their return Follow-up visit.
5. An aliquot of the remaining urine samples will be banked and may be analyzed for NGAL and KIM-1 after the end of 
the study if a clinical signal is detected. Instructions for collection and storage of these urine samples are included in 
the Study Reference Manual.
6. Assessed before dosing on Day 15 (Part 2) only.
All laboratory tests with values that are considered clinically significantly abnormal 
during participation in the study (from first dose of study treatment through the 
Follow-up visit) should be repeated until the values return to normal or baseline. If such 
values do not return to normal within a period judged reasonable by the investigator, the 
etiology should be identified and the sponsor notified.
7.4.
Pharmacokinetics
7.4.1.
Blood Sample Collection
Blood samples for PK analysis of GSK3342830 will be collected at the time points 
indicated in the Time and Events Tables (Section 7.1). The actual date and time of each 
blood sample collection will be recorded. The timing of PK samples may be altered 
and/or PK samples may be obtained at additional time points to ensure thorough PK 
monitoring.
At the end of the study, the saved blood samples from a predicted therapeutically-relevant
dose level and higher dose level for plasma PK analysis of parent and the highest dose 
level completed for metabolite profile, will be transferred to a GSK specified laboratory.
A total of 3 mL of blood will be collected from each subject.
Details of PK blood sample processing, storage, and shipping procedures are provided in 
the SRM.
7.4.2.
Urine Sample Collection
Urine samples for PK analysis of GSK3342830 will be collected at the time points 
indicated in the Time and Events Tables (Section 7.1). The actual date and time of each 
urine sample collection will be recorded. The timing of urine samples may be altered 
and/or samples may be obtained at additional time points to ensure thorough PK 
monitoring.


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At the end of the study, saved urine samples from a predicted therapeutically-relevant 
dose level and higher dose level for urinary PK analysis of parent and the highest dose 
level completed for potential metabolite profile, will be transferred to a GSK specified 
laboratory. 
Urine will be collected in opaque bottles to maintain the blind of blinded study site 
personnel.
Details of PK urine sample processing, storage, and shipping procedures are provided in 
the SRM.
7.4.3.
Sample Analysis
Concentrations of GSK3342830 will be determined in blood and urine samples using the 
currently approved bioanalytical methodology. Raw data will be archived at the 
bioanalytical site (detailed in the SRM).
Once the plasma and urine have been analyzed for GSK3342830 any remaining blood 
and urine may be analyzed for other compound-related metabolites and the results 
reported under a separate protocol.
7.5.
Genetics
Depending on the clinical study results, exploratory pharmacogenomics analyses may be 
performed to examine the potential relationship between genetic variants and clinical 
endpoints.
Information regarding genetic research is included in Appendix 4.
8.
DATA MANAGEMENT

For this study subject data will be entered via an eCRF into Oracle Clinical Remote 
Data Capture System (OC RDC). Subject data will be available for viewing through 
access to the OC RDC system. Data provided from other sources will be received, 
reconciled, combined, and transferred to GSK at predetermined time points.

Management of clinical data will be performed in accordance with applicable GSK 
standards and data cleaning procedures to ensure the integrity of the data, e.g., 
removing errors and inconsistencies in the data.

Adverse events and concomitant medications terms will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) and an internal validated medication 
dictionary, GSKDrug.

The eCRFs (including queries and audit trails) will be sent at the end of the study in 
electronic format to GSK to be retained, and copies will be sent to the investigator to 
maintain as the investigator copy. Subject initials will not be collected or transmitted 
to GSK according to GSK policy.


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9.
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
All statistical analyses will be performed by PPD using SAS (SAS Institute Inc., Cary, 
North Carolina, USA), version 9.2 or higher. Pharmacokinetic parameters will be 
calculated using Phoenix WinNonlin (Certara, L.P., 1699 S Hanley Road, St Louis, 
Missouri 63144, USA), version 6.3 or higher.
Before database lock, a reporting and analysis plan (RAP) will be issued as a separate 
document, providing detailed methods for the analyses outlined below.
Any deviations from the planned analyses will be described in a RAP addendum and 
justified in the final integrated clinical study report.
9.1.
Hypotheses
The primary objective of this study is to investigate the safety and tolerability of 
GSK3342830 after administration of single and repeat IV doses in healthy adult subjects
and after administration of single IV dose in adult Japanese subjects. The pharmacokinetics 
of GSK3342830 after administration of single and repeat IV doses in healthy subjects
(and in adult Japanese subjects after administration of single IV dose) will also be 
determined. No formal statistical hypotheses are to be tested. For dose proportionality, 
accumulation, time invariance, and assessment of steady-state, an estimation approach 
will be taken, and point estimates and confidence intervals (CIs) will be constructed. For 
safety parameters, comparisons to placebo will be made based on descriptive statistics.
9.2.
Sample Size Considerations
9.2.1.
Sample Size Assumptions
Sample size is based on feasibility. No formal calculation of power or sample size for 
Parts 1 or 2 of the study will be performed. A sample size of 6 to 10 subjects per dose 
level cohort should be sufficient to provide useful estimates of both inter- and 
intra-subject variability for GSK3342830 PK parameters, and initial safety assessment.
Although the sample size is not based on statistical criteria, general probabilities can be 
determined on the likelihood of observing AEs. With 6 subjects receiving each dose of 
active drug, if the true adverse outcome rate is 5%, the chance of observing at least 
1 adverse outcome at a given dose is 26%. Similarly if the true adverse outcome rate is 
20%, the chance of observing at least 1 adverse outcome at a given dose is 73%. This 
level of predictivity is deemed adequate within this FTIH setting before commencing to 
repeat dosing (Part 2) and Phase II studies.
9.2.2.
Sample Size Sensitivity
Not applicable.


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9.2.3.
Sample Size Re-estimation or Adjustment
Not applicable.
9.3.
Data Analysis Considerations
In general, descriptive summaries will include number of subjects, mean, standard 
deviation, median, minimum, and maximum for continuous variables; and percent for 
categorical variables. Summaries will present data by dose level and where appropriate, 
by assessment time.
9.3.1.
Analysis Populations
The Safety Population will consist of all subjects who receive at least 1 dose of study 
drug and have at least on post-dose safety assessment.
The PK Population will consist of all subjects who receive at least 1 dose of 
GSK3342830 and for whom a PK sample is collected and analyzed.
The PK Parameter Population will consist of all subjects in the PK population for 
whom valid and evaluable PK parameters were derived.
9.3.2.
Interim Analysis
No formal interim analysis is planned for this study. However, one may be conducted in 
the event of clinically significant safety or PK findings. All preliminary safety, 
tolerability, and available PK data will be reviewed internally at GSK and with the 
clinical study site before each dose escalation in Part 1, before initiation of Part 2, and 
before each dose escalation in Part 2. All preliminary safety and tolerability data from 
Part 1 will be reviewed internally at GSK and with the clinical study site before dose 
selection for and initiation of Part 3. Section 6.4 provides further detail on data access 
and the handling of treatment blinding.
The relationship between dose and plasma GSK3342830 exposure, and associated 
variability will be characterized by a power model once data are available from 3 dose 
levels. Prior to that, prediction of the human exposure at the next dose will be based on 
population PK modeling (if feasible) or on the assumption of dose–exposure 
proportionality (i.e., doubling the dose gives an approximate doubling of exposure). If 
prior PK results show less than proportional increase in exposure with increasing dose, 
the prediction will be based on the assumption that the fold exposure increase to fold 
dose increase ratio will be the same with the current dose escalation as it was with the 
previous one. If prior PK results show more than proportional increase in exposure with 
dose, subsequent dose escalations will not be higher than 3-fold. The power model will 
be updated as data become available throughout the study. During dose escalation, a 
Bayesian predictive probability that a dose level will have mean AUC (AUC[0-t] or 
AUC[0-24] for single dose and AUC[0-24] for repeat dose) and Cmax values greater than 
2875 hμg/mL and 2270 μg/mL (mean exposures at the NOAEL dose in the rat and 
monkey), respectively, and Bayesian predictive probability that an individual will have 
AUC(0-24) and Cmax values greater than 3460 hμg/mL and 2590 μg/mL (maximum 


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exposures at the NOAEL dose in the rat for AUC and the monkey for Cmax), 
respectively, may be calculated for the next dose level and used together with safety and 
tolerability data to aid the next dose selection.
The Bayesian predictive probability will be based on Whitehead’s model 
[Whitehead, 2001]:
 = 	 +  +  + 
where  is log-PK of i-th subject to j-th dose,  is j-th log-dose administered to i-th 
subject, 	 and  are population intercept and slope, respectively,  is random effect of 
i-th subject and  is random error of i-th subject in j-th dose.
9.4.
Key Elements of Analysis Plan
9.4.1.
Primary Analyses
Safety Analyses
The following safety evaluations will be performed:

Monitoring for AEs

Routine clinical laboratory tests including chemistry, hematology, and urinalysis

Vital signs

Twelve-lead ECG readings

Continuous cardiac monitoring (dual-lead telemetry)
Safety endpoints will include AEs, clinical laboratory test results (chemistry [including 
liver function parameters], hematology, and urinalysis), vital signs (BP, heart rate, 
respiratory rate, and body temperature), and 12-lead ECG readings.
All safety data will be presented in data listings. Subject demographics, medical history, 
and prior and concomitant medications will be summarized for each dose level using 
descriptive statistics. For continuous variables, these summaries will include number of 
subjects, mean, median, standard deviation, minimum, and maximum.
For categorical variables, the summaries will include frequencies and corresponding 
percentages. No inferential hypothesis testing will be performed on the safety variables.
Adverse events will be coded using the MedDRA classification system. 
Treatment-emergent AEs will be defined as any AEs, regardless of relationship to study 
drug, that occur after the dose of study drug until the Follow-up visit. The 
treatment-emergent AEs will be summarized for each dose level at AE onset for the 
overall number of AEs and percentage of subjects who experience them. The total 
number of AEs will be summarized by dose level and overall. The AEs will be further 
summarized by severity and relationship to the study drug. If relationship information is 
missing, the AE will be considered treatment related. Listings for the subsets of SAEs 


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and treatment-related SAEs will be provided. The SAEs and number of AEs leading to 
discontinuation will be summarized. The incidence of AEs will also be summarized by 
system organ class and preferred term.
Clinical laboratory test results, vital signs, and 12-lead ECG results will be summarized 
by actual values and change from baseline. Clinical laboratory values that are outside of 
the reference ranges will be flagged and evaluated for clinical significance by the 
investigator. Any 12-lead ECG abnormalities will be summarized by each dose level. 
Physical examination findings and cardiac telemetry results will be listed.
Detailed descriptions of the analyses in this study will be presented in the RAP.
9.4.2.
Secondary Analyses
Pharmacokinetic Analyses
Plasma GSK3342830 concentration versus time data will be analyzed by 
non-compartmental methods with WinNonlin Version 5.2 or higher. Calculations will be 
based on the actual sampling times recorded during the study. From the plasma and urine 
concentration versus time data, the following PK parameters will be determined, as data 
permit:
Plasma:
Cmax
Maximum plasma concentration
Tmax
Time to Cmax
AUC(0-t)
AUC from time zero to the last quantifiable concentration after dosing
AUC(0-)
AUC extrapolated from time zero to infinity (estimated for single dose in 
Parts 1 and 3, and on Day 1 for repeat dose in Part 2)
AUC(0-)
AUC over the dosing interval 
t1/2
Terminal elimination half-life 
CL
Total systemic clearance 
Vss
Steady-state volume of distribution
C
Trough concentration
Urine:
Feu(t1-t2)
Urinary excretion ratio relative to dose
CLr
Renal clearance
Ae
Amount excreted in urine
Plasma GSK3342830 concentration data will be listed and summarized by time point for 
each dose level using descriptive statistics (number of subjects, mean, median, standard 
deviation, minimum, maximum, and coefficient of variation). Urine GSK3342830 
concentration and volume data will be listed. Mean, median, and individual plasma 


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concentration versus time profiles will be presented graphically on linear and 
semi-logarithmic scales.
Actual sampling times, rather than scheduled sampling times, will be used in all 
calculations of PK parameters. However, for ease of presentation, scheduled sampling 
times will be used to present results in tables, listings, and figures.
Tmax of GSK3342830 will be separately analyzed using non-parametric Wilcoxon rank 
test to compute point estimates and associated 90% CIs for the median differences.
Detailed descriptions of the analyses in this study will be presented in the RAP.
Dose Proportionality
Dose proportionality of AUC(0-) and Cmax on Day 1 in Part 1 and for repeat dose 
groups AUC(0-) and Cmax of GSK3342830 on Day 15 in Part 2 will be assessed 
separately by day using the following power model:
y = * dose.
where y denotes the PK parameter being analyzed and depends on the random error in 
the repeat dose phase where subjects take the study drug in a parallel-group fashion. Dose 
proportionality implies that =1 and will be assessed by estimating along with its 
90% CI. The exponent, , in the power model will be estimated by regressing the 
loge-transformed PK parameter on loge dose.
log(y) = log() + * log(dose)
The power model will be fitted by restricted maximum likelihood using Statistical 
Analysis Software (SAS) Proc Mixed, with a fixed effect term for dose. The PK 
parameter endpoint and the factor dose will be loge-transformed before the analysis. An 
estimate of slope (with corresponding 90% CI) will be provided as a measure of potential 
dose proportionality (i.e. a slope of approximately 1 implies dose proportionality). Dose 
proportionality is the prerequisite of the Bayesian predictive model.
In the case where dose proportionality is not established over the entire dosing range, 
secondary analysis of dose proportionality will be assessed for select doses over the 
higher dosing range with the power model or by pair-wise analysis of variance (ANOVA) 
using the SAS mixed models procedure. If the secondary analysis using the pair-wise 
ANOVA approach is performed, a reference dose would be chosen based on the lowest 
clinically relevant dose over which the pharmacokinetics can be adequately described and 
the other doses would be treated as test doses.
Time Invariance
For the repeat dose cohorts (Part 2), the time invariance ratio will be assessed by fitting a 
mixed effect model for AUC(0-) on Day 1 and AUC(0-) on Day 15 data with subject 
as a random effect and group (group=1 for AUC(0-) on Day 1, and group=2 for 
AUC(0-) on Day 15) as a fixed effect for each cohort. The time invariance ratio of 
GSK3342830 will be estimated by calculating the ratio of the geometric least squares 


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means of group 1 (AUC(0-) on Day 15) to group 2 (AUC(0-) on Day 1) and the 
corresponding 90% CI for each cohort. The time invariance ratio will be listed and 
summarized along with other PK parameters.
Accumulation Ratio
For the repeat dose cohorts (Part 2), the accumulation ratio (Ro) will be calculated as the 
ratio of AUC(0-) on Day 15 to AUC(0-) on Day 1 for each subject. The dosing 
interval () will be equal to 8 hours. The accumulation ratio will be listed and 
summarized along with other PK parameters.
Following log-transformation, AUC(0-) of GSK3342830 on Days 1 and 15 will be 
analyzed by a mixed effect model, fitting dose, day, and dose-by-day interaction as fixed 
effects and subject as a random effect. For each dose, point estimate and 90% CI for the 
difference “AUC(0-) on Day 15 - AUC(0-) on Day 1” will be constructed using the 
appropriate error term. The point estimate and associated 90% CI will then be 
exponentially back-transformed to provide point and 90% CI estimates for the ratios 
“AUC(0-) on Day 15: AUC(0-) on Day 1.” If dose-by-day interaction is not significant, 
then a single point estimate and 90% CI pooled across all doses for the ratio AUC(0-) on 
Day 15: AUC(0-) on Day 1 may be constructed with all estimates for each dose.
Steady State Assessment
To evaluate whether steady state was achieved, statistical analysis of steady-state Cwill 
be performed after log-transformation of Con Days 3, 6, 9, 12, 13, and 15. A mixed 
effect model will be fitted by dose and day (as a continuous covariate) as a fixed effect 
term and subject as a random effect term. The coefficients for the slope of the day effect 
on the log-scale will be used to evaluate steady-state for each dose group. Using the 
pooled estimate of variance, the 90% CIs for the slope will be calculated.
Distributional assumptions underlying the statistical analyses will be assessed by visual 
inspection of residual plots. Normality will be examined by normal probability plots, 
while homogeneity of variance will be assessed by plotting the residuals against the 
predicted values for the model. Alternative analyses of the data will be performed if any 
of the model assumptions appear to be violated.
9.4.3.
Exploratory Analyses
Exploratory analyses will be performed to correlate PK parameters (AUC[0-t], 
AUC[0-], and Cmax for Parts 1 and 3; AUC[0-t], AUC[0-], AUC[0-], and Cmax for 
Part 2) of GSK3342830 with safety findings of GSK3342830 in healthy adult subjects 
(Parts 1 and 2) and healthy adult Japanese subjects (Part 3), and to evaluate the 
production of any GSK3342830 metabolites in plasma and urine.
Detailed descriptions of the analyses in this study will be presented in the RAP.


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10.
STUDY GOVERNANCE CONSIDERATIONS
10.1.
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
10.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Prior to initiation of a site, GSK will obtain favorable opinion/approval from the 
appropriate regulatory agency to conduct the study in accordance with International 
Council for Harmonisation (ICH) Good Clinical Practice (GCP) and applicable 
country-specific regulatory requirements.
The study will be conducted in accordance with all applicable regulatory requirements, 
and with GSK policy.
The study will also be conducted in accordance with ICH GCP, all applicable subject 
privacy requirements, and the guiding principles of the current version of the Declaration 
of Helsinki. This includes, but is not limited to, the following:

IRB/IEC review and favorable opinion/approval of the study protocol and 
amendments as applicable.

Obtaining signed informed consent.

Investigator reporting requirements (e.g., reporting of AEs/SAEs/protocol 
deviations to IRB/IEC).

GSK will provide full details of the above procedures, either verbally, in writing, 
or both.

Signed informed consent must be obtained for each subject before participation in 
the study.

The IRB/IEC, and where applicable the regulatory authority, approve the clinical 
protocol and all optional assessments, including genetic research.

Optional assessments (including those in a separate protocol and/or under separate 
informed consent) and the clinical protocol should be concurrently submitted for 
approval unless regulation requires separate submission.

Approval of the optional assessments may occur after approval is granted for the 
clinical protocol where required by regulatory authorities. In this situation, written 
approval of the clinical protocol should state that approval of optional 
assessments is being deferred and the study, with the exception of the optional 
assessments, can be initiated.


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10.3.
Quality Control (Study Monitoring)

In accordance with applicable regulations including GCP, and GSK procedures, 
GSK monitors will contact the site before the start of the study to review with the 
site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK requirements.

When reviewing data collection procedures, the discussion will also include 
identification, agreement, and documentation of data items for which the eCRF 
will serve as the source document.
GSK/PPD will monitor the study and site activity to verify that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements.
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.
10.4.
Quality Assurance

To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and 
the regulatory agencies may conduct a regulatory inspection at any time during or 
after completion of the study.

In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s), and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss 
the conduct of the study, any findings/relevant issues and to implement any 
corrective and/or preventative actions to address any findings/issues identified.
10.5.
Study and Site Closure

Upon completion or premature discontinuation of the study, the GSK/PPD 
monitor will conduct site closure activities with the investigator or site staff, as 
appropriate, in accordance with applicable regulations including GCP, and GSK 
Standard Operating Procedures.

GSK reserves the right to temporarily suspend or prematurely discontinue this 
study at any time for reasons including, but not limited to, safety or ethical issues 
or severe non-compliance. For multicenter studies, this can occur at one or more 
or at all sites.

If GSK determines such action is needed, GSK will discuss the reasons for taking 
such action with the investigator or the head of the medical institution (where 
applicable). When feasible, GSK will provide advance notification to the 


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investigator or the head of the medical institution, where applicable, of the 
impending action.

If the study is suspended or prematurely discontinued for safety reasons, GSK 
will promptly inform all investigators, heads of the medical institutions (where 
applicable), and/or institution(s) conducting the study. GSK will also promptly
inform the relevant regulatory authorities of the suspension or premature 
discontinuation of the study and the reason(s) for the action.

If required by applicable regulations, the investigator or the head of the medical 
institution (where applicable) must inform the IRB/IEC promptly and provide the 
reason for the suspension or premature discontinuation.
10.6.
Records Retention

Following closure of the study, the investigator or the head of the medical 
institution (where applicable) must maintain all site study records (except for 
those required by local regulations to be maintained elsewhere) in a safe and 
secure location.

The records must be maintained to allow easy and timely retrieval, when needed 
(e.g., for a GSK audit or regulatory inspection) and must be available for review 
in conjunction with assessment of the facility, supporting systems, and relevant 
site staff.

Where permitted by local laws/regulations or institutional policy, some or all of 
these records can be maintained in a format other than hard copy (e.g., 
microfiche, scanned, electronic); however, caution needs to be exercised before 
such action is taken.

The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, 
including re-generating a hard copy, if required. Furthermore, the investigator 
must ensure there is an acceptable back-up of these reproductions and that an 
acceptable quality control process exists for making these reproductions.

GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements. The minimum retention time 
will meet the strictest standard applicable to that site for the study, as dictated by 
any institutional requirements or local laws or regulations, GSK 
standards/procedures, and/or institutional requirements.

The investigator must notify GSK of any changes in the archival arrangements, 
including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated with 
the site.


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10.7.
Provision of Study Results to Investigators, Posting of 
Information on Publically Available Clinical Trials Registers 
and Publication
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 site or other 
mutually-agreeable location.
GSK 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 subjects, as 
appropriate.
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy.


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11.
REFERENCES
Chen H, Yu KD, Xu GZ. Association between Variant Y402H in Age-Related Macular 
Degeneration (AMD) Susceptibility Gene CFH and Treatment Response of AMD: A 
Meta-Analysis. PloS ONE 2012; 7: e42464.
Department of Health and Human Services (DHHS), Food and Drug Administration, 
Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research 
(US). Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial 
Clinical Trials for Therapeutics in Adult Healthy Volunteers. Rockville, MD; July 2005. 
[30 screens]. Available from: 
http://www.fda.gov/downloads/Drugs/.../Guidances/UCM078932.pdf
Department of Health and Human Services (DHHS), Food and Drug Administration, 
Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research 
(US). Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation. July 2009. [28 screens]. Available from: 
http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-
gen/documents/document/ucm174090.pdf
European Medicines Agency. Guideline on Strategies to Identify and Mitigate Risks for 
First-In-Human Clinical Trials With Investigational Medicinal Products Committee for 
Medicinal Products for Human Use. Canary Wharf, London; July 2007. EMEA 
Publication. No. EMEA/CHMP/SWP/28367/07. [12 screens]. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/
WC500002988.pdf
GlaxoSmithKline Document Number 2015N255155_00. GSK3442830 Investigator’s 
Brochure. 04-Feb-2016
Gorin MB. Genetic insights into age-related macular degeneration: Controversies 
addressing risk, causality, and therapeutics. Mol. Asp. Med. 2012; 33: 467-86.
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. 
Contraceptive Technology. 19th edition. New York: Ardent Media, 2007: 24. Table 3-2.
International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use (ICH). Guidance on Nonclinical Safety Studies for the 
Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals
M3 (R2); June 2009. [31 screens]. Available from: 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplina
ry/M3_R2/Step4/M3_R2__Guideline.pdf
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-84.
Levey AS, Stevens LA, et al. A New Equation to Estimate Glomerular Filtration Rate. 
Ann Intern Med. 2009 May 5; 150 (9): 604-12.


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Stranz M, Kastango ES. A Review of pH and Osmolarity, Int J Pharm Compd.
2002 May/June; 6(3): 216-20.
Whitehead J, Patterson S, Webber D, Francis S, Zhou Y. Easy-to-implement Bayesian 
methods for dose-escalation studies in healthy volunteers. Biostatistics. 
2001 Mar;2(1):47-61.


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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
Abbreviations
5-HT
5-hydroxytryptamine, serotonin
ACR
albumin to creatinine ratio
AE
adverse event
Ae
amount excreted in urine
ALT
alanine aminotransferase 
ANOVA
analysis of variance
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC(0-)
AUC extrapolated from time zero to infinity
AUC(0-)
AUC over the dosing interval 
AUC(0-24) 
AUC from time zero to 24 hours after dosing
AUC(0-t)
AUC from time zero to the last quantifiable concentration after dosing
BP
blood pressure
CL
total systemic clearance
CI
confidence interval
CLr
renal clearance
Cmax
maximum plasma concentration
C
trough concentration
dL
deciliter
DMID
Division of Microbiology and Infectious Diseases
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
EM
erythema multiforme
FDA
Food and Drug Administration
Feu(t1-t2)
urinary excretion ratio relative to dose
FSH
follicle-stimulating hormone
FTIH
first time in human
g
gram
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
GSK
GlaxoSmithKline
hCG
human chorionic gonadotropin
Hgb
hemoglobin
Hct
hematocrit
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator’s Brochure
ICH
International Council for Harmonisation


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IEC
Independent Ethics Committee
INR
international normalized ratio
IRB
Institutional Review Board
IV
intravenous
kg
kilogram
KIM-1
kidney injury molecule 1
L
liter
lb
pound
g
microgram
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
mL
milliliter
mm Hg
millimeters of mercury
msec
millisecond
NGAL
neutrophil gelatinase-associated lipocalin
NOAEL
no observed adverse effect level
NOEL
no observed effect level
OC RDC
Oracle Clinical Remote Data Capture System 
PK
pharmacokinetic
QTc
corrected QT; the measure of time between the start of the Q wave and 
the end of the T wave
QTcB
corrected QT interval using Bazett’s formula
QTcF
corrected QT interval using Fridericia’s formula
SAE
serious adverse event
SJS
Stevens-Johnson syndrome
SRM
study reference manual
RAP
reporting and analysis plan
RBC
red blood cell
t1/2
terminal elimination half-life
TEN
toxic epidermal necrolysis
TID
3-times daily
Tmax
time to Cmax
ULN
upper limit of normal 
Vss
steady-state volume of distribution
WBC
white blood cell
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
GSKDrug
MedDRA
SAS
WinNonlin


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12.2.
Appendix 2: Liver Chemistry Stopping Criteria
Phase I Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm
Continue Study Treatment 
Discontinue Study Treatment 
*INR value not applicable to subjects on anticoagulants 
ALT ≥3xULN 
No
Yes
Must refer to Liver Safety Required Actions and Follow up Assessments  section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*
Liver safety required actions and follow-up assessments section can be found in 
Appendix 3. 


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12.3.
Appendix 3: Liver Safety Required Actions and Follow-up 
Assessments
Phase I liver chemistry stopping criteria have been designed to assure subject safety and 
to evaluate liver event etiology (in alignment with the FDA guidance, “Drug-Induced 
Liver Injury: Premarketing Clinical Evaluation,” [DHHS, 2009].
Phase I Liver Chemistry Stopping Criteria and Required Follow-up Assessments
Liver Chemistry Stopping Criteria – Liver Stopping Event
ALT-absolute
ALT ≥3× ULN
If ALT ≥3× ULN AND bilirubin1,2 2× ULN (>35% direct bilirubin) or INR >1.5, 
report as an SAE.
See additional Actions and Follow-up assessments listed below.
Required Actions and Follow-Up Assessments after Liver Stopping Event
Actions
Follow-Up Assessments

Immediately discontinue study treatment

Report the event to GSK within 24 hours

Complete the liver event eCRF, 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 subject until liver chemistries 
resolve, stabilize, or return to within baseline 
(see MONITORING below)
MONITORING:
If ALT ≥3× ULN AND bilirubin 2× ULN  or 
INR >1.5

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow-up assessments within 
24 hours

Monitor subjects twice weekly until liver 
chemistries resolve, stabilize or return to 
within baseline

A specialist or hepatology consultation is 
recommended
If ALT ≥3× ULN AND bilirubin <2× ULN and 
INR ≤1.5:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow-up assessments within 
24 to 72 hours

Monitor subjects weekly until liver 
chemistries resolve, stabilize or return to 

Viral hepatitis serology3

Blood sample for PK analysis, obtained 
within 1 day of last dose4

Serum creatine phosphokinase and lactate 
dehydrogenase.

Fractionate bilirubin, if total bilirubin 
2× ULN

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 case report form
If ALT ≥3× ULN AND bilirubin 2× ULN 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 HPLC assay 
(quantifies potential acetaminophen 
contribution to liver injury in subjects with 
definite or likely acetaminophen use in the 


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Liver Chemistry Stopping Criteria – Liver Stopping Event
within baseline
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 eCRF forms.
ALT = alanine aminotransferase, AST = aspartate aminotransferase, eCRF = electronic case report form, HPLC = high 
pressure liquid chromatography, IgG = Immunoglobulin G, IgM = Immunoglobulin M, INR = international 
normalized ratio, PK = pharmacokinetic, SAE = serious adverse event, ULN = upper limit of normal.
NOTES:
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that subject if ALT 3× ULN and bilirubin 2× ULN. 
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 3× ULN and bilirubin 2× ULN (>35% direct bilirubin) or ALT 3× ULN and 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); INR measurement is not required and the threshold value stated will 
not apply to subjects receiving anticoagulants
3. Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis C 
RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing);  Hepatitis E IgM antibody 
4. Pharmacokinetic sample may not be required for subjects known to be receiving placebo or non-GSK comparator 
treatments. Record the date and time of the PK blood sample draw and the date and time of the last dose of study 
treatment before blood sample draw on the eCRF. If the date or time of the last dose is unclear, provide the 
subject’s best approximation. If the date or 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 Study Reference Manual.


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12.4.
Appendix 4: Genetic Research
Genetics – Background
Naturally occurring genetic variation may contribute to inter-individual variability in 
response to medicines, as well as an individual’s risk of developing specific diseases. 
Genetic factors associated with disease characteristics may also be associated with 
response to therapy, and could help to explain some clinical study outcomes. For 
example, genetic variants associated with age-related macular degeneration are reported 
to account for much of the risk for the condition [Gorin, 2012] with certain variants 
reported to influence treatment response [Chen, 2012]. Thus, knowledge of the genetic 
etiology of disease may better inform understanding of disease and the development of 
medicines. Additionally, genetic variability may impact the pharmacokinetics 
(absorption, distribution, metabolism, and elimination), or pharmacodynamics 
(relationship between concentration and pharmacologic effects or the time course of 
pharmacologic effects) of a specific medicine and/or clinical outcomes (efficacy and/or 
safety) observed in a clinical study.
Genetic Research Objectives and Analyses
The objectives of the genetic research are to investigate the relationship between genetic 
variants and: 

Response to medicine, including GSK3342830 or any concomitant medicines;
Enterobacteriaceae susceptibility, severity, and progression and related conditions
Genetic data may be generated while the study is underway or after completion of the 
study. Genetic evaluations may include focused candidate gene approaches and/or
examination of a large number of genetic variants throughout the genome (whole genome 
analyses). Genetic analyses will utilize data collected in the study and will be limited to 
understanding the objectives highlighted above. Analyses may be performed using data 
from multiple clinical studies to investigate these research objectives.
Appropriate descriptive and/or statistical analysis methods will be used. A detailed 
description of any planned analyses will be documented in a RAP before initiation of the 
analysis. Planned analyses and results of genetic investigations will be reported either as 
part of the clinical RAP and study report, or in a separate genetics RAP and report, as 
appropriate.
Study Population
Any subject who is enrolled in the study can participate in genetic research. Any subject 
who has received an allogeneic bone marrow transplant must be excluded from the 
genetic research.
Study Assessments and Procedures
A key component of successful genetic research is the collection of samples during
clinical studies. Collection of samples, even when no a priori hypothesis has been 


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identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.

A 6 mL blood sample will be taken for DNA extraction. A blood sample is collected 
at the baseline visit, after the subject has been randomized and provided informed 
consent for genetic research. Instructions for collection and shipping of the genetic 
sample are described in the SRM. The DNA from the blood sample may undergo 
quality control analyses to confirm the integrity of the sample. If there are concerns 
regarding the quality of the sample, then the sample may be destroyed. The blood 
sample is taken on a single occasion unless a duplicate sample is required due to an 
inability to utilize the original sample.
The genetic sample is labelled (or “coded”) with the same study-specific number used to 
label other samples and data in the study. This number can be traced or linked back to the 
subject by the investigator or site staff. Coded samples do not carry personal identifiers 
(such as name or social security number). 
Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study, or GSK may destroy the samples sooner. GSK or those working 
with GSK (for example, other researchers) will only use samples collected from the study 
for the purpose stated in this protocol and in the informed consent form. Samples may be 
used as part of the development of a companion diagnostic to support the GSK medicinal 
product.
Subjects can request their sample to be destroyed at any time.
Informed Consent
Subjects who do not wish to participate in the genetic research may still participate in the 
study. Genetic informed consent must be obtained before any blood is taken.
Subject Withdrawal from Study
If a subject who has consented to participate in genetic research withdraws from the 
clinical study for any reason other than being lost to follow-up, the subject will be given a
choice of one of the following options concerning the genetic sample, if already 
collected:

Continue to participate in the genetic research in which case the genetic DNA sample 
is retained

Discontinue participation in the genetic research and destroy the genetic DNA 
sample 
If a subject withdraws consent for genetic research or requests sample destruction for any 
reason, the investigator must complete the appropriate documentation to request sample 
destruction within the timeframe specified by GSK and maintain the documentation in 
the site study records.


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Genotype data may be generated during the study or after completion of the study and 
may be analyzed during the study or stored for future analysis.

If a subject withdraws consent for genetic research and genotype data have not 
been analyzed, it will not be analyzed or used for future research.

Genetic data that have been analyzed at the time of withdrawn consent will 
continue to be stored and used, as appropriate.
Screen and Baseline Failures
If a sample for genetic research has been collected and it is determined that the subject 
does not meet the entry criteria for participation in the study, then the investigator should 
instruct the subject that their genetic sample will be destroyed. No forms are required to 
complete this process as it will be completed as part of the consent and sample 
reconciliation process. In this instance a sample destruction form will not be available to 
include in the site files.
Provision of Study Results and Confidentiality of Subject’s Genetic Data
GSK may summarize the genetic research results in the clinical study report, or 
separately and may publish the results in scientific journals.
GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the subject, 
family members, insurers, or employers of individual genotyping results that are not 
known to be relevant to the subject’s medical care at the time of the study, unless 
required by law. This is due to the fact that the information generated from genetic 
studies is generally preliminary in nature, and therefore the significance and scientific 
validity of the results are undetermined. Further, data generated in a research laboratory 
may not meet regulatory requirements for inclusion in clinical care.


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12.5.
Appendix 5: Definition of and Procedures for Recording, 
Evaluating, Follow-Up and Reporting of Adverse Events
12.5.1.
Definition of Adverse Events
Adverse Event Definition:

An AE is any untoward medical occurrence in a patient or clinical investigation 
subject, temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product.

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 medicinal product.
Events meeting AE definition include:

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECGs, radiological scans, vital signs measurements), 
including those that worsen from baseline, and felt to be clinically significant in the 
medical and scientific judgment of the investigator.

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 treatment administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication (overdose per se will not be reported as an 
AE/SAE unless this is an intentional overdose taken with possible suicidal/self-
harming intent. This should be reported regardless of sequelae).
Events NOT meeting definition of an AE include:

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 subject’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 subject’s 
condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE.

Situations where an untoward medical occurrence did not occur (social and/or 


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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.
12.5.2.
Definition of Serious Adverse Events
If an event is not an AE per definition in Section 12.5.1, 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, etc).
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose:
a.
Results in death
b.
Is life-threatening
NOTE:
The term “life-threatening” in the definition of “serious” refers to an event in which the 
subject was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires hospitalization or prolongation of existing hospitalization
NOTE:

In general, hospitalization signifies that the subject 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 out-patient setting. Complications that occur during hospitalization are AEs.  
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.
d.
Results in disability/incapacity
NOTE:

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 or prevent everyday 
life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect


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f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether 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 subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious.

Examples of such events are 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.
g.
Is associated with liver injury and impaired liver function defined as:
ALT 3× ULN and total bilirubin* 2× ULN (>35% direct), or
ALT 3× ULN and international normalized ratio (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 3× ULN 
and total bilirubin 2× ULN, 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 
subjects receiving anticoagulants. If INR measurement is obtained, the value is to be 
recorded on the SAE form.
12.5.3.
Definition of Cardiovascular Events
Cardiovascular Events Definition:
Investigators will be required to fill out the specific cardiovascular event page of the 
eCRF for the following AEs and SAEs:

Myocardial infarction/unstable angina

Congestive heart failure

Arrhythmias

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularization


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12.5.4.
Recording of AEs and SAEs
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) 
relative to the event.

The investigator will then record all relevant information regarding an AE/SAE in the 
eCRF.

It is not acceptable for the investigator to send photocopies of the subject’s medical 
records to GSK in lieu of completion of the GSK, AE/SAE eCRF page.

There may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers, with the exception of the 
subject number, will be blinded 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. In such cases, the diagnosis will be 
documented as the AE/SAE and not the individual signs/symptoms.
12.5.5.
Evaluating AEs and SAEs
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study according to the US National Institute of Allergy and Infectious 
Diseases DMID criteria for toxicity assessment (Appendix 6). 
An event is defined as “serious” when it meets at least one of the predefined outcomes as 
described in the definition of an SAE (Section 12.5.2). 
Assessment of Causality

The investigator is obligated to assess the relationship between study treatment and 
the occurrence of each AE/SAE.

A “reasonable possibility” is meant to convey that there are facts/evidence 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 natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the study 
treatment will be considered and investigated.


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
The investigator will also consult the IB and/or Product Information, for marketed 
products, in the determination of 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 when an SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK. However, it is very 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, amending the SAE data collection tool accordingly.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to 
elucidate as fully as possible the nature and/or causality of the AE or SAE.

The investigator is obligated to assist. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health care 
professionals.

If a subject 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 eCRF.

The investigator will submit any updated SAE data to GSK within the designated 
reporting time frames.
12.5.6.
Reporting of SAEs to GSK
SAE reporting to GSK via electronic data collection tool

Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool.

If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the medical monitor.

Site will enter the SAE data into the electronic system as soon as it becomes 
available.

The investigator will be required to confirm review of the SAE causality by ticking 
the “reviewed” box at the bottom of the eCRF page within 72 hours of submission of 


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the SAE.

After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) 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 subject or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
off-line, the site can report this information on a paper SAE form or to the medical 
monitor by telephone.

Contacts for SAE receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page.


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12.6.
Appendix 6: DMID Adult Toxicity Tables for AE Assessment
ESTIMATING SEVERITY GRADE: For abnormalities NOT found elsewhere in the 
Toxicity Tables, use the following scale to estimate grade of severity:
GRADE 1
Mild
Transient or mild discomfort (<48 hours); no medical 
intervention/therapy required
GRADE 2
Moderate
Mild to moderate limitation in activity – some assistance may 
be needed; no or minimal medical intervention/therapy 
required
GRADE 3
Severe
Marked limitation in activity, some assistance usually 
required; medical intervention/therapy required, 
hospitalizations possible
GRADE 4
Life-threatening
Extreme limitation in activity, significant assistance required; 
significant medical intervention/therapy required, 
hospitalization or hospice care probable
SERIOUS OR LIFE-THREATENING AEs: ANY clinical event deemed by the 
investigator to be serious or life-threatening should be considered a Grade 4 event. 
Clinical events considered to be serious or life-threatening include, but are not limited to: 
seizures, coma, tetany, diabetic ketoacidosis, disseminated intravascular coagulation, 
diffuse petechiae, paralysis, acute psychosis, and severe depression.
COMMENTS REGARDING THE USE OF THESE TABLES

Standardized and commonly used toxicity tables (Division of AIDS, National 
Cancer Institute’s Common Toxicity Criteria, and World Health Organization) 
have been adapted for use by the Division of Microbiology and Infectious 
Diseases (DMID) and modified to better meet the needs of participants in DMID 
trials.

For parameters not included in the following Toxicity Tables, sites should refer to 
the “Guide for Estimating Severity Grade” located above.

Criteria are generally grouped by body system.

Some protocols may have additional protocol-specific grading criteria, which will 
supersede the use of these tables for specified criteria.


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
9.5 to 10.5 g/dL
8.0 to 9.4 g/dL
6.5 to 7.9 g/dL
<6.5 g/dL
Absolute Neutrophil Count
1000 to 1500 /mm3
750 to 999 /mm3
500 to 749 /mm3
<500 /mm3
Platelets
75,000 to 99,999 /mm3
50,000 to 74,999 /mm3
20,000 to 49,999 /mm3
<20,000 /mm3
White Blood Cells
11,000 to 13,000 /mm3
13,000 to 15,000 /mm3
15,000 to 30,000 /mm3
>30,000 or <1000 /mm3
% Polymorphonuclear Leukocytes + 
Band Cells
>80%
90 to 95%
>95%
N/A
Abnormal Fibrinogen
Low: 100 to 200 mg/dL
High: 400 to 600 mg/dL
Low: <100 mg/dL
High: >600 mg/dL
Low: <50 mg/dL
High: N/A
Fibrinogen associated with gross bleeding or 
with disseminated coagulation
Fibrin Split Product
20 to 40 mcg/mL
41 to 50 mcg/mL
51 to 60 mcg/mL
>60 mcg/mL
Prothrombin Time (PT)
1.01 to 1.25 ULN
1.26 to 1.5 ULN
1.51 to 3.0 ULN
>3 ULN
Activated Partial Thromboplastin (APTT)
1.01 to 1.66 ULN
1.67 to 2.33 ULN
2.34 to 3 ULN
>3 ULN
Methemoglobin
5.0 to 9.9%
10.0 to 14.9%
15.0 to 19.9%
>20.0%
N/A = not applicable, ULN = upper limit of normal. 


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CHEMISTRIES
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia
130 to 135 mEq/L
123 to 129 mEq/L
116 to 122 mEq/L
<116 mEq/L or abnormal sodium with mental 
status changes or seizures
Hypernatremia
146 to 150 mEq/L
151 to 157 mEq/L
158 to 165 mEq/L
>165 mEq/L or abnormal sodium with mental 
status changes or seizures
Hypokalemia
3.0 to 3.4 mEq/L
2.5 to 2.9 mEq/L
2.0 to 2.4 mEq/L or intensive 
replacement therapy of 
hospitalization required
<2.0 mEq/L or abnormal potassium with
paresis, ileus, or life-threatening arrhythmia
Hyperkalemia
5.6 to 6.0 mEq/L
6.1 to 6.5 mEq/L
6.6 to 7.0 mEq/L
>7.0 mEq/L or abnormal potassium with
life-threatening arrhythmia
Hypoglycemia
55 to 64 mg/dL
40 to 54 mg/dL
30 to 39 mg/dL
<30 mg/dL or abnormal glucose with mental 
status changes or coma
Hyperglycemia
(nonfasting and no prior 
diabetes)
116 to 160 mg/dL
161 to 250 mg/dL
251 to 500 mg/dL
>500 mg/dL or abnormal glucose with
ketoacidosis or seizures
Hypocalcemia
(corrected for albumin)
8.4 to 7.8 mg/dL
7.7 to 7.0 mg/dL
6.9 to 6.1 mg/dL
<6.1 mg/dL or abnormal calcium with
life-threatening arrhythmia or tetany
Hypercalcemia
(corrected for albumin)
10.6 to 11.5 mg/dL
11.6 to 12.5 mg/dL
12.6 to 13.5 mg/dL
>13.5 mg/dL or abnormal calcium with
life-threatening arrhythmia
Hypomagnesemia
1.4 to 1.2 mEq/L
1.1 to 0.9 mEq/L
0.8 to 0.6 mEq/L
<0.6 mEq/L or abnormal magnesium with
life-threatening arrhythmia
Hypophosphatemia
2.0 to 2.4 mg/dL
1.5 to 1.9 mg/dL or 
replacement Rx required
1.0 to 1.4 mg/dL
intensive therapy or hospitalization 
required
<1.0 mg/dL or abnormal phosphate with
life-threatening arrhythmia
Hyperbilirubinemia (when 
accompanied by any increase in 
other liver function test)
1.1 to <1.25 ULN
1.25 to <1.5 ULN
1.5 to 1.75 ULN
>1.75 ULN
Hyperbilirubinemia (when other 
liver function tests are in the 
normal range)
1.1 to <1.5 ULN
1.5 to <2.0 ULN
2.0 to 3.0 ULN
>3.0 ULN
Blood urea nitrogen 
1.25 to 2.5 ULN
2.6 to 5 ULN
5.1 to 10 ULN
>10 ULN
Hyperuricemia (uric acid)
7.5 to 10.0 mg/dL
10.1 to 12.0 mg/dL
12.1 to 15.0 mg/dL
>15.0 mg/dL
Creatinine
1.1 to 1.5 ULN
1.6 to 3.0 ULN
3.1 to 6.0 ULN
>6 ULN or dialysis required
Rx = therapy, ULN = upper limit of normal.


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ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
Aspartate aminotransferase (AST)
1.1 to <2.0 ULN
2.0 to <3.0 ULN
3.0 to 8.0 ULN
>8.0 ULN
Alanine aminotransferase (ALT)
1.1 to <2.0 ULN
2.0 to <3.0 ULN
3.0 to 8.0 ULN
>8.0 ULN
Gamma glutamyl transferase (GGT)
1.1 to <2.0 ULN
2.0 to <3.0 ULN
3.0 to 8.0 ULN
>8.0 ULN
Alkaline Phosphatase
1.1 to <2.0 ULN
2.0 to <3.0 ULN
3.0 to 8.0 ULN
>8.0 ULN
Amylase
1.1 to 1.5 ULN
1.6 to 2.0 ULN
2.1 to 5.0 ULN
>5.1 ULN
Lipase
1.1 to 1.5 ULN
1.6 to 2.0 ULN
2.1 to 5.0 ULN
>5.1 ULN
ULN = upper limit of normal.
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Proteinuria
1+ or
200 mg to 1 g loss/day
2 to 3+ or
1 to 2 g loss/day
4+ or
2 to 3.5 g loss/day
Nephrotic syndrome or
>3.5 g loss/day
Hematuria
Microscopic only
<10 RBC/hpf
Gross, no clots
>10 RBC/hpf
Gross, with or without clots,
or red blood cells casts
Obstructive or 
required transfusion
HPF = high powered field, RBC = red blood cells.


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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac rhythm
N/A
Asymptomatic, transient signs, no 
Rx required
Recurrent/persistent; symptomatic 
Rx required
Unstable dysrhythmia; 
hospitalization and treatment 
required
Hypertension
Transient increase >20 mm Hg;
no treatment 
Recurrent, chronic increase 
>20 mm Hg;
treatment required 
Acute treatment required; 
outpatient treatment or 
hospitalization possible 
End organ damage or 
hospitalization required 
Hypotension
Transient orthostatic hypotension 
with heart rate increased by 
<20 beats/minute or decreased by 
<10 mm Hg systolic BP.
No treatment required
Symptoms due to orthostatic 
hypotension or BP decreased by 
<20 mm Hg systolic; correctable 
with oral fluid treatment
Requires IV fluids;
no hospitalization required
Mean arterial pressure <60 mm Hg 
or end organ damage or shock;
requires hospitalization and 
vasopressor treatment
Pericarditis
Minimal effusion
Mild/moderate asymptomatic 
effusion, no treatment
Symptomatic effusion; pain; EKG 
changes
Tamponade; pericardiocentesis or 
surgery required
Hemorrhage, Blood Loss
Microscopic/occult
Mild, no transfusion
Gross blood loss; 
1 to 2 units transfused
Massive blood loss; >3 units 
transfused
BP = blood pressure, EKG = electrocardiogram, IV = intravenous, N/A = not applicable, Rx = therapy.
RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Cough
Transient; no treatment
Persistent cough; treatment responsive
Paroxysmal cough; uncontrolled with treatment
N/A
Bronchospasm, 
Acute
Transient; no treatment; 
FEV1 70 to 80% of peak flow
Requires treatment; normalizes with 
bronchodilator; FEV1 50 to 70% of peak 
flow
No normalization with bronchodilator; FEV1 25 
to 50% of peak flow; or retractions present
Cyanosis: FEV1 <25% of peak 
flow; or intubation necessary
Dyspnea
Dyspnea on exertion
Dyspnea with normal activity
Dyspnea at rest
Dyspnea requiring oxygen 
therapy
FEV1 = forced expiratory volume in 1 second, N/A = not applicable.


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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Nausea
Mild or transient; maintains 
reasonable intake
Moderate discomfort; intake 
decreased significantly; some 
activity limited
No significant intake; requires IV fluids
Hospitalization required
Vomiting
1 episode in 24 hours
2 to 5 episodes in 24 hours
>6 episodes in 24 hours or needing IV 
fluids
Physiologic consequences requiring 
hospitalization or requiring parenteral nutrition
Constipation
Requiring stool softener or 
dietary modification
Requiring laxatives
Obstipation requiring manual evacuation 
or enema
Obstruction or toxic megacolon
Diarrhea
Mild or transient; 3 to 
4 loose stools/day or mild 
diarrhea lasting <1 week
Moderate or persistent; 5 to 
7 loose stools/day or diarrhea 
lasting >1 week
>7 loose stools/day or bloody diarrhea; or 
orthostatic hypotension or electrolyte 
imbalance or >2 L IV fluids required
Hypotensive shock or physiologic 
consequences requiring hospitalization
Oral discomfort/
Dysphagia
Mild discomfort; no difficulty 
swallowing
Some limits on eating/drinking
Eating/talking very limited; unable to 
swallow solid foods
Unable to drink fluids; requires IV fluids
IV = intravenous.
NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Neuro-Cerebellar
Slight incoordination 
dysdiadochokinesis
Intention tremor, dysmetria, slurred 
speech; nystagmus
Locomotor ataxia
Incapacitated
Psychiatric
Mild anxiety or depression
Moderate anxiety or depression; 
therapy required; change in normal 
routine
Severe mood changes requiring therapy; 
or suicidal ideation; or aggressive 
ideation
Acute psychosis requiring 
hospitalization; or suicidal 
gesture/attempt or hallucinations
Muscle strength
Subjective weakness; no objective 
symptoms/signs
Mild objective signs/symptoms; no 
decrease in function
Objective weakness; function limited
Paralysis
Paresthesia
(burning, tingling, etc.)
Mild discomfort; no treatment 
required
Moderate discomfort; non- narcotic 
analgesia required
Severe discomfort; or narcotic analgesia 
required with symptomatic improvement
Incapacitating; or not responsive 
to narcotic analgesia
Neurosensory
Mild impairment in sensation 
(decreased sensation, e.g., 
vibratory, pinprick, hot/cold in great 
toes) in focal area or symmetrical 
distribution; or change in taste, 
smell, vision, and/or hearing
Moderate impairment (moderately 
decreased sensation, e.g., 
vibratory, pinprick, hot/cold to 
ankles) and/or joint position or mild 
impairment that is not symmetrical
Severe impairment (decreased or loss of 
sensation to knees or wrists) or loss of 
sensation of at least moderate degree in 
multiple different body areas (i.e., upper 
and lower extremities)
Sensory loss involves limbs and 
trunk; paralysis; or seizures


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MUSCULOSKELETAL
Grade 1
Grade 2
Grade 3
Grade 4
Arthralgia 
(joint pain)
Mild pain not interfering with function
Moderate pain, analgesics and/or pain 
interfering with function but not with ADL
Severe paid; pain and/or analgesics 
interfering with ADL
Disabling pain
Arthritis
Mild pain with inflammation, erythema or 
joint swelling, but not interfering with 
function
Moderate pain with inflammation, erythema or 
joint swelling; interfering with function but not 
with ADL
Severe pain with inflammation, erythema 
or joint swelling, and interfering with ADL
Permanent and/or 
disabling joint 
destruction
Myalgia
Myalgia with no limitation of activity
Muscle tenderness (at other than injection site) 
or with moderate impairment of activity
Severe muscle tenderness with marked 
impairment of activity
Frank myonecrosis
ADL = activities of daily living.
SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Mucocutaneous
Erythema; pruritus
Diffuse, maculo papular rash, dry 
desquamation
Vesiculation or moist 
desquamation or ulceration
Exfoliative dermatitis, mucous membrane 
involvement or erythema, multiforme or suspected 
Stevens-Johnson or necrosis requiring surgery
Induration
<15 mm
15 to 30 mm
>30 mm
N/A
Erythema
<15 mm
15 to 30 mm
>30 mm
N/A
Edema
<15 mm
15 to 30 mm
>30 mm
N/A
Rash at injection site
<15 mm
15 to 30 mm
>30 mm
N/A
Pruritus
Slight itching at injection site
Moderate itching at injection extremity
Itching over entire body
N/A
N/A = not applicable.
SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Allergic reaction
Pruritus without rash
Localized urticarial
Generalized urticarial; angioedema
Anaphylaxis
Headache
Mild, no treatment required
Transient, moderate; treatment 
required
Severe; responds to initial narcotic 
therapy
Intractable; requires repeated 
narcotic therapy
Fever: oral
37.7 to 38.5C or 100.0 to 101.5F
38.6 to 39.5C or 101.6 to 102.9F
39.6 to 40.5C or 103 105F
>40C or >105F
Fatigue
Normal activity reduced <48 hours
Normal activity decreased 25 to 50%; 
>48 hours
Normal activity decreased >50%; 
cannot work
Unable to care for self


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12.7.
Appendix 7: Allergic Reactions Including Anaphylaxis
ALLERGIC REACTION
Pruritus without rash (Grade 1 allergic reaction):
Subjects with Grade 1 allergic reaction should be evaluated by the investigator 
immediately. The study drug should be permanently discontinued if the following signs 
or symptoms are noted at any time:
1.
Temperature >38.5°C
2.
Eosinophilia
3.
Respiratory involvement including bronchospasm, laryngospasm, or 
angioedema
4.
Any indication of internal organ involvement (hepatitis, nephritis)
In the absence of the above signs or symptoms, subjects with Grade 1 allergic reaction 
may continue the study drug at the discretion of the investigator. The subject should be 
advised to contact the investigator immediately if there is any worsening of the allergic 
reaction and/or if any systemic signs or symptoms worsen. If the allergic reaction is 
considered to be most likely due to concomitant illness or non-study medication, standard 
management, including discontinuation of the likely causative agent, should be 
undertaken. If no other causative factor is found after clinical evaluation, the subject may 
be treated symptomatically until the rash resolves. Antihistamines, topical corticosteroids, 
or antipruritic agents may be prescribed. The subject should remain on the study to be 
followed for safety and pharmacokinetics as outlined in Section 7.1.
Localized urticaria (Grade 2 allergic reaction):
Subjects with Grade 2 allergic reaction should be evaluated by the investigator 
immediately. The study drug should be permanently discontinued if the following signs 
or symptoms are noted at any time:
1.
Temperature >38.5°C
2.
Eosinophilia
3.
Respiratory involvement including bronchospasm, laryngospasm, or 
angioedema
4.
Any indication of internal organ involvement (hepatitis, nephritis)
In the absence of the above signs or symptoms, subjects with Grade 2 allergic reaction 
may continue the study drug at the discretion of the investigator. The subject should be 
advised to contact the investigator immediately if there is any worsening of the allergic 
reaction and/or if any systemic signs or symptoms worsen. If the allergic reaction is 
considered to be most likely due to concomitant illness or non-study medication, standard 
management, including discontinuation of the likely causative agent, should be 
undertaken. If no other causative factor is found after clinical evaluation, the subject may 


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be treated symptomatically until the rash resolves. Antihistamines, topical corticosteroids, 
or antipruritic agents may be prescribed. The subject should remain on the study to be 
followed for safety and pharmacokinetics as outlined in Section 7.1.
Generalized urticaria or angioedema (Grade 3 allergic reaction):
Subjects will permanently discontinue the study drug and be withdrawn from the trial. 
Subjects will be treated as clinically appropriate. Subjects should be followed up until 
resolution of the AE and standard management should be undertaken.
Anaphylaxis (Grade 4 allergic reaction):
Anaphylaxis is an immediate and potentially life-threatening systemic reaction to an 
exogenous stimulus e.g., a drug.
Anaphylaxis typically involves 2 or more body systems (cutaneous, respiratory, 
cardiovascular, neurologic, or gastrointestinal) usually within 60 minutes of exposure but 
can be delayed up to several hours and can less commonly be biphasic or protracted 
despite treatment.
The term anaphylaxis typically has been reserved for allergic, 
Immunoglobulin E-mediated immediate hypersensitivity reactions. Anaphylactoid 
responses (also included here) are clinically indistinguishable reactions that occur by
non-antigen/antibody-mediated mechanisms. Both reactions produce clinical sequelae 
due to the massive release of mediators from mast cells and basophils but hypotension 
and associated cardiac AEs are less common in anaphylactoid reactions. In contrast to 
anaphylactic reactions, anaphylactoid reactions can occur upon initial exposure to 
exogenous stimulus.
Subjects will permanently discontinue the study drug and be withdrawn from the trial. 
Subjects will be treated as clinically appropriate. Subjects should be followed up until 
resolution of the AE and standard management should be undertaken.
Revised ACTG Toxicity Grade
Definitions
Investigator Action
Grade 1
Pruritus without rash
May continue therapy
Grade 2
Localized urticaria
May continue therapy
Grade 3
Generalized urticaria
Angioedema
Discontinue therapy
Grade 4
Anaphylaxis
Discontinue therapy


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12.8.
Appendix 8: Modified List of Highly Effective Methods for 
Avoiding Pregnancy in Females of Reproductive Potential 
and Collection of Pregnancy Information
12.8.1.
Modified List of Highly Effective Methods for Avoiding Pregnancy 
in Females of Reproductive Potential
This list does not apply to females of reproductive potential with same sex partners, when 
this is their preferred and usual lifestyle or for subjects who are and will continue to be 
abstinent from penile-vaginal intercourse on a long term and persistent basis.
Contraceptive subdermal implant 
Intrauterine device or intrauterine system 
Oral contraceptive, either combined or progestogen alone [Hatcher, 2007] 
Injectable progestogen [Hatcher, 2007]
Contraceptive vaginal ring [Hatcher, 2007]
Percutaneous contraceptive patches [Hatcher, 2007]
Male partner sterilization with documentation of azoospermia before the female 
subject’s entry into the study, and this male is the sole partner for that subject 
[Hatcher, 2007]. The documentation on male sterility can come from the clinic 
personnel’s review of the subject’s medical records, medical examination and/or 
semen analysis, or medical history interview provided by her or her partner.
Male condom plus partner use of one of the previously listed contraceptive 
options
This is an all-inclusive list of those methods that meet the GSK definition of highly 
effective: having a failure rate of less than 1% per year when used consistently and, 
correctly and, when applicable, in accordance with the product label. For non-product 
methods (e.g., male sterility), the investigator determines what is consistent and correct 
use. The GSK definition is based on the definition provided by the ICH 
[ICH, M3 (R2), 2009].
The investigator is responsible for ensuring that subjects understand how to properly use 
these methods of contraception.
12.8.2.
Contraceptive Requirements for Male Subjects with Female 
Partners of Reproductive Potential
Male subjects with female partners of child-bearing potential must agree to use one of the 
following contraception requirements from the time of first dose of study drug until 
completion of the Follow-up visit:
a. Vasectomy with documentation of azoospermia


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b. Male condom plus partner use of one of the following contraceptive options:
Contraceptive subdermal implant 
Intrauterine device or intrauterine system 
Oral contraceptive, either combined or progestogen alone [Hatcher, 2007]
Injectable progestogen [Hatcher, 2007]
Contraceptive vaginal ring [Hatcher, 2007]
Percutaneous contraceptive patches [Hatcher, 2007]
This is an all-inclusive list of those methods that meet the following GSK definition of 
highly effective: having a failure rate of less than 1% per year when used consistently and 
correctly and, when applicable, in accordance with the product label. For non-product 
methods (e.g., male sterility), the investigator determines what is consistent and correct 
use. The GSK definition is based on the definition provided by the ICH 
[ICH, M3 (R2), 2009].
The investigator is responsible for ensuring that subjects understand how to properly use 
these methods of contraception.
12.8.3.
Collection of Pregnancy Information

Investigator will collect pregnancy information on any female subject, who 
becomes pregnant while participating in this study.

Information will be recorded on the appropriate form and submitted to GSK 
within 2 weeks of learning of a subject’s pregnancy.

Subject will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on mother and infant, 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 will be reported as an AE or 
SAE.

A spontaneous abortion is always considered to be an SAE and will be reported as 
such.

Any SAE occurring as a result of a post-study pregnancy that is considered 
reasonably related to the study treatment by the investigator will be reported to 
GSK as described in Appendix 5. 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 subject who becomes pregnant while participating:

Will be withdrawn from the study.


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Pregnancy information for female partner of male subject

Investigator will attempt to collect pregnancy information on any female partner 
of a male study subject who becomes pregnant while participating in this study. 
This applies only to subjects who are randomized to receive study drug. 

After obtaining the necessary signed informed consent from the female partner 
directly, the investigator will record pregnancy information on the appropriate 
form and submit it to GSK within 2 weeks of learning of the partner’s pregnancy.

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 after 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.


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12.9.
Appendix 9: Additional Details on the in vivo Efficacy 
Calculations and Animal to Human Scaling
Efficacy studies using an infusion system to reproduce human drug exposures in the rat 
were conducted to explore the activity of GSK3342830 (based on relevant human 
exposure profiles for a compound of similar series). The profile was used to evaluate the 
efficacy of GSK3342830 against a range of challenge strains in a rat pneumonia model. 
GSK3342830 was highly efficacious against multi-drug resistant P. aeruginosa and 
carbapenemase-producing K. pneumoniae using an exposure curve based on a modelled 
1-g, 1-hour infusion administered every 8 hours (free AUC[0-8] of 80 hμg/mL). Studies 
against A. baumannii isolates suggest a higher exposure would likely be needed for 
efficacy. A 2 g, 3-hour infusion regimen administered every 8 hours was efficacious 
against most A. baumannii strains (free AUC[0-8] of 168 hμg/mL) but higher doses may 
be needed for some strains. Using these data, the range for the target therapeutic 
exposures to be achieved in humans are:

Free AUC(0-t) of 80 to 336 hμg/mL after administration of single doses.
o
336 hμg/mL was derived from 2 × 168 hμg/mL, based on the assumption 
that an additional 2-fold increase in dose may provide an efficacious exposure 
against certain A. baumannii strains.

Based on a human free fraction of 72%, this would predict single dose total drug 
AUC(0-t) values of 112 to 467 hμg/mL.

This corresponds to a target a total AUC(0-24) exposure range of 336 to 
1401 hμg/mL in humans after administration of repeat TID doses.
Simulations were conducted to predict AUC and Cmax values for the nominal doses 
proposed for this protocol. A 3-compartment model developed for a similar siderophore 
β-lactam with healthy volunteer data was adapted for GSK3342830 by using the 
predicted clearance and volume of distribution values obtained from scaling with the 
dedrick monkey method. A total of 3000 subjects were simulated for each dose level and 
predicted AUC and Cmax values after administration of single doses and administration 
of repeat doses are shown in Table 8 and Table 9, respectively.
Table 8
Predicted Exposure Values After Administration of Single Doses
Dose (mg)
AUC(0-) hμg/mL
Cmax μg/mL
5th
percentile
50th
percentile
95th
percentile
5th
percentile
50th
percentile
95th
percentile
250
51.6
64.3
80.6
20.9
27.5
35.4
500
103
128
161
42.2
54.4
71.1
1000
206
259
320
84.8
110
143
2000
409
512
640
168
218
286
4000
820
1026
1282
334
437
569
6000
1236
1545
1933
509
657
849
NOTES:
Systemic NOAEL exposures: AUC(0-24) = 2875 hμg/mL and Cmax = 2270 μg/mL.
Target therapeutic exposure range for AUC(0-) is 112 to 467 hμg/mL.
Data given as median and percentile range (range for 90% of the simulated individual data values).


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Table 9
Predicted Exposure Values After Administration of Repeat Doses
Dose (mg) 
TID
AUC(0-24) hμg/mL
Cmax μg/mL
5th
percentile
50th
percentile
95th
percentile
5th
percentile
50th
percentile
95th
percentile
500
309
385
483
42.2
54.4
71.1
1000
618
777
960
84.8
110
143
2000
1227
1536
1920
168
218
286
4000
2460
3078
3846
334
437
569
NOTES:
Systemic NOAEL exposures: AUC(0-24) = 2875 hμg/mL and Cmax = 2270 μg/mL.
Target therapeutic exposure range for AUC(0-24) is 336 to 1401 hμg/mL.
Data given as median and percentile range (range for 90% of the simulated individual data values).
Repeat dose data were not simulated but are based on the single dose simulation.


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12.10.
Appendix 10: Clostridium difficile Testing Procedure and 
Algorithm
The most critical aspect of Clostridium difficile (C. difficile) testing is specimen handling 
and storage. It is imperative that the site and/or laboratory freezes ALL stool samples for 
possible future testing as quickly as possible after sample collection and testing, but no 
later than 24 hours after collection. If C. difficile laboratory tests cannot be performed 
within 24 hours of collection, the specimen should be frozen immediately.


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12.11.
Appendix 11: Chronic Kidney Disease Epidemiology 
Collaboration Formula
The glomerular filtration rate will be calculated using the Chronic Kidney Disease 
Epidemiology Collaboration formula [Levey, 2009] as follows:
GFR = 141 × min (Scr/,1)× max (Scr/,1)–1.209 × 0.993Age × 1.018 [if female] × 1.159 
[if black]
Where:
Scr is serum creatinine (mg/dL)
is 0.7 for females and 0.9 for males
is –0.329 for females and –0.411 for males
min indicates the minimum of Scr/or 1
max indicates the maximum of Scr/or 1


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12.12.
Appendix 12: Country-Specific Requirements
No country-specific requirements exist.


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12.13.
Appendix 13: Protocol Changes
Protocol Amendment 1
Where the Amendment Applies
To all sites participating in 204847
Summary of Amendment Changes with Rationale
An additional cohort will be added to the study. This cohort will consist of Japanese 
subjects and this component of the study will be designated Part 3. Subjects in Part 3 will 
receive a single IV dose of GSK3342830. The dose to be administered in Part 3 is 
planned to be based on preliminary safety and tolerability results of doses determined to 
be safe and well tolerated in subjects of non-Japanese heritage after completion of the 
single escalation dose cohorts (Part 1). Parts 2 and 3 are planned to be conducted in 
parallel.
List of Specific Changes
The changes to the protocol and their location within the protocol are noted below; the 
rationale for the changes is also provided. Added text is underlined, while removed text is 
shown in strikethrough. Minor stylistic or formatting changes that do not alter the 
conduct of the study are not summarized in this appendix.
Protocol synopsis
Updated to reflect overall changes in the protocol
Section 2.1 Study Rationale
This study represents the first administration of GSK3342830 in humans. It will be 
conducted to define the safety, tolerability, and pharmacokinetics of GSK3342830 after 
administration of single and repeat IV doses in healthy adult subjects, and after 
administration of a single IV dose in healthy adult Japanese subjects.
Rationale: The addition of a cohort consisting of a specific population, Japanese subjects, 
will provide PK data and enable future pivotal Phase III studies in the respective country.
Section 3 Objectives and Endpoints: Part 2 Exploratory Objectives and Part 3
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
AUC[0-], and Cmax) of GSK3342830 with safety 
findings in healthy adult subjects and evaluate urine 
discoloration after administration of repeat IV doses 
in healthy adult subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine


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Part 3
Primary

To investigate the safety and tolerability of 
GSK3342830 after administration of a single IV 
dose in healthy adult Japanese subjects

Clinical safety data from AEs, clinical laboratory tests, 
vital signs (blood pressure, heart rate, temperature, 
and respiration rate), and 12-lead ECG readings
Secondary

To determine the pharmacokinetics of GSK3342830 
after administration of a single IV dose in healthy 
adult Japanese subjects

Plasma and urine concentrations and PK endpoints 
include AUC(0 t), AUC(0-), Cmax, Tmax, CL, Vss, 
t1/2, Feu(t1-t2), Ae, and CLr of GSK3342830, as data 
permit
Exploratory

To correlate PK parameters (AUC[0-t], AUC[0-], 
and Cmax) of GSK3342830 with safety findings 
after administration of a single IV dose in healthy 
adult Japanese subjects

Exposure-response analyses, as data permit

To evaluate the production of any GSK3342830 
metabolites in plasma and urine and determine the 
need to perform a more detailed analysis of any 
metabolites

Metabolite characterization in plasma and urine and 
estimation of observed drug-related material in 
plasma to determine the presence of any metabolite 
>10%, and estimate the percentage dose eliminated 
via urine
Rationale: The objectives and endpoints were updated to include the exploratory 
objective of urine discoloration after repeat IV doses (Part 2) and to include the additional 
cohort (Part 3). The drug may cause urine to appear red or reddish brown (this was seen 
in animal studies). The inclusion of this exploratory objective will allow an evaluation to 
determine if this effect is seen in the clinic in order to inform conduct of clinical trials. 
The additional cohort will consist of Japanese subjects who will receive a single IV dose 
of GSK3342830. The dose in Part 3 will be selected based on preliminary safety and
tolerability results from Part 1. The addition of this cohort will provide PK data and 
enable future pivotal Phase III studies in the respective country.
Section 4.1 Overall Study Design: Paragraph 1
This is a Phase I, first-time-in-human (FTIH), randomized, double-blind (sponsor 
unblinded), single-center, placebo-controlled, dose-escalation study to determine the 
safety, tolerability, and pharmacokinetic (PK) profile of GSK3342830 after 
administration of single (Part 1) and repeat (Part 2) IV doses in healthy adult subjects. , 
and after administration of a single IV dose in healthy adult Japanese subjects (Part 3).
Part 1 will investigate escalating single IV doses of GSK3342830. Part 2 will investigate 
escalating repeat IV doses of GSK3342830 with repeat dosing for 14 days and multiple 
dosing per day for 13 days as follows: a single IV infusion on Day 1, TID IV infusions on 
Days 2 through 14 (approximately every 8 hours), and a single IV infusion on Day 15. 
Part 3 will investigate a single IV dose of GSK3342830 in Japanese subjects.
On For Parts 1 and 2, on Day 1, before study drug administration, subjects who meet the 
criteria for study entry will be assigned to the current dose level cohort and randomized 
to receive GSK3342830 or placebo. For Part 3, on Day 1, before study drug 
administration, subjects who meet the criteria for study entry will be randomized to 
receive GSK3342830 or placebo. All doses of GSK3342830 or placebo are planned to be 
administered as a 1-hour infusion.


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Rationale: The overall study design text was updated to include the additional cohort
(Part 3). The updated text clarifies that the Part 3 component will investigate the safety, 
tolerability, and PK of GSK3342830 after a single IV dose of GSK3342830 administered 
to healthy adult Japanese subjects. Consistent with Parts 1 and 2, eligible subjects in 
Part 3 will be randomized to receive either GSK3342830 or placebo.
Section 4.1 Overall Study Design: Paragraph 8
The single dose administration in Japanese subjects component (Part 3) of this study is 
planned to be conducted in parallel with Part 2. The dose for the Part 3 cohort will be 
based on preliminary safety and tolerability results of doses determined to be safe and 
well tolerated in subjects of non-Japanese heritage after completion of the single 
escalation dose cohorts (Part 1).
Rationale: Part 3 was added to accommodate an additional cohort. It is planned to be 
conducted in parallel with Part 2. A one-time single dose is planned for Part 3. The 
updated text clarifies how the dose for Part 3 will be determined and includes planned 
conduction timing and dose selection for Part 3.
Section 4.2 Treatment Arms and Duration: Part 1 Paragraph 1
Part 1 is planned to include 6 dose level cohorts. Up to 2 a Additional doses (1 per 
cohort) may be evaluated to further understand the study drug. The planned starting 
GSK3342830 dose in Part 1 is 250 mg administered as a single IV infusion. The dose is 
planned to increase in subsequent cohorts to 500, 1000, 2000, 4000, and 6000 mg IV as 
shown in Figure 1. Doses >6000 mg may be administered if the predicted Cmax 
exposures will not exceed the NOAEL.
Rationale: The maximum planned dose in Part 1 is 6000 mg. However, if the predicted 
Cmax will not exceed the NOAEL, the addition of this text will allow doses beyond 
6000 mg to be administered.
Section 4.2 Treatment Arms and Duration: Part 3
Part 3: Single Dose in Healthy Adult Japanese Subjects
Part 3 is planned to include 1 cohort (Cohort J). The planned GSK3342830 dose in Part 3
will be either 250, 500, 1000, 2000, 4000, or 6000 mg based on preliminary safety and 
tolerability results of doses determined to be safe and well tolerated in subjects of 
non-Japanese heritage after completion of the single escalation dose cohorts (Part 1). The 
dose in Part 3 will be administered as a single IV infusion on Day 1.
On Day 1, before study drug administration, subjects will be randomized to treatment 
with either GSK3342830 or placebo in a 4:1 ratio. Study assessments will be performed 
as indicated in the Time and Events Tables (Section 7.1).
In Part 3, subjects will remain confined to the clinical unit from admission on Day –1 
until all scheduled safety and PK assessments have been completed on Day 3. The 
duration of study (from Screening to the Follow-up visit) for each subject will be up to 
approximately 43 days.


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Rationale: Part 3 was added to accommodate an additional cohort planned to be 
conducted in parallel with the repeat dosing component. The additional text clarifies how 
the dose for Part 3 will be determined, when the subjects will be randomized, and the 
duration for each subject.
Section 4.3 Type and Number of Subjects: Paragraph 1
For Part 1, approximately 48 healthy adult subjects will be enrolled with approximately 
8 subjects in each of the 6 planned cohorts. In each Part 1 cohort, approximately 
6 subjects will be assigned to active treatment and approximately 2 subjects will be 
assigned to placebo. For Part 2, approximately 30 healthy adult subjects will be enrolled 
with approximately 10 subjects in each of the 3 planned cohorts. In each For Part 3, 
approximately 10 healthy adult Japanese subjects will be enrolled. In each Part 2 cohort 
and the Part 3 cohort, approximately 8 subjects will be randomized to receive active 
treatment and approximately 2 subjects will be randomized to receive placebo.
Rationale: Part 3 was added to accommodate an additional cohort. The type and number 
of subjects text was updated to clarify the number of subjects in each part of the study 
and the number of subjects in each cohort within each part.
Section 4.6.1 Risk Assessment: Mitigation Strategy Column, Telemetry Monitoring 
in Rows 1 and 2
Conduct study in inpatient clinical unit for first time in human (FTIH)
Normal vital signs on study entry
Frequent vital signs over the dosing interval
QTc <450 msec
12-lead electrocardiograms (ECGs) across the initial exposure
Telemetry monitoring for Parts 1 and 3 and initial doses in Part 2
Conduct study in inpatient clinical unit for FTIH
Starting dose free Cmax margin: approximately 26×
Cmax at highest planned dose (6000 mg) similar to (1.1×) Cmax of the no observed effect level (NOEL) dose 
(250 mg/kg)
Normal vital signs on study entry
Frequent vital signs over the dosing interval
12-lead ECGs across the exposures
Telemetry monitoring for Parts 1 and 3 and initial doses in Part 2
Blood pressure and heart rate stopping criteria:
Systolic BP >160 mm Hg for >1 hour
Diastolic BP >100 mm Hg for >1 hour
Heart rate >120 beats per minute for >1 hour
Rationale: Part 3 was added to accommodate an additional cohort. The text in the 
mitigation strategy for the of death in preliminary monkey cardiovascular study (row 1) 
and blood pressure, heart rate, and body temperature changes in monkey cardiovascular 
study (row 2) potential risks of clinical significance was updated to include telemetry 
monitoring in Part 3.


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Section 5.1 Inclusion Criteria: Type of Subject and Diagnosis Including Disease 
Severity
3. Additional inclusion criteria for Japanese subjects (Part 3 only):

The subject is a non-naturalized Japanese citizen and holds a Japanese passport.

The subject has 2 Japanese parents and 4 Japanese grandparents who are 
non-naturalized Japanese citizens, as confirmed by interview.

The subject has been living outside of Japan for less than 10 years, as confirmed 
by interview.
Rationale: The additional cohort (Part 3) will consist of Japanese subjects. An inclusion 
criterion specific for a Japanese population was added.
Section 6.1 Investigational Product and Other Study Treatment: Unit Dose 
strengths/Dosage levels and Dosing Instructions
Study Treatment
Product name:
GSK3342830
Placebo
Unit dose 
strengths/Dosage levels:
Unit dose strength:1000 mg/vial 
as free base equivalent
Dosage levels:
Part 1: 250, 500, 1000, 2000, 
4000, and 6000 mg
Part 2: 1000, 2000, and 
4000 mg
Part 3: 250, 500, 1000, 2000, 
4000, or 6000 mg
Not applicable
Dosing instructions:
Parts 1 and 3: Single IV 
infusion.
Part 2: Single IV infusion on 
Day 1, TID IV infusions 
(approximately every 8 hours) 
on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 
11, 12, 13, and 14, and a single 
IV infusion on Day 15. 
Instructions for the preparation 
of the IV drug are included in 
the Pharmacy Manual.
Parts 1 and 3: Single IV 
infusion.
Part 2: Single IV infusion on 
Day 1, TID IV infusions 
(approximately every 8 hours) 
on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 
11, 12, 13, and 14, and a single 
IV infusion on Day 15. 
Instructions for the preparation 
of the IV drug are included in 
the Pharmacy Manual.
Rationale: Part 3 was added to accommodate an additional cohort. Information in the 
treatment table was updated to allow for the dose for Part 3 to be determined during the 
course of the study and to reflect that it will be administered as a one-time single IV 
infusion.
Section 6.3 Planned Dose Adjustments: Bullet Point 1 and Figure 3

This protocol allows some alteration from the currently outlined dosing schedule. 
The maximum daily dose is planned to not exceed 6000 mg in Parts 1 and 3, and 
4000 mg in Part 2.


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Figure 3
Planned Study Schematic
Rationale: The dose for administration in Part 3 will be selected based on safety and 
tolerability findings in Part 1. In bullet 1, the text was updated to clarify the planned 
maximum dose in Part 3 will not exceed the planned maximum dose in Part 1. The 
planned study schematic (Figure 3) was updated to include the additional cohort (Part 3).
Section 6.10.1 Meals and Dietary Restrictions: Paragraph 4
Subjects will fast from food and drink (except water) for at least 10 hours before dosing 
on Day 1 (Parts 1, 2, and Part 3) and Day 15 (Part 2 only). Meals at all other times will be 
provided at times that will not interfere with fasting required for clinical laboratory 
testing.
Rationale: Part 3 was added to accommodate an additional cohort. The text in the meals 
and dietary restrictions section was updated to clarify the timing of the required fast for 
each part of the study.
Section 7.1 Time and Events Tables: Table 3, Table 4, and Table 6 Titles
Table 3
Time and Events Table: Screening and Day –1; Single and Repeat Dose 
Escalation (Part 1 and Part 2) and Single Dose (Part 3)
Table 4
Time and Events Table: Part 1 - Single Dose Escalation and Part 3 - Single 
Dose


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Table 6
Time and Events Table: Follow-up Visit; Single and Repeat Dose 
Escalation (Part 1 and Part 2) and Single Dose (Part 3)
Rationale: Part 3 was added to accommodate an additional cohort planned to be 
conducted in parallel with the repeat dosing component. GSK3342830 will be 
administered as a single dose in Parts 1 and 3; therefore the procedures and timing of 
procedures is the same these parts of the study. The titles of the time and events tables 
were updated to clarify which the part of the study is applicable in each table.
Section 7.1 Time and Events Table 3
Procedure
Screening (up to 30 days 
before Day 1)
Day –1
Notes
Blood collection for additional 
iron tests
X
In Part 2 only. Samples will be collected for 
potential analysis of some or all of the 
additional iron tests at the end of the study if a 
clinical signal is detected.
Rationale: Row was added for blood collection on Day –1 (Part 2 only) for possible 
analysis of iron biomarkers at the end of the study if a clinical signal is detected.
Section 7.1 Time and Events Table 5
Procedure
Study Day
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Blood collection for 
additional iron tests4
X
X
X
Rationale: Row was added for blood collection at predose on Days 1, 5 and 15 for 
possible analysis of iron biomarkers at the end of the study if a clinical signal is detected.
Section 7.1 Time and Events Table 5, Notes 3 and 4
3. An aliquot of the urine sample will be collected for neutrophil gelatinase-associated lipocalin (NGAL) and kidney 
injury molecule 1 (KIM-1). These samples may be analyzed after the end of the study if a clinical signal is detected. 
Instructions for collection and storage of these urine samples are included in the Study Reference Manual. 
Hematology assessments on Days 5 and 15 will also include total iron, total iron binding capacity, ferritin, and 
reticulocytes. The albumin to creatinine ratio will be determined using the first morning void urine on Days 5 and 15. 
Urinalysis assessments before dosing on Day 15 will also include urine color.
4. Blood samples will be collected on Day –1, and predose (at least 1 hour before dosing) on Days 1, 5, and 15, and at 
Follow up visit for potential analysis for some or all of the additional iron tests at the end of the study if a clinical 
signal is detected.
Rationale: A urine color assessment was added to Day 15 of Part 2. The drug may cause 
urine to appear red or reddish brown (this was seen in animal studies). Therefore, this 
assessment was added to determine if this effect is seen in the clinic in order to inform 
conduct of clinical trials. The note pertaining to the urinalysis assessments in the Time 
and Events Table for Part 2 was updated to include the urine color assessment.
Blood samples will be collected for possible analysis of iron biomarkers at the end of the 
study if a clinical signal is detected. This note in the Time and Events Table for Part 2 
was added to clarify when the samples will be collected.


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Section 7.3.7 Clinical Safety Laboratory Assessments: Table 7 Additional Iron 
Tests, Urinalysis Parameters, and Notes 1, 2, 4 and 6
Laboratory 
Assessments
Parameters
Additional Iron 
Tests2
Transferring (apotransferrin)
Ceruloplasmin
Haptoglobin/Hemopexin
Lactoferrin
Hepcidin
Urinalysis

Specific gravity

pH, glucose, protein, blood and ketones by dipstick

ACR3

Microscopic examination (if blood or protein is abnormal)

NGAL4

KIM-145

Urine color6
NOTES:
1. In Parts 1 and 3, analyzed on Day –1 and at Follow-up visit. In Part 2, analyzed on Day –1, Day 5, Day 15, and at 
Follow-up visit.
2. In Part 2 only, blood samples will be collected on Day –1, and predose (at least 1 hour before dosing) on Days 1, 5, 
and 15, and at Follow up visit, for potential analysis of some or all of the additional iron tests at the end of the study if 
a clinical signal is detected.
34. The ACR on urine albumin and creatinine will be determined using the first morning void urine at Screening and 
Follow-up visit for all subjects in both parts of the study. In addition, the ACR will be determined on Day 2 in Parts 1 
and 3 and Days 5 and 15 in Part 2. Screening ACR may be performed on urine during the screening visit. Subjects 
should be provided a sterile urine transport container and instructions on how to collect a first void urine at home for 
screening. In the event a subject fails by ACR, the subject should be contacted to bring back first void urine for 
recheck. For the Follow-up visit, subjects must be provided a sterile urine transport container on discharge from the 
clinical unit and instructed to bring back the first morning void urine on the day of their return Follow-up visit.
6. Assessed before dosing on Day 15 (Part 2 only).
Rationale: Blood samples will be collected for possible analysis of iron biomarkers at the 
end of the study if a clinical signal is detected. The iron tests are specified in this table. 
Note 2 was added to clarify when the blood samples for these tests will be collected.
GSK3342830 will be administered as a single dose in Parts 1 and 3; therefore the timing 
of the total iron and TIBC assessments (note 1) and ACR determination (note 4) will be 
the same for these parts of the study. A urine color assessment was added to Day 15 of 
Part 2. The drug may cause urine to appear red or reddish brown (this was seen in animal 
studies). Therefore, this assessment was added to determine if this effect is seen in the 
clinic in order to inform conduct of clinical trials. The text in notes 1, 4, and 6 was 
updated to include the urine color assessment and to clarify when the total iron, TIBC, 
and urine color assessments and ACR determination will be performed in each part of the 
study.
Section 9.3.1 Analysis Populations: PK Population and PK Parameter Population
The PK Population will consist of all subjects who receive at least 1 dose of 
GSK3342830 and have evaluable PK data for GSK3342830 for whom a PK sample is 
collected and analyzed.


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The PK Parameter Population will consist of all subjects in the PK population for 
whom valid and evaluable PK parameters were derived.
Rationale: A PK parameter population that will be used in the assessment and 
characterization of PK parameters was added. The text in the analysis populations section 
was updated to include this population.
Section 9.3.2 Interim Analysis: Paragraph 1
No formal interim analysis is planned for this study. However, one may be conducted in 
the event of clinically significant safety or PK findings. All preliminary safety, 
tolerability, and available PK data will be reviewed internally at GSK and with the 
clinical study site before each dose escalation in Part 1, before initiation of Part 2, and 
before each dose escalation in Part 2. All preliminary safety and tolerability data from 
Part 1 will be reviewed internally at GSK and with the clinical study site before dose 
selection for and initiation of Part 3. Section 6.4 provides further detail on data access 
and the handling of treatment blinding.
Rationale: Part 3 was added to accommodate an additional cohort. The text in the interim 
analysis section was updated to clarify when interim analysis will occur in relation to 
each part of the study.
Section 9.4.2 Secondary Analyses: Pharmacokinetic Analyses, Plasma, AUC(0-) 
and Dose Proportionality, Paragraph 1
Pharmacokinetic Analyses, Plasma, AUC(0-)
AUC(0-)
AUC extrapolated from time zero to infinity (estimated for single dose in 
Parts 1 and 3, and on Day 1 for repeat dose in Part 2)
Dose Proportionality, Paragraph 1
Dose proportionality of AUC(0-) and Cmax on Day 1 in Part 1 and for repeat dose 
groups AUC(0-) and Cmax of GSK3342830 on Day 15 in Part 2 will be assessed 
separately by day using the following power model:
y = * dose.
Rationale: Part 3 was added to accommodate an additional cohort. Single dose 
administration is planned for Parts 1 and 3, and repeat dose administration is planned for 
Part 2. The text in the appropriate secondary analysis sections was updated to clarify 
which data will be used for AUC (0-) and dose proportionality for each part of the 
study.
Section 9.4.3 Exploratory Analyses: Paragraph 1
Exploratory analyses will be performed to correlate PK parameters (AUC[0-t], 
AUC[0-] and Cmax for Parts 1 and 3; AUC[0-t], AUC[0-], AUC[0-] and Cmax for 
Part 2) of GSK3342830 with safety findings of GSK3342830 in healthy adult subjects 
(Parts 1 and 2) and healthy adult Japanese subjects (Part 3), and to evaluate the 
production of any GSK3342830 metabolites in plasma and urine.
Rationale: Part 3 was added to accommodate an additional cohort, which will consist of 
healthy adult Japanese subjects. Single dose administration is planned for Parts 1 and 3, 


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and repeat dose administration is planned for Part 2. The text in the exploratory analyses 
section was updated to clarify which PK parameters will be correlated with safety 
findings in each part of the study.

SAP_001.pdf: 
 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
204847 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for A Phase I, Randomized, 
Double-Blind (Sponsor Unblinded), Single-Center, 
Placebo-Controlled, Three-Part Study to Evaluate the Safety, 
Tolerability, and Pharmacokinetics of Ascending Single and 
Repeat Intravenous Doses of GSK3342830 in Healthy Adult 
Subjects 
Compound Number  
: GSK3342830 
Effective Date  
: 17-AUG-2017 
 
Description : 
 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 204847. 
 
This RAP is intended to describe the safety, tolerability, and pharmacokinetic 
analyses required for the study. 
 
This RAP is updated based upon Protocol Amendment 1. However,, Part 3 (Japanese 
subjects) that was added in Protocol Amendment 1 will not be conducted. 
 
This RAP will be provided to the study team members to convey the content of the 
Dose Escalation (DE) and Statistical Analysis Complete (SAC) deliverable. 
 
Author’s Name and Functional Area:  
 
28-AUG-2017 
Biostatistics Team Leader (Biostatistics, Early Development 
Services) 
 
28-AUG-2017 
Senior Pharmacokineticist (Biostatistics) 
 
Approved by:  
 
28-AUG-2017 
Director Clinical Statistics, GSK 
 
Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
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TABLE OF CONTENTS 
PAGE 
1. 
REPORTING & ANALYSIS PLAN SYNPOSIS .......................................................... 4 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION ................................................... 7 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 7 
2.2. 
Study Objective(s) and Endpoint(s) ................................................................ 7 
2.3. 
Study Design .................................................................................................. 9 
2.4. 
Statistical Hypotheses .................................................................................. 10 
3. 
PLANNED ANALYSES ............................................................................................ 11 
3.1. 
Interim Analyses ........................................................................................... 11 
3.2. 
Final Analyses .............................................................................................. 11 
4. 
ANALYSIS POPULATIONS ..................................................................................... 11 
4.1. 
Protocol Deviations ...................................................................................... 12 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ....................................................................................................... 13 
6. 
STUDY POPULATION ANALYSES ......................................................................... 14 
6.1. 
Overview of Planned Analyses..................................................................... 14 
7. 
PRIMARY STATISTICAL ANALYSES ..................................................................... 15 
7.1. 
Safety Analyses ........................................................................................... 15 
7.1.1. 
Overview of Planned Safety Analyses .......................................... 15 
8. 
SECONDARY STATISTICAL ANALYSES ............................................................... 17 
8.1. 
Pharmacokinetic Analyses ........................................................................... 17 
8.1.1. 
Overview of Planned Pharmacokinetic Analyses .......................... 17 
8.1.2. 
Drug Concentration Measures ...................................................... 17 
8.1.3. 
Pharmacokinetic Parameters ........................................................ 17 
8.1.3.1. 
Deriving Pharmacokinetic Parameters ........................ 17 
8.1.3.2. 
Statistical Analysis of Pharmacokinetic 
Parameters .................................................................. 18 
8.2. 
Bayesian Dose Escalation Analyses ............................................................ 22 
8.2.1. 
Overview of Planned Bayesian Dose Escalation Analyses .......... 22 
8.2.2. 
Planned Bayesian Statistical Analyses ......................................... 22 
8.2.3. 
Deviations from RAP Planned Analysis ........................................ 26 
9. 
REFERENCES ........................................................................................................ 27 
10.  APPENDICES .......................................................................................................... 28 
10.1. 
Appendix 1: Time & Events .......................................................................... 29 
10.1.1. 
Protocol Defined Time & Events ................................................... 29 
10.2. 
Appendix 2: Treatment States and Phases .................................................. 35 
10.2.1. 
Treatment Phases ......................................................................... 35 
10.2.2. 
Treatment States .......................................................................... 35 
10.2.2.1.  Treatment States for Safety Data ................................ 35 
10.2.2.2.  Treatment States for AE Data ..................................... 35 
10.3. 
Appendix 3: Data Display Standards & Handling Conventions .................... 36 


 
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204847 
 
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10.3.1. 
Study Treatment & Sub-group Display Descriptors ...................... 36 
10.3.2. 
Baseline Definition & Derivations .................................................. 37 
10.3.2.1.  Baseline Definitions ..................................................... 37 
10.3.2.2.  Derivations and Handling of Missing Baseline 
Data ............................................................................. 37 
10.3.3. 
Reporting Process & Standards .................................................... 37 
10.4. 
Appendix 4: Derived and Transformed Data ................................................ 40 
10.4.1. 
General ......................................................................................... 40 
10.4.2. 
Study Population ........................................................................... 40 
10.4.3. 
Safety ............................................................................................ 40 
10.5. 
Appendix 5: Premature Withdrawals and Handling of Missing Data ............ 42 
10.5.1. 
Premature Withdrawals ................................................................. 42 
10.5.2. 
Handling of Missing Data .............................................................. 42 
10.5.2.1.  Handling of Missing Dates ........................................... 42 
10.5.2.2.  Handling of Partial Dates ............................................. 43 
10.6. 
Appendix 6: Values of Potential Clinical Importance .................................... 44 
10.6.1. 
ECG .............................................................................................. 44 
10.6.2. 
Vital Signs ..................................................................................... 44 
10.7. 
Appendix 7: DMID Adult Toxicity Tables for Adverse Event 
Assessment .................................................................................................. 45 
10.7.1. 
Laboratory Values ......................................................................... 45 
10.8. 
Appendix 8: Multiple Comparisons & Multiplicity .......................................... 48 
10.8.1. 
Handling of Multiple Comparisons & Multiplicity ........................... 48 
10.9. 
Appendix 9: Model Checking and Diagnostics for Statistical 
Analyses ....................................................................................................... 49 
10.9.1. 
Statistical Analysis Assumptions ................................................... 49 
10.10.  Appendix 10 – Abbreviations & Trade Marks ............................................... 50 
10.10.1.  Abbreviations ................................................................................ 50 
10.10.2.  Trademarks ................................................................................... 51 
10.11.  Appendix 11: List of Data Displays ............................................................... 52 
10.11.1.  Data Display Numbering ............................................................... 52 
10.11.2.  Mock Example Shell Referencing ................................................. 52 
10.11.3.  Deliverable [Priority] ...................................................................... 52 
10.11.4.  Study Population Tables ............................................................... 53 
10.11.5.  Safety Tables ................................................................................ 54 
10.11.6.  Safety Figures ............................................................................... 56 
10.11.7.  Pharmacokinetic Tables ................................................................ 57 
10.11.8.  Pharmacokinetic Figures .............................................................. 60 
10.11.9.  ICH Listings ................................................................................... 62 
 


 
CONFIDENTIAL 
 
 
 
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1. 
REPORTING & ANALYSIS PLAN SYNPOSIS 
Overview 
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CONFIDENTIAL 
 
 
 
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204847 
 
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Overview 
Key Elements of the RAP 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
Not applicable. 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Part 1 
Primary Objectives
Primary Endpoints
 
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Primary Objectives 
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 
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;M>;N;J?LGCN


 
CONFIDENTIAL 
 
 
 
204847 
 
8 
 
Objectives 
Endpoints 
 
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Primary Objectives
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204847 
 
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2.3.  
Study Design 
Overview of Study Design and Key Features 
Part 1 Single Dose Escalation Study Design Schematic 
 
 
Part 2 Repeat Dose Escalation Study Design Schematic 
 
Design 
Features 
 
 
 


 
CONFIDENTIAL 
 
 
 
204847 
 
10 
 
Overview of Study Design and Key Features 
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2.4. 
Statistical Hypotheses 
No inferential hypothesis testing will be performed. 
  


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
No formal interim analysis is planned for this study. However, one may be conducted in 
the event of clinically significant safety or PK findings. All preliminary safety, 
tolerability, and available PK data will be reviewed internally at GSK and with the 
clinical study site before each dose escalation in Part 1, before initiation of Part 2, and 
before each dose escalation in Part 2. 
The relationship between dose and plasma GSK3342830 exposure, and associated 
variability will be characterized by a power model once data are available from 3 dose 
levels. Prior to that, prediction of the human exposure at the next dose will be based on 
population PK modeling (if feasible) or on the assumption of dose–exposure 
proportionality (i.e., doubling the dose gives an approximate doubling of exposure). If 
prior PK results show less than proportional increase in exposure with increasing dose, 
the prediction will be based on the assumption that the fold exposure increase to fold 
dose increase ratio will be the same with the current dose escalation as it was with the 
previous one. If prior PK results show more than proportional increase in exposure with 
dose, subsequent dose escalations will not be higher than 3-fold. The power model will 
be updated as data become available throughout the study. During dose escalation, 
Bayesian inferential probability that a group mean will have AUCs (AUC[0-t] for single 
dose and AUC[0-8]x3 as AUC[0-24] for repeat dose) and Cmax values greater than 2875 
hμg/mL and 2270 μg/mL (mean exposures at the NOAEL dose in the rat and monkey), 
respectively, and Bayesian predictive probability that an individual will have AUC(0-24) 
and Cmax values greater than 3460 hμg/mL and 2590 μg/mL (maximum exposures at 
the NOAEL dose in the rat for AUC and the monkey for Cmax), respectively, may be 
calculated for the next dose level and used together with safety and tolerability data to aid 
the next dose selection. 
3.2. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the 
following sequential steps: 
1. All subjects have completed the study as defined in the protocol. 
2. All required database cleaning activities have been completed and final database 
release and database freeze has been declared by Data Management. 
3. All criteria for unblinding the randomisation codes have been met.  
4. Randomisation codes have been distributed according to PPD procedures. 
4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
/;@?NS
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 /NO>S,IJOF;NCIH
 /;@?NS


 
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204847 
 
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Population 
Definition / Criteria 
Analyses Evaluated 
 0BCMJIJOF;NCIHQCFF<?<;M?>IHNB?NL?;NG?HN
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NOTES :  
 
,F?;M?L?@?LNIJJ?H>CR(CMNI@ ;N; CMJF;SMQBC=B>?N;CFMNB?JIJOF;NCIHNI<?OM?>@IL?;=B>CMJF;SM<?CHA
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4.1. 
Protocol Deviations 
 
Important protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarised and listed. 
 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations and deviations which may lead to exclusion from the 
analysis are captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
 
A separate summary and listing of all inclusion/exclusion criteria deviations will also 
be provided. This summary will be based on data as recorded on the 
inclusion/exclusion page of the eCRF. 


 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
Table 1 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions.  
Table 1 
Overview of Appendices 
Section Component 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Analyses 
The study population analyses will be based on the Safety population, unless otherwise 
specified. 
Table 2 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 11: List of Data Displays. 
Table 2 
Overview of Planned Study Population Analyses 
Display Type 
Data Displays Generated 
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Randomisation
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5
Subject Disposition
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5

5
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5

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5
Demography
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5

5
Medical Conditions and Concomitant Medications 
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5

5
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5

5
NOTES : 
55?M>CMJF;SA?H?L;N?> 
 


 
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7. 
PRIMARY STATISTICAL ANALYSES 
7.1. 
Safety Analyses 
7.1.1. 
Overview of Planned Safety Analyses 
The safety analyses will be based on the Safety population, unless otherwise specified. 
Table 3 provides an overview of the planned Safety analyses, with full details of data 
displays being presented in Appendix 11: List of Data Displays. 
Table 3 
Overview of Planned Safety Analyses 
Display Type 
Absolute 
Change from Baseline 
/OGG;LS
%H>CPC>O;F
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5
5






 
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NOTES : 
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8. 
SECONDARY STATISTICAL ANALYSES 
8.1. 
Pharmacokinetic Analyses 
8.1.1. 
Overview of Planned Pharmacokinetic Analyses 
The pharmacokinetic (PK) analyses will be based on the PK population, unless otherwise 
specified. 
Table 4 provides an overview of the planned PK analyses, with further details of data 
displays being presented in Appendix 11: List of Data Displays. 
Table 4 
Overview of Planned Pharmacokinetic Analyses 
Endpoint / 
Display Type 
Untransformed 
Log-Transformed 
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8.1.2. 
Drug Concentration Measures 
Refer to Appendix 3: Data Display Standards & Handling Conventions (Section 10.3.3 
Reporting Process & Standards). 
8.1.3. 
Pharmacokinetic Parameters 
8.1.3.1. 
Deriving Pharmacokinetic Parameters 
 Refer to Appendix 3: Data Display Standards & Handling Conventions 
(Section 10.3.3 Reporting Process & Standards). 
 The pharmacokinetic parameters will be calculated by standard non-compartmental 
analysis according to current working practices and using Phoenix WinNonlin 
Version 6.2.1 or higher. 


 
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 All calculations of non-compartmental parameters will be based on actual sampling 
times. 
 Pharmacokinetic parameters described in Table 5 will be determined from the plasma 
GSK3342830 concentration-time data, as data permits. 
 Pharmacokinetic parameters described in Table 6 will be determined from the urinary 
GSK3342830 concentration data, as data permits. 
Table 5 
Derived Plasma Pharmacokinetic Parameters 
Parameter 
Parameter Description 
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NOTES: 
 
>>CNCIH;FJ;L;G?N?LMG;S<?CH=FO>?>;ML?KOCL?>
 
Table 6 
Derived Urinary Pharmacokinetic Parameters 
Parameter 
Parameter Description 
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8.1.3.2. 
Statistical Analysis of Pharmacokinetic Parameters 
The following pharmacokinetic statistical analyses will only be performed, if sufficient 
data is available (i.e. if subjects have well defined plasma profiles).  
Pharmacokinetic Statistical Analyses 
Assessment 
  IM?JLIJILNCIH;FCNSI@#/'


 
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Pharmacokinetic Statistical Analyses 
Endpoint(s) 
 H?MNCG;N?I@MFIJ?QCNB=ILL?MJIH>CHA%
Model Specification 
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Model Results Presentation 
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Endpoint(s)
 H?MNCG;N?I@NCG?CHP;LC;H=?L;NCIQCNB=ILL?MJIH>CHA%
Model Specification
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Model Results Presentation
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Assessment


 
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Pharmacokinetic Statistical Analyses 
 ==OGOF;NCIHL;NCII@#/'
Endpoint(s)
 H?MNCG;N?I@;==OGOF;NCIHL;NCIQCNB=ILL?MJIH>CHA%
Model Specification
 "ILNB?L?J?;N>IM?=IBILNM,;LN
NB?;==OGOF;NCIHL;NCI.IQCFF<?=;F=OF;N?>;MNB?L;NCI
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Model Checking & Diagnostics
 .?@?LNIJJ?H>CR)I>?FB?=ECHA;H> C;AHIMNC=M@IL/N;NCMNC=;FH;FSM?M
Model Results Presentation
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Endpoint(s)
 H?MNCG;N?I@NB?MFIJ?QCNB=ILL?MJIH>CHA%
Model Specification
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MN;NCMNC=;F;H;FSMCMI@MN?;>SMN;N?QCFF<?
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Model Checking & Diagnostics
 .?@?LNIJJ?H>CR)I>?FB?=ECHA;H> C;AHIMNC=M@IL/N;NCMNC=;FH;FSM?M
Model Results Presentation
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NB?M;G?>IM?F?P?F,;LNQCFF<?=;F=OF;N?>
Assessment 
 MM?MMG?HNI@#/','CHB?;FNBS;>OFN&;J;H?M?MO<D?=NMPMNB?M;G?>IM?F?P?FI@


 
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Pharmacokinetic Statistical Analyses 
B?;FNBS;>OFNMO<D?=NMCH,;LN
Endpoint(s) 
 0B?A?IG?NLC=G?;HL;NCI;H>;MMI=C;N?>%@IL,;LNPM,;LN
Model Specification 
 0I?P;FO;N?QB?NB?LNB?L?CM;>C@@?L?H=?CHNB?,'J;L;G?N?LMCHB?;FNBS;>OFN&;J;H?M?
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Model Checking & Diagnostics 
 .?@?LNIJJ?H>CR)I>?FB?=ECHA;H> C;AHIMNC=M@IL/N;NCMNC=;FH;FSM?M
Model Results Presentation 
 0B?A?IG?NLC=G?;HL;NCI;H>;MMI=C;N?>%QCFF<?JL?M?HN?>CH;N;<F?


 
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8.2. 
Bayesian Dose Escalation Analyses 
8.2.1. 
Overview of Planned Bayesian Dose Escalation Analyses 
The Bayesian Dose Escalation analyses will be based on the PK population, unless 
otherwise specified. 
Table 7 provides an overview of the planned Bayesian analyses, with further details of 
data displays being presented in Appendix 11: List of Data Displays. 
Table 7 
Overview of Planned Bayesian Analyses 
Endpoint / 
Display Type 
Untransformed 
Log-Transformed 
/N;NMH;FSMCM
/OGG;LS
%H>CPC>O;F
/N;NMH;FSMCM
/OGG;LS
%H>CPC>O;F
0
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(
0
"
"
(
0
"
(
0
"
"
(
 
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5
5

5
5
5





NOTES : 
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 
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 
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8.2.2. 
Planned Bayesian Statistical Analyses 
Table 8 
Bayesian Statistical Analyses 
Bayesian Statistical Analyses 
Endpoint(s) 
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L?MJ?=NCP?FS


 
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 
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<?@IL?Q?;==?JN


 
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;H>IP?LF;C>IHNB?


 
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*IN;JJFC=;<F?  
 


 
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8.2.3. 
Deviations from RAP Planned Analysis  
To ensure transparency, any deviations from the above analyses will be documented in a 
log appended to the CSR.  These deviations may include (although are not limited to) 
algebraically different model parameterizations or changes in the prior structure to 
support convergence of the parameter estimations in SAS.  These possible issues and 
solutions for them are discussed above in the appropriate sections. 


 
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9. 
REFERENCES 
GlaxoSmithKline Document Number 2015N257523_01 (Amendment 1 – 01-NOV-
2016):  A Phase I, Randomized, Double-Blind (Sponsor Unblinded), Single-Center, 
Placebo-Controlled, Three-Part Study to Evaluate the Safety, Tolerability, and 
Pharmacokinetics of Ascending Single and Repeat Intravenous Doses of GSK3342830 in 
Healthy Adult Subjects. 
 
 


 
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10. 
APPENDICES 
Section 
Appendix 
RAP Section 5 : General Considerations for Data Analyses & Data Handling Conventions
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JJ?H>CR(CMNI@ ;N; CMJF;SM
 


 
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10.1. 
Appendix 1: Time & Events 
10.1.1. 
Protocol Defined Time & Events 
Time and Events Table: Screening and Day –1; Single and Repeat Dose Escalation (Part 1 and Part 2) and Single Dose (Part 3) 
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CONFIDENTIAL 
 
 
 
204847 
 
31 
 
Time and Events Table: Part 1 - Single Dose Escalation and Part 3 – Single Dose 
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CONFIDENTIAL 
 
 
 
204847 
 
32 
 
Time and Events Table: Part 2 - Repeat Dose Escalation 
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CONFIDENTIAL 
 
 
 
204847 
 
33 
 
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CONFIDENTIAL 
 
 
 
204847 
 
34 
 
Time and Events Table: Follow-up Visit; Single and Repeat Dose Escalation (Part 1 and Part 2) and Single Dose (Part 3) 
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CONFIDENTIAL 
 
 
 
204847 
 
35 
 
10.2. 
Appendix 2: Treatment States and Phases 
10.2.1. 
Treatment Phases 
Assessments and events will be classified according to the time of occurrence relative to 
dosing. 
Treatment Phase 
Definition 
,L?0L?;NG?HN
 ;N?/NO>S0L?;NG?HN/N;LN ;N?
+H0L?;NG?HN
/NO>S0L?;NG?HN/N;LN ;N?≤ ;N?≤/NO>S0L?;NG?HN/NIJ ;N?
,IMN0L?;NG?HN
 ;N?/NO>S0L?;NG?HN/NIJ ;N?
 
10.2.2. 
Treatment States 
Assessments and events will be classified according to time of occurrence relative to the 
start and/or stop date of the study treatment. 
10.2.2.1. 
Treatment States for Safety Data 
Treatment State 
Definition 
,L?0L?;NG?HN
 ;N?NCG?/NO>S0L?;NG?HN/N;LN ;N?NCG?
+H0L?;NG?HN
/NO>S0L?;NG?HN/N;LN ;N?NCG?≤ ;N?NCG?≤/NO>S0L?;NG?HN/NIJ ;N?NCG?	
>;SM
,IMN0L?;NG?HN
 ;N?NCG?/NO>S0L?;NG?HN/NIJ ;N?NCG?	>;SM
NOTES:  
 
%@NB?MNO>SNL?;NG?HNMNIJ>;N?CMGCMMCHANB?HNB?;MM?MMG?HNQCFF<?=IHMC>?L?>NI<?+H0L?;NG?HN
 
10.2.2.2. 
Treatment States for AE Data 
Treatment State 
Definition 
,L?0L?;NG?HN
!/N;LN ;N?NCG?/NO>S0L?;NG?HN/N;LN ;N?NCG?
+H0L?;NG?HN
%@!IHM?N>;N?NCG?CMIHIL;@N?LNL?;NG?HNMN;LN>;N?IHIL<?@IL?NL?;NG?HNMNIJ
>;N?NCG?
/NO>S0L?;NG?HN/N;LN ;N?NCG?≤!/N;LN ;N?NCG?≤/NO>S0L?;NG?HN/NIJ
 ;N?NCG?	>;SM
,IMN0L?;NG?HN
%@!IHM?N>;N?NCG?CM;@N?LNB?NL?;NG?HNMNIJ>;N?NCG?
!/N;LN ;N?NCG?/NO>S0L?;NG?HN/NIJ ;N?NCG?	>;SM
+HM?N0CG?
/CH=?MN IM?
 ;SM
%@0L?;NG?HN/N;LN ;N?NCG?˃!+HM?N ;N?NCG?
!+HM?N ;N?0L?;NG?HN/N;LN
 ;N?
%@0L?;NG?HN/N;LN ;N?NCG?≤!+HM?N ;N?NCG?
!+HM?N ;N?0L?;NG?HN/N;LN
 ;N?	
)CMMCHAINB?LQCM?
 OL;NCIH ;SM
!.?MIFONCIH ;N?Z!+HM?N ;N?	
 LOAL?F;N?>
%@L?F;NCIHMBCJCMG;LE?>V5!/WIH."+.P;FO?CMGCMMCHA
NOTES:  
 
%@NB?MNO>SNL?;NG?HNMNIJ>;N?CMGCMMCHANB?HNB?!QCFF<?=IHMC>?L?>NI<?+H0L?;NG?HN


 
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10.3. 
Appendix 3: Data Display Standards & Handling 
Conventions 
10.3.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
Randomization Schedule 
Data Displays for Reporting  
Part 
Code 
Description 
Description 
Order [1] 


IBILN#/'
#/'GA



IBILN#/'
#/'GA



IBILN#/'
#/'GA



IBILN #/'
#/'GA



IBILN!#/'
#/'GA



IBILN"#/'
#/'GA



IBILN4#/'
#/'444478GA



IBILN4#/'
#/'444478GA


,
,F;=?<I
,F;=?<I



IBILN##/'
#/'GA0% 



IBILN$#/'
#/'GA0% 



IBILN%#/'
#/'GA0% 



IBILN5#/'
#/'444478GA0% 



IBILN5#/'
#/'444478GA0% 

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,
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,F;=?<I


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IBILN&#/'
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IBILN6#/'
#/'444478GA


,&
,F;=?<I
,F;=?<I

NOTES: 
 
+L>?LL?JL?M?HNMNL?;NG?HNM<?CHAJL?M?HN?>CH0"(
;M;JJLIJLC;N?
 
IBILN4
4
5
;H>5;L?=L?;N?>J?LJLINI=IFNI;FFIQ;>>CNCIH;F>IM?MQBC=BG;S<??P;FO;N?>NI@OLNB?L
OH>?LMN;H>NB?MNO>S>LOA0B?.;H>IGCT;NCIH/=B?>OF?>I?MHIN=IHN;CHNB?;=NO;F>IM?F?P?FM<ONCHMN?;>
L?@?LMNINB?IBILN>IM?F?P?F IM?F?P?FMG;S=B;HA?@LIGNB?JLINI=IF>?@CH?>F?P?FM0B?0("MQCFF>CMJF;S
NB?;=NO;F>IM?F?P?FMOM?>CHNB?MNO>S
 
0B?>IM?@ILIBILN4
4
5
;H>5QCFF<?>?N?LGCH?>IH=?NB?>?=CMCIHCMG;>?NI?HLIFFNBIM?IJNCIH;F
=IBILNM
 
0B?>IM?@ILIBILN&QCFF?CNB?L



IL≤GA<;M?>IHJL?FCGCH;LSM;@?NS;H>
NIF?L;<CFCNSL?MOFNMI@>IM?M>?N?LGCH?>NI<?M;@?;H>Q?FFNIF?L;N?>CHMO<D?=NMI@HIH&;J;H?M?B?LCN;A?;@N?L
=IGJF?NCIHI@NB?MCHAF??M=;F;NCIH>IM?=IBILNM,;LN


 
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10.3.2. 
Baseline Definition & Derivations 
10.3.2.1. 
Baseline Definitions 
For all endpoints (expect as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment.  
Parameter 
Study Assessments Considered As Baseline 
Baseline Used in 
Data Display 
Screening 
Day -1 
Day 1 (Pre-Dose) 
Safety 
$?G;NIFIAS
4
4

 ;S
FCHC=;FB?GCMNLS
4
4

 ;S
(?;>!#
4
4
4
 ;S,L?>IM?
2CN;F/CAHM
4
4
4
 ;S,L?>IM?
NOTES : 
 
1HF?MMINB?LQCM?MN;N?>
NB?G?;HI@L?JFC=;N?;MM?MMG?HNM;N;HSACP?HNCG?JICHNQCFF<?OM?>;MNB?P;FO?@IL
NB;NNCG?JICHN
10.3.2.2. 
Derivations and Handling of Missing Baseline Data 
Definition 
Reporting Details 
B;HA?@LIG;M?FCH?
 ,IMN IM?2CMCN2;FO?Z;M?FCH?
NOTES : 
 
1HF?MMINB?LQCM?MJ?=C@C?>
NB?<;M?FCH?>?@CHCNCIHMMJ?=C@C?>CH/?=NCIH;M?FCH? ?@CHCNCIHMQCFF<?OM?>
@IL>?LCP;NCIHM@IL?H>JICHNMJ;L;G?N?LM;H>CH>C=;N?>IHMOGG;LC?M;H>FCMNCHAM
 
1HF?MMINB?LQCM?MN;N?>
C@<;M?FCH?>;N;CMGCMMCHAHI>?LCP;NCIHQCFF<?J?L@ILG?>;H>QCFF<?M?NNIGCMMCHA
 
0B?<;M?FCH?>?@CHCNCIHQCFF<?@IINHIN?>IH;FF=B;HA?@LIG<;M?FCH?>CMJF;SM
 
10.3.3. 
Reporting Process & Standards 
Reporting Process 
Software 
 0B?=OLL?HNFSMOJJILN?>P?LMCIHMI@//MI@NQ;L?7%HM?LN+NB?L/I@NQ;L?;M.?KOCL?>8QCFF<?
OM?>
Analysis Datasets  
 H;FSMCM>;N;M?NMQCFF<?=L?;N?>;==IL>CHANI %/MN;H>;L>M/ 0)%#2?LMCIH
>;)%#2?LMCIH
 "IL=L?;NCIHI@ ;)>;N;M?NM ) !
NB?M;G?P?LMCIHI@>C=NCIH;LS>;N;M?NMQCFF<?
CGJF?G?HN?>@IL=IHP?LMCIH@LIG/%NI/ 0)
Generation of RTF Files 
 .0"@CF?MQCFF<?A?H?L;N?>@IL;FFL?JILNCHA?@@ILNM>?M=LC<?>CHNB?.,
 
Reporting Standards 
General 


 
CONFIDENTIAL 
 
 
 
204847 
 
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Reporting Standards 
 0B?=OLL?HN#/'%HN?AL;N?> ;N;/N;H>;L>M(C<L;LS% /(QCFF<?;JJFC?>@ILL?JILNCHA
OHF?MM
INB?LQCM?MN;N?>
o NI#?H?L;F,LCH=CJF?M
o NI,LCH=CJF?M.?F;N?>NI ;N;(CMNCHAM
o NI,LCH=CJF?M.?F;N?>NI/OGG;LS0;<F?M
o NI,LCH=CJF?M.?F;N?>NI#L;JBC=M
Formats 
 FF>;N;QCFF<?L?JILN?>;==IL>CHANINB?;=NO;FNL?;NG?HNNB?MO<D?=NL?=?CP?>OHF?MM
INB?LQCM?MN;N?>
 #/'% /(/N;NCMNC=;F,LCH=CJF?M@IL>?=CG;FJF;=?M ,WMQCFF<?;>IJN?>@IL
L?JILNCHAI@>;N;<;M?>IHNB?L;Q>;N;=IFF?=N?>
 *OG?LC=>;N;QCFF<?L?JILN?>;NNB?JL?=CMCIH=IFF?=N?>IHNB??."
 0B?L?JILN?>JL?=CMCIH@LIGHIH?."MIOL=?MQCFF@IFFIQNB?% /(MN;NCMNC=;FJLCH=CJF?M<ON
G;S<?;>DOMN?>NI;=FCHC=;FFSCHN?LJL?N;<F?HOG<?LI@ ,WM
Planned and Actual Time 
 .?JILNCHA@ILN;<F?M
@CAOL?M;H>@ILG;FMN;NCMNC=;F;H;FSM?M
 ,F;HH?>NCG?L?F;NCP?NI>IMCHAQCFF<?OM?>CH@CAOL?M
MOGG;LC?M
MN;NCMNC=;F;H;FSM?M;H>
=;F=OF;NCIHI@;HS>?LCP?>J;L;G?N?LM
OHF?MMINB?LQCM?MN;N?>
 0B?CGJ;=NI@;HSG;DIL>?PC;NCIH@LIGNB?JF;HH?>;MM?MMG?HNNCG?M;H>ILM=B?>OF?>
PCMCN>;SMIHNB?;H;FSM?M;H>CHN?LJL?N;NCIHI@NB?L?MOFNMQCFF<?;MM?MM?>;M;JJLIJLC;N?
 .?JILNCHA@IL ;N;(CMNCHAM
 ,F;HH?>;H>;=NO;FNCG?L?F;NCP?NIMNO>S>LOA>IMCHAQCFF<?MBIQHCHFCMNCHAM.?@?LNI
% /(/N;NCMNC=;F,LCH=CJF?
 1HM=B?>OF?>ILOHJF;HH?>L?;>CHAMQCFF<?JL?M?HN?>QCNBCHNB?MO<D?=NWMFCMNCHAM
 2CMCNMIONMC>?NB?JLINI=IF>?@CH?>NCG?QCH>IQMC?L?=IL>?>;MJLINI=IF>?PC;NCIHMQCFF
<?CH=FO>?>CHFCMNCHAM<ONIGCNN?>@LIG@CAOL?M
MOGG;LC?M;H>MN;NCMNC=;F;H;FSM?M
Unscheduled Visits 
 1HM=B?>OF?>PCMCNMQCFFHIN<?CH=FO>?>CHMOGG;LSN;<F?M
 1HM=B?>OF?>PCMCNMQCFFHIN<?CH=FO>?>CH@CAOL?M
 FFOHM=B?>OF?>PCMCNMQCFF<?CH=FO>?>CHFCMNCHAM
Descriptive Summary Statistics 
IHNCHOIOM ;N;
.?@?LNI% /(/N;NCMNC=;F,LCH=CJF? 
;N?AILC=;F ;N;
*
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Reporting of Pharmacokinetic Concentration Data
 ?M=LCJNCP?
/OGG;LS/N;NCMNC=M
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Reporting of Pharmacokinetic Parameters 
 ?M=LCJNCP?
/OGG;LS/N;NCMNC=M
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*
H
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MN;H>;L>>?PC;NCIH/ 
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<?L?JILN?>
2<√?RJ/ 
/ / I@FIANL;HM@ILG?>>;N;


 
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Reporting Standards 
,;L;G?N?LM*IN
?CHA(IA
0L;HM@ILG?>
0G;R
1?R
NF;MN
F;G<>;:T
F;G<>;:T:FIQ?L
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.;NCII@NCG?CHP;LC;H=?
.;NCII@;==OGOF;NCIH

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?
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1∞
1N
1

N
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2MM
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.;NCII@NCG?CHP;LC;H=?
.;NCII@;==OGOF;NCIH
0G;R

1?R
NF;MN
F;G<>;:T
F;G<>;:T:FIQ?L
F;G<>;:T:OJJ?L

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(L
?
Graphical Displays 
 .?@?LNI% /(/N;NCMNC=;F,LCH=CJ;FMNI


 
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204847 
 
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Reporting Standards 
10.4. 
Appendix 4: Derived and Transformed Data 
10.4.1. 
General 
Multiple Measurements at One Time Point 
 )?;HI@NB?G?;MOL?G?HNMQCFF<?=;F=OF;N?>;H>OM?>CH;HS>?LCP;NCIHI@MOGG;LSMN;NCMNC=M
<ONC@FCMN?>
;FF>;N;QCFF<?JL?M?HN?>
 %@NB?L?;L?NQIP;FO?MQCNBCH;NCG?QCH>IQNB?P;FO?=FIM?MNNINB?N;LA?N>;S@ILNB;NQCH>IQ
QCFF<?OM?>%@P;FO?M;L?NB?M;G?>CMN;H=?@LIGNB?N;LA?NNB?HNB?G?;HQCFF<?N;E?H
 /O<D?=NMB;PCHA<INB$CAB;H>(IQP;FO?M@IL*ILG;F.;HA?M;N;HSJIMN<;M?FCH?PCMCNM@IL
M;@?NSJ;L;G?N?LMQCFF<?=IOHN?>CH<INBNB?$CAB;H>(IQ=;N?AILC?MI@XHSPCMCNJIMN
<;M?FCH?YLIQI@L?F;N?>MOGG;LSN;<F?M0BCMQCFF;FMI<?;JJFC=;<F?NIL?F?P;HN,IN?HNC;F
FCHC=;F%GJILN;H=?MOGG;LSN;<F?M
Study Day 
 ;F=OF;N?>;MNB?HOG<?LI@>;SM@LIGNL?;NG?HN>;N?
 .?@ ;N?)CMMCHA→/NO>S ;S)CMMCHA
 .?@ ;N?0L?;NG?HN ;N?→/NO>S ;S.?@ ;N?Z0L?;NG?HN ;N?
 .?@ ;N;≥0L?;NG?HN ;N?→/NO>S ;S.?@ ;N?Z0L?;NG?HN ;N?	
 
10.4.2. 
Study Population 
Demographics 
Age 
 #/'MN;H>;L>% /(;FAILCNBGMQCFF<?OM?>@IL=;F=OF;NCHA;A?QB?L?<CLNB>;N?QCFF<?CGJON?>
;M@IFFIQM
o HSMO<D?=NQCNB;GCMMCHA>;SQCFFB;P?NBCMCGJON?>;M>;SVW
o HSMO<D?=NQCNB;GCMMCHA>;N?;H>GIHNBQCFFB;P?NBCMCGJON?>;MVNB&OH?W
 CLNB>;N?QCFF<?JL?M?HN?>CHFCMNCHAM;MV5555W
Body Mass Index (BMI) 
 ;F=OF;N?>;MWeight (kg) / [Height (m)2 
 
10.4.3. 
Safety 
ECG Parameters 
RR Interval 
 %"!#P;FO?M;L?G;=BCH?L?;>;H>..CHN?LP;FGM?=CMHINJLIPC>?>>CL?=NFS
NB?H..
CHN?LP;F=;H<?>?LCP?>;M
78 %@-0=CMG;=BCH?L?;>..CMHINJLIPC>?>
NB?H

78 %@-0="CMG;=BCH?L?;>;H>..CMHINJLIPC>?>
NB?H


 
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ECG Parameters 
 
 %@!#M;L?G;HO;FFSL?;>
NB?..P;FO?JL?=?>CHANB?G?;MOL?G?HN-0CHN?LP;FMBIOF><?;
=IFF?=N?>P;FO?0$!*>IHIN>?LCP?
 %GJILN;HN*IN?);=BCH?L?;>P;FO?MI@..MBIOF>HIN<?L?JF;=?>QCNBL?>?LCP?>P;FO?M
Corrected QT Intervals 
 3B?HHIN?HN?L?>>CL?=NFSCHNB??."
=ILL?=N?>-0CHN?LP;FM<S;T?NNWM-0=;H>
"L?>?LC=C;WM-0="@ILGOF;MQCFF<?=;F=OF;N?>
CHGM?=
>?J?H>CHAIHNB?;P;CF;<CFCNSI@INB?L
G?;MOL?G?HNM
 %"..CHN?LP;FGM?=CMJLIPC>?>NB?HGCMMCHA-0=;H>IL-0="QCFF<?>?LCP?>;M


 %GJILN;HN*IN?);=BCH?L?;>P;FO?MI@-0=;H>-0="MBIOF>HIN<?L?JF;=?>QCNBL?>?LCP?>
P;FO?M%@H?CNB?LG;=BCH?L?;>-0=IL-0=";L?;P;CF;<F?<ON-0;H>..;L?=IFF?=N?>
NB?H
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N?;G;H>NB?0("MGOMNB;P?;H;JJLIJLC;N?@IINHIN?>?HINCHANBIM?J;L;G?N?LM;L?>?LCP?>
 
Adverse Events 
AE’S OF Special Interest 
 (CP?L?P?HNM
 2?P?HNM
 %H@OMCIHMCN?L?;=NCIHM
 ,IN?HNC;FMSMN?GC=;FF?LAC=L?;=NCIHM
 $?G;NIFIAC=?P?HNM
 .;MB!P?HNM
 
 
 


 
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10.5. 
Appendix 5: Premature Withdrawals and Handling of Missing 
Data 
10.5.1. 
Premature Withdrawals 
Element 
Reporting Detail 
#?H?L;F
 /O<D?=NMNO>S=IGJF?NCIHC?;MMJ?=C@C?>CHNB?JLINI=IFQ;M>?@CH?>;MIH?
QBIB;M=IGJF?N?>;FFJB;M?MI@NB?MNO>SCH=FO>CHANB?@IFFIQOJPCMCN
 3CNB>L;QHMO<D?=NMG;S<?L?JF;=?>CHNB?MNO>S
 FF;P;CF;<F?>;N;@LIGMO<D?=NMQBIQ?L?QCNB>L;QH@LIGNB?MNO>SQCFF<?FCMN?>
;H>;FF;P;CF;<F?JF;HH?>>;N;QCFF<?CH=FO>?>CHMOGG;LSN;<F?M;H>@CAOL?M

OHF?MMINB?LQCM?MJ?=C@C?>
 
10.5.2. 
Handling of Missing Data 
Element 
Reporting Detail 
#?H?L;F
 )CMMCHA>;N;I==OLMQB?H;HSL?KO?MN?>>;N;CMHINJLIPC>?>
F?;>CHANI<F;HE
@C?F>MIHNB?=IFF?=NCIHCHMNLOG?HN
o 0B?M?>;N;QCFF<?CH>C=;N?><SNB?OM?I@;X<F;HEYCHMO<D?=NFCMNCHA
>CMJF;SM1HF?MM;FF>;N;@IL;MJ?=C@C=PCMCN;L?GCMMCHACHQBC=B=;M?NB?
>;N;CM?R=FO>?>@LIGNB?N;<F?
o HMQ?LMMO=B;MX*IN;JJFC=;<F?Y;H>X*IN?P;FO;<F?Y;L?HIN=IHMC>?L?>NI
<?GCMMCHA>;N;;H>MBIOF><?>CMJF;S?>;MMO=B
+ONFC?LM
 HSMO<D?=NM?R=FO>?>@LIGNB?MOGG;LC?M;H>ILMN;NCMNC=;F;H;FSM?MQCFF<?
>I=OG?HN?>;FIHAQCNBNB?L?;MIH@IL?R=FOMCIHCHNB?=FCHC=;FMNO>SL?JILN
10.5.2.1. 
Handling of Missing Dates 
Element 
Reporting Detail 
#?H?L;F
,;LNC;F>;N?MQCFF<?>CMJF;S?>;M=;JNOL?>CHMO<D?=NFCMNCHA>CMJF;SM
>P?LM?
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 0B??.";FFIQM@ILNB?JIMMC<CFCNSI@J;LNC;F>;N?MC?
IHFSGIHNB;H>S?;LNI
<?L?=IL>?>@IL!MN;LN;H>?H>>;N?MNB;NCM
NB?>;SI@NB?GIHNBG;S<?
GCMMCHA%HMO=B;=;M?
NB?@IFFIQCHA=IHP?HNCIHMQCFF<?;JJFC?>@IL=;F=OF;NCHA
NB?NCG?NIIHM?N;H>NB?>OL;NCIHI@NB??P?HN
o )CMMCHA/N;LN ;S"CLMNI@NB?GIHNBQCFF<?OM?>OHF?MMNBCMCM<?@IL?NB?
MN;LN>;N?I@MNO>SNL?;NG?HNCHNBCM=;M?NB?MNO>SNL?;NG?HNMN;LN>;N?QCFF
<?OM?>;H>B?H=?NB??P?HNCM=IHMC>?L?>+HNL?;NG?HN;MJ?LJJ?H>CR
0L?;NG?HN/N;N?M;H>,B;M?M
o )CMMCHA/NIJ ;S(;MN>;SI@NB?GIHNBQCFF<?OM?>
OHF?MMNBCMCM;@N?LNB?
MNIJ>;N?I@MNO>SNL?;NG?HNCHNBCM=;M?NB?MNO>SNL?;NG?HNMNIJ>;N?QCFF
<?OM?>
 IGJF?N?FSGCMMCHAMN;LNIL?H>>;N?MQCFFL?G;CHGCMMCHA
QCNBHICGJON;NCIH
;JJFC?>IHM?KO?HNFS
NCG?NIIHM?N;H>>OL;NCIHI@MO=B?P?HNMQCFF<?
GCMMCHA


 
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204847 
 
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Element 
Reporting Detail 
 /N;LNIL?H>>;N?MQBC=B;L?=IGJF?N?FSGCMMCHAC?HIS?;LMJ?=C@C?>QCFF
L?G;CHGCMMCHA
QCNBHICGJON;NCIH;JJFC?>
 
10.5.2.2. 
Handling of Partial Dates 
Element 
Reporting Detail 
IH=IGCN;HN
)?>C=;NCIHM
 ,;LNC;F>;N?M@IL;HS=IH=IGCN;HNG?>C=;NCIHML?=IL>?>CHNB?."QCFF<?
CGJON?>OMCHANB?@IFFIQCHA=IHP?HNCIH
o %@NB?J;LNC;F>;N?CM;MN;LN>;N?
;QCFF<?OM?>@ILNB?>;S;H>&;HQCFF
<?OM?>@ILNB?GIHNB
o %@NB?J;LNC;F>;N?CM;MNIJ>;N?
;QCFF<?OM?>@ILNB?>;S
>?J?H>?HNIHNB?GIHNB;H>S?;L;H> ?=QCFF<?OM?>@ILNB?GIHNB
 0B?L?=IL>?>J;LNC;F>;N?QCFF<?>CMJF;S?>CHFCMNCHAM
 
>P?LM?
!P?HNM
 HSJ;LNC;F>;N?M@IL;>P?LM??P?HNMQCFF<?L;CM?>NI>;N;G;H;A?G?HN%@NB?
@OFF>;N?=;HHIN<?;M=?LN;CH?>
NB?@IFFIQCHA;MMOGJNCIHMQCFF<?G;>?
o %@NB?J;LNC;F>;N?CM;MN;LN>;N?
;QCFF<?OM?>@ILNB?>;S;H>&;HQCFF
<?OM?>@ILNB?GIHNB
o $IQ?P?L
C@NB?M?L?MOFNMCH;>;N?JLCILNI3??E ;S;H>NB??P?HN
=IOF>JIMMC<FSB;P?I==OLL?>>OLCHANL?;NG?HN@LIGNB?J;LNC;FCH@ILG;NCIH

NB?HNB?3??E ;S>;N?QCFF<?;MMOG?>NI<?NB?MN;LN>;N?
o 0B?!QCFFNB?H<?=IHMC>?L?>NIMN;LNIHNL?;NG?HNQILMN=;M?
o %@NB?J;LNC;F>;N?CM;MNIJ>;N?
;QCFF<?OM?>@ILNB?>;S
>?J?H>?HNIHNB?GIHNB;H>S?;L;H> ?=QCFF<?OM?>@ILNB?GIHNB
 0B?L?=IL>?>J;LNC;F>;N?QCFF<?>CMJF;S?>CHFCMNCHAM


 
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10.6. 
Appendix 6: Values of Potential Clinical Importance 
10.6.1. 
ECG 
ECG Parameter 
Units 
Potential Clinical Importance Range 
Lower 
Upper 
Absolute 
<MIFON?-0=%HN?LP;F
GM?=
78

78
≤[2]
≥78
≤[2]
≥78

<MIFON?,.%HN?LP;F
GM?=
78
78
<MIFON?-./%HN?LP;F
GM?=
78
78
Change from Baseline 
%H=L?;M?@LIG;M?FCH?-0=
GM?=
≤78

GM?=
78
≤[2]
GM?=
≥78

NOTES: 
 
.?JL?M?HNMN;H>;L>!#P;FO?MI@,%@IL$2MNO>C?M
 
.?JL?M?HN@OLNB?LMO<>CPCMCIHMI@!#P;FO?M@IL;H;FSMCM
10.6.2. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Potential Clinical Importance Range 
Lower 
Upper 
/SMNIFC=FII>,L?MMOL?
GG$A


 C;MNIFC=FII>,L?MMOL?
GG$A


$?;LN.;N?
<JG


 
 


 
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10.7. 
Appendix 7: DMID Adult Toxicity Tables for Adverse Event Assessment 
10.7.1. 
 Laboratory Values 
Parameter values are converted to use SI units. 
 

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Grade 1 
Grade 2 
Grade 3 
Grade 4 
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Grade 2 
Grade 3 
Grade 4 
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CONFIDENTIAL 
 
 
 
204847 
 
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FC@?NBL?;N?HCHA;LLBSNBGC;
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ENZYMES

Grade 1 
Grade 2 
Grade 3 
Grade 4 
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Grade 4 
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10.8. 
Appendix 8: Multiple Comparisons & Multiplicity 
10.8.1. 
 Handling of Multiple Comparisons & Multiplicity 
No adjustments for multiplicity will be made. 


 
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10.9. 
Appendix 9: Model Checking and Diagnostics for Statistical 
Analyses 
10.9.1. 
Statistical Analysis Assumptions 
Endpoint(s)  ,'?H>JICHNM1;H>G;R
Analysis 
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>;N;
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  CMNLC<ONCIH;F;MMOGJNCIHMOH>?LFSCHANB?MN;NCMNC=;F;H;FSM?MQCFF<?;MM?MM?><SPCMO;F
CHMJ?=NCIHI@L?MC>O;FJFINM*ILG;FCNSQCFF<??R;GCH?><SHILG;FJLI<;<CFCNSJFINM
QBCF?
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@ILNB?GI>?F
 
 


 
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10.10. 
Appendix 10 – Abbreviations & Trade Marks 
10.10.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
Ae 
Amount excreted in urine 
AUC 
Area under the curve 
AUC(0-t) 
AUC from time zero to the time of last quantifiable concentration 
AUC(0-) 
AUC from time zero to infinity 
AUC(0-) 
AUC over the dosing interval  
A&R 
Analysis and Reporting  
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CL 
Total systemic clearance 
CLr 
Renal clearance 
Cmax 
Concentration at maximum 
C 
Trough concentration 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CrI 
Credible interval 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
CTR 
Clinical Trial Register 
CVb / CVw 
Coefficient of Variation (Between) / Coefficient of Variation (Within) 
DOB 
Date of Birth 
DP 
Decimal Places 
eCRF 
Electronic Case Record Form 
Feu(t1-t2) 
Urinary excretion ratio relative to dose 
IA 
Interim Analysis 
ICH 
International Conference on Harmonisation 
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
IP 
Investigational Product 
GUI 
Guidance 
MCMC 
Markov Chain Monte Carlo 
PCI 
Potential Clinical Importance  
PDMP 
Protocol Deviation Management Plan 
PK 
Pharmacokinetic 
PP 
Per Protocol 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 


 
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Abbreviation 
Description 
Ratio of 
accumulation 
Accumulation ratio, calculated by AUC(0-) on day 15/ AUC(0-) on 
day 1 
Ratio of time 
invariance 
Time invariance ratio, calculated by AUC(0-) on day 15/ AUC(0-) on 
day 1 
SAC 
Statistical Analysis Complete 
SDTM 
Study Data Tabulation Model 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings  
t1/2 
Terminal elimination half-life 
Tmax 
Time of maximum concentration 
Vss 
Steady-state volume of distribution 
GSK 
GlaxoSmithKline 
 
10.10.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
NONE 
 
WinNonlin 
 
 
SAS 
 
 
 
 


 
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10.11. 
Appendix 11: List of Data Displays 
10.11.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
/NO>S,IJOF;NCIH
NI

/;@?NS
NI

,B;LG;=IECH?NC=
NI
NI
Section 
Listings 
%$(CMNCHAM
NI
 
10.11.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided in the TLF Specification documents. 
Section 
Figure 
Table 
Listing 
/NO>S,IJOF;NCIH
,+,:"H
,+,:0H
,+,:(H
/;@?NS
/"!:"H
/"!:0H
/"!:(H
,B;LG;=IECH?NC=
,':"H
,':0H
,':(H
NOTES:  
 
*IH/N;H>;L>>CMJF;SM;L?CH>C=;N?>CHNB?V% /(0/0% !R;GJF?/B?FFWILV,LIAL;GGCHA*IN?MW=IFOGH;M
V7*IH/N;H>;L>8	.?@?L?H=?W
 
10.11.3. 
Deliverable [Priority] 
Delivery [Priority] [1] 
Description 
 !748
 IM?!M=;F;NCIH
/748
"CH;F/N;NCMNC=;FH;FSMCMIGJF?N?
NOTES:  
 
%H>C=;N?MJLCILCNSC?IL>?LCHQBC=B>CMJF;SMQCFF<?A?H?L;N?>@ILNB?L?JILNCHA?@@ILN
 


 
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10.11.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition and Analysis Sets 

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% 

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 2
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/78
Medical Conditions 

/;@?NS
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/OGG;LSI@;L>CIP;M=OF;L.?F;N?>)?>C=;FIH>CNCIHM

/78
 


 
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10.11.5. 
Safety Tables 
Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Adverse Events

/;@?NS
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,L?@?LL?>0?LGM;H>
2?L<;NCG0?RN

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/;@?NS
!
/OGG;LSI@ LOA.?F;N?>>P?LM?!P?HNM

/78

/;@?NS

/OGG;LSI@IGGIH*IHM?LCIOM>P?LM?!P?HNM<S/SMN?G+LA;H
F;MM;H>,L?@?LL?>0?LG*OG<?LI@/O<D?=NM;H>+==OLL?H=?M

/78

/;@?NS

/OGG;LSI@/?LCIOM>P?LM?!P?HNM<S/SMN?G+LA;HF;MM;H>,L?@?LL?>
0?LG*OG<?LI@/O<D?=NM;H>+==OLL?H=?M

/78
Laboratory Measurements 

/;@?NS
(
/OGG;LSI@FCHC=;FB?GCMNLS2;FO?M

/78

/;@?NS
(
/OGG;LSI@FCHC=;FB?GCMNLSB;HA?@LIG;M?FCH?

/78

/;@?NS
(
/OGG;LSI@$;?G;NIFIAS2;FO?M

/78

/;@?NS
(
/OGG;LSI@$;?G;NIFIASB;HA?@LIG;M?FCH?

/78

/;@?NS
1.<
/OGG;LSI@1LCH;FSMCM CJMNC=E.?MOFNM

/78
Electrocardiograms 

/;@?NS
!#
/OGG;LSI@!#"CH>CHAM

/78

/;@?NS
!#
/OGG;LSI@!#2;FO?M

/78

/;@?NS
!#
/OGG;LSI@B;HA?@LIG;M?FCH?CH!#2;FO?M

/78

/;@?NS
/"!:0
/OGG;LSI@"L?KO?H=SI@);RCGOG,IMN IM?!#,;L;G?N?LILL?=N?>-0=
%HN?LP;F

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
55 
 
Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 

/;@?NS
/"!:0
/OGG;LSI@"L?KO?H=SI@);RCGOGB;HA?@LIG;M?FCH?@IL!#,;L;G?N?L
ILL?=N?>-0=%HN?LP;F

/78
Vital Signs 

/;@?NS
2/
/OGG;LSI@2CN;F/CAHM

/78

/;@?NS
2/
/OGG;LSI@2CN;F/CAHMB;HA?@LIG;M?FCH?

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
56 
 
10.11.6. 
Safety Figures 
Safety : Figures 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Cytokine Plots 

/;@?NS
/"!:"
IRJFINI@SNIECH? ;N;

/78

/;@?NS
/"!:"
%H>CPC>O;FSNIECH?,FIN

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
57 
 
10.11.7. 
Pharmacokinetic Tables 
Pharmacokinetic : Tables 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK Concentration Data 

,'
,'
/OGG;LSI@#/'/CHAF? IM?,F;MG;,B;LG;=IECH?NC=
IH=?HNL;NCIH0CG? ;N;OHCNM<S0L?;NG?HNCH,;LN;H>,;LN


/78

,'
,'
/OGG;LSI@#/',F;MG;,B;LG;=IECH?NC=
IH=?HNL;NCIH0CG? ;N;OHCNM<S0L?;NG?HNCH,;LN

/78
PK Parameters 

,',;L;G?N?L
,',0
/OGG;LSI@1HNL;HM@ILG?>#/'/CHAF? IM?,F;MG;
,B;LG;=IECH?NC=,;L;G?N?LMCH,;LN;H>,;LN 
0G;R
1?R
NF;MN
F;G<>;:T

F;G<>;:T:FIQ?L
F;G<>;:T:OJJ?L

F;G<>;:T:HII@JICHNM
/78

,',;L;G?N?L
,',0
/OGG;LSI@(IANL;HM@ILG?>#/'/CHAF? IM?,F;MG;
,B;LG;=IECH?NC=,;L;G?N?LMCH,;LN;H>,;LN 
G;R
1N
1∞
N
(

2MM
/78

,',;L;G?N?L
,',0
/OGG;LSI@1HNL;HM@ILG?>#/'/CHAF? IM?1LCH?
,B;LG;=IECH?NC=,;L;G?N?LMCH,;LN;H>,;LN
"?ONN
(L
?
/78

,',;L;G?N?L
,',0
/OGG;LSI@1HNL;HM@ILG?>#/',F;MG;
,B;LG;=IECH?NC=,;L;G?N?LMCH,;LN
G;R
1N
1∞
1

N
(
2MM

.;NCII@NCG?
CHP;LC;H=?
.;NCII@;==OGOF;NCIH

0G;R
1?R
NF;MN
F;G<>;:T

F;G<>;:T:FIQ?L
F;G<>;:T:OJJ?L

F;G<>;:T:HII@JICHNM
/78

,',;L;G?N?L
,',0
/OGG;LSI@(IANL;HM@ILG?>#/',F;MG;
,B;LG;=IECH?NC=,;L;G?N?LMCH,;LN
G;R
1N
1∞
1

N
(
2MM

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
58 
 
Pharmacokinetic : Tables 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 

,',;L;G?N?L
,',0
/OGG;LSI@1HNL;HM@ILG?>#/'1LCH?
,B;LG;=IECH?NC=,;L;G?N?LMCH,;LN
"?ONN
(L
?
/78
PK Analysis Tables

,',;L;G?N?L
,':0
/OGG;LSI@/N;NCMNC=;FH;FSMCMI@#/',F;MG; IM?
,LIJILNCIH;FCNSCH,;LN 
G;R
1∞
/78

,',;L;G?N?L
,':0
/OGG;LSI@/N;NCMNC=;FH;FSMCMI@#/',F;MG; IM?
,LIJILNCIH;FCNSCH,;LN
G;R
1
/78

,',;L;G?N?L
,':0
/OGG;LSI@/N;NCMNC=;FH;FSMCMI@#/',F;MG;0CG?
%HP;LC;H=?CH,;LN
1∞IH ;S;H>1IH
 ;S
/78

,',;L;G?N?L
,':0
/OGG;LSI@/N;NCMNC=;FH;FSMCMI@#/',F;MG;
==OGOF;NCIH.;NCICH,;LN
1
/78

,',;L;G?N?L
,':0
/OGG;LSI@/N;NCMNC=;FH;FSMCMI@#/',F;MG;/N?;>S
/N;N?MM?MMG?HNCH,;LN

/78
Bayesian Dose Escalation

,',;L;G?N?L
,':0
/OGG;LSI@)I>?F,;L;G?N?LM@IL,;LN,IMN?LCIL
 CMNLC<ONCIHM

 !78

,',;L;G?N?L
,':0
/OGG;LSI@)I>?F,;L;G?N?LM@IL,;LN,IMN?LCIL
 CMNLC<ONCIHM

 !78

,',;L;G?N?L
,':0
/OGG;LSI@,',;L;G?N?LM@IL,;LN;S?MC;H,L?>C=NCIHI@
%H>CPC>O;F/O<D?=NM

 !78

,',;L;G?N?L
,':0
/OGG;LSI@,',;L;G?N?LM@IL,;LN;S?MC;H,L?>C=NCIHI@
%H>CPC>O;F/O<D?=NM

 !78

,',;L;G?N?L
,':0
/OGG;LSI@,',;L;G?N?LM@IL,;LN;S?MC;H,L?>C=NCP?
,LI<;<CFCNS

 !78


 
CONFIDENTIAL 
 
 
 
204847 
 
59 
 
Pharmacokinetic : Tables 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 

,',;L;G?N?L
,':0
/OGG;LSI@,',;L;G?N?LM@IL,;LN;S?MC;H,L?>C=NCP?
,LI<;<CFCNS

 !78

,',;L;G?N?L
,':0
/OGG;LSI@,',;L;G?N?LM@IL,;LN;S?MC;H%H@?L?HNC;F
,LI<;<CFCNS

 !78

,',;L;G?N?L
,':0
/OGG;LSI@,',;L;G?N?LM@IL,;LN;S?MC;H%H@?L?HNC;F
,LI<;<CFCNS

 !78

,',;L;G?N?L
,':0
/OGG;LSI@/N;NCMNC=;FH;FSMCMI@#/'/CHAF? IM?
,F;MG;,B;LG;=IECH?NC=,;L;G?N?LMCH,;LN;H>,;LN
/O<D?=NM

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
60 
 
10.11.8. 
Pharmacokinetic Figures 
Pharmacokinetic : Figures 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Concentration Plots 

,'
,'"
)?;H/ #/'/CHAF? IM?,F;MG;IH=?HNL;NCIH
,F;HH?>0CG?,FINM@IL,;LN;H>,;LN(CH?;L;H>/?GC
(IA

/78

,'
,'"
)?>C;HL;HA?#/'/CHAF? IM?,F;MG;
IH=?HNL;NCIH,F;HH?>0CG?,FINM@IL,;LN;H>,;LN(CH?;L
;H>/?GC(IA

/78

,'
,'"
)?;H/ #/',F;MG;IH=?HNL;NCIH,F;HH?>0CG?
,FINM@IL,;LN(CH?;L;H>/?GC(IA

/78

,'
,'"
)?>C;HL;HA?#/',F;MG;IH=?HNL;NCIH,F;HH?>
0CG?,FINM@IL,;LN(CH?;L;H>/?GC(IA

/78

,'
,'"
)?>C;HL;HA?#/',F;MG;,L?>IM?IH=?HNL;NCIH
P?LMOM ;S@IL,;LN(CH?;L;H>/?GC(IA

/78

,'
,'",
%H>CPC>O;F#/'/CHAF? IM?,F;MG;IH=?HNL;NCIH
,F;HH?>0CG?,FINM@IL,;LN;H>,;LN(CH?;L;H>/?GC(IA

/78

,'
,'",
%H>CPC>O;F#/',F;MG;IH=?HNL;NCIH,F;HH?>0CG?
,FINM@IL,;LN(CH?;L;H>/?GC(IA

/78
PK Parameters

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;1N
2?LMOM IM?@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;1CH@
2?LMOM IM?@IL,;LN

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
61 
 
Pharmacokinetic : Figures 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;G;R
2?LMOM IM?@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;?2?LMOM
 IM?@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;1N
2?LMOM IM?IH ;S@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;1∞
2?LMOM IM?IH ;S@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;G;R
2?LMOM IM?IH ;S@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;?2?LMOM
 IM?IH ;S@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;1N;O
2?LMOM IM?IH ;S@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;G;R
2?LMOM IM?IH ;S@IL,;LN

/78

,',;L;G?N?L
,',"
IGJ;L;NCP?,FINI@%H>CPC>O;F#/',F;MG;?2?LMOM
 IM?IH ;S@IL,;LN

/78
Bayesian Dose Escalation

,',;L;G?N?L
,':"
17N8\ABG(CH,;LN IM?.?MJIHM?OLP?

 !78

,',;L;G?N?L
,':"
G;R\AG(CH,;LN IM?.?MJIHM?OLP?

 !78

,',;L;G?N?L
,':"
178\ABG(CH,;LN IM?.?MJIHM?OLP?

 !78

,',;L;G?N?L
,':"
G;R\AG(CH,;LN IM?.?MJIHM?OLP?

 !78


 
CONFIDENTIAL 
 
 
 
204847 
 
62 
 
10.11.9. 
ICH Listings 
ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Randomisation 

/;@?NS
0
(CMNCHAI@.;H>IGCT?>;H>=NO;F0L?;NG?HNM 

/78
Subject Disposition 

/;@?NS
!/
(CMNCHAI@.?;MIHM@IL/NO>S3CNB>L;Q;F 

/78

/=L??H?>
!/
(CMNCHAI@.?;MIHM@IL/=L??HCHA";CFOL?

/78

/=L??H?>
 2
(CMNCHAI@%GJILN;HN,LINI=IF ?PC;NCIHM

/78

/;@?NS
%!
(CMNCHAI@/O<D?=NMQCNB%H=FOMCIH!R=FOMCIHLCN?LC; ?PC;NCIHM

/78
Demographics

/;@?NS
 )
(CMNCHAI@ ?GIAL;JBC=B;L;=N?LCMNC=M
%H=FO>?B?CABN
Q?CABN

)%
/GIECHA$CMNILS

F=IBIF$CMNILS

;@@?CH?$CMNILS
;H>
 LOA1M?$CMNILS
/78

/;@?NS
 )
(CMNCHAI@.;=?

/78
Medical Conditions and Concomitant Medications

/;@?NS
)$
(CMNCHAI@)?>C=;FIH>CNCIHM

/78

/;@?NS
)
(CMNCHAI@IH=IGCN;HN)?>C=;NCIHM

/78
Exposure

/;@?NS
/"!:(
(CMNCHAI@!RJIMOL? ;N;

/78
Safety 

/;@?NS
!
(CMNCHAI@/O<D?=N*OG<?LM@IL%H>CPC>O;F>P?LM?!P?HNM

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
63 
 
ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 

/;@?NS
!
(CMNCHAI@FF>P?LM?!P?HNM

/78

/;@?NS
!
(CMNCHAI@ LOA.?F;N?>>P?LM?!P?HNM

/78

/;@?NS
/"!:(
(CMNCHAI@/?LCIOM>P?LM?!P?HNM

/78

/;@?NS
!
(CMNCHAI@>P?LM?!P?HNM(?;>CHANI3CNB>L;Q;F@LIG/NO>S

/78

/;@?NS
/"!:(
(CMNCHAI@%H@OMCIH/CN?.?;=NCIH>P?LM?!P?HNM
IH>CNCIH;F>CMJF;S
/78

/;@?NS
/"!:(
(CMNCHAI@(CP?L>P?LM?!P?HNM
IH>CNCIH;F>CMJF;S
/78

/;@?NS
/"!:(
(CMNCHAI@;L>CIP;M=OF;L>P?LM?!P?HNM
IH>CNCIH;F>CMJF;S
/78

/;@?NS
/"!:(
(CMNCHAI@.;MB!P?HNM
IH>CNCIH;F>CMJF;S
/78
Laboratory Measurements

/;@?NS
(
(CMNCHAI@FCHC=;FB?GCMNLS0IRC=CNC?MI@#L;>?IL$CAB?L

/78

/;@?NS
(
(CMNCHAI@FFFCHC=;FB?GCMNLS ;N;@IL/O<D?=NMQCNB0IRC=CNC?MI@
#L;>?IL$CAB?L

/78

/;@?NS
(
(CMNCHAI@$;?G;NIFIAS0IRC=CNC?MI@#L;>?IL$CAB?L

/78

/;@?NS
(
(CMNCHAI@FF$;?G;NIFIAS ;N;@IL/O<D?=NMQCNB0IRC=CNC?MI@#L;>?
IL$CAB?L

/78

/;@?NS
1.;
(CMNCHAI@1LCH;FSMCM0IRC=CNC?MI@#L;>?IL$CAB?L

/78

/;@?NS
1.;
(CMNCHAI@1LCH;FSMCM ;N;@IL/O<D?=NMQCNB0IRC=CNC?MI@#L;>?IL
$CAB?L

/78
ECGs

/;@?NS
!#
(CMNCHAI@<HILG;F!#"CH>CHAM

/78

/;@?NS
!#
(CMNCHAI@FF!#"CH>CHAM@IL/O<D?=NMQCNB;H<HILG;F"CH>CHA

/78

/;@?NS
!#
(CMNCHAI@!#2;FO?MI@,IN?HNC;FFCHC=;F%GJILN;H=?

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
64 
 
ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 

/;@?NS
!#
(CMNCHAI@FF!#2;FO?M@IL/O<D?=NMQCNBHS2;FO?I@,IN?HNC;F
FCHC=;F%GJILN;H=?

/78
Vital Signs

/;@?NS
2/
(CMNCHAI@2CN;F/CAHMI@,IN?HNC;FFCHC=;F%GJILN;H=?

/78

/;@?NS
2/
(CMNCHAI@FF2CN;F/CAHM@IL/O<D?=NMQCNB,IN?HNC;FFCHC=;F%GJILN;H=?
2;FO?M

/78
Liver Events

/;@?NS
(%2!.
(CMNCHAI@(CP?L)IHCNILCHA/NIJJCHA!P?HN.?JILNCHA
IH>CNCIH;F>CMJF;S
/78

/;@?NS
)$
(CMNCHAI@)?>C=;FIH>CNCIHM@IL/O<D?=NMQCNB(CP?L/NIJJCHA!P?HNM
IH>CNCIH;F>CMJF;S
/78

/;@?NS
/"!:(
(CMNCHAI@F=IBIF%HN;E?;N+HM?NI@(CP?L!P?HN
IH>CNCIH;F>CMJF;S
/78

/;@?NS
,'(4
(CMNCHAI@,F;MG;IH=?HNL;NCIH ;N;@IL/O<D?=NMQCNB(CP?L/NIJJCHA
!P?HNM
IH>CNCIH;F>CMJF;S
/78

/;@?NS
(%2!.
(CMNCHAI@(CP?LCIJMS ?N;CFM
IH>CNCIH;F>CMJF;S
/78

/;@?NS
(%2!.
(CMNCHAI@(CP?L%G;ACHA ?N;CFM
IH>CNCIH;F>CMJF;S
/78
Cardiac Telemetry

/;@?NS
/"!:(
(CMNCHAI@;L>C;=0?F?G?NLS)IHCNILCHA

/78


/;@?NS
/"!:(
(CMNCHAI@SNIECH? ;N;

/78
Pharmacokinetic Concentration 

,'
,'(4
(CMNCHAI@#/',B;LG;=IECH?NC=,F;MG;IH=?HNL;NCIH0CG?
 ;N;<S0L?;NG?HNCH,;LN;H>,;LN

/78

,'
,'1(,
(CMNCHAI@#/',B;LG;=IECH?NC=1LCH?IH=?HNL;NCIH0CG?
 ;N;<S0L?;NG?HNCH,;LN;H>,;LN

/78


 
CONFIDENTIAL 
 
 
 
204847 
 
65 
 
ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 

,'
,'(4
(CMNCHAI@#/',B;LG;=IECH?NC=,F;MG;IH=?HNL;NCIH0CG?
 ;N;<S0L?;NG?HNCH,;LN

/78

,'
,'1(,
(CMNCHAI@#/',B;LG;=IECH?NC=1LCH?IH=?HNL;NCIH0CG?
 ;N;<S0L?;NG?HNCH,;LN

/78
Pharmacokinetic Parameter

,',;L;G?N?L
,(,(4
(CMNCHAI@#/',F;MG;,B;LG;=IECH?NC=,;L;G?N?LM<S
0L?;NG?HNCH,;LN;H>,;LN

/78

,',;L;G?N?L
,(,(4
(CMNCHAI@#/'1LCH?,B;LG;=IECH?NC=,;L;G?N?LM<S
0L?;NG?HNCH,;LN;H>,;LN

/78

,',;L;G?N?L
,(,(4
(CMNCHAI@#/',F;MG;,B;LG;=IECH?NC=,;L;G?N?LM<S
0L?;NG?HNCH,;LN

/78

,',;L;G?N?L
,(,(4
(CMNCHAI@#/'1LCH?,B;LG;=IECH?NC=,;L;G?N?LM<S
0L?;NG?HNCH,;LN

/78
 
 


GlaxoSmithKline 
Example  
: SAFE_F1  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: Safety 
 
 
 
Figure 2.1 
Part: xx 
Cytokine Parameter (Unit) 
Cytokine Parameter (Unit) 
Boxplot of Cytokine Data  
 
Visit 
 
 
Programming notes: Present each cytokine parameter on a separate page for all scheduled visits.  Include a separate line for 
each treatment and use different symbols for each treatment. Include a legend to describe the treatments. 


GlaxoSmithKline 
Example  
: SAFE_F2  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: Safety 
 
 
 
Figure 2.2 
Part: xx 
Cytokine Parameter (Unit) 
Individual Cytokine Plot 
Subject = xxxxx 
 
Visit 
Source Data: Listing 39 
 
 
Programming notes: Present each subject separately (one per page) and then present all cytokine parameters on the same page for 
that subject. Include a separate line for each parameter and use different symbols for each parameter. Include a legend to 
describe the parameters and the units. 
Present all scheduled results by visit for the x-axis. 


GlaxoSmithKline 
Example  
: PKCF4   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK  
 
 
 
 
 
Figure 3.01 
Mean (SD) GSK3342830 Single Dose Plasma Concentration‐Planned Time Plots for Part 1 and Part 3 (Linear and Semi‐Log)
 
 
 
 
 
Part: Part 1 
 
 
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Concentration (units) 
 
Concentration (units) 
 
 
 
 
 
Planned Relative Time (Hrs) 
 
Planned Relative Time (Hrs) 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present Part 1 first, then Part 3. Dashed line represents the LLQ. Present all dose levels by part 
in the same plots. Add legend for doses at the bottom. 
 
Source Data: Listing 39 


GlaxoSmithKline 
Example  
: PKCF5   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK  
 
Figure 3.02 
Median (range) GSK3342830 Single Dose Plasma Concentration‐Planned Time Plots
for Part 1 and Part 3 
(Linear and Semi‐Log) 
 
 
 
 
 
Part: Part 1 
 
 
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Concentration (units) 
 
Concentration (units) 
 
 
 
 
 
Planned Relative Time (Hrs) 
 
Planned Relative Time (Hrs) 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present Part 1 first, then Part 3. Display dashed line to represent the LLQ. Present 
all cohort groups in the same plots. Add legend for doses at the bottom. 
 
Note: LLQ = xx units 
Source Data: Listing 39 


GlaxoSmithKline 
Example  
: PKCF4   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK  
 
Figure 3.03 
Mean (SD) GSK3342830 Plasma Concentration‐Planned Time Plots  for Part 2 (Linear and Semi‐Log)
 
 
Day: 1 
 
 
 
 
 
 
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Concentration (units) 
 
Concentration (units) 
 
 
 
 
 
Actual Relative Time (Hrs) 
 
Actual Relative Time (Hrs) 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Display dashed line to represent the LLQ. Present all cohort groups in the same plots. 
Add legend for doses at the bottom. Repeat for Day 15.
 
Note: LLQ = xx units 
Source Data: Listing 41 
 
 
 
 
 
 
 


GlaxoSmithKline 
Example  
: PKCF5   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK  
 
 
 
Figure 3.04 
Median (range) GSK3342830 Plasma Concentration‐Planned Time Plots for Part 2 (Linear and Semi‐Log)
 
 
Day : 1 
 
 
 
 
 
 
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Concentration (units) 
 
Concentration (units) 
 
 
 
 
 
Actual Relative Time (Hrs) 
 
Actual Relative Time (Hrs) 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Display dashed line to represent the LLQ. Present all cohort groups in the same plots. 
Add legend for doses at the bottom. Repeat for Day 15.
 
Note: LLQ = xx units 
Source Data: Listing 41 


GlaxoSmithKline 
Example  
: PKCF5   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3.05 
Median (range) GSK3342830 Plasma Pre‐dose Concentration versus Day for Part 2 (Linear and Semi‐Log)
 
 
 
 
 
 
 
 
 
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Concentration (units) 
 
Concentration (units) 
 
 
 
 
 
Day  
 
Day  
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Display dashed line to represent the LLQ. Present all cohort groups in the same plots. 
Add legend for doses at the bottom. 
 
Note: LLQ = xx units 
Source Data: Listing 41 


GlaxoSmithKline 
 
Example  
: PKCF1P 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK  
 
 
 
Figure 3.06 
Individual GSK3342830 Single Dose Plasma Concentration‐Planned Time Plots for Part 1 and Part 3 (Linear and Semi‐Log)
Subject ID: XXXX
 
 
 
 
 
Part: Part 1 
 
 
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Concentration (units) 
 
Concentration (units) 
 
 
 
 
 
Actual Relative Time (Hrs) 
 
Actual Relative Time (Hrs) 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present Part 1 first, then Part 3. Display dashed line to represent the LLQ.  
 
Note: LLQ = xx units 
Source Data: Listing 39 


GlaxoSmithKline 
Example  
: PKCF1P  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK  
Figure 3.07 
Individual GSK3342830 Plasma Concentration‐Planned Time Plots for Part 2 (Linear and Semi‐Log)
Subject ID: XXXX
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Concentration (units) 
 
Concentration (units) 
 
 
 
 
 
Actual Relative Time (Hrs) 
 
Actual Relative Time (Hrs) 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Display dashed line to represent the LLQ. Display Day 1 and Day 15 on the same figure.
 
 
Note: LLQ = xx units 
Source Data: Listing 41 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.08 
Comparative Plot of Individual GSK3342830 Plasma AUC(0-t) Versus Dose for Part 1 and Part 3
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
AUC(0-t) (units) 
 
AUC(0-t) (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present box plot for all cohort groups in the same plot. Place Part 3 at the right end 
of the axis, footnote will be added for the Part 3 dose. 
Source Data: Listing 43 
 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
 
 
Figure 3.09 
Comparative Plot of Individual GSK3342830 Plasma AUC(0-inf) Versus Dose for Part 1 and Part 3
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
AUC(0-inf) (units) 
 
AUC(0-inf) (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present box plot for all cohort groups in the same plot. Place Part 3 at the right end 
of the axis, footnote will be added for the Part 3 dose.3 
Source Data: Listing 41 
 
 
 
 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
Figure 3.10 
Comparative Plot of Individual GSK3342830 Plasma Cmax Versus Dose for Part 1 and Part 3
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Cmax (units) 
 
Cmax (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present box plot for all cohort groups in the same plot. Place Part 3 at the right end 
of the axis, footnote will be added for the Part 3 dose. 
Source Data: Listing 43 
 
 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.11 
Comparative Plot of Individual GSK3342830 Plasma Ae Versus Dose for Part 1
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Ae (units) 
 
Ae (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 44 
 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.12 
Comparative Plot of Individual GSK3342830 Plasma AUC(0-t) Versus Dose on Day 1 for Part 2 
 
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
AUC(0-t) (units) 
 
AUC(0-t) (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 45 
 
 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.13 
Comparative Plot of Individual GSK3342830 Plasma AUC(0-inf) Versus Dose on Day 1 for Part 2 
 
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
AUC(0-inf) (units) 
 
AUC(0-inf) (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 45 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.14 
Comparative Plot of Individual GSK3342830 Plasma Cmax Versus Dose on Day 1 for Part 2 
 
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Cmax (units) 
 
Cmax (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 45 
 
 
 
 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.15 
Comparative Plot of Individual GSK3342830 Plasma Ae Versus Dose on Day 1 for Part 2 
 
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Ae (units) 
 
Ae (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 46 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.16 
Comparative Plot of Individual GSK3342830 Plasma AUC(0-tau) Versus Dose on Day 15 for Part 2 
 
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
AUC(0-tau) (units) 
 
AUC(0-tau) (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 45 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
Figure 3.17 
Comparative Plot of Individual GSK3342830 Plasma Cmax Versus Dose on Day 15 for Part 2 
 
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Cmax (units) 
 
Cmax (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 45 
 
 
 


GlaxoSmithKline 
Example  
: PKPF3   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.18 
Comparative Plot of Individual GSK3342830 Plasma Ae Versus Dose on Day 15 for Part 2 
 
 
 
 
 
 
 
 
 
  
 
 
Linear Scale 
 
Semi-Logarithmic Scale 
 
 
 
 
 
 
Ae (units) 
 
Ae (units) 
 
 
 
 
 
Dose (Units) 
 
Dose (Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all cohort groups in the same plots. 
Source Data: Listing 46 
 


GlaxoSmithKline 
Example  
: PK_F1    
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.19 
AUC(0-t) (µg.h/mL) in Part 1 - Dose Response Curve  
 
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term. 
Source Table: T3.16  
 
Programming notes: 
 


GlaxoSmithKline 
Example  
: PK_F1    
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.20 
Cmax (µg/mL) in Part 1 - Dose Response Curve 
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
 
Programming notes: repeat figure 3.19 for Cmax (µg/mL) 
 


GlaxoSmithKline 
Example  
: PK_F1    
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.21 
AUC(0-8)x3 (µg.h/mL) in Part 2 - Dose Response Curve 
 
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
Source Table: T3.17  
 
 
Programming notes: repeat figure 3.19 for AUC[0-8]x3 with X-axis only has 3 dose levels: 1000, 2000, 4000 mg 
 


GlaxoSmithKline 
Example  
: PK_F1    
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol : 204847 
Population 
: PK Parameter 
 
 
Figure 3.22 
Cmax (µg/mL) in Part 2 - Dose Response Curve 
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
Source Table: T3.17  
 
 
Programming notes: repeat figure 3.19 for Cmax (µg/mL) with X-axis only has 3 dose levels: 1000, 2000, 4000 mg 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: TA1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Randomized 
Listing 1 
Listing of Randomized and Actual Treatments 
Part: xx 
 
 
 
 
 
 
 
Subject ID. 
Cohort 
Randomisation 
Number 
Randomization 
Date 
Randomised Treatment Actual Treatment 
 
 
 
 
 
 
xxx 
x 
xxxxxx 
DDMMMYYYY 
xxxxxxxxxxxxx 
xxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
x 
xxxxxx 
DDMMMYYYY 
xxxxxxxxxxxxx 
xxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: ES2  
  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 2 
Listing of Reasons for Study Withdrawal 
Part: xx 
Treatment: xxxx 
 
 
 
 
Subject ID. 
Date of Withdrawal 
Study Day Primary Reason 
 
 
 
 
xxx 
DDMMMYYYY 
x 
xxxxxxxxxxxxxx 
 
 
 
 
xxx 
DDMMMYYYY 
x 
xxxxxxxxxxxxxxxx 
 
 
 
 
xxx 
DDMMMYYYY 
x 
xxxxxxxxxxxxxx 
 
 
 
 
xxx 
DDMMMYYYY 
x 
xxxxxxxxxxxxxxxx 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: ES7  
  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Screened 
Listing 3 
Listing of Reasons for Screening Failure 
 
 
 
 
 
Subject ID. 
Date of Screen Failure 
Reason 
 
 
 
xxx 
DDMMMYYYY 
xxxxxxxxxxxxxx 
 
 
 
xxx 
DDMMMYYYY 
xxxxxxxxxxxxxxxx 
 
 
 
xxx 
DDMMMYYYY 
xxxxxxxxxxxxxx 
 
 
 
xxx 
DDMMMYYYY 
xxxxxxxxxxxxxxxx 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: DV2  
  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Screened 
Listing 4 
Listing of Important Protocol Deviations 
Part: xx 
Treatment: xxxx 
Subject 
ID. 
 
 
 
 
Date of 
Deviation/ 
Study day 
Category/ 
Subcategory 
Description 
Outcome 
 
 
 
 
 
xxxxxx/ 
xxxxxx 
 
ddmmmyyyy/ 
xx 
xxxxxxxxxx/ 
xxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxx 
 
xxxxxxxx 
 
ddmmmyyyy/ 
xx 
xxxxxxxxxx/ 
xxxxxxxxxx 
xxxxxxxxxxxxxx 
xxxxxxxx 
 
 
 
 
 
xxxxxx/ 
xxxxxx 
 
ddmmmyyyy/ 
xx 
xxxxxxxxxxxxxxxxxx  
xxxxxxxxxxxxxx 
xxxxxxxx 
 
 
 
 
 
xxxxxx/ 
xxxxxx 
 
ddmmmyyyy/ 
xx 
xxxxxxxxxx/ 
xxxxxxxxxx 
xxxxxxxxxxxxxx 
xxxxxxxx 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: IE3   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 5 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
Part: xx 
Treatment: xxxx 
 
 
 
Subject ID. 
Type 
Criterion 
 
 
 
xxx 
Inclusion 
xxxxxxxxxxxxxx 
 
 
 
xxx 
Exclusion 
xxxxxxxxxxxxxxxx 
 
 
 
xxx 
xxxxxxxxxx 
xxxxxxxxxxxxxx 
 
 
 
xxx 
xxxxxxxxxx 
xxxxxxxxxxxxxxxx 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: DM2   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 6 
Listing of Demographic Characteristics 
Part: xx 
Treatment: xxxx 
 
 
Subject 
ID. 
Year 
of 
Birth 
Age 
(yrs) Sex 
 
 
Ethnicity 
Height
(cm) 
Weight
(kg) 
BMI 
(kg/m^2)
History of 
Smoking/Date 
Last Smoked 
Subject Consume 
Alcohol/Avg. 
Consumed Weekly 
Subject Consume 
Caffeine/Avg. 
Servings per Day 
Subjects 
History 
of Drug 
Use 
 
 
 
 
  
 
 
 
 
 
 
 
xxxx 
YYYY xx 
Female  Hispanic/Latino xxx.x xxx.x xxx.x 
Yes 
xx 
xx 
xx 
 
 
 
 
  
 
 
 
 
 
 
 
xxxx 
YYYY xx 
Female  Not 
Hispanic/Latino
xxx.x xxx.x xxx.x 
Yes 
xx/DDMMYYYY 
xxx/xx 
xx 
… 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: DM9   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 7 
Listing of Race 
Part: xx 
Treatment: xxxx 
 
 
 
 
Subject 
ID. 
Race 
  
 
 xxxx 
XXXXXXXXXXXXXXXXXX 
  
XXXXXXXXXXXXXXXX 
 xxxx 
XXXXXXXXXXXXXXXXXXXXXX 
 … 
XXXXXXXXXXXXXXXXXX 
 
 
XXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: MH2  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Randomized 
 Listing 8 
Listing of Medical Conditions  
Part: xx 
Treatment: xxxx 
 Subject 
Classification 
Condition 
Status 
PPD - This section has been excluded to protect patient privacy.


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: CM3  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Randomized 
 Listing 9 
Listing of Concomitant Medications  
Part: xx 
Treatment: xxxx 
 
 
Subj. ID 
ATC Level 1/  
Ingredient/ 
Verbatim Text/ 
Indication 
Dose/     
Units/ 
Freq/     
Route 
Start 
Date/Time  
Study Day/ 
Period Day 
Stop Date/Time 
Study Day/ 
Period Day 
 
Started 
Pre- 
Trial? 
 
Ongoing 
Medi-
cation? 
  
 
 
 
 
 
 
 XXXX 
 
Endocrine & metabolic/  
Fluticasone propionate/ 
FLIXOTIDE/ 
Asthma 
2/  
MG/ 
2XD/ 
IH 
27SEP1999/ 
12:30/ 
15/ 
7 
 
 
Y 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: SAFE_L1 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
 Listing 10 
Listing of Exposure Data 
Part: xx 
Treatment: xxxx 
 
 
 Subject ID. 
 
Treatment 
Start 
Date/Time 
of Dose 
End 
Date/Time 
of Dose 
Dose
Dose 
Unit 
Was infusion 
interrupted?/ 
Reason/ 
Interrupt Date/Time/
Restart Date/Time 
Was infusion 
discontinued?/ 
Reason/ 
Discontinuation 
Date/Time 
Did subject receive 
correct treatment?/ 
Comment 
   
 
 
 
 
 
 
 
 
  xxx 
XXXXXXX  
DDMMMYYYY/
hh:mm 
DDMMMYYYY/
hh:mm 
xx 
xx 
No 
No 
Yes 
   
XXXXXXX 
DDMMMYYYY/
hh:mm 
DDMMMYYYY/
hh:mm 
xx 
xx 
Yes/xxxxxxxxxxx 
DDMMMYYYY/hh:mm/ 
DDMMMYYYY/hh:mm 
Yes/xxxxxxxxx 
DDMMMYYYY/hh:mm 
 
No/xxxxxxxx 
   
… 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: AE7  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 11 
Listing of Subject Numbers for Individual Adverse Events 
Part: xx 
Treatment: xxxx 
System Organ Class 
  Preferred Term 
Group 
No. with Event 
Subject Numbers 
 
 
 
 
SOC #1 
 
 
 
  Preferred Term #1 xxxxxx 
X 
xxxx, xxxxx, xxxxxxx 
 
xxxxxx 
X 
xxxx, xxxxx, xxxxxxx 
 xxxx, xxxxx, xxxxxxx 
 
 
 
 
  Preferred Term #2 xxxxxx 
X 
xxxx, xxxxx, xxxxxxx 
 
xxxxxx 
X 
xxxx, xxxxx, xxxxxxx 
 xxxx, xxxxx, xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: AE8  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 12 
Listing of All Adverse Events 
 
Part: x 
Treatment: xxxxx 
 
 
 
Subj.  
ID 
 
Age(y)/ 
Sex/ 
Race/ 
Weight 
(kg) 
 
 
 
System Organ Class/ 
Preferred Term/ 
VERBATIM TEXT
 
Outcome/ 
Onset Date/Time 
Date/Time of 
Resolution/ 
Duration
Time Since 
1st Dose/ 
Time Since 
Last Dose
Maximum  
Intensity/ 
Maximum  
Serious/ 
Withdrawal
 
 
 
Frequency/ 
Action Taken/ 
Relation to 
Study Drug
  
 
 
 
xxxxx 
xx/ 
xxxx/xxx/ 
xx.x 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
Resolved/ 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
1 d
19 d/ 
19 d/ 
 1 d 
Mild/ 
No/ 
No 
xxxxxxx/ 
Dose reduced/ 
No 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
Resolving/ 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
1 d
21 d/ 
 1 d/ 
 1 d 
Moderate/ 
No/ 
No 
xxxxxxx/ 
Dose inter-
rupted/ 
No
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
Not resolved/ 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
120 d
36 d/ 
16 d/ 
16 d 
Severe/ 
No/ 
Yes 
xxxxxxx/ 
Withdrawn/ 
No 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
Resolved with 
sequelae/ 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
85 d
99 d/ 
79 d/ 
 1 d 
Mild/ 
No/ 
No 
xxxxxxx/ 
None/ 
Possible 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: AE8  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 13 
Listing of Drug-Related Adverse Events 
 
Note to programmer: Use the same shell as Listing 12. 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: SAFE_L1 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 14 
Listing of Serious Adverse Events 
Part: x 
Treatment: xxxxx 
Outcome: xxxxxxxxxxxxxxx 
 
 
 
Subj.  
ID 
 
Age(y)/ 
Sex/ 
Race/ 
Weight 
(kg) 
 
 
 
System Organ Class/ 
Preferred Term/ 
VERBATIM TEXT
 
Onset Date/Time 
Date/Time of 
Resolution/ 
Duration
Time Since 
1st Dose/ 
Time Since 
Last Dose
Maximum  
Intensity/ 
Maximum  
Serious/ 
Withdrawal
 
 
 
Frequency/ 
Action Taken/ 
Relation to 
Study Drug
  
 
 
 
xxxxx 
xx/ 
xxxx/xxx/ 
xx.x 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
1 d
19 d/ 
19 d/ 
 1 d 
Mild/ 
No/ 
No
xxxxxxx/ 
Dose reduced/ 
No
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
1 d 
21 d/ 
 1 d/ 
 1 d 
Moderate/ 
No/ 
No 
xxxxxxx/ 
Dose inter-
rupted/ 
No
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
120 d
36 d/ 
16 d/ 
16 d 
Severe/ 
No/ 
Yes
xxxxxxx/ 
Withdrawn/ 
No
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
85 d
99 d/ 
79 d/ 
 1 d 
Mild/ 
No/ 
No
xxxxxxx/ 
None/ 
Possible
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Listing 14 
Listing of Serious Adverse Events 
 
Part: x 
Treatment: xxxxx 
Outcome: xxxxxxxxxxxxxxx 
 
 
 
Subj.  
ID 
 
Age(y)/ 
Sex/ 
Race/ 
Weight 
(kg) 
 
 
 
System Organ Class/ 
Preferred Term/ 
VERBATIM TEXT 
Reason  
Considered 
SAE/Recur After 
Invetigational 
Product 
Administered?
Possible 
Causes of 
SAE 
Relevant 
Medical  
Conditions/Onset 
Date/Present at 
Time of SAE
Relevant Risk 
Factors
  
 
 
 
xxxxx xx/ 
xxxx/xxx/ 
xx.x 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
xxxxxxxxxxxx/xx 
xxxx: 
xxxxxxxxx 
xxxxxxxxxxxxx 
(DDMMMYYYY)xxx/ 
xxxxx 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
xxxxxxxxxxxx/xx 
xxxx: 
xxxxxxxxx 
xxxxxxxxxxxxx 
(DDMMMYYYY)xxx/ 
xxxxxxxxxxxxx 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
xxxxxxxxxxxx/xx 
xxxx: 
xxxxxxxxx 
xxxxxxxxxxxxx 
(DDMMMYYYY)xxx/ 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
xxxxxxxxxxxx/xx 
xxxx: 
xxxxxxxxx 
xxxxxxxxxxxxx 
(DDMMMYYYY)xxx/ 
xxxxxxxx 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Listing 14 
Listing of Serious Adverse Events 
 
Part: x 
Treatment: xxxxx 
Outcome: xxxxxxxxxxxxxxx 
 
 
 
Subj.  
ID 
 
Age(y)/ 
Sex/ 
Race/ 
Weight 
(kg) 
 
 
 
System Organ Class/ 
Preferred Term/ 
VERBATIM TEXT 
Relevant Concomitant 
Medications/ 
Dose/Frequency/Route/Taken Prior 
to Study/ 
Start Date/Stop Date/Ongoing/ 
Reason
Details of 
Investigational 
Product
Relevant 
Assessments
Narrative 
Remarks
  
 
 
 
xxxxx xx/ 
xxxx/xxx/ 
xx.x 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
xxxxxxxxxxx/xxx (unit)/xxxxx/ 
xxxxxxx/xxx/ 
DDMMMYYYY/DDMMMYYY/ 
xxxxxxxxx
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx 
xxxxxxxxxxx/xxx (unit)/xxxxx/ 
xxxxxxx/xxx/ 
DDMMMYYYY/Ongoing/ 
xxxxxxxxx
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx
 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: AE8  
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 15 
Listing of Adverse Events Leading to Withdrawal from Study 
 
 
Note to programmer: Use the same shell as Listing 11. 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
 
Example  
: SAFE_L2 
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 16 
Listing of Infusion Site Reaction Adverse Events 
Part: xx 
Treatment: xxxx 
 
 
 
 
 
 
Require 
Biopsy 
Recent 
exposure?/ 
Allergic 
Reactions 
 
 
 
 
Reaction  Reaction  
Management?/ 
Taken?/ 
Other 
 
 
 
 
Details/ 
Time/ 
Photographs  
Interp- 
Drugs?/ 
 
 
 
Date/Time 
Skin 
Inter- 
Taken? 
retation/ 
History of  
Subject 
AE/SAE 
Date of 
of 
Rash 
vention/  
Reaction 
Diagnostic  
Allergic 
ID. 
Number 
Infusion 
Reaction 
Type 
Treatment? 
Length, Width (cm) 
Tests 
Reaction/ 
 
 
 
 
 
 
 
 
 
xxx 
xxxxx 
DDMMMYYYY 
DDMMMYYYY/ 
hh:mm 
xxxxx/ 
xxxxx 
xxxxx/ 
xxxxx 
xx/ 
xx/ 
xx, xx cm 
xx/ 
xxxxxxx/ 
xxxxxxxx 
xx/ 
xx/ 
 NONE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
 Example  
: SAFE_L3 
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 17 
Listing of Liver Adverse Events  
 
Note to programmer: Use the same shell as Listing 11. Present all applicable variables recorded on the eCRF. 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: SAFE_L4 
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 18 
Listing of Cardiovascular Adverse Events  
 
Note to programmer: Use the same shell as Listing 15. Present all applicable variables recorded on the eCRF. 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: SAFE_L5 
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 19 
Listing of Rash Events 
Part: xx 
Treatment: xxxx 
 
 
 
 
Require 
Biopsy 
Recent 
exposure?/ 
Allergic 
Reactions 
 
 
 
 
Management?/ 
Taken?/ 
Other 
 
 
 
Description/ 
Photographs  
Interp- 
Drugs?/ 
 
 
 
Appearance/ 
Taken? 
retation/ 
History of  
Subject 
Rash Onset 
Rash Symptoms/ 
Appearance/ 
Reaction 
Diagnostic  
Allergic 
ID. 
Date/Time 
Type 
Site 
Length, Width (cm) 
Tests 
Reaction/ 
 
 
 
 
 
 
 
xxx 
DDMMMYYYY/hh:mm 
xxxxxxxx/ 
xxxxxxx/ 
xx/ 
xx/ 
xx, xx cm 
xx/ 
xxxxxxx/ 
xxxxxxxx 
xx/ 
xx/ 
 NONE 
 
 
xxxxxxxxxxxxxxx 
xxxxxxxxxxx/ 
 
 
 
 
 
 
xxxxxxxxxx/ 
 
 
 
 
 
 
xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LB5  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 20 
Listing of Clinical Chemistry Toxicities of Grade 3 or Higher 
Part: xx 
Treatment: xxxx 
Subj. 
ID 
Age(y)/  
Sex/  
Race 
Lab test 
(units) 
Planned 
Relative Time 
 
 
Date 
Study 
 Day 
 
Converted Data 
 
Flag[1] 
Value 
Normal Range 
NR 
TG 
BL 
 
 
 
 
 
 
 
 
 
 
 
xxxxx 
xx/  
xxxxxx (xxx) 
xxxxxxx      
DDMMMYYYY 
x 
 xx.x 
 xx.x-xx.x 
 
 
 
 
xxxx/ 
 
xxxxxxx       DDMMMYYYY 
x 
 xx.x 
 xx.x-xx.x 
   
 
 
 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx (xxx) 
xxxxxxxxx     DDMMMYYYY 
x 
 xx.x 
 xx.x-xx.x 
 
 
 
 
 
 
xxxxxxxxx 
DDMMMYYYY 
x 
 xx.x 
 xx.x-xx.x 
H 
x 
H 
[1] NR for Normal Range flag, TG for Toxicity flag; BL for Change from Baseline flag. H=Above range, L=Below range  


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LB5  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 21 
Listing of All Clinical Chemistry Data for Subjects with Toxicities of Grade 3 or Higher 
 
Note to programmer: Use the shell from Listing 20. 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LB5  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 22 
Listing of Haematology Toxicities of Grade 3 or Higher 
 
Note to programmer: Use the shell from Listing 20. 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LB5  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 23 
Listing of Haematology Data for Subjects with Toxicities of Grade 3 or Higher 
 
Note to programmer: Use the shell from Listing 20. 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: UR2a  
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 24 
Listing of Urinalysis Toxicities of Grade 3 or Higher 
 
Part: xx 
Treatment: xxxx 
 
Subject ID. 
 
Visit 
 
Sample Date 
Sample Time 
Study Day 
Urinalysis Test 
 
Result 
Toxicity  
Grade 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxx 
DDMMMYYYY 
HH:MM 
1 
Blood 
++ or 2+ 
x 
 
xxxxx 
DDMMMYYYY 
HH:MM 
1 
Blood 
+ or 1+ 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxx 
DDMMMYYYY 
HH:MM 
1 
Blood 
+ or 1+ 
 
 
 
 
 
 
Protein 
+++ or 3+ 
x 
 
xxxxx 
DDMMMYYYY 
HH:MM 
1 
Blood 
+ or 1+ 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: UR2a  
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 25 
Listing of Urinalysis for Subjects with Toxicities of Grade 3 or Higher 
 
Note to programmer: Use the shell from Listing 24. 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: EG5  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 26 
Listing of Abnormal ECG Findings 
Part: xx 
Treatment: xxxx 
 
 
Subj. 
ID 
 
Age/ 
Sex/ 
Race 
Planned Rel 
Time/ 
ECG Date/ 
Time 
Study 
Day 
 
 
 
ECG Finding 
Clinically 
Significant 
Change from 
Baseline? 
 
Clinically  
Significant Abnormality 
 
 
 
 
 
 
 
xxxxx 
xx/ 
xxxxx/ 
xxxx 
xxxxxxx/ 
DDMMMYYYY 
/hh:mm 
xx 
Abnormal–not 
clinically 
significant 
No 
 
 
 
xxxxxxx/ 
DDMMMYYYY 
/hh:mm 
xx 
Abnormal–not 
clinically 
significant 
No 
 
 
 
xxxxxxx/ 
DDMMMYYYY 
/hh:mm 
xx 
Abnormal–clinically 
significant 
Yes 
Sinus tachycardia 
 
 
xxxxxxx/ 
DDMMMYYYY 
/hh:mm 
xx 
Abnormal–not 
clinically 
significant 
No 
 
xxxxx 
xx/ 
xxxxx/ 
xxxx 
xxxxxxx/ 
DDMMMYYYY 
/hh:mm 
xx 
Abnormal–clinically 
significant 
Yes 
Ectopic ventricular 
 beats 
 
 
xxxxxxx/ 
DDMMMYYYY 
/hh:mm 
xx 
Abnormal–clinically 
significant 
No 
Ectopic ventricular 
 beats 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: EG5  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 27 
Listing of All ECG Findings for Subjects with an Abnormal Finding 
 
 
Note to programmer: Use the shell from Listing 26. 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: EG3  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 28 
Listing of ECG Values of Potential Clinical Importance 
Part: xx 
Treatment: xxxx 
 
 
 
Subj. ID 
 
Age/ 
Sex/ 
Race 
Planned 
Rel Time 
ECG Date/ Time 
Study
Day 
Heart  
Rate 
(beats/ 
min.) 
PR 
Inter- 
val 
(msec) 
QRS 
Dura- 
tion 
(msec) 
QRS 
Axis 
(deg) 
QT 
Inter- 
val 
(msec) 
QTc 
Inter- 
val 
(msec) 
QTc 
(Baz-
ett) 
(msec) 
QTc 
(Frid-
ericia) 
(msec) 
RR 
Inter- 
val 
(msec) 
 xxxxxx 
xx/ 
xxxxxx/ 
xxxxx 
xxxxxxx 
 
DDMMMYYYY/hh:mm xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm xx 
xx 
xx L 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm xx 
80 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm xx 
xx 
xx 
xx 
xx 
xx 
xx H 
xx 
xx 
xx 
 xxxxx 
xx/ 
xxxxxx/ 
xxxxx 
xxxxxxx 
DDMMMYYYY/hh:mm xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm xx 
xx 
xx 
xx 
xx 
xx 
xx I 
xx 
xx 
xx 
Note: L=Low, H=High, I=Increase, D=Decrease 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: EG3  
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 29 
Listing of All ECG Values for Subjects with Any Value of Potential Clinical Importance 
 
Note to programmer: Use shell for Listing 28.


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: VS4  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 30 
Listing of Vital Signs of Potential Clinical Importance  
Part: xx 
Treatment: xxxx 
 
 
 
Subj. ID 
 
Age(y)/ 
Sex/ 
Race 
 
Planned 
Relative 
Time 
 
 
Actual 
Date/Time 
Body 
Position
Study 
Day 
Systolic 
 Blood 
Pressure 
(mmHg) 
Diastolic 
 Blood 
Pressure  
(mmHg) 
 
Pulse 
(beats/ 
min) 
Temper-
ature 
(C) 
Comment 
  
 
 
 
 
 
 
 
 
 
 
 xxx 
xx/ 
xxxxxx/ 
xxxxx 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx 
xxx 
 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx 
 
 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
Xxx H 
Xxx H 
xxx 
 
xxxxxxxxxx
  
 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx 
 
 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx 
 
 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx 
 
 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx L 
 
 
 xxx 
xx/ 
xxxxxx/ 
xxxxx 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx 
xxx 
 
  
 
xxxxxxx 
DDMMMYYYY/hh:mm
xxxxxxx 
x 
xxx 
xxx 
xxx 
 
 
Note: L=Low, H=High 
 
 
 
  


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: VS4  
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 31 
Listing of All Vital Signs for Subjects with Potential Clinical Importance Values 
 
 
 
Note to programmer: Use shell for Listing 30.


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LIVER5 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 32 
Listing of Liver Monitoring/Stopping Event Reporting 
Part: xxxxx 
Treatment: xxxxxx 
 
 
Site Id./ 
Unique Subject Id. 
 
 
Age(YEARS)/ 
Sex/ 
Race Detail 
 
 
 
Maximum Status of the 
Liver Event 
 
 
Date First 
Detected/ 
Study Day 
Time  
Since 
First 
Dose 
(days) 
Time 
Since 
Last 
Dose 
(days) 
 
Restart/Re-challenge 
After Stopping 
Criteria Was Met 
 
 
 
Resolved?/ 
Date resolved 
PPD - This section has been excluded to protect patient privacy.


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: MH2  
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 33 
Listing of Medical Conditions for Subjects with Liver Stopping Events 
Part: xx 
Treatment: xxxx 
 
 
Subject ID 
 
Classification 
 
Condition 
 
Status 
 
 
 
 
xxxx 
xxxxxxxxxxxx 
XXXXXXXXXXXX 
Current 
 
xxxxxxxxx 
XXXXXXXXXXXXXXXXXXXXXX 
Past 
 
 
 
 
xxxx 
xxxx 
XXXXXXXXXXXXXXXXX 
Current 
 
 
 
 
xxxx 
xxxxxxxxxxxx 
XXXXXXXXXXXXXXXXXXX 
Current 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: SAFE_L9 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 34 
Listing of Alcohol Intake at Onset of Liver Event 
Part: xx 
Treatment: xxxx 
 
Subject ID 
Age(y)/ 
Sex/ 
Race 
Exam Date/Time 
Consume Alcohol? 
Average Number Units Consumed per Week? 
 
 
 
 
 
xxxx 
xx/xx/xxxxxxx 
DDMMMYYYY/hh:mm 
xxx 
x 
 
 
 
 
 
 
 
 
 
 
xxxx 
xx/xx/xxxxxxx 
DDMMMYYYY/hh:mm 
xx 
xx 
 
 
 
 
 
xxxx 
xx/xx/xxxxxxx 
DDMMMYYYY/hh:mm 
xx 
x 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PKCL1X 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 35 
Listing of Plasma Concentration Data for Subjects with Liver Stopping Events 
 
 
Note to programmer: Use shell for Listing 40.


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LIVER7 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 36 
Listing of Liver Biopsy Details 
Part: xx 
Treatment: xxxx 
 
Subject 
ID 
 
 
Age(y)/ 
Sex/ 
Race 
Biopsy Date/ 
Study Day 
Biopsy Size 
Liver Biopsy Test 
Liver Biopsy Result 
 
 
 
 
 
 
xxxx 
xx/ 
xxxxxx/ 
xxxxx 
DDMMMYYYY/ 
xx 
xx 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LIVER8 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 37 
Listing of Liver Imaging Details 
Part: xx 
Treatment: xxxx 
 
Subject 
ID 
 
 
Age(y)/ 
Sex/ 
Race 
Imaging Date/ 
Study Day 
Liver Imaging 
Method 
Are Images 
Technically 
Adequate 
Liver Imaging Test Liver Imaging Result 
 
 
 
 
 
 
 
xxxx 
xx/ 
xxxxxx/ 
xxxxx 
DDMMMYYYY/ 
xx 
xx 
xxxx 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: SAFE_L10 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 38 
Listing of Cardiac Telemetry Monitoring 
Part: xx 
Treatment: xxxx 
 
Subject ID 
Start Date/Time 
End Date/Time 
Overall Interpretation 
Specify 
Abnormality/Comments 
 
 
 
 
 
xxxx 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
xxxxxxxxxxx 
xxxxxxxxxxx/xxxxxx 
 
 
 
 
 
xxxx 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
xxxxxxxxx 
 
 
 
 
 
 
xxxx 
DDMMMYYYY/hh:mm 
DDMMMYYYY/hh:mm 
xxxxxxxxxxxxx 
 
 
 
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: LB5  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Listing 39 
Listing of Cytokine Data 
 
Note to programmer: Use the shell from Listing 20.  Do not present toxicity (TG) column. 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PKCL1X  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK  
 
Listing 40 
Listing of GSK3342830 Pharmacokinetic Plasma Concentration-Time Data by Treatment in Part 1 and Part 3 
 
 
Part: Part 1 
Dose: XXXX mg 
Subject 
ID. 
Age 
(y)/ 
Sex/ 
Race 
Visit 
Date 
Study Day 
Planned 
Relative 
Time 
Actual Time 
Time 
Deviation 
(h) 
Actual Relative 
Time (h) 
Concentration 
(units) 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xxxx 
MMDDYYYY 1 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
0.5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1.25h  
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1.5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
2h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
3h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
3.5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
4h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
4.5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
6h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
8h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
10h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
12h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
16h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
2 
24h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
36h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
3 
48h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
Note to Programmer: Present all Part 1 first, then repeat for Part 3. Please list all the concentration data including 
unscheduled.  
 
LLOQ = xx.x (units)  
NQ=Not quantifiable  
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PKUL1P  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK  
 
Listing 41 
Listing of GSK3342830 Pharmacokinetic Urine Concentration-Time Data by Treatment in Part 1 and Part 3 
 
 
Part: Part 1 
Dose: XXXX mg 
Subject 
ID. 
Age 
(y)/ 
Sex/ 
Race 
Visit 
Date 
Study 
Day 
Planned  
Relative 
Time 
Actual 
Midpt. of 
Collection 
Actual 
Duration 
(h) 
Urine 
Conc. 
(units) 
Total  
Sample 
Volume  
(units) 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xxxx 
MMDDYYYY 
xxxx 
0-4h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
4-8h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
8-12h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
12-24h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
24-48h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Present all Part 1 first, then repeat for Part 3. Please list all the concentration data including 
unscheduled.  
 
LLOQ = xx.x (units)  
NQ=Not quantifiable  


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PKCL1X  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK  
 
Listing 42 
Listing of GSK3342830 Pharmacokinetic Plasma Concentration-Time Data by Treatment in Part 2 
 
Dose: XXXX mg 
Subject 
ID. 
Age 
(y)/ 
Sex/ 
Race 
Visit 
Date 
Study Day 
Planned 
Relative 
Time 
Actual Time 
Time 
Deviation 
(h) 
Actual Relative 
Time (h) 
Concentration 
(units) 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xxxx 
MMDDYYYY 1 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
0.5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1h  
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1.25h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1.5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
2h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
… 
… 
.. 
… 
… 
 
 
 
 
 
16h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
2 
24h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
3 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
6 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
9 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
12 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
13 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
15 
pre-dose HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
0.5h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1h  
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
1.25h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
… 
… 
… 
… 
… 
 
 
 
 
 
6h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
 
 
 
 
8h 
HH:MM 
xx 
0h 0m 0s 
xx.xx 
 
Note to Programmer: Please list all the concentration data including unscheduled.  
Timepoints on day 1 is Pre-dose, 0.5, 1.25,1.5, 2,2.5,3,3.5,4,4.5,5,6,8,10,12,16 and 24. Timepoints on day 15 is Pre-
dose,0.5,1,1.25,1.5,2,2.5,3,3.5,4,4.5, 5, 6 and 8. 
LLOQ = xx.x (units)  
NQ=Not quantifiable  
 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PKUL1P  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK  
 
 
 
Listing 43 
Listing of GSK3342830 Pharmacokinetic Urine Concentration-Time Data by Treatment in Part 2 
 
Dose: XXXX mg 
Subject 
ID. 
Age 
(y)/ 
Sex/ 
Race 
Visit 
Date 
Study 
Day 
Planned  
Relative 
Time 
Actual 
Midpt. of 
Collection 
Actual 
Duration 
(h) 
Urine 
Conc. 
(units) 
Total  
Sample 
Volume  
(units) 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xxxx 
MMDDYYYY 
1 
0-8h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
8-24h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
15 
0-8h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
8-24h 
HH MM 
HH MM 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Please list all the concentration data including unscheduled.  
 
LLOQ = xx.x (units)  
NQ=Not quantifiable  
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PLPL1X  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
 
Listing 44 
Listing of GSK3342830 Plasma Pharmacokinetic Parameters by Treatment in Part 1 and Part 3 
 
 
Part: Part 1 
Dose: XXX mg 
Subject 
ID. 
Age (y)/ 
Sex/ 
Race 
AUC(0-t) 
(units) 
AUC(0-∞) 
(units) 
Cmax 
(units) 
Tmax 
(unit) 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
NC 
xx.xx 
xx.xx 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
Note to Programmer: Present all Part 1 first, then repeat for Part 3 
Additional parameters include  t1/2, CL, Vss, %AUCex, tlast, lambda_z, lambda_z_lower, lambda_z_upper, lambda_z_no. of 
points 
 
 
Source Data: Listing 40 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PLPL1X  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
Listing 45 
Listing of GSK3342830 Urine Pharmacokinetic Parameters by Treatment in Part 1 and Part 3 
 
 
Part: Part 1 
Dose: XXX mg 
Subject 
ID. 
Age (y)/ 
Sex/ 
Race 
Ae 
(units) 
CLr 
(units) 
Feu(0-4)  
(units) 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
Note to Programmer: Present all Part 1 first, then repeat for Part 3 
Additional parameters include  Feu(4-8) (units), Feu(8-12) (units), Feu (12-24)  (units), Feu (24-48) (units)  
 
Source Data: Listing 40 
 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PLPL1X  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
Listing 46 
Listing of GSK3342830 Plasma Pharmacokinetic Parameters by Treatment in Part 2 
 
Dose: XXX mg 
Subject 
ID. 
Age (y)/ 
Sex/ 
Race 
Day 
AUC(0-t) 
(units) 
AUC(0-∞) 
(units) 
AUC(0-)               
(units) 
Cmax 
(unit) 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
NC 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
NC 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
Note to Programmer:  
Additional parameters include Tmax, t1/2, CL, Vss, C, Ratio of time invariance, Ratio of accumulation, %AUCex, tlast, 
lambda_z, lambda_z_lower, lambda_z_upper, lambda_z_no. of points 
 
Source Data: Listing 41 
 


GlaxoSmithKline 
 
<DIRECTORY PATH>PROGRAM NAME Executed: DDMONYYYY hh:mm 
Example  
: PLPL1X  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
Listing 47 
Listing of GSK3342830 Urine Pharmacokinetic Parameters by Treatment in Part 2 
 
 
Dose: XXX mg 
Subject 
ID. 
Age (y)/ 
Sex/ 
Race 
Day 
Ae 
(units) 
CLr 
(units) 
Feu(0-8)  
(units) 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
xxxx 
xx/ 
xxxx/ 
xxxxx 
1 
xx.xx 
xx.xx 
xx.xx 
 
 
15 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
Note to Programmer:  
Additional parameters include Feu(8-24) (units).  
 
Source Data: Listing 42 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: NS1  
  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 1.1 
Summary of Number of Subjects Enrolled by Country and Site ID 
Study Part: 1 
 
 
 
 
 
 
 
 
 
 
Investigator 
GSK3342830 250 mg 
GSK3342830 500 mg 
…
Placebo 
Total 
Country 
Site ID 
Name 
(N=xx) 
(N=xx) 
…
(N=xx) 
(N=xx) 
 
xxxxxxxxxxx 
xxxxxxxxx 
xxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
xxxxxxxxxxx 
xxxxxxxxx 
xxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
  
 
Note to programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate 
pages. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: ES1  
  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 1.2 
Summary of Subject Disposition 
Study Part: 1 
 
 
 
 
 
 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
…
Placebo 
Total 
 
(N=xx) 
(N=xx) 
…
(N=xx) 
(N=xx) 
Subject Status 
  Completed 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  Withdrawn 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  
 
 
 
 
 
Primary reason for study withdrawal 
 
 
 
 
 
  Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  Protocol Deviation 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  Subject reached protocol-defined stopping 
criteria 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  Study closed/terminated 
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 discretion 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  Withdrew Consent 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  Other 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
  
 
Note to programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate 
pages. 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: ES6   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Screened 
Table 1.3 
Summary of Reasons for Screening Failures 
 
  
 
Screened 
 
 
  
 
Subjects 
 
 
  
 
(N=xx) 
 
Screening Status 
  Enrolled 
  
 
xx (xx.x%) 
 
  Failed 
  
 
xx (xx.x%) 
 
  
  
 
 
 
Reason for failure 
  
 
 
 
  Did not meet inclusion/exclusion criteria 
  
 
xx (xx.x%) 
 
  Adverse event 
  
 
xx (xx.x%) 
 
  Protocol deviation 
  
 
xx (xx.x%) 
 
  Medical or Surgical Condition Exclusion 
  
 
xx (xx.x%) 
 
  Investigator discretion 
  
 
xx (xx.x%) 
 
  Participant withdrew consent 
  
 
xx (xx.x%) 
 
  Lost to follow up 
   
xx (xx.x%) 
 
  Other 
   
xx (xx.x%) 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: DV1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Screened 
Table 1.4 
Summary of Important Protocol Deviations 
Study Part: 1 
 
 
… 
 
 
Category/Subcategory 
GSK3342830 250 mg 
(N=xx) 
GSK3342830 500 mg 
(N=xx) 
… 
Placebo 
(N=xx) 
Total 
(N=xx) 
 
 
 
 
 
 
Any protocol deviations 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Informed Consent 
 
 
 
 
 
  xxxxxxxxxxxxxxx 
 
 
 
 
 
  xxxxxxxxxxxxxx 
 
 
 
 
 
  … 
 
 
 
 
 
Eligibility criteria not met 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
  xxxxxxxxxxxxxxx 
 
 
 
 
 
Not withdrawn after developing withdrawal criteria 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
Excluded medication, vaccine, or device 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
Visit Completion 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
Assessment or time point completion 
 
 
 
 
 
Wrong study treatment/administration/dose or incorrect 
dose 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
Study Procedures 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
Failure to report safety events per protocol 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. Present 
all Categories and Subcategories on the eCRF for which there is non-zero count.   


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: DM1   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 1.5 
Summary of Demographic Characteristics 
Study Part: 1 
 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
 
Total 
 
 
(N=xx) 
(N=xx) 
… 
(N=xx) 
 
Sex 
  n 
xx 
xx 
… 
xx 
 
  Male 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Female 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
 
 
 
Age (YEARS)[1] 
  n 
       xx 
       xx 
… 
       xx 
 
  Mean 
       xx.x 
       xx.x 
… 
       xx.x 
 
  SD 
       xx.xx 
       xx.xx 
… 
       xx.xx 
 
  Median 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Min. 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Max. 
       xx.x 
       xx.x 
… 
       xx.x 
 
 
 
 
 
 
Ethnicity 
  n 
       xx 
       xx 
… 
       xx 
 
  Hispanic/Latino 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Not Hispanic/Latino 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
 
 
 
 
Height (cm) 
  n 
       xx 
       xx 
… 
       xx 
 
  Mean 
       xx.x 
       xx.x 
… 
       xx.x 
 
  SD 
       xx.xx 
       xx.xx 
… 
       xx.xx 
 
  Median 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Min. 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Max. 
       xx.x 
       xx.x 
… 
       xx.x 
 
 
 
 
 
 
Weight (kg) 
  n 
       xx 
       xx 
… 
       xx 
 
  Mean 
       xx.x 
       xx.x 
… 
       xx.x 
 
  SD 
       xx.xx 
       xx.xx 
… 
       xx.xx 
 
  Median 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Min. 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Max. 
       xx.x 
       xx.x 
… 
       xx.x 
 
 
 
 
 
 
BMI (kg/m2) 
  n 
       xx 
       xx 
… 
       xx 
 
  Mean 
       xx.x 
       xx.x 
… 
       xx.x 
 
  SD 
       xx.xx 
       xx.xx 
… 
       xx.xx 
 
  Median 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Min. 
       xx.x 
       xx.x 
… 
       xx.x 
 
  Max. 
       xx.x 
       xx.x 
… 
       xx.x 
Note to programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate 
pages. 
[1] Age is imputed when full date of birth is not provided. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: DM11  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 1.6 
Summary of Age Ranges 
Study Part: 1 
 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
 
Total 
 
 
(N=xx) 
(N=xx) 
… 
(N=xx) 
 
 
 
 
 
 
 
Age Ranges [1] 
 
 
 
 
 
Adult (18-64 years)      
 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
 
 
 
 
 
Note to programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate 
pages. 
[1] Age is imputed when full date of birth is not provided. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: DM5   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 1.7 
Summary of Race and Racial Combinations 
 
 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
 
Total 
Race 
 
(N=xx) 
(N=xx) 
… 
(N=xx) 
 
n 
 
xx 
xx 
 
xx 
AMERICAN INDIAN OR ALASKA NATIVE 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
ASIAN 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
BLACK OR AFRICAN AMERICAN 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
WHITE 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
MULTIPLE 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
… 
 
 
 
 
 
Programmer’s note: Do not display “MULTIPLE” unless present in the data. Percentages will add up to 100. 
Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: DM6   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 1.8 
Summary of Race and Racial Combinations Details 
 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
Total
 
 
(N=xx) 
(N=xx) 
…
(N=xx)
 
 
 
Race 
n 
xx 
xx 
 
xx 
 
AMERICAN INDIAN OR ALASKA NATIVE 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
ASIAN 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
BLACK OR AFRICAN AMERICAN 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
WHITE 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
 
 
 
Programmer’s note: A subject may be displayed more than once, ie. percentages may add up to more than 100. 
Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: MH1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 1.9 
Summary of Cardiovascular Related Medical Conditions 
Study Part: 1 
 
 
 
 
 
 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
… 
Placebo 
Total 
 
Classification 
(N=xx) 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Any condition 
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%) 
 
Angina pectoris 
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%) 
Myocardial infarction 
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%) 
Stroke 
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%) 
... 
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%)
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: AE2   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.1 
Relationship of Adverse Event System Organ Classes, Preferred Terms and Verbatim Text 
 
 
 
 
 
 
 
System Organ Class 
Preferred Term 
Verbatim Text 
 
 
 
SOC #1 
 
Preferred Term # 1 
 
XXXXXXXXX 
 
Preferred Term # 2
 
XXXXXXXXX
 
Preferred Term # 3
 
XXXXXXXXX
 
Preferred Term # 4
 
XXXXXXXXX
 
SOC #2 
Preferred Term # 1
 
XXXXXXXXX
 
Preferred Term # 2
 
XXXXXXXXX
 
Preferred Term # 3
 
XXXXXXXXX
 
Preferred Term # 4
 
XXXXXXXXX
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: AE1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.2 
Summary of All Adverse Events 
 
Study Part: 1 
System Organ Class 
GSK3342830 250 mg 
GSK3342830 500 mg 
 
Total 
 
  Preferred Term 
(N=xx) 
(N=xx) 
… 
(N=xx) 
 
 
Any Event 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class #1 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Preferred Term #1 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Preferred Term #2 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Preferred Term #3 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
 
 
 
 
 
... 
 
 
 
 
 
Note to programmer: System Organ Class (SOC) is displayed in descending order of frequency for ‘Overall’ then alphabetically.  
Preferred Term is displayed in descending order of frequency for ‘Overall’ then alphabetically within SOC.  
Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
 
At each level of subject summarization, a subject is counted once if the subject reported one or more events. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: AE1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.3 
Summary of Drug-Related Adverse Events 
 
Study Part: 1 
System Organ Class 
GSK3342830 250 mg 
GSK3342830 500 mg 
 
Total 
 
  Preferred Term 
(N=xx) 
(N=xx) 
… 
(N=xx) 
 
 
Any Event 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class #1 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Preferred Term #1 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Preferred Term #2 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  Preferred Term #3 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
 
 
 
 
 
... 
 
 
 
 
 
Note to programmer: System Organ Class (SOC) is displayed in descending order of frequency for ‘Overall’ then alphabetically.  
Preferred Term is displayed in descending order of frequency for ‘Overall’ then alphabetically within SOC.  
Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
 
At each level of subject summarization, a subject is counted once if the subject reported one or more events. 
 
 
 
 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: AE15   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.4 
Summary of Common (>=5%) Non-serious Adverse Events by System Organ Class and Preferred Term   
 (Number of Subjects and Occurrences) 
 
Study Part: 1 
System Organ Class 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
 
Total 
 
  Preferred Term 
 
(N=xx) 
(N=xx) 
… 
(N=xx) 
 
 
Any Event 
Number of Subject 
with AEs 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
Number of AEs 
xx 
xx 
 
xx 
 
 
 
 
 
 
 
 
System Organ Class #1 
 
 
 
 
 
 
  Preferred Term #1 
Number of Subject 
with AEs 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  ... 
Number of AEs 
xx 
xx 
 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: System Organ Class (SOC) is displayed in descending order of frequency for ‘Overall’ then alphabetically.  
Preferred Term is displayed in descending order of frequency for ‘Overall’ then alphabetically within SOC.  
Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
 
 
At each level of subject summarization, a subject is counted once if the subject reported one or more events. 
 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: AE16   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.5 
Summary of Serious Adverse Events by System Organ Class and Preferred Term  
(Number of Subjects and Occurrences) 
 
Study Part: 1 
System Organ Class 
 
GSK3342830 250 mg 
GSK3342830 500 mg 
 
Total 
 
  Preferred Term 
 
(N=xx) 
(N=xx) 
… 
(N=xx) 
 
 
Any Event 
Number of Subjects 
with SAEs 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
 
Number of SAEs 
xx 
xx 
 
xx 
 
 
Number of Drug-
related SAEs 
xx 
xx 
 
xx 
 
 
Number of Fatal SAEs 
xx 
xx 
 
xx 
 
 
Number of Drug-
related Fatal SAEs 
xx 
xx 
 
xx 
 
 
 
 
 
 
 
 
System Organ Class #1 
 
 
 
 
 
 
  Preferred Term #1 
Number of Subjects 
with SAEs 
xx (xx.x%) 
xx (xx.x%) 
… 
xx (xx.x%) 
 
  ... 
Number of SAEs 
xx 
xx 
 
xx 
 
 
Number of Drug-
related SAEs 
xx 
xx 
 
xx 
 
 
Number of Fatal SAEs 
xx 
xx 
 
xx 
 
 
Number of Drug-
related Fatal SAEs 
xx 
xx 
 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: System Organ Class (SOC) is displayed in descending order of frequency for ‘Overall’ then alphabetically.  
Preferred Term is displayed in descending order of frequency for ‘Overall’ then alphabetically within SOC.  
Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
 
 
At each level of subject summarization, a subject is counted once if the subject reported one or more events. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: LB1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.6 
Summary of Clinical Chemistry Values 
Study Part: 1 
 
 
 
 
 
 
 
 
 
 
Lab Test 
Treatment 
N 
Planned Relative Time 
n 
Mean 
SD 
Median 
Min. 
Max. 
 
 
 
 
 
 
XXXXXXXX (XXX) 
GSK3342830 250 
mg 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Day 2 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Follow-Up 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
GSK3342830 500 
mg 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Day 2 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Follow-Up 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
… 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Day 2 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Follow-Up 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
... 
 
 
 
 
 
 
Note to programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
Timepoints for Part 1 and Part 3 are Baseline, Day 2, Follow-Up. Timepoints for Part 2 are Baseline, Day 2, Day 5, Day 10, Day 15, 
and Follow-Up. 
Note: For subjects Baseline is defined as the last nonmissing measurement before dosing.  
      Unscheduled measurements are not included in this summary table except when calculating baseline. 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: LB1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.7 
Summary of Clinical Chemistry Change from Baseline 
 
Note to programmer: Please use the shell from Table 2.6 and include only Planned Relative Time after Baseline. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: LB1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.8 
Summary of Haematology Values 
 
Note to programmer: Please use the shell from Table 2.6. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: LB1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.9 
Summary of Haematology Change from Baseline 
 
 
Note to programmer: Please use the shell from Table 2.6 and include only Planned Relative Time after Baseline. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: UR3   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.10 
Summary of Urinalysis Dipstick Results 
Study Part: 1 
 
Planned 
 
GSK3342830 250 mg
GSK3342830 500 mg
...
Placebo
Test 
Relative Time 
Result 
 (N=xx)
 (N=xx)
 (N=xx)
(N=xx)
 
 
 
Urine General 
Dipstick 
Baseline 
Positive 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
Negative
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
No Result
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
Not Done
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
Day 2 
... 
... 
... 
... 
... 
 
Follow-up 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
Urine Occult 
Blood 
(Dipstick) 
Baseline 
None 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
Trace 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
1+ 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
2+ 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
3+ 
  xx (xx.x%)
  xx (xx.x%) 
  xx (xx.x%)
  xx (xx.x%)
 
 
4+ 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
5+ 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
No Result
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
   xx (xx.x%) 
 
 
Not Done
  xx (xx.x%)
  xx (xx.x%) 
  xx (xx.x%)
  xx (xx.x%)
 
 
 
 
 
 
... 
 
... 
... 
... 
... 
... 
Note to Programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages. 
 
  


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: EG1   
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.11 
Summary of ECG Findings 
 
Study Part: 1 
 
GSK3342830 250 mg
GSK3342830 500 mg 
... 
Total 
 
(N=XX) 
(N=XX) 
 
(N=XX) 
 
 
 
 
Baseline 
 
 
 
 
  n 
xx 
xx 
... 
xx 
  Normal 
xx (xx%) 
xx (xx%) 
... 
xx (xx%) 
  Abnormal, not clinically 
significant 
xx (xx%) 
xx (xx%) 
... 
xx (xx%) 
  Abnormal, clinically significant 
xx (xx%) 
xx (xx%) 
... 
xx (xx%) 
 
 
 
 
 
Day 1 – 0.5 HR 
 
 
 
 
  n 
xx 
xx 
... 
xx 
  Normal 
xx (xx%) 
xx (xx%) 
... 
xx (xx%) 
  Abnormal, not clinically 
significant 
xx (xx%) 
xx (xx%) 
... 
xx (xx%) 
  Abnormal, clinically significant 
xx (xx%) 
xx (xx%) 
... 
xx (xx%) 
... 
... 
... 
 
... 
 
 
 
 
Note to Programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages.  
Timepoints for Part 1 and Part 3  are Baseline, Day 1 – 0.5 HR, Day 1 – 1 HR, Day 1 – 1.5 HR, Day 1 – 2 HR, Day 1 – 3 HR, Day 1 – 4 
HR, Day 1 – 6 HR, Day 1 – 12 HR, Day 2, Day 3, Follow-Up. Timepoints for Part 2 are Baseline, Day 1 – 0.5 HR, Day 1 – 1 HR, Day 1 – 
1.5 HR, Day 1 – 2 HR, Day 1 – 3 HR, Day 1 – 4 HR, Day 1 – 6 HR, Day 1 – 12 HR, Day 2 through Day 14, Day 15 – 0.5 HR, Day 15 – 1 HR, 
Day 15 – 1.5 HR, Day 15 – 2 HR, Day 15 – 3 HR, Day 15 – 4 HR, Day 15 – 6 HR, Day 15 – 12 HR, Day 16, and Follow-Up. 
Note: Baseline is defined as the last nonmissing measurement before dosing. 
      Unscheduled measurements are not included in this summary table except when calculating baseline. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: EG2  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.12 
Summary of ECG Values 
Study Part: 1 
 
 
 
 
 
 
 
 
 
 
ECG Test 
Group 
N 
Planned Relative Time 
n 
Mean 
SD 
Median 
Min. 
Max. 
 
 
 
 
 
 
XXXXXXXX (XXX) 
GSK3342830 250 mg 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Day 1 – 0.5 HR 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
Follow-Up 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
XXXXXXXX (XXX) 
GSK3342830 500 mg 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXX (XXX) 
... 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
... 
 
 
 
 
 
 
 
Note to Programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages.  
Timepoints for Part 1 and Part 3  are Baseline, Day 1 – 0.5 HR, Day 1 – 1 HR, Day 1 – 1.5 HR, Day 1 – 2 HR, Day 1 – 3 HR, Day 1 – 4 
HR, Day 1 – 6 HR, Day 1 – 12 HR, Day 2, Day 3, Follow-Up. Timepoints for Part 2 are Baseline, Day 1 – 0.5 HR, Day 1 – 1 HR, Day 1 – 
1.5 HR, Day 1 – 2 HR, Day 1 – 3 HR, Day 1 – 4 HR, Day 1 – 6 HR, Day 1 – 12 HR, Day 2 through Day 14, Day 15 – 0.5 HR, Day 15 – 1 HR, 
Day 15 – 1.5 HR, Day 15 – 2 HR, Day 15 – 3 HR, Day 15 – 4 HR, Day 15 – 6 HR, Day 15 – 12 HR, Day 16, and Follow-Up. 
ECG measurements summarized are: Heart Rate (beats/min), PR Interval (msec), QT Interval (msec), QTc Interval (msec), QTcB Interval 
(msec), QTcF Interval (msec), QRS Duration (msec), QRS Axis (deg), and RR Interval (msec). 
Note: Baseline is defined as the last nonmissing measurement before dosing for the respective treatment period 
      Unscheduled measurements are not included in this summary table except when calculating baseline. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: EG2  
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.13 
Summary of Change from Baseline in ECG Values 
 
 
Note to programmer: Please use the shell from Table 2.12 and include only Planned Relative Time after Baseline. 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: SAFE_T1  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.14 
Summary of Frequency of Maximum Post-Dose ECG Parameter Corrected QTc Interval 
 
Study Part: 1 
 
 
GSK3342830 250 mg  
(N=XX) 
GSK3342830 550 mg  
(N=XX) 
… 
(N=XX) 
Placebo 
(N=XX) 
QTcB (msec) 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  <=450 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >450-<=479 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >=480-<=499 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >=500 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
QTcF (msec) 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  <=450 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >450-<=479 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >=480-<=499 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >=500 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
Note to Programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages.   
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: SAFE_T1  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.15 
Summary of Frequency of Maximum Change from Baseline for ECG Parameter Corrected QTc Interval 
 
Study Part: 1 
 
 
GSK3342830 250 mg  
(N=XX) 
GSK3342830 550 mg  
(N=XX) 
… 
(N=XX) 
Placebo 
(N=XX) 
QTcB (msec) 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  <=30 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >30-<=59 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >=60 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
QTcF (msec) 
 
 
 
 
  n 
xx 
xx 
xx 
xx 
  <=30 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >30-<=59 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  >=60 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
Note to Programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages.   
Note: Baseline is defined as the last nonmissing measurement before dosing for the respective treatment period. 
      Unscheduled measurements are not included in this summary table except when calculating baseline. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: VS1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.16 
Summary of Vital Signs 
Study Part: 1 
 
 
 
 
 
 
 
 
 
 
Vital Sign 
Group 
N 
Planned Relative Time 
n 
Mean 
SD 
Median 
Min. 
Max. 
 
 
 
 
 
 
XXXXXXXX (XXX) 
GSK3342830 250 mg 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
Day 1 – 0.5 HR 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
Follow-Up 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
XXXXXXXX (XXX) 
GSK3342830 500 mg 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXXXX (XXX) 
... 
XXX 
Baseline 
xx 
xx.x 
xx.xx 
xx 
xx 
xx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to Programmer: Continue for all treatments in Part 1, Part 2, and Part 3.  Present Part 2 and Part 3 on separate pages.  
Timepoints for Part 1 and Part 3  are Baseline, Day 1 – 0.5 HR, Day 1 – 1 HR, Day 1 – 1.5 HR, Day 1 – 2 HR, Day 1 – 3 HR, Day 1 – 4 
HR, Day 1 – 6 HR, Day 1 – 12 HR, Day 2, Day 3, Follow-Up. Timepoints for Part 2 are Baseline, Day 1 – 0.5 HR, Day 1 – 1 HR, Day 1 – 
1.5 HR, Day 1 – 2 HR, Day 1 – 3 HR, Day 1 – 4 HR, Day 1 – 6 HR, Day 1 – 12 HR, Day 2 through Day 14, Day 15 – 0.5 HR, Day 15 – 1 HR, 
Day 15 – 1.5 HR, Day 15 – 2 HR, Day 15 – 3 HR, Day 15 – 4 HR, Day 15 – 6 HR, Day 15 – 12 HR, Day 16, and Follow-Up. 
Vital sign measurements summarized are: Systolic Blood Pressure (mmHg), Diastolic Blood Pressure (mmHg), Oral Temperature (C), and 
Pulse Rate (beats per min). 
Note: Baseline is defined as the last nonmissing measurement before dosing. 
      Unscheduled measurements are not included in this summary table except when calculating baseline. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: VS1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: Safety 
Table 2.17 
Summary of Change from Baseline in Vital Signs 
 
 
Note to programmer: Please use the shell from Table 2.14 and include only Planned Relative Time after Baseline. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK01  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK  
 
Table 3.01 
Summary of GSK3342830 Single Dose Plasma Pharmacokinetic Concentration-Time Data (units) by Treatment in Part 1 
and Part 3 
 
Part: Part 1  
Dose 
Study Day 
 
 
N 
Planned 
Relative 
 Time 
n 
No. 
Imputed 
Mean 
SD 
CV% 
Median 
Min. 
Max. 
xxx mg 
1 
xx 
pre-dose 
xx 
xx 
NQ 
· 
· 
· 
· 
· 
 
 
 
0.5h 
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
1h  
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
1.25h 
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
1.5h 
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
… 
… 
… 
… 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
… 
… 
… 
… 
Note to Programmer: Present all part 1 first then repeat for Part 3. Blood samples for PK analysis will be collected at predose time 
point and  0.5, 1,1.25,1.5, 2, 2.5, 3,3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24 ,36 and 48 hours after dosing.If mean is below the level 
of quantification, report the mean value as NQ. 
Note: NQ=Not quantifiable.  
Source Data: Listing 40 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
 
Example  
: PK01  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK  
 
 
Table 3.02 
Summary of GSK3342830 Plasma Pharmacokinetic Concentration-Time Data (units) by Treatment in Part 2 
 
Dose 
Day  
 
 
N 
Planned 
Relative 
 Time 
n 
No. 
Imputed 
Mean 
SD 
CV% 
Median 
Min. 
Max. 
xxx mg 
1 
xx 
pre-dose 
xx 
xx 
NQ 
· 
· 
· 
· 
· 
 
 
 
0.5h 
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
1h  
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
1.25h 
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
1.5h 
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
… 
… 
… 
… 
… 
… 
… 
… 
… 
  
15 
xx 
pre-dose 
xx 
xx 
NQ 
· 
· 
· 
· 
· 
 
 
 
0.25h 
xx 
0 
xxxx.x 
xx.xx 
xx.x 
xxxx.x 
xxxx 
xxxx 
 
 
 
… 
… 
… 
… 
… 
… 
… 
… 
… 
Note to Programmer: Blood samples for PK analysis on day 1 will be collected at predose, 0.5, 1.25,1.5, 
2,2.5,3,3.5,4,4.5,5,6,8,10,12,16 and 24. Timepoints on day 15 is Pre-dose,0.5,1,1.25,1.5,2,2.5,3,3.5,4,4.5, 5,6 and 8.If mean is 
below the level of quantification, report the mean value as NQ. 
Note: NQ=Not quantifiable.  
Source Data: Listing 42 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PKPT1  
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
Table 3.03 
Summary of Untransformed GSK3342830 Single Dose Plasma Pharmacokinetic Parameters in Part 1 and Part 3 
 
 
 
Part: Part 1 
Parameter 
Summary 
Statistics 
Dose level 
XX mg  
XX mg 
XX mg 
XX mg 
XX mg 
XX mg 
 
 
 
 
 
Cmax (units) 
N 
xx 
xx 
xx 
xx 
xx 
xx 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
Arithmetic Mean 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
   95% CI 
(xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
(xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
 
SD 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
 
Median 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
Min 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Max 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Note to Programmer: Present all Part 1 first, then repeat for Part 3 
Additional untransformed parameters include AUC(0-t), AUC(0-∞), Tmax, t1/2, CL, Vss,  %AUCex, tlast, lambda_z, lambda_z_lower, 
lambda_z_upper, lambda_z_no. of points. 
Note: NQ=Not quantifiable. 
Source Data: Listing 44 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PKPT3   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
Table 3.04 
Summary of Log-transformed GSK3342830 Single Dose Plasma Pharmacokinetic Parameters in Part 1 and Part 3 
 
 
 
Part: Part 1 
Parameter 
Summary 
Statistics 
Dose level 
XX mg  
XX mg 
XX mg 
XX mg 
XX mg 
XX mg 
 
 
 
 
 
Cmax (units) 
N 
xx 
xx 
xx 
xx 
xx 
xx 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
Geometric Mean 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
   95% CI 
(xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
(xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
 
Geometric SD 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
 
%CVb 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
Note to Programmer: Present all Part 1 first, then repeat for Part 3 
Additional untransformed parameters include AUC(0-t), AUC(0-∞),  t1/2, CL, Vss. 
Note: NQ=Not quantifiable. 
Source Data: Listing 45 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PKPT1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
 
Table 3.05 
Summary of Untransformed GSK3342830 Single Dose Urine Pharmacokinetic Parameters in Part 1 and Part 3 
 
 
 
Part: Part 1 
Parameter 
Summary 
Statistics 
Dose level 
XX mg  
XX mg 
XX mg 
XX mg 
XX mg 
XX mg 
 
 
 
 
 
Ae (units) 
N 
xx 
xx 
xx 
xx 
xx 
xx 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
Geometric Mean 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
   95% CI 
(xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
(xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
 
Geometric SD 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
 
%CVb 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
Note to Programmer: Present all Part 1 first, then repeat for Part 3 
Additional untransformed parameters include Clr, Feu(0-4) (units), Feu(4-8) (units), Feu(8-12) (units), Feu (12-24)  (units), Feu 
(24-48) (units).  
Note: NQ=Not quantifiable. 
Source Data: Listing 45 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PKPT1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
 
 
Table 3.06 
Summary of Untransformed GSK3342830 Plasma Pharmacokinetic Parameters in Part 2 
 
 
 
Day 
Parameter 
Summary 
Statistics 
Dose level 
XX mg  
XX mg 
XX mg 
XX mg 
XX mg 
XX mg 
 
 
 
 
 
 
1 
Cmax (units) N 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Arithmetic 
Mean 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
   95% CI 
(xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) (xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x) 
 
 
SD 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
 
 
Median 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
Min 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Max 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
Note to Programmer:  
Additional untransformed parameters include AUC(0-t), AUC(0-∞), AUC(0-), Tmax, t1/2, CL, Vss,  %AUCex, tlast, lambda_z, 
lambda_z_lower, lambda_z_upper, lambda_z_no. of points, C, Ratio of time invariance, Ratio of accumulation. Repeat for day 15 
 
Note: NQ=Not quantifiable. 
Source Data: Listing 46 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PKPT3   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
 
Table 3.07 
Summary of Log-transformed GSK3342830 Plasma Pharmacokinetic Parameters in Part 2 
 
 
 
Day 
Parameter 
Summary 
Statistics 
Dose level 
XX mg  
XX mg 
XX mg 
XX mg 
XX mg 
XX mg 
 
 
 
 
 
 
1 
Cmax 
(units) 
N 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Geometric Mean 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
   95% CI 
(xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
 
 
Geometric SD 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
 
 
%CVb 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
 
Note to Programmer:  
Additional untransformed parameters include AUC(0-t), AUC(0-∞), AUC(0-), t1/2, CL, Vss, C. Repeat for Day 15. 
Note: NQ=Not quantifiable. 
Source Data: Listing 46 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PKPT1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
 
 
Table 3.08 
Summary of Untransformed GSK3342830 Urine Pharmacokinetic Parameters in Part 2 
 
 
 
Day 
Parameter 
Summary 
Statistics 
XX mg  
XX mg  
XX mg 
XX mg 
XX mg 
XX mg  
 
 
 
 
 
1 
Ae (units) 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
(xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
(xxxx.x,xxxx.x) (xxxx.x,xxxx.x) (xxxx.x,xxxx.x)
(xxxx.x,xxxx.x) 
 
 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
xxxx.xxx 
 
 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
xxxx.xx 
 
 
Note to Programmer:  
Additional untransformed parameters include Clr, Feu(0-8) (units), Feu(8-24) (units). Repeat for Day 15. 
Note: NQ=Not quantifiable. 
Source Data: Listing 47 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
 
Table 3.09 
Summary of Statistical Analysis of GSK3342830 Plasma Dose Proportionality in Part 1 
 
 
 
 
Dose 
 
Estimated Slope 
Standard 
90% CI 
P-Value 
(units) 
Parameter 
for log(dose) 
Error 
Lower–Upper 
(b=1) 
XX mg 
Cmax 
(units) 
x.xxx 
x.xxx 
x.xxxx–x.xxxx 
x.xxxx 
 
 
x.xxx 
x.xxx 
x.xxxx–x.xxxx 
x.xxxx 
 
 
 
 
 
 
 
Note: The power model, log(parameter) = log(a) + b*log(dose), was used to estimate the slope, corresponding 90% confidence interval, 
and the p-value testing dose proportionality (b=1). Natural log-transformation was used. 
Source Data: Listing 44. 
 
Note to programmer: In the case where dose proportionality is not established over the entire dosing range, secondary analysis of 
dose proportionality will be assessed for select doses over the higher dosing range with the power model or by pair-wise analysis of 
variance (ANOVA) using the SAS mixed models procedure. If the secondary analysis using the pair-wise ANOVA approach is performed, a 
reference dose would be chosen based on the lowest clinically relevant dose over which the pharmacokinetics can be adequately 
described and the other doses would be treated as test doses. 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
_ 
Table 3.10 
Summary of Statistical Analysis of GSK3342830 Plasma Dose Proportionality in Part 2 
 
 
 
 
Day  
Dose 
Parameter Estimated Slope 
Standard 
90% CI 
P-Value 
 
(Units) 
 
for log(dose) 
Error 
Lower–Upper 
(b=1) 
15 
XX mg 
Cmax 
(units) 
x.xxx 
x.xxx 
x.xxxx–x.xxxx 
x.xxxx 
 
 
 
x.xxx 
x.xxx 
x.xxxx–x.xxxx 
x.xxxx 
 
 
 
 
 
 
 
 
Note: The power model, log(parameter) = log(a) + b*log(dose), was used to estimate the slope, corresponding 90% confidence interval, 
and the p-value testing dose proportionality (b=1). Natural log-transformation was used. 
Source Data: Listing 46. 
 
Note to programmer: In the case where dose proportionality is not established over the entire dosing range, secondary analysis of 
dose proportionality will be assessed for select doses over the higher dosing range with the power model or by pair-wise analysis of 
variance (ANOVA) using the SAS mixed models procedure. If the secondary analysis using the pair-wise ANOVA approach is performed, a 
reference dose would be chosen based on the lowest clinically relevant dose over which the pharmacokinetics can be adequately 
described and the other doses would be treated as test doses. 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
 
Table 3.11 
Summary of Statistical Analysis of GSK3342830 Plasma Time Invariance in Part 2 
 
Dose: XX mg  
Parameter (Unit) 
Day  
N 
 
Geometric  
LS Means 
Regimen  
Comparison 
Ratio of  
Geometric  
LS Means (%) 
90% Confidence 
Interval of 
Ratio (%)  
 
 
CVw(%) 
AUC(0-inf) (Unit) 
1 
xx 
x.xxx 
15/1 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
AUC(0-tau) (Unit) 
15 
xx 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes to programmer: Repeat for each dose level.  
 
Note: A linear mixed-effect model with group (group=1 for AUC(0-inf) on Day 1, and group=2 for AUC(0-tau) on Day 15) as a fixed 
effect and subject as a random effect was fitted to the natural log transformed PK parameters. 
Source Data: Listing 46. 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
Table 3.12 
Summary of Statistical Analysis of GSK3342830 Plasma Accumulation Ratio in Part 2 
 
 
Parameter 
(Unit) 
Dose* 
(mg) 
Day  
N 
 
Geometric  
LS Means 
Regimen  
Comparison 
Ratio of  
Geometric  
LS Means (%) 
90% Confidence 
Interval of 
Ratio (%)  
 
 
CVw(%) 
AUC(0-tau) 
(Unit) 
xx 
1 
xx 
x.xxx 
15/1 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
 
 
15 
xx 
x.xxx 
 
 
 
 
 
yy 
1 
xx 
x.xxx 
15/1 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
15 
xx 
x.xxx 
 
 
 
 
 
zz 
1 
xx 
x.xxx 
15/1 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
15 
xx 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: A linear mixed-effect model with dose, day, and dose-by-day interaction as fixed effects and subject as a random effect was 
fitted to the natural log transformed PK parameters. 
* If dose-by-day interaction is significant (p-value less then 0.05), then point estimate and 90% CI will be reported for each dose 
level. 
Source Data: Listing 46. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
Table 3.13 
Summary of Statistical Analysis of GSK3342830 Plasma Steady State Assessment in Part 2 
 
 
 
Estimated Slope 
90% CI 
Parameter 
Days Included 
for Day 
Lower–Upper 
Ctrough (units) 
3, 6, 9, 12, 13, 15 
x.xxx 
x.xxxx–x.xxxx 
 
 
 
 
 
 
 
 
Note to programmer: If the 90% CI does not include zero, repeat the analysis without the data for the earliest day used in the 
previous analysis. Display the results for all models run.  
 
Note:  A mixed effect model will be fitted by dose and day (as a continuous covariate) as a fixed effect term and subject as a random 
effect term. No formal statistical hypothesis tested. Steady state is estimated to be achieved by the earliest day included in the 
analysis when the 90% CI of the slope includes 0.  
Source Data: Table 3.06. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T2   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
Table 3.14 
Summary of Model Parameters for Part 1 - Posterior Distributions 
 
PK Parameter on log scale 
  Model Parameter 
   
Mean 
SD 
MC error 
5th Percentile 
Median 
95th Percentile 
 
 
 
 
 
 
 
AUC[0-t](µg.h/mL)  
 
 
 
 
 
 
    Intercept 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Slope of log dose 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Precision   
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
 
 
 
 
 
 
 
Cmax (µg/mL) 
 
 
 
 
 
 
    Intercept 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Slope of log dose 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Precision   
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
 
 
 
 
 
 
 
 
Note: The posterior distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
 
Programmer note: Decimals will be adjusted to include approximately 5 significant digits. 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T2   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
Table 3.15 
Summary of Model Parameters for Part 2 - Posterior Distributions 
 
PK Parameter on log scale 
  Model Parameter 
   
Mean 
SD 
MC error 
5th Percentile 
Median 
95th Percentile 
 
 
 
 
 
 
 
AUC[0-8]x3(µg.h/mL)  
 
 
 
 
 
 
    Intercept 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Slope of log dose 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Precision   
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
 
 
 
 
 
 
 
Cmax (µg/mL) 
 
 
 
 
 
 
    Intercept 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Slope of log dose 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Precision   
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
xxxx.x 
 
 
 
 
 
 
 
 
 
Note: The posterior distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
 
Programmer note: Decimals will be adjusted to include approximately 5 significant digits.


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T3   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
Table 3.16 
Summary of PK Parameters for Part 1 - Bayesian Prediction of Individual Subjects 
 
PK Parameter  
  Statistics 
250 mg 
500 mg 
1000 mg 
2000 mg 
4000 mg 
6000 mg 
AUC[0-t] (µg.h/mL) 
 
 
 
 
 
 
  n 
  Observed Mean 
xxx 
xxxx.x 
xxx 
xxxx.x 
xxx 
xxxx.x 
xxx 
xxxx.x 
xxx 
xxxx.x 
xxx 
xxxx.x 
  Predictive Distribution 
 
 
 
 
 
 
    Mean 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    5th Percentile   
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Median 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    95th Percentile 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
 
 
 
 
 
 
 
Cmax (µg/mL) 
 
 
 
 
 
 
  Observed Mean 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
  Predictive Distribution 
 
 
 
 
 
 
    Mean 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    5th Percentile   
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    Median 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
    95th Percentile 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
xxxx.x 
 
 
 
 
 
 
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
 
Programming notes:  
1. Decimals will be adjusted to include approximately 5 significant digits as a guideline not as a requirement. 
2. If no observed values available for some doses, use ‘NA’ for the observed mean/n. 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T4   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
Table 3.17 
Summary of PK Parameters for Part 2 - Bayesian Prediction of Individual Subject 
 
PK Parameter  
  Statistics 
1000 mg 
2000 mg 
4000 mg 
 
AUC[0-8]x3 (µg.h/mL) 
 
 
 
 
  n 
  Observed Mean 
xxx 
xxxx.x 
xxx 
xxxx.x 
xxx 
xxxx.x 
 
  Predictive Distribution 
 
 
 
 
    Mean 
xxxx.x 
xxxx.x 
xxxx.x 
 
    5th Percentile   
xxxx.x 
xxxx.x 
xxxx.x 
 
    Median 
xxxx.x 
xxxx.x 
xxxx.x 
 
    95th Percentile 
xxxx.x 
xxxx.x 
xxxx.x 
 
 
 
 
 
 
Cmax (µg/mL) 
 
 
 
 
  Observed Mean 
xxxx.x 
xxxx.x 
xxxx.x 
 
  Predictive Distribution 
 
 
 
 
    Mean 
xxxx.x 
xxxx.x 
xxxx.x 
 
    5th Percentile   
xxxx.x 
xxxx.x 
xxxx.x 
 
    Median 
xxxx.x 
xxxx.x 
xxxx.x 
 
    95th Percentile 
xxxx.x 
xxxx.x 
xxxx.x 
 
 
 
 
 
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
 
Programming notes: Decimals will be adjusted to include approximately 5 significant digits. 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T4   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
Table 3.18 
Summary of PK Parameters for Part 1 - Bayesian Predictive Probability 
 
PK Parameter  
   
Threshold on 
actual scale 
Probability (greater than threshold | observed data) 
 
 
250 mg 
500 mg 
1000 mg 
2000 mg 
4000 mg 
6000 mg 
AUC[0-t] (µg.h/mL) 
3460 
x.xx%
x.xx%
x.xx%
x.xx%
xx.xx%
xx.xx%
 
 
 
 
 
 
 
 
Cmax (µg/mL) 
2590 
x.xx%
x.xx%
x.xx%
x.xx%
xx.xx%
xx.xx%
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
 
Note: Each probability is the posterior predictive probability of the PK parameter exceeding the threshold, for a hypothetical future 
study subject.  
 
 
Programming notes: 
Please keep at least 4 decimal points for each probability value. If prob <0.0001, please display as <0.0001. If prob > 0.9999, then 
display as > 0.9999.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T4   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
Table 3.19 
Summary of PK Parameters for Part 2 – Bayesian Predictive Probability 
 
PK Parameter 
   
Threshold on actual 
scale 
Probability (greater than threshold | observed data) 
 
 
1000 mg 
2000 mg 
4000 mg 
AUC[0-8]x3 (µg.h/mL) 
3460 
x.xx%
x.xx%
xx.xx%
 
 
 
 
 
Cmax (µg/mL) 
2590 
x.xx%
x.xx%
xx.xx%
 
Note: The predictive distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
Note: Each probability is the posterior predictive probability of the PK parameter exceeding the threshold, for a hypothetical future 
study subject.  
 
Programming notes: 
Please keep at least 4 decimal points for each probability value. If prob <0.0001, please display as <0.0001. If prob > 0.9999, then 
display as > 0.9999.  


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T4   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
Table 3.20 
Summary of PK Parameters for Part 1 - Bayesian Inferential Probability  
 
PK Parameter  
   
Threshold on 
actual scale 
Probability (greater than threshold | observed data) 
 
 
250 mg 
500 mg 
1000 mg 
2000 mg 
4000 mg 
6000 mg 
AUC[0-t] (µg.h/mL) 
2875 
0.xxxx
0.xxxx
0.xxxx 
0.xxxx
0.xxxx
0.xxxx
 
 
 
 
 
 
 
 
Cmax (µg/mL) 
2270 
0.xxxx
0.xxxx
0.xxxx 
0.xxxx
0.xxxx
0.xxxx
 
Note: The inferential probability are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
 
Note: Each probability is the posterior inferential probability of the mean PK parameter exceeding the threshold. 
 
Programming notes: 
Please keep at least 4 decimal points for each probability value. If prob <0.0001, please display as <0.0001. If prob > 0.9999, then 
display as > 0.9999.  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T4   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
Table 3.21 
Summary of PK Parameters for Part 2 - Bayesian Inferential Probability  
Protocol 
: 204847 
PK Parameter 
   
Threshold on actual 
scale 
Probability (greater than threshold | observed data) 
 
 
1000 mg 
2000 mg 
4000 mg 
 
 
 
 
 
AUC[0-8]x3 (µg.h/mL) 
2875 
0.xxxx
0.xxxx
0.xxxx
 
 
 
 
 
Cmax (µg/mL) 
2270 
0.xxxx
0.xxxx
0.xxxx
Note: The inferential distributions are derived from linear model log-PK-parameter = intercept + slope*log-dose + error term.  
Note: Each probability is the posterior inferential probability of the mean PK parameter exceeding the threshold. 
 
Programming notes: 
Please keep at least 4 decimal points for each probability value. If prob <0.0001, please display as <0.0001. If prob > 0.9999, then 
display as > 0.9999.  


 
GlaxoSmithKline 
 
 
<DIRECTORY PATH>PROGRAM NAME  Executed: DDMONYYYY  hh:mm 
Example  
: PK_T1   
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 204847 
Population 
: PK Parameter 
 
 
Table 3.22 
Summary of Statistical Analysis of GSK3342830 Single Dose Plasma Pharmacokinetic Parameters in Part 1 and Part 3 Subjects 
 
 
Parameter 
(Unit) 
Dose 
(mg) 
Study Part  
N 
 
Geometric  
LS Means 
Regimen  
Comparison 
Ratio of  
Geometric  
LS Means (%)
90% Confidence 
Interval of 
Ratio (%)  
 
AUC(0-t) 
(Unit) 
xx 
Part 1 
xx 
x.xxx 
Part 3/Part 1
x.xxx 
(x.xxx, x.xxx) 
 
 
 
Part 3 
xx 
x.xxx 
 
 
 
 
AUC(0-inf) 
(Unit) 
yy 
Part 1 
xx 
x.xxx 
Part 3/Part 1
x.xxx 
(x.xxx, x.xxx) 
 
 
 
Part 3 
xx 
x.xxx 
 
 
 
 
Cmax (Unit) 
zz 
Part 1 
xx 
x.xxx 
Part 3/Part 1
x.xxx 
(x.xxx, x.xxx) 
 
 
 
Part 3 
xx 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: A linear mixed-effect model with study part as fixed effect was fitted to the natural log transformed PK parameters. 
Part 1 subjects were normal healthy volunteers and Part 3 subjects were Japanese healthy volunteers. 
Source Data: Listing 44.