Conditions: HIV Infections
Keywords: Dolutegravir GSK3640254 Fixed Dose Combinations Bioavailability
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 41
Healthy volunteers: yes

Brief summary:
This is a two part study to compare the relative bioavailability (BA) of 2 fixed dose combinations (FDCs) of GSK3640254/DTG with GSK3640254 and DTG administered together as single agents (Part 1) and to assess the effect of food on the pharmacokinetic (PK) of the selected FDC of GSK3640254/DTG (Part 2).

Detailed description:

Arms:
arm 1: Participants will receive a single oral dose of GSK3640254 25 milligrams (mg) (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A) in Period 1, followed by a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B) in Period 2. In Period 3, participants will receive a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C). arm 2: Participants will receive a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B) in Period 1, followed by a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C) in Period 2. In Period 3 participants will receive a single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A). arm 3: Participants will receive a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C) in period 1, followed by a single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A) in Period 2. In Period 3 participants will receive a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B). arm 4: Participants will receive a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under high fat and calorie conditions (Treatment D) in Period 1 followed by a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under fasted conditions (Treatment E) in Period 2. arm 5: Participants will receive a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under fasted conditions (Treatment E) in Period 1 followed by a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under high fat and calorie conditions (Treatment D) in Period 2.

Interventions: intervention 1: GSK3640254 intervention 2: DTG intervention 3: GSK3640254/DTG
Intervention descriptions: intervention 1: GSK3640254 will be administered via oral route. intervention 2: DTG will be administered via oral route. intervention 3: GSK3640254/DTG will be administered via oral route.

Protocol document:
Prot_000.pdf: 
TMF-13328213 
CONFIDENTIAL 
 
ViiV Healthcare group of companies 
 
213055 
 
1 
 
TITLE PAGE 
Protocol Title: A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical 
Study to Assess the Relative Bioavailability of Fixed-Dose Combinations of 
GSK3640254 and Dolutegravir and to Assess the Effect of Food on the Select Fixed 
Dose Combination of GSK3640254 and Dolutegravir in Healthy Participants 
Protocol Number: 213055 
Compound Number 
or Name: 
GSK3640254, GSK4107821 
Brief Title: A Relative Bioavailability and Food-Effect Study of the Fixed Dose 
Combination of GSK3640254 and Dolutegravir in Healthy Participants 
Study Phase: Phase 1 
Sponsor Name and Legal Registered Address:  
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
In some countries, local law requires that the Clinical Study sponsor is a local company 
legal entity. In these instances, the appropriate company to be identified as Sponsor must 
be agreed with the global ViiV Healthcare clinical team and signed off by the Vice 
President, Global Research and Medical Strategy. 
This study is sponsored by ViiV Healthcare. PPD with GlaxoSmithKline are supporting 
ViiV Healthcare in the conduct of this study. 
Medical Monitor Name and Contact Information: Can be found in the Study 
Reference Manual. 
Regulatory Agency Identifying Number: IND 139,838 
Approval Date: 05-MAY-2021 
Copyright 2021 ViiV Healthcare group of companies. All rights reserved. Unauthorized 
copying or use of this information is prohibited. 
 


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SPONSOR SIGNATORY: 
Protocol Title: A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical 
Study to Assess the Relative Bioavailability of Fixed-Dose Combinations of 
GSK3640254 and Dolutegravir and to Assess the Effect of Food on the Select Fixed 
Dose Combination of GSK3640254 and Dolutegravir in Healthy Participants 
Protocol Number: 213055 
Compound Number 
or Name: 
GSK3640254, GSK4107821 
 
 
 
Max Lataillade, DO, MPH 
VP and Head, Global Research Strategy 
ViiV Healthcare 
 
Date 
 
 
 
The signed page is a separate document. 
 
Medical Monitor Name and Contact Information will be provided separately 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 1 
05-May -2021 
TMF-13328213 
Original Protocol 
25-Mar-2021 
TMF-11919451 
 
Amendment 1 [05-May-2021] 
Overall Rationale for the Amendment: The primary driver for the protocol amendment 
was to clarify specific errors which related to the conduct of this protocol before study 
initiation.   
Section # and 
Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
Changed the number of days in 
Part 1 & Part 2 of this study. 
Also changed the number of 
washout days to 7.  
The days for participation was 
previously incorrect & washout was 
shortened to 7 days.   
1.3 Schedule of 
Activities 
Changed he number of 
screening days 
The number of screening days was 
previously incorrect  
1.3 Schedule of 
Activities 
Added Day 7 Safety 
assessments 
Additional safety checks prior to 
dosing 
1.3 Schedule of 
Activities 
Sub-script 1 was changed to 
reflect a corrected baseline 
visit, with a 7-day washout.  
Washout was changed to 7 days to 
shorten time between doses.  
1.3 Schedule of 
Activities 
Day 5 PK sampling for 
GSK3640254 & DTG was 
added as 96h collection 
timepoints 
Day 5 was not included previously, 
however 96h was reflected correctly.  
5.2 Exclusion 
Criteria 
Deleted exclusion # 21 as it 
was a duplicate of exclusion # 
23 
Duplicate exclusion criteria 
6.1 Study 
Interventions 
Administered 
 
Corrected the source of 
GSK3640254 / DTG 
formulation as sponsor 
supplied 
DTG was previously listed as “locally 
sourced” in error 
 
 


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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY: ............................................................................................... 2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1. 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1. 
Synopsis ....................................................................................................... 7 
1.2. 
Schema ...................................................................................................... 10 
1.3. 
Schedule of Activities (SoA) ........................................................................ 11 
2. 
INTRODUCTION .................................................................................................... 18 
2.1. 
Study Rationale .......................................................................................... 18 
2.2. 
Background ................................................................................................ 18 
2.2.1. 
Key Safety Data with a Prior Maturation Inhibitor 
(GSK3532795) ............................................................................. 18 
2.2.2. 
Key Clinical Data on GSK3640254 to date ................................... 19 
2.2.3. 
Dolutegravir ................................................................................. 20 
2.2.4. 
Drug interaction Potential with GSK3640254 and 
Dolutegravir ................................................................................. 20 
2.3. 
Benefit/Risk Assessment ............................................................................ 21 
2.3.1. 
Risk Assessment ......................................................................... 22 
2.3.2. 
Benefit Assessment ..................................................................... 28 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 28 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 28 
4. 
STUDY DESIGN .................................................................................................... 29 
4.1. 
Overall Design ............................................................................................ 29 
4.2. 
Scientific Rationale for Study Design .......................................................... 30 
4.3. 
Justification for Dose .................................................................................. 31 
4.4. 
End of Study Definition ............................................................................... 32 
5. 
STUDY POPULATION ........................................................................................... 32 
5.1. 
Inclusion Criteria ......................................................................................... 32 
5.2. 
Exclusion Criteria ........................................................................................ 33 
5.3. 
Lifestyle Considerations .............................................................................. 36 
5.3.1. 
Meals and Dietary Restrictions .................................................... 36 
5.3.2. 
Caffeine, Alcohol, and Tobacco ................................................... 37 
5.3.3. 
Activity ......................................................................................... 38 
5.4. 
Screen Failures........................................................................................... 38 
5.5. 
Criteria for Temporarily Delaying ................................................................ 38 
6. 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY ................................ 38 
6.1. 
Study Interventions Administered ............................................................... 38 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 39 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 40 
6.4. 
Study Intervention Compliance ................................................................... 40 
6.5. 
Dose Modification ....................................................................................... 40 


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6.6. 
Continued Access to Study Intervention after the End of the Study ............ 40 
6.7. 
Treatment of Overdose ............................................................................... 41 
6.8. 
Concomitant Therapy.................................................................................. 41 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 41 
7.1. 
Discontinuation of Study Intervention .......................................................... 41 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 42 
7.1.2. 
QTc Stopping Criteria .................................................................. 42 
7.1.3. 
Rash/Hypersensitivity Evaluation Criteria..................................... 42 
7.1.4. 
Columbia-Suicide Severity Rating Scale Criteria .......................... 43 
7.1.5. 
Individual Participant Laboratory Abnormality and Adverse 
Event Stopping Criteria ................................................................ 43 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 43 
7.3. 
Lost to Follow Up ........................................................................................ 44 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 44 
8.1. 
Efficacy Assessments ................................................................................. 45 
8.2. 
Safety Assessments ................................................................................... 45 
8.2.1. 
Physical Examinations ................................................................. 45 
8.2.2. 
Vital Signs .................................................................................... 45 
8.2.3. 
Electrocardiograms ...................................................................... 46 
8.2.4. 
Clinical Safety Laboratory Assessments ...................................... 46 
8.2.5. 
Pregnancy Testing ....................................................................... 47 
8.2.6. 
Suicidal Ideation and Behaviour Risk Monitoring ......................... 47 
8.2.7. 
Gastrointestinal Intolerability Evaluation and Monitoring 
Plan (with Stopping Criteria) ........................................................ 48 
8.2.8. 
COVID-19 Measures ................................................................... 50 
8.3. 
Adverse Events, Serious Adverse Events and Other Safety 
Reporting .................................................................................................... 50 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 50 
8.3.2. 
Method of Detecting AEs and SAEs ............................................. 51 
8.3.3. 
Follow-up of AEs and SAEs ......................................................... 51 
8.3.4. 
Regulatory Reporting Requirements for SAEs ............................. 51 
8.3.5. 
Pregnancy ................................................................................... 51 
8.3.6. 
Adverse Events of Special Interest .............................................. 52 
8.4. 
Pharmacokinetics ....................................................................................... 52 
8.5. 
Genetics ..................................................................................................... 52 
8.6. 
Biomarkers ................................................................................................. 53 
8.7. 
Immunogenicity Assessments ..................................................................... 53 
8.8. 
Medical Resource Utilization and Health Economics .................................. 53 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 53 
9.1. 
Statistical Hypotheses................................................................................. 53 
9.2. 
Sample Size Determination ........................................................................ 53 
9.2.1. 
Sample Size Assumptions ........................................................... 53 
9.2.2. 
Sample Size Sensitivity ................................................................ 55 
9.3. 
Analysis Sets .............................................................................................. 56 
9.4. 
Statistical Analyses ..................................................................................... 56 
9.4.1. 
Pharmacokinetic Analyses ........................................................... 56 
9.4.2. 
Safety Analyses ........................................................................... 58 


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9.4.3. 
Other Analysis ............................................................................. 58 
9.5. 
Interim Analysis .......................................................................................... 58 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 59 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 59 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 59 
10.1.2. 
Financial Disclosure ..................................................................... 59 
10.1.3. 
Informed Consent Process .......................................................... 60 
10.1.4. 
Data Protection ............................................................................ 60 
10.1.5. 
Committees Structure .................................................................. 61 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 61 
10.1.7. 
Data Quality Assurance ............................................................... 61 
10.1.8. 
Source Documents ...................................................................... 62 
10.1.9. 
Study and Site Start and Closure ................................................. 63 
10.1.10. Publication Policy ......................................................................... 63 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 65 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting ............................................................................................. 67 
10.3.1. 
Definition of Adverse Event .......................................................... 67 
10.3.2. 
Definition of Serious Adverse Event ............................................. 68 
10.3.3. 
Recording and Follow-Up of Adverse Events and Serious 
Adverse Events............................................................................ 69 
10.3.4. 
Reporting of Serious Adverse Events to VH/GSK ........................ 71 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 73 
10.4.1. 
Definitions: ................................................................................... 73 
10.4.2. 
Contraception Guidance: ............................................................. 74 
10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 75 
10.6. 
Appendix 6: COVID-19 Pandemic and Clinical Study Continuity ................. 77 
10.6.1. 
Changes to Study Visits and Study Procedures ........................... 77 
10.6.2. 
COVID-19 Specific Data Capture ................................................. 77 
10.7. 
Appendix 7: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Corrected Version 2.1, July 2017 ................. 80 
10.8. 
Appendix 8: Abbreviations and Trademarks ................................................ 81 
11. REFERENCES ....................................................................................................... 84 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical 
Study to Assess the Relative Bioavailability of Fixed Dose Combinations of 
GSK3640254 and Dolutegravir and to Assess the Effect of Food on the Select Fixed 
Dose Combination of GSK3640254 and Dolutegravir in Healthy Participants 
Brief Title: A Relative Bioavailability (BA) and Food-Effect Study of the Fixed Dose 
Combination (FDC) of GSK3640254 and Dolutegravir (DTG) in Healthy Participants 
Rationale: This is a Phase 1, 2-part, randomized, open-label, single-dose, crossover 
study to compare the relative BA of 2 FDCs of GSK3640254 / DTG with GSK3640254 
and DTG administered together as single agents. Data from this study will inform 
formulation decisions for future clinical studies. 
In addition, this study will investigate the effect of food on the pharmacokinetics (PK) of 
the selected FDC of GSK3640254 / DTG. Most GSK3640254 completed clinical studies 
to date have been conducted with moderate fat and calorie meals. This study will 
investigate the effect of a high fat and calorie meal on the PK, safety, and tolerability of 
the FDC of GSK3640254 / DTG, in comparison with administration under fasting 
conditions. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Part 1 
• To assess the relative bioavailability of 
FDCs of GSK3640254 / DTG compared 
with GSK3640254 and DTG 
administered together as single agents 
when administered with a moderate fat 
and calorie meal 
Part 2 
• To assess the effect of food on the PK 
of the selected FDC of GSK3640254 / 
DTG when administered with a high fat 
and calorie meal compared to fasted 
conditions 
Parts 1 and 2 
• AUC(0-), AUC(0-t), and Cmax for 
GSK3640254 and DTG 


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Objectives 
Endpoints 
Secondary 
Part 1 
• To assess the safety and tolerability of 
FDCs of GSK3640254 / DTG compared 
with GSK3640254 and DTG 
administered together as single agents 
Part 2 
• To assess the safety and tolerability of 
selected FDC of GSK3640254 / DTG 
following single oral administration to 
healthy participants under fasted or fed 
conditions  
  
 
Parts 1 and 2 
• Safety and tolerability parameters for 
AEs or SAEs, observed and change 
from baseline clinical laboratory 
assessments, ECGs, and vital sign 
measurements 
 
 
 
 
 
  
AE = adverse event; AUC(0-) = area under the plasma concentration-time curve from time zero extrapolated to 
infinity; AUC(0-t) = area under the plasma concentration-time curve from time zero to time t; C24 = plasma 
concentration at 24 hours post-dose; CL/F = apparent oral clearance; Cmax = maximum observed concentration; 
DTG = dolutegravir; ECG = electrocardiogram; FDC = fixed-dose combination; PK = pharmacokinetics; 
SAE = serious adverse event; t1/2 = apparent terminal phase half-life; tlag = lag time for absorption; Tmax = time 
of maximum observed concentration. 
Overall Design: This is a Phase 1, 2-part, randomized, open-label, single-dose, crossover 
study in healthy participants to compare the relative BA of 2 FDCs of GSK3640254 / 
DTG with GSK3640254 and DTG administered together as single agents (Part 1) and to 
assess the effect of food on the PK of the selected FDC of GSK3640254 / DTG from Part 
1 (Part 2). Participants in both Part 1 and Part 2 will be screened within 35 days before 
the first dose of study intervention. 
Part 1 will consist of a screening period and 3 treatment periods with a single dose of 
study intervention per treatment period. 
Part 2 will consist of a screening period and 2 treatment periods with a single dose of 
study intervention per treatment period. This will be followed by an End of Study 
analysis. 
In Part 1, Treatments A, B, and C will be administered in the fed state. Participants will 
fast overnight for at least 10 hours prior to breakfast and will receive a moderate fat and 
calorie meal 30 minutes prior to dosing. Participants will eat this meal in 25 minutes or 
less. Dose administration will occur within 5 minutes of completion of meal 
consumption. Participants will not receive any further food until 4 hours after dosing. 
Part 2 will be dosed using a formulation selected from Part 1 based on PK data. 
Treatment D will be administered in the fed state. Participants will fast overnight for at 
least 10 hours prior to breakfast and will receive a high fat and calorie meal 30 minutes 


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prior to dosing. Participants will eat this meal in 25 minutes or less. Dose administration 
will occur within 5 minutes of completion of meal consumption. Participants will not 
receive any further food until 4 hours after dosing. Treatment E will be administered in 
the fasted state. Participants will fast overnight for at least 10 hours prior to dosing and 
until 4 hours after dosing. 
In both Part 1 and Part 2, PK blood samples for the analysis of GSK3640254 and DTG 
will be collected prior to dosing (0 hour) on Day 1 and up to 96 hours post-dose in each 
period. 
Safety and tolerability will be assessed by monitoring and recording of adverse events 
(AEs) and serious AEs (SAE), clinical laboratory test results, vital sign measurements, 
12-lead electrocardiogram (ECG) results, and physical examination findings. 
Study assessments will be performed as indicated in the Schedule of Activities (SoA; 
Section 1.3). For Part 1, study participants will be confined to the clinic from Day -2 of 
Period 1 until discharge on Day 5 of Period 3. For Part 2, study participants will be 
confined to the clinic from Day -2 of Period 1 until discharge on Day 5 of Period 2. 
Brief Summary: A relative BA and food-effect study of the FDC of GSK3640254 / 
DTG in healthy participants. Study details include: 
Part 1: 
• Study Duration: 56 days (including screening) 
• Treatment Duration: 3 days (Day 1 of each period) 
Part 2: 
• Study Duration: 49 days (including screening) 
• Treatment Duration: 2 days (Day 1 of each period) 
Number of Participants: For each part, approximately 18 participants will be enrolled to 
ensure that 14 evaluable participants complete the study. 
Note: "Enrolled" means a participant's, or their legally acceptable representative’s, 
agreement has been obtained to participate in a clinical study following completion of the 
informed consent process and screening. Potential participants who are screened for the 
purpose of determining eligibility for the study, but do not participate in the study, are not 
considered enrolled, unless otherwise specified by the protocol.  
Intervention Groups and Duration: Participants in Part 1 and Part 2 will be randomly 
assigned to a treatment sequence prior to dosing on Day 1 of Period 1. Participants will 
receive each of the following treatments administered as 1 treatment per period: 


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Part 1 (Treatment sequence ABC, BCA, or CAB): 
• Treatment A: A single oral dose of GSK3640254 25 mg (2 x tablets), 
GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered 
together under moderate fat and calorie conditions (reference) 
• Treatment B: A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg (1 x 
monolayer tablet) FDC administered under moderate fat and calorie conditions 
• Treatment C: A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg (1 x 
bilayer tablet) FDC administered under moderate fat and calorie conditions 
Part 2 (Treatment sequence DE or ED): 
• Treatment D: A single oral dose of selected FDC from Part 1 of GSK3640254 / 
DTG, 150mg / 50mg  administered under high fat and calorie conditions 
• Treatment E: A single oral dose of selected FDC from Part 1 of GSK3640254 / 
DTG, 150 mg / 50 mg administered under fasted conditions 
To ensure adequate washout, there will be at least 7 days between each dose of study 
intervention, with an allowance window of 4 hours (i.e., 7 days minus 4 hours) to allow 
flexibility in scheduling participants for dosing at the clinic. 
Data Monitoring/ Other Committee: No 
1.2. 
Schema 
 
FDC = fixed dose combination; WO = washout 
Treatment A: A single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 100 
mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and 
calorie conditions. 
Treatment B: A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg (1 x monolayer 
tablet) FDC administered under moderate fat and calorie conditions. 
Treatment C: A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg (1 x bilayer 
tablet) FDC administered under moderate fat and calorie conditions. 
Treatment D: A single oral dose of selected FDC of GSK3640254 / DTG, 150 mg /50 mg 
administered under high fat and calorie conditions. 
Treatment E: A single oral dose of selected FDC of GSK3640254 / DTG, 150 mg / 50 mg 
administered under fasted conditions. 


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1.3. 
Schedule of Activities (SoA) 
• Screening procedures may be completed over more than 1 visit but must all be 
completed within 35 days prior to the first dose of study intervention.  
• The following demographic parameters will be captured: year of birth, sex, race, and 
ethnicity. 
• Medical/medication/family history will be assessed as related to the inclusion or 
exclusion criteria. 
SCREENING VISIT – PART 1 AND PART 2 
Procedure 
Screening 
(up to 35 days before Day 1) 
Outpatient visit 
X 
Informed consent 
X 
Inclusion and exclusion criteria 
X 
Demography 
X 
Full physical examination including height and weight1 
X 
Laboratory assessments (hematology, clinical chemistry, urinalysis)  
X 
12-lead electrocardiogram 
X 
Vital sign measurements 
X 
Medication/drug/alcohol history 
X 
Past and current medical conditions 
X 
Columbia-Suicide Severity Rating Scale  
X 
Serum pregnancy test 
X 
Follicle-stimulating hormone (as needed, to confirm postmenopausal status) 
X 
Drug, alcohol, and cotinine screen 
X 
Human immunodeficiency virus, hepatitis B and C screening  
X 
Molecular test for SARS-CoV-22 
X 
1. 
A full physical examination will include at a minimum, assessments of the skin, cardiovascular, respiratory, 
gastrointestinal, and neurological systems. 
2. 
Two consecutive approved molecular tests (polymerase chain reaction or antigen test). The first test should be 
performed ≥7 days prior to admission.  
  


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TIME AND EVENTS – PART 1 
Procedure 
Check-in 
Baseline1 
Period 1 & 2 
Period 3 
Notes 
Day –2 
Day -1 
Day 1 
Washout 
Day 1 Day 2 
Days 
3-4 
Day 52  
Day 2 Days 3-5 Days 6-7 
Admit to clinic 
X 
 
 
 
 
 
 
 
 
 
 
Discharge from clinic 
 
 
 
 
 
 
 
 
 
X 
Discharge from clinic following completion of the 
last study procedure on Day 5 of Period 3. 
Brief physical examination 
 
X 
 
 
 
D7 
 
 
 
X 
Interim or symptom-targeted physical examination 
will be performed at the discretion of the 
investigator. See Section 8.2.1 for description of 
brief physical examination.  
Vital signs 
 
X 
X 
X 
D3 
D7 
X 
X 
X 
X 
Blood pressure and pulse will be measured in 
triplicate at predose on Day 1 in all periods. Single 
blood pressure and pulse will be measured on 
other study days. 
Temperature check 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG 
 
X 
X 
 
 
 
X 
 
 
X 
The ECGs on Day 1 in all periods will be taken at 
predose, and post-dose at 2, 4, and 6 hours. The 
predose ECGs will be taken in triplicate to establish 
a baseline QTcF. The post-dose ECGs are single 
ECGs. 
Drug, alcohol, and 
cotinine screen 
X 
 
 
 
 
 
 
 
 
 
See Appendix 2 for specific tests to be performed. 


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Procedure 
Check-in 
Baseline1 
Period 1 & 2 
Period 3 
Notes 
Day –2 
Day -1 
Day 1 
Washout 
Day 1 Day 2 
Days 
3-4 
Day 52  
Day 2 Days 3-5 Days 6-7 
Molecular test for 
SARS-CoV-2 
X* 
 
 
 
D5  
 
 
 
 
X  
* The second test will be performed on Day -2 after 
admission to the clinic. Participants will be 
quarantined within the clinic until the second test 
result is negative. Once the second test result is 
confirmed negative, participants can be released 
into the study unit and will follow infection control 
practices. 
Laboratory assessments 
(hematology, chemistry, 
urinalysis) 
 
X3 
 
X 
 
D7 
 
X 
 
X 
See Appendix 2 for specific tests to be performed. 
Day 2 samples in each period to be collected 
24 hours after dosing. 
Pregnancy test 
X 
 
 
 
 
 
 
 
 
X 
Serum testing on Day –2 
Columbia-Suicide Severity 
Rating Scale  
 
X 
 
 
 
D7 
 
 
 
X 
 
Study intervention:  
GSK3640254 25 mg, 100 
mg or GSK3640254 / 
DTG 150 mg / 50 mg 
fixed-dose combination 
Or DTG 50 mg 
 
 
X 
 
 
 
X 
 
 
 
See Section 4.1. 
GSK3640254 PK 
sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
X 
Blood for PK analysis of GSK3640254 will be 
collected within 40 minutes prior to dosing and 0.5, 
1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 
and 96 hours post-dose in all periods. 
Dolutegravir PK sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
X 
Blood for PK analysis of dolutegravir will be 
collected within 40 minutes prior to dosing and 0.5, 
1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 
and 96 hours post-dose in all periods. 


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Procedure 
Check-in 
Baseline1 
Period 1 & 2 
Period 3 
Notes 
Day –2 
Day -1 
Day 1 
Washout 
Day 1 Day 2 
Days 
3-4 
Day 52  
Day 2 Days 3-5 Days 6-7 
AE review 
 
 
============================X==================➔ 
 
SAE review 
=====================================X================================➔  
Concomitant medications 
=====================================X================================➔  
AE = adverse event; D = day; ECG = electrocardiogram; PK = pharmacokinetic; QTcF = QT interval corrected using Fridericia’s formula; SAE = serious adverse event.  
1 
Baseline assessments will be collected on Day -1 before Period 1.  
2 
Evaluations scheduled for Day 5 in Period 3 will also be performed for participants who discontinue early. 
3 
Review and approval prior to dosing on Day 1 in Periods 1, 2 and 3. 
 
 


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TIME AND EVENTS – PART 2 
Procedure 
Check-in 
BaselineEr
ror! Reference 
source not 
found. 
Period 1 
Period 2 
Notes 
 
Day –2 
Day -1 
Day 
1 
Washout 
Day 1 Day 2 
Days 
3-4 
Day 51  
Day 2 
Days 
3-5 
Days 6-7 
Admit to clinic 
X 
 
 
 
 
 
 
 
 
 
 
Discharge from clinic 
 
 
 
 
 
 
 
 
 
X 
Discharge from clinic following completion of the last 
study procedure on Day 5 of Period 2. 
Brief physical examination 
 
X 
 
 
 
D7 
 
 
 
X 
Interim or symptom-targeted physical examination will be 
performed at the discretion of the investigator. See 
Section 8.2.1 for description of brief physical 
examination.  
Vital signs 
 
X 
X 
X 
D3 
D7 
X 
X 
X 
X 
Blood pressure and pulse will be measured in triplicate 
predose on Day 1 in both periods. Single blood pressure 
and pulse will be measured on other study days. 
Temperature check 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG 
 
X 
X 
 
 
D7 
X 
 
 
X 
The ECGs on Day 1 in all periods will be taken at 
predose, and post-dose at 2, 4 and 6 hours. The predose 
ECGs will be taken in triplicate to establish a baseline 
QTcF. The post-dose ECGs are single ECGs. 
Drug, alcohol, and 
cotinine screen 
X 
 
 
 
 
 
 
 
 
 
See Appendix 2 for specific tests to be performed. 


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Procedure 
Check-in 
BaselineEr
ror! Reference 
source not 
found. 
Period 1 
Period 2 
Notes 
 
Day –2 
Day -1 
Day 
1 
Washout 
Day 1 Day 2 
Days 
3-4 
Day 51  
Day 2 
Days 
3-5 
Days 6-7 
Molecular test for 
SARS-CoV-2 
X* 
 
 
 
 D5 
 
 
 
 
X 
* The second test will be performed on Day -2 after 
admission to the clinic. Participants should be 
quarantined within the clinic until the second test result is 
negative. Once the second test result is confirmed 
negative, they can be released into the study unit and will 
follow infection control practices. 
Laboratory assessments 
(hematology, chemistry, 
urinalysis) 
 
X3 
 
X 
 
D7 
 
X 
 
X 
See Appendix 2 for specific tests to be performed. Day 2 
samples in each period to be collected 24 hours after 
dosing. 
Pregnancy test 
X 
 
 
 
 
 
 
 
 
X 
Serum testing on Day –2 
Columbia-Suicide Severity 
Rating Scale  
 
X 
 
 
 
D7 
 
 
 
X 
 
Study intervention:  
GSK3640254 / DTG 150 
mg / 50 mg fixed-dose 
combination 
 
 
X 
 
 
 
X 
 
 
 
See Section 4.1. 
GSK3640254 PK 
sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
 
Blood for PK analysis of GSK3640254 will be collected 
within 40 minutes prior to dosing and 0.5, 1, 1.5, 2, 2.5, 3, 
3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, and 96 hours 
post-dose in both periods. 
Dolutegravir PK sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
 
Blood for PK analysis of dolutegravir will be collected 
within 40 minutes prior to dosing and 0.5, 1, 1.5, 2, 2.5, 3, 
3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, and 96 hours 
post-dose in both periods. 


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Procedure 
Check-in 
BaselineEr
ror! Reference 
source not 
found. 
Period 1 
Period 2 
Notes 
 
Day –2 
Day -1 
Day 
1 
Washout 
Day 1 Day 2 
Days 
3-4 
Day 51  
Day 2 
Days 
3-5 
Days 6-7 
AE review 
 
 
=========================X=================➔ 
 
SAE review 
===============================X==============================➔ 
 
Concomitant medications 
===============================X==============================➔ 
 
Abbreviations: AE = adverse event; D = day; ECG = electrocardiogram; PK = pharmacokinetic; SAE = serious adverse event.  
1 
Baseline assessments will be collected on Day -1 before Period 1.  
2 
Evaluations scheduled for Day 5 in Period 2 will also be performed for participants who discontinue early. 
3 
Review and approval prior to dosing on Day 1 of Periods 1, 2 and 3. 
 
• The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data review 
(e.g., to obtain data closer to the time of peak plasma concentrations) to ensure appropriate monitoring.  
• Any changes in the timing of time points for any planned study assessments as the result of emerging PK data from this study must be 
documented and approved by the relevant study team member and then archived in the sponsor and site study files but will not 
constitute a protocol amendment.  
• The Institutional Review Board (IRB) or Independent Ethics Committee (IEC) will be informed of any safety issues that constitute a 
substantial amendment and require alteration of the safety monitoring scheme or amendment of the informed consent form (ICF). The 
changes will be approved by the healthy authority and the ethics committee before implementation. 
 


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2. 
INTRODUCTION 
2.1. 
Study Rationale  
This is a Phase 1, 2-part, randomized, open-label, single-dose, crossover study to 
compare the relative bioavailability (BA) of 2 fixed-dose combination (FDCs) of 
GSK3640254 and Dolutegravir (DTG) with GSK3640254 and DTG administered 
together as single agents. Data from this study will inform formulation decisions for 
future clinical studies. 
In addition, this study will investigate the effect of food on the pharmacokinetics (PK) of 
the selected FDC of GSK3640254 + DTG. Most GSK3640254 completed clinical studies 
to date have been conducted with moderate fat and calorie meal. This study will 
investigate the effect of a high fat and calorie meal on the PK, safety, and tolerability of 
the FDC of GSK3640254 + DTG, in comparison with administration under fasting 
conditions. 
2.2. 
Background 
An FDC of GSK3640254 + DTG is being developed for the treatment of patients with 
human immunodeficiency virus (HIV-1). 
Fixed-dose combinations have greatly simplified the treatment of patients with HIV. The 
promise of improved adherence is important; FDCs potentially allow simplification of 
dosing and can reduce pill burden. Adherence to therapy is essential to achieve viral 
suppression and prevent emergence of resistance mutations. Among regimens of 
comparable efficacy, physicians and HIV-1-infected patients who receive antiretroviral 
therapy rate total pill burden, dosing frequency, and safety concerns among the greatest 
obstacles to achieving adherence. Drug resistant virus eventually emerges in most 
patients who struggle with consistent adherence. Thus, an FDC of GSK3640254 + DTG 
may improve adherence, achieve/maintain virologic suppression and prevent drug 
resistance. 
2.2.1. 
Key Safety Data with a Prior Maturation Inhibitor (GSK3532795) 
GSK3640254 is a next-generation HIV-1 maturation inhibitor (MI); this novel class of 
anti-HIV-1 medicines prevents the maturation of HIV-1 virions by binding near a key 
structural element within the Gag polyprotein that is required for virion maturation and 
assembly. Laboratory studies confirm that GSK3640254 is an MI with a mechanism of 
action distinct from current anti-retroviral agents, suggesting little if any risk of 
cross-resistance to current therapeutic agents. 
Key safety data from the Week 24 primary endpoint analysis of a Phase 2b study 
(205891) of a structurally similar MI, GSK3532795, showed GSK3532795 was not 
optimal for Phase 3 development due to gastrointestinal (GI) intolerability and treatment 
emergent resistance. Specifically, a relatively higher rate of GI intolerability 
(predominately Grade 1 and 2 diarrhea in 38 to 61% of participants and abdominal pain 
in 8 to 22% of participants) and a higher rate of nucleoside reverse transcriptase inhibitor 
resistance (6.5%) with clinically significant changes in GSK3532795 susceptibility was 


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observed across all 3 GSK3532795 treatment arms [Morales-Ramirez, 2018]. Given these 
clinical and tolerability issues, ViiV Healthcare (VH) terminated Study 205891 and did 
not advance GSK3532795 into Phase 3 studies. 
Aside from mild to moderate GI intolerability, 2 serious adverse events (SAEs) occurred 
in the Phase I thorough QT study AI468044/206220 [BMS Document Control Number 
930109388] at supratherapeutic doses: 1 healthy participant had an episode of acute 
psychosis and another had suicidal ideation/homicidal ideation as diagnosed through an 
interview by a psychiatrist. The 2 participants received 240 mg of GSK3532795 twice 
daily and 240 mg once daily with food, respectively. These events were assessed as 
related to study drug but were not observed in any other clinical study with 
GSK3532795. The most frequent neuropsychiatric adverse events (AEs) in studies with 
GSK3532795 were headache, dizziness, and sleep abnormalities (e.g., insomnia and 
abnormal dreams). Neither of these GI or psychiatric safety findings have been 
reproduced in the completed or ongoing clinical trials of GSK3640254 in healthy 
participants or treatment-naïve participants living with HIV-1. 
2.2.2. 
Key Clinical Data on GSK3640254 to date 
A summary of safety data from the completed clinical studies performed to date is 
summarized here. Note, data from the Phase 2a POC study is preliminary and 
unvalidated. Prior to a formal report being made available, key findings from this trial are 
included below and in the dose justification in Section 4.3. 
• No deaths or treatment-related SAEs have been reported during clinical studies 
with GSK3640254. 
• Treatment-related dermatologic AEs (including AEs leading to study 
discontinuation) included rash, drug eruption, pruritis, urticaria, and 
maculopapular rash. AEs of uticaria and maculopapular rash led to 
discontinuation. 
• Treatment emergent drug-related Grade 2-4 AEs included: 1) Headache (2 
participants both Grade 2; 1 participant in Studies 207187 and 208132, each), 2) 
Nausea (2 participants both Grade 2; 1 participant in Studies 208134 and 208132, 
each), and Abdominal Pain (1 participant with Grade 2 AE in Study 208132). 
• Clinically notable AEs of elevated transaminases occurred in Studies 207187 
(SAD/MAD, n = 1 healthy volunteer) and 208135 (DDI with oral contraceptive 
Portia® [Ethinyl Estradiol and Levongestrel], n = 8 healthy volunteers). 
Subsequent analysis in Study 208135 showed no PK/PD relationship with either 
GSK3640254 or Portia® and elevated transaminases. The elevated transaminases 
were likely due to the recent initiation of hormonal contraception in study 
participants. 
• Treatment-related AEs reported in more than 1 study included headache (Studies 
207187, 208131, and 208132) and nausea (Studies 207187 and 208132). 


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• Across trials, the most common AEs regardless of grade, relationship, 
concomitant medication administration were: headache (11.9%), contact 
dermatitis and related events (7.8%), diarrhea (5.5%), and abdominal pain (4.1%). 
• Across studies, low grade GI intolerability have been observed: the majority were 
mild. Both Studies 207187 (MAD) and 208312 (POC) are relevant to this study 
given dosing of 7-14 days; most AEs in 207187 were unrelated and most AEs in 
208132 were related. 
• Across studies, there were generally no clinically significant changes in vital sign 
measurements, ECG results, or safety laboratory parameters (other than the 
elevated transaminases due to Portia®, noted above). Specifically, no participant 
has demonstrated QT prolongation: absolute value >500 msec, or increase from 
baseline >60 msec. 
A comprehensive description of other clinical data of GSK3640254 can be found in 
Section 5 of the clinical investigator’s brochure (CIB) [GSK Document Number 
2018N379610_02] and the supporting clinical study reports (available upon request). 
2.2.3. 
Dolutegravir 
Dolutegravir is a potent dual cation binding integrase strand transfer inhibitor, exhibiting 
rapid reduction in HIV-1 RNA, reasonable efficacy, and a high barrier to resistance. In 
addition, due to its mechanism of metabolism, DTG lacks many of the frequent drug 
interactions associated with other medications commonly taken by people living with 
HIV. To date, the efficacy, PK, safety, and drug interaction potential of DTG has been 
evaluated in an extensive program of Phase 1 to 3b clinical trials and can be found in the 
CIB. [GSK Document Number RM2007/00683/14]. 
Dolutegravir 50 mg tablet is currently approved for marketing in more than 90 countries 
and in the European Union. Dolutegravir-based regimens have been shown to be a highly 
effective treatment option for individuals with HIV infection. Dolutegravir50 mg once 
daily was effective for treatment-naïve and treatment-experienced (integrase 
inhibitor-naïve) adults [Raffi, 2013; Walmsley, 2013; Clotet, 2014; Buzzi, 2017]. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of DTG is 
provided in the CIB [GSK Document Number RM2007/00683/14] and prescribing 
information [Tivicay, 2020]. 
2.2.4. 
Drug interaction Potential with GSK3640254 and Dolutegravir 
GSK3640254 has not shown any clinically meaningful impact on the steady state PK of 
DTG in healthy participants under fed conditions nor has DTG shown any clinically 
meaningful impact on the steady state PK of GSK3640254 (Study 209712). In addition, 
no major tolerability findings (including AEs, vital signs, ECG findings, or laboratory 
values) were noted when GSK3640254 was given in combination with DTG. 
GSK3640254 can be administered with DTG without any dose adjustments. 


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2.3. 
Benefit/Risk Assessment 
Based upon preclinical and clinical studies (including the prior MI GSK3532795), the 
potential risks for GSK3640254 are GI intolerability (e.g., abdominal pain and diarrhea) 
and gastric toxicity (effects on parietal cell and chief cells), prolongation of the QT 
interval (QT), neuropsychiatric safety, and skin and subcutaneous tissue disorders. 
Gastrointestinal intolerability and gastric toxicity (e.g., single-cell parietal cell necrosis) 
will be assessed using clinical monitoring. Gastric toxicity is not expected following 
single doses of GSK3640254. 
Prolongation of the QT interval is a potential risk. One preclinical study showed 1 dog 
with an increased QTc interval when given a single dose of GSK3640254. A 
cardiodynamic analysis of healthy participants in Study 207187 (SAD/MAD) was 
conducted. A final model from the MAD data showed a QT effect (∆ΔQTcF) of 
GSK3640254 could be predicted to be 5.38 msec (90% CI: 1.66 to 9.10) and 6.70 msec 
(90% CI: 2.79 to 10.61) for the 200 mg (1779 ng/mL) and 320 mg (2154 ng/mL) doses 
(administered with a moderate fat and calorie meal), respectively, on Day 14 (the top 
2 doses in the study). Based on this concentration-QTc analysis, a QTcF effect above 
10 msec could be excluded up to GSK3640254 plasma concentrations of approximately 
2000 ng/mL (corresponding to doses approximately 200 mg once daily). Importantly, in 
GSK3640254 clinical studies to date, there have been no abnormal clinically significant 
arrhythmias, and no participants met the trial based QTc stopping criteria for QTcF 
prolongations: values >500 msec or increases >60 msec from baseline. This study 
contains specific cardiac exclusion criteria (Section 5.2), has ECG monitoring (at Tmax) 
(Section 1.3), and has QTcF based stopping criteria (Section 7.1.2). 
Based on the risk of psychiatric events seen with another MI GSK3532795, (see 
Section 2.2.1) the protocol will exclude potential participants with any significant 
pre-existing psychiatric condition or clinical assessment of suicidality based upon the 
Columbia Suicide Severity Rating Scale (C-SSRS). Participants will also be required to 
provide response to the C-SSRS during the on-treatment portion of the study and will be 
clinically evaluated for suicidality as indicated (See Section 7.1.4).  
Across clinical studies in participants living with HIV-1 and healthy participants, skin 
and subcutaneous tissue disorders have been observed (in some cases leading to 
discontinuation). Participants will be followed regularly for the development of AEs and 
will undergo physical examinations throughout the study. 
To ensure the overall safety of participants (including, but not limited to, the risk of GI 
intolerability/reversible gastric toxicity, QT prolongation, skin and subcutaneous tissue 
disorders, and neuropsychiatric safety), this clinical study will include healthy adult 
participants. 
More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of GSK3640254 may be found in the CIB [GSK Document 
Number 2018N379610_02]. 
 


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2.3.1. 
Risk Assessment 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product GSK3640254 
Cardiovascular (QT 
prolongation)  
Non-clinically, GSK3640254 inhibited cardiac hERG/IKr potassium, 
cardiac SCN5A sodium and L‑type calcium channel currents 
recorded from HEK 293 cells stably transfected with 
complementary DNA from the ion channels. In a single-dose safety 
pharmacology study in telemeterized dogs, increases in the QT 
interval (up to 20 msec) occurred primarily in 1 dog given 
17 mg/kg. There were no GSK3640254-related effects on ECG 
parameters in dogs given up to 25 mg/kg/day for up to 39 weeks. 
As described earlier, in Study 207187 (MAD) the 
concentration-QTc analysis, a QTcF effect above 10 msec could 
be excluded up to GSK3640254 plasma concentrations of 
approximately 2000 ng/mL (corresponding to doses approximately 
200 mg QD). Importantly, in GSK3640254 clinical trials to date, 
there have been no abnormal clinically significant arrhythmias and 
no participants have met the study-based stopping criteria for 
QTcF prolongations: values >500 msec or increases of >60 msec 
from baseline. 
Protocol exclusion criteria based on screening ECG parameters 
and cardiac medical history (see Section 5.2). 
Participants will have regular ECG monitoring during the course 
of the study (see Section 1.3) with QTc stopping criteria (see 
Section 7.1.2). 
As noted in Section 7.1.2, if a clinically significant finding is 
identified (including but not limited to changes from baseline in 
QT interval corrected using Fridericia’s formula [QTcF]) after 
enrollment, the investigator or qualified designee will determine if 
the participant meets QTc stopping criteria, and if any change in 
participant management is needed. This review of the ECG 
printed at the time of collection must be documented. Any new 
clinically relevant finding should be reported (at minimum) as an 
AE. 
GI intolerability 
Non-clinically, signs of gastrointestinal intolerability (sporadic 
vomiting and abnormal faeces beginning on Day 1 and continuing 
throughout the dosing periods) occurred mainly in dogs at 
≥1 mg/kg/day. In humans, GI intolerability (predominately 
abdominal pain and diarrhea) was seen with a structurally related 
compound GSK3532795 which was evaluated through Phase 2b 
dosing. 
While summarized in detail in the CIB, the rates of all GI AEs (all 
Grade 1 regardless of relationship) in the MAD portion of Study 
Protocol exclusion criterion based on pre-existing GI pathology or 
baseline GI signs/symptoms (see Section 5.2). 
Participants will undergo continuous evaluation for AEs during 
their participation in the trial; there are clinical stopping criteria 
based upon intensity of treatment-emergent AEs (see 
Section 7.1). Additionally, a GI intolerability evaluation and 
monitoring plan is available to guide the investigator should GI 
AEs emerge (see Section 8.2.7). 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
207187 (Phase 1 FTIH) were 33%, 0%, 24%, and 29% in 
participants who received GSK3640254 50, 100, 200, and 320 mg 
daily for 14 days (the only completed study with the greatest 
duration and dose of dosing), respectively (relative to a rate of 21% 
in participants who received placebo). 
. 
Gastric toxicity 
 
Gastric toxicity effects on parietal cells and/or chief cells 
associated with changes in serum gastrin levels were present in 
preclinical species. These findings were reversible. 
 
It is unclear if gastric toxicity occurs in humans; and if present 
what the histopathological findings are (whether they correlate 
with AEs, biomarkers, etc). There is no clinical approach for 
evaluating gastric toxicity in this study. 
 
Neurologic/psychiatric 
safety 
Two psychiatric SAEs in the previous MI GSK3532795 clinical 
program (acute psychosis and homicidal/suicidal ideation) at 
supratherapeutic doses were seen in healthy participants in the 
TQT study. 
From a neurologic and psychiatric AE summary and 
PK/pharmacodynamic analysis for GSK3532795 across all studies, 
mild Grade 1 headache and Grade 1 sleep abnormalities were the 
predominant AEs, with a trend for increasing neurologic and 
psychiatric AEs with increasing dose (based on TQT and Phase 2b 
studies). No exposure-response relationship was seen for select 
neurologic and psychiatric AEs (based on TQT and Phase 2b 
studies). Central nervous system penetration data for 
GSK3532795 and GSK3640254 in rats demonstrated a similarly 
low brain distribution/penetration. 
While summarized in the CIB, the rates of all nervous system and 
psychiatric AEs in the MAD (Study 207187 FTIH) ranged from 
Screening: Protocol exclusion criterion based on any pre-existing 
psychiatric condition (including results of psychological 
assessment) for participants. Participants will have a clinician (or 
qualified designee) administered C-SSRS and will be included 
given no positive (abnormal) response (Section 5.2). 
Protocol exclusion criterion based on any pre-existing psychiatric 
condition (including results of psychological assessment and the 
C-SSRS tool) in participants. 
Continuous evaluation for AEs during their participation in the trial 
including direct AE inquiry as noted in Section 1.3. 
Participants will also provide responses to the C-SSRS 
throughout the study. Ultimately, in the event of a new onset 
suicidality ideation or behavior, as determined by the investigator 
(in consultation with psychiatry, as needed), the participant will 
discontinue from the trial and the investigator will arrange for 
urgent specialist psychiatric evaluation and management. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
24 to 57% and 0 to 17%, respectively, across doses (50 to 320 mg 
for 14 days) without any trend. 
No GSK3640254 clinical trial has observed SAEs of acute 
psychosis or homicidal/suicidal ideation.  
Guidance for the management of emergent psychiatric symptoms 
are available (see Section 8.2.6). 
There are clinical stopping criteria based upon intensity of 
treatment-emergent psychiatric AEs (see Section 7.1). 
Skin and subcutaneous 
tissue disorders 
Across clinical trials, AEs leading to discontinuation have included 
urticaria and maculopapular rash. 
Participants with a history of drug or other allergy that, in the 
opinion of the investigator or medical monitor, contraindicates 
their participation are excluded. Participants will undergo 
continuous evaluation for AEs during their participation in the 
study supplemented by the use of physical examinations. 
Protocol includes individual participant stopping criteria, including: 
• 
Any Grade 3 or higher rash or Grade 2 rash with 
evidence of systemic involvement. 
• 
Any allergic or hypersensitivity reactions (Section 7.1.3) 
Dolutegravir 
Refer to the full prescribing information for additional information on TIVICAY (DTG) 
Hypersensitivity and 
rash 
Hypersensitivity rash has been observed uncommonly with DTG. 
Rash was commonly reported in DTG Phase 2b and 3 clinical 
studies; episodes were generally mild to moderate in intensity; no 
episodes of severe rash, such as Stevens-Johnson Syndrome, 
toxic epidermal necrolysis, and erythema multiforme were 
reported. 
Participants with a history of drug or other allergy that, in the 
opinion of the investigator or medical monitor, contraindicates 
their participation are excluded. 
Rash and hypersensitivity evaluation criteria are provided in 
Section 7.1.1. See Section 7.1 for discontinuation of study 
intervention. 
The participant ICF includes information on this risk and the 
actions participants should take in the event of a hypersensitivity 
reaction or associated signs and symptoms. 
Drug induced liver 
injury (DILI) and other 
Non-clinical data suggested a possible, albeit low, risk for 
hepatobiliary toxicity with DTG. Drug-related hepatitis is considered 
Participants meeting either of the following criteria during the 
screening period are excluded from participating (Section 5.2). 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
clinically significant 
liver chemistry 
elevations 
an uncommon risk for ART containing DTG regardless of dose or 
treatment population. For participants with hepatitis B virus and/or 
hepatitis C virus co-infection, improvements in immunosuppression 
as a result of HIV virologic and immunologic responses to 
DTG-containing ART, along with inadequate therapy for hepatitis B 
virus co-infected participants, likely contributed to significant 
elevations in liver chemistries. A review of postmarketing data 
found that the number of cases reporting particularly severe liver 
dysfunction was found to be very low in the context of exposure to 
DTG and DTG/abacavir/lamivudine. The reported cases of severe 
liver dysfunction (including acute hepatic failure) are complex with 
potential confounding factors but in a very small number of cases, 
drug-induced liver injury is likely and the role of DTG-containing 
regimens cannot be ruled out particularly in those involving DTG. 
• 
ALT 1.5 × the ULN (isolated bilirubin >1.5 × ULN is 
acceptable if bilirubin is fractionated and direct bilirubin 
35%). 
• 
Positive for HBV (+HBsAg) or positive HCV (positive hepatitis 
C antibody test) within 3 months of Day 1 of Period 1. 
Specific/detailed liver chemistry stopping criteria are provided 
(Section 7.1.1). 
Theoretical serious 
drug interaction with 
dofetilide 
Co-administration of DTG may increase dofetilide plasma 
concentration via inhibition of organic cation transporter 2 
transporter, resulting in potentially life-threatening toxicity. 
Concomitant medications (e.g., dofetilide) are prohibited in the 
study (Section 5.2 and Section 6.8). 
Renal function 
Mild elevations of creatinine have been observed with DTG that 
are related to a benign effect on creatinine secretion with blockade 
of the octamer transcription factor-2 receptor. DTG has been 
shown to have no significant effect on glomerular filtration rate or 
effective renal plasma flow. 
Participants with a creatinine clearance <60 mL/min are excluded 
(Section 5.2). 
Increases in serum creatinine are not expected to have any 
adverse effect and will reverse during the wash out period after 
each single dosing of DTG, and; therefore, do not require 
mitigation in this protocol for DTG. 
Psychiatric disorders 
Psychiatric disorders including suicidal ideation and behaviors are 
common in people living with HIV. Events of suicidal ideation, 
attempt, behavior and completion were observed in clinical studies 
of DTG, primarily in participants with a pre-existing history of 
depression or other psychiatric illness. 
Screening: Protocol exclusion criterion based on any pre-existing 
psychiatric condition (including results of psychological 
assessment) for participants. Participants will have a clinician (or 
qualified designee) administered C-SSRS and will be included 
given no positive (abnormal) response. 
On-Treatment: Participants will undergo physical examinations 
and laboratory testing. In addition, participants will undergo 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
continuous evaluation for AEs during their participation in the 
study; there are individual clinical stopping criteria and monitoring 
based upon incidence and intensity of treatment-emergent 
psychiatric AEs (Section 7.1.5 and Section 8.2.6)  
Participants will be housed throughout study conduct to ensure 
rapid diagnosis and management of any potential event. 
Participants will also provide responses to the C-SSRS 
throughout the study. Ultimately, in the event of a new onset 
suicidality ideation or behavior, as determined by the investigator 
(in consultation with psychiatry, as needed), the participant will 
discontinue from the study and the investigator will arrange for 
urgent specialist psychiatric evaluation and management. 
Guidance for the investigator on the management of emergent 
psychiatric symptoms is available (Section 8.2.6).  
There are clinical stopping criteria based upon intensity of 
treatment-emergent psychiatric AEs (see Section 7.1). 
Neural tube defects 
In a birth outcome surveillance study in Botswana there have been 
7 cases of neural tube defects reported in 3,591 deliveries (0.19%) 
to mothers taking DTG-containing regimens from the time of 
conception, compared with 21 cases in 19,361 deliveries (0.11%) 
to mothers taking non-DTG-containing regimens from the time of 
conception (prevalence difference 0.09%; 95% CI 0.03, 0.30). 
In the same study, no increased risk of neural tube defects was 
reported in women who started DTG during pregnancy. Two out of 
4,448 deliveries (0.04%) to mothers who started DTG during 
pregnancy had a neural tube defect, compared with 5 out of 
6,748 deliveries (0.07%) to mothers who started 
non-DTG-containing regimens during pregnancy. 
Women who are pregnant will be excluded from the study 
(Section 5.1). 
Females of childbearing potential are required to have a negative 
pregnancy test at both screening and Day 1 of the study and 
agree to use one of the methods documented in Appendix 4 to 
avoid pregnancy during the study. Pregnant women will be 
withdrawn from this study and their pregnancy followed to 
determine outcome (including premature termination) and status 
of mother and child. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
A causal relationship of these events to the use of DTG has not 
been established. The incidence of neural tube defects in the 
general population ranges from 0.5 to 1 case per 1,000 live births. 
As neural tube defects occur within the first 4 weeks of fetal 
development (at which time the neural tubes are sealed) this 
potential risk would concern women exposed to DTG at the time of 
conception and in early pregnancy. 
Data analyzed to date from other sources including the 
antiretroviral pregnancy Registry, clinical trials, and post-marketing 
data are insufficient to address the risk of neural tube defects with 
DTG. 
More than 1,000 outcomes from second and third trimester 
exposure in pregnant women indicate no evidence of increased 
risk of adverse birth outcomes. 
In animal reproductive toxicity studies, no adverse development 
outcomes, including neural tube defects, were identified. 
Dolutegravir was shown to cross the placenta in animals. 
AE = adverse event; ALT = alanine aminotransferase; ART = antiretroviral therapy; AUC = area under the plasma concentration-time curve; CPK = creatinine phosphokinase; C-SSRS 
= Columbia-Suicide Severity Rating Scale; DTG = dolutegravir; ECG = electrocardiogram; FTIH = first time in human; GI = gastrointestinal; HBV = hepatitis B virus; 
HBsAg = hepatitis B virus surface antigen; HCV = hepatitis C virus; ms = millisecond; HIV = human immunodeficiency virus; PK = pharmacokinetic; QD = once daily; 
QTc = corrected QT interval; QTcF = corrected QT interval using Fridericia's formula; SAD = single ascending dose; SoA = schedule of activities; TQT = thorough QT; 
ULN = upper limit of normal. 


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2.3.2. 
Benefit Assessment 
This is a study in healthy participants and as such there is no expected benefit to 
administration of GSK3640254 or DTG. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Given the preclinical profile of GSK3640254, the clinical profile of a structurally similar 
MI (GSK3532795), the clinical data gathered from Phase 1 and 2a studies, and the 
planned clinical procedures and evaluations in this study, the potential risks to 
participants receiving GSK3640254 are low, evaluable, and manageable. 
Dolutegravir is frequently used in HIV clinical practice and has a well-characterized and 
acceptable safety profile. Given that only healthy participants will be enrolled and that 
participants will be confined to a clinical facility after dosing, the safety risk of 
participation in this study is expected to be low. To minimize risk further, the protocol 
contains exclusions relevant to the study intervention. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
Part 1 
• To assess the relative bioavailability of 
FDCs of GSK3640254 / DTG compared 
with GSK3640254 / DTG administered 
together as single agents when 
administered with a moderate fat and 
calorie meal 
Part 2 
• To assess the effect of food on the PK of 
the selected FDC of GSK3640254 / DTG 
when administered with a high fat and 
calorie meal compared to fasted 
conditions 
Parts 1 and 2 
• AUC(0-), AUC(0-t), and Cmax for 
GSK3640254 and DTG 
Secondary 
Part 1 
• To assess the safety and tolerability of 
FDCs of GSK3640254 / DTG compared 
with GSK3640254 / DTG administered 
together as single agents 
Part 2 
Parts 1 and 2 
• Safety and tolerability parameters for AEs 
or SAEs, observed and change from 
baseline clinical laboratory assessments, 
ECGs, and vital sign measurements 
 


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Objectives 
Endpoints 
• To assess the safety and tolerability of 
selected FDC of GSK3640254 / DTG 
following single oral administration to 
healthy participants under fasted or fed 
conditions  
 
 
 
AE = adverse event; AUC(0-) = area under the plasma concentration-time curve from time zero extrapolated to 
infinity; AUC(0-t) = area under the plasma concentration-time curve from time zero to time t; C24 = plasma 
concentration at 24 hours post-dose; CL/F = apparent oral clearance; Cmax = maximum observed concentration; 
DTG = dolutegravir; ECG = electrocardiogram; FDC = fixed-dose combination; PK = pharmacokinetics; 
SAE = serious adverse event; t1/2 = apparent terminal phase half-life; Tmax = time of maximum observed 
concentration. 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 1, 2-part, randomized, open-label, single-dose, crossover study in healthy 
participants to compare the relative BA of 2 FDCs of GSK3640254 /DTG , 150 mg/50 
mg with GSK3640254 / DTG, 150 mg/ 50 mg administered together as single agents 
(Part 1) and to assess the effect of food on the PK of the selected FDC of GSK3640254 / 
DTG from Part 1 (Part 2). Participants in both Part 1 and Part 2 will be screened within 
35 days before the first dose of study intervention. 
Part 1 will consist of a screening period and 3 treatment periods with a single dose of 
study intervention per treatment period. 
Part 2 will consist of a screening period and 2 treatment periods with a single dose of 
study intervention per treatment period. This will be followed by an End of Study 
analysis. 
Participants will be randomly assigned to receive treatment sequence ABC, BCA or CAB 
in 1:1:1 ratio in Part 1 and treatment sequence DE or ED in 1:1 ratio in Part 2. 
Participants will receive each of the following treatments administered as 1 treatment per 
period: 
Part 1 (Treatment Sequence ABC, BCA, or CAB): 
• Treatment A: A single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 
100 mg (1 x tablet), and DTG 50 mg (1 x tablet) administered together under 
moderate fat and calorie conditions (reference) 
• Treatment B: A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg (1 x 
monolayer tablet) FDC administered under moderate fat and calorie conditions 
• Treatment C: A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg (1 x bilayer 
tablet) FDC administered under moderate fat and calorie conditions 


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Treatments A, B, and C will be administered in the fed state. Participants will fast 
overnight for at least 10 hours prior to breakfast and will receive a moderate fat and 
calorie meal 30 minutes prior to dosing (Section 5.3.1). Participants will eat this meal in 
25 minutes or less. Dose administration will occur within 5 minutes of completion of 
meal consumption. Participants will not receive any further food until 4 hours after 
dosing. 
Part 2 (Treatment Sequence DE or ED): 
• Treatment D: A single oral dose of selected FDC from Part 1 of GSK3640254 / DTG, 
150 mg / 50 mg administered under high fat and calorie conditions 
• Treatment E: A single oral dose of selected FDC from Part 1 of GSK3640254 / DTG, 
150 mg / 50 mg administered under fasted conditions 
Treatment D will be administered in the fed state. Participants will fast overnight for at 
least 10 hours prior to breakfast and will receive a high fat and calorie meal 30 minutes 
prior to dosing (Section 5.3.1). Participants will eat this meal in 25 minutes or less. Dose 
administration will occur within 5 minutes of completion of meal consumption. 
Participants will not receive any further food until 4 hours after dosing. Treatment E will 
be administered in the fasted state. Participants will fast overnight for at least 10 hours 
prior to dosing and until 4 hours after dosing. 
In both Part 1 and Part 2, PK blood samples for the analysis of GSK3640254 and DTG 
will be collected prior to dosing (0 hour) on Day 1 and up to 96 hours post-dose in each 
period (Section 1.3). 
Safety and tolerability will be assessed by monitoring and recording of AEs and SAEs, 
clinical laboratory test results, vital sign measurements, 12-lead ECG results, and 
physical examination findings. 
Study assessments will be performed as indicated in the Schedule of Activities (SoA; 
Section 1.3). For Part 1, study participants will be confined to the clinic from Day –2 of 
Period 1 until discharge on Day 5 of Period 3. For Part 2, study participants will be 
confined to the clinic from Day –2 of Period 1 until discharge on Day 5 of Period 2.  
4.2. 
Scientific Rationale for Study Design 
This is a Phase 1, 2-part, randomized, open-label, single-dose, crossover study to 
compare the relative BA of 2 FDCs of GSK3640254 and DTG with GSK3640254 and 
DTG administered together as single agents. In addition, this study will investigate the 
effect of food on the PK of the selected FDC of GSK3640254 + DTG. 
Most GSK3640254 completed clinical studies to date have been conducted with 
moderate fat and calorie meal. Part 2 of this study will investigate the effect of high fat 
and calorie meals on the PK, safety, and tolerability of the FDC of GSK3640254 + DTG, 
in comparison with administration under fasting conditions in accordance with the Food 
and Drug Administration (FDA) guidance for industry on food-effect BA and fed 
bioequivalence [DHHS, 2002]. 


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The open-label crossover design of this study will specifically evaluate the relative BA of 
different FDC forms and for studying the effect of food on BA. Random assignment to 
treatment sequences is an attempt to prevent bias. The washout of at least 7 days between 
each dose of study intervention should eliminate the possibility of carryover of drug 
exposure from the previous dose.  
This study is participant to the appropriate regulatory and ethics committee approval and 
will be listed on the website ClinicalTrials.gov. No blinding or placebo control will be 
used, as these are not necessary for the purposes of this study. 
4.3. 
Justification for Dose 
The therapeutic dose range of GSK3640254 being studied in HIV-1 infected adults is 
100 to 200 mg (Study 208379, GSK Document Number 2019N399207_03). The dose of 
150 mg GSK3640254 was selected for this study as this is below the maximum projected 
clinically therapeutic dose of GSK3640254. The highest GSK3640254 dose given with a 
moderate fat and calorie meal was 400 mg. The high fat and calorie meal may increase 
BA compared with moderate fat and calorie meal but will be below 400 mg SD dosed 
with moderate fat and calorie meal. The FDC of 150 mg GSK3640254 + 50 mg DTG 
strength is the starting dose that is a reasonable estimate of the GSK3640254 dose, based 
on current data. Furthermore, coadministration of DTG (50 mg) and GSK3640254 
(200 mg) resulted in no clinically meaningful difference in the steady-state systemic 
exposure of GSK3640254 compared to GSK3640254 administered alone with geometric 
least squares mean ratios of 1.04, 0.991, and 0.996 for AUC(0-τ), Cmax, and Cτ, 
respectively [GSK Document Number 2019N399318_00]. The apparent terminal phase 
half-life (t1/2) of GSK3640254 was approximately 22 hours in the MAD portion of 
Study 207187 at the 200-mg dose [GSK document number 2020N430256_00]. To ensure 
adequate washout, there will be at least 7 days between each dose of study intervention, 
with an allowance window of 4 hours (i.e., 7 days minus 4 hours) to allow flexibility in 
scheduling participants for dosing at the clinic. 
The US FDA-approved dose of DTG for treatment naive HIV-infected adult and pediatric 
patients 12 years and older (and ≥40 kilogram) is 50 mg once daily. Dolutegravir has low 
to moderate interparticipant PK variability, a predictable exposure-response relationship, 
and a 14-hour plasma T1/2. Although coadministration of DTG with low-, moderate-, 
and high-fat and calorie meals in Study ING113674 [GSK Document Number 
2010N105142_00] increased DTG exposures (AUC[0-∞]) by 33%, 41%, and 66%, 
respectively, the TIVICAY® product label states that the approved dose regimen is 50 mg 
once daily taken with or without food based on efficacy and safety results of Phase 3 
studies where DTG was taken without regard to meal times. Furthermore, 
coadministration of DTG (50 mg) and GSK3640254 (200 mg) resulted in no clinically 
meaningful difference in the steady-state systemic exposure of DTG compared to DTG 
administered alone with geometric least squares mean ratios of 1.17, 1.09, and 1.24 for 
AUC(0-τ), Cmax, and Cτ, respectively [GSK Document Number 2019N399318_00]. 
Dolutegravir is available as the single entity product TIVICAY and as a component of 
other FDCs.  


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4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study or last scheduled procedure shown in the SoA (Section 1.3) for the last participant 
in the study. 
A participant is considered to have completed the study if he or she has completed all 
phases of the study including the last scheduled procedure shown in the SoA 
(Section 1.3). 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Participant must be 18 to 65 years of age inclusive, at the time of signing the 
informed consent. 
Type of Participant and Disease Characteristics 
2. Participants who are overtly healthy as determined by medical evaluation including 
medical history, physical examination, laboratory tests, and cardiac monitoring 
(history and ECG). 
Weight 
3. Body weight ≥50.0 kg (110 lbs) for males and ≥45 kg (99 lbs) for females and body 
mass index within the range 18.5 to 35.0 kg/m2 (inclusive). 
Sex and Contraceptive or Barrier Requirements 
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
4. Male or female 
a. 
Male Participants:  
i. Male participants should not engage in intercourse while confined in the 
clinic. There is no need for an extended period of double barrier use or 
prolonged abstinence after study discharge. 


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b. 
Female Participants:  
i. A female participant is eligible to participate if she is not pregnant (as 
confirmed by a negative serum human chorionic gonadotrophin test), not 
lactating or breastfeeding, and at least 1 of the following conditions 
applies: 
• Is not a woman of childbearing potential (WOCBP) as defined in 
Appendix 4. 
OR 
• Is a WOCBP and using a nonhormonal contraceptive method that is 
highly effective, with a failure rate of <1%, as described in Appendix 
4, for 30 days before study intervention, during the treatment periods, 
and for at least 28 days after the last dose of study intervention and 
completion of the follow up visit. The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first 
dose of study intervention. 
ii. A WOCBP must have a negative highly sensitive serum 
pregnancy test (Appendix 2) at screening and check-in (Day -2). 
iii. Additional requirements for pregnancy testing during and after 
study intervention are outlined in Appendix 4. 
The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
Informed Consent 
5. Capable of giving signed informed consent as described in Appendix 1 which 
includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Current or chronic history of liver disease or known hepatic or biliary abnormalities 
(with the exception of Gilbert’s syndrome or asymptomatic gallstones). 
2. A pre-existing condition interfering with normal GI anatomy or motility 
(e.g., gastroesophageal reflux disease, gastric ulcers, gastritis) or hepatic and/or renal 
function that could interfere with the absorption, metabolism, and/or excretion of the 
study intervention or render the participant unable to take oral study intervention. 
3. Prior cholecystectomy surgery (prior appendectomy is acceptable). 
4. Clinically significant illness, including viral syndromes within 3 weeks of dosing. 


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5. A participant with known or suspected active COVID-19 infection OR contact with 
an individual with known COVID-19, within 14 days of study enrollment (World 
Health Organization [WHO] definitions in Appendix 6). 
6. Any history of significant underlying psychiatric disorder, including, but not limited 
to, schizophrenia, bipolar disorder with or without psychotic symptoms, other 
psychotic disorders, or schizotypal (personality) disorder. 
7. Any history of major depressive disorder with or without suicidal features, or anxiety 
disorders that required medical intervention (pharmacologic or not) such as 
hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient 
treatment. Participants with other conditions such as adjustment disorder or 
dysthymia that have required shorter term medical therapy (<6 months) without 
inpatient treatment and are currently well-controlled clinically or resolved may be 
considered for entry after discussion and agreement with the VH/GSK medical 
monitor. 
8. Any pre-existing physical or other psychiatric condition (including alcohol or drug 
abuse), which, in the opinion of the investigator (with or without psychiatric 
evaluation), could interfere with the participant’s ability to comply with the dosing 
schedule and protocol evaluations or which might compromise the safety of the 
participant. 
9. Medical history of cardiac arrhythmias, prior myocardial infarction in the past 
3 months, or cardiac disease or a family or personal history of long QT syndrome. 
Laboratory Assessment 
10. Presence of hepatitis B surface antigen at screening or within 3 months prior to 
starting study intervention. 
11. Positive hepatitis C antibody test result at screening or within 3 months prior to 
starting study intervention. 
12. Positive HIV-1 and -2 antigen/antibody immunoassay at screening. 
13. Alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN). A single 
repeat of ALT is allowed within a single screening period to determine eligibility. 
14. Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%). A single repeat of any laboratory 
abnormality is allowed within a single screening period to determine eligibility. 
15. Estimated serum creatinine clearance (using Chronic Kidney Disease-Epidemiology 
Collaboration equation) <60 mL/min. 
16. Any acute laboratory abnormality at screening which, in the opinion of the 
investigator or medical monitor, should preclude participation in the study of an 
investigational compound. 
17. Any Division of Aids (DAIDS) Grade 2 to 4 laboratory abnormality at screening, 
with the exception of creatine phosphokinase (CPK), lipid abnormalities (e.g., total 
cholesterol, triglycerides), and ALT (described above), will exclude a participant 
from the study unless the investigator can provide a compelling explanation for the 
laboratory result(s) and has the assent of the sponsor. A single repeat of any 


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laboratory abnormality is allowed within a single screening period to determine 
eligibility. 
18. Urine drug screen positive (showing presence of): amphetamines, barbiturates, 
cannabinoids, cocaine, or phencyclidine, or nonprescribed opiates, oxycodone, 
benzodiazepines, methadone, MDMA, methamphetamines, or tricyclic 
antidepressants at screening or before the first dose of study intervention. 
Prior or Concomitant Therapy 
19. Unable to refrain from the use of prescription (i.e., dofetilide) or nonprescription 
drugs including vitamins, herbal and dietary supplements (including St John's wort) 
within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives 
(whichever is longer) prior to the first dose of study intervention and for the duration 
of the study. (Note: Acetaminophen/paracetamol at doses of 2 grams/day and topical 
hydrocortisone cream 1% are permitted for use any time during the study.) 
20. Exposure to an experimental drug, human blood product, monoclonal antibody, or 
vaccine (which does not have emergency, conditional, or standard market 
authorization) within 28 days prior to the first dose of study treatment; 
Note: Consult with the Medical Monitor if clarification is needed. Receipt of a 
SARS-CoV-2 vaccine that has received emergency, conditional, or standard 
market authorization is allowed if the PI determines that the benefit-risk profile 
for that individual study participant is favourable.  The use of other 
investigational COVID vaccines that have not received emergency, conditional, 
or standard market authorization and are still only used in clinical trials will not 
be allowed at this time. 
21. Unwillingness to abstain from excessive consumption (defined in Section 5.3.1) of 
any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood 
oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study 
intervention(s) until the end of the study. 
Prior or Concurrent Clinical Study Experience 
22. Participation in another concurrent clinical study or prior clinical study (with the 
exception of imaging trials) prior to the first dosing day in the current study: 30 days, 
5 half-lives, or twice the duration of the biological effect of the study intervention 
(whichever is longer). 
23. Current enrollment or past participation within the last 30 days before signing of 
consent in any other clinical study involving an investigational study intervention 
(including an investigational COVID vaccine) or any other type of medical research. 
24. Prior exposure to GSK3640254 or prior intolerance to DTG in this or another clinical 
study. 
25. Where participation in the study would result in donation of blood or blood products 
in excess of 500 mL within 56 days.  


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Diagnostic assessments 
26. Any positive (abnormal) response confirmed by the investigator on a screening 
clinician- or qualified designee-administered C-SSRS. 
27. A sustained supine systolic blood pressure >140 mm Hg or <90 mm Hg or a 
supinediastolic blood pressure >95 mm Hg or <50 mm Hg at Screening or Check-in . 
Up to 2 repeats are allowed for confirmation. 
28. Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the 
past 3 months, symptomatic bradycardia, non-sustained or sustained atrial 
arrhythmias, non-sustained or sustained ventricular tachycardia, any degree of 
atrioventricular block, or conduction abnormality) which, in the opinion of the 
investigator or VH/GSK medical monitor, will interfere with the safety for the 
individual participant. 
29. Exclusion criteria for screening ECG (a single repeat is allowed for eligibility 
determination): 
Heart rate1 
<50 or >100 bpm 
PR interval 
>200 msec 
QRS interval 
>110 msec 
QTc2 
>450 msec 
1 
A heart rate from 101 to 110 beats per minute (bpm) can be rechecked by ECG or vital signs within 30 minutes to 
verify eligibility. 
2 
The QTc is the QT interval corrected for heart rate using Fridericia’s formula (QTcF). It is either machine read or 
manually over-read. The specific formula used to determine eligibility and discontinuation for an individual 
participant will be Fridericia’s formula. The investigator’s or VH/GSK medical monitor’s over-read can supersede 
that of the machine at any time. 
Other Exclusions 
30. History of regular alcohol consumption within 6 months of the study, defined as an 
average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a half 
pint (~240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits. 
31. Unable to refrain from tobacco or nicotine-containing products within 3 months prior 
to screening. 
32. History of sensitivity to any of the study interventions, or components thereof, or a 
history of drug or other allergy that, in the opinion of the investigator or medical 
monitor, contraindicates their participation. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
• Refrain from excessive consumption of red wine, grapefruit and grapefruit juice, 
Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to 
the first dose of study intervention until the end of the study. Excessive consumption 
is defined as more than 1 glass of wine or 8 oz juice or one of these fruits per day, in 
combination. 


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• Once in the clinical unit, participants will not be allowed to eat anything other than 
the food provided by the clinical unit. 
• An evening meal and/or snack, identical across each period, will be provided by the 
unit (e.g. on Day -1). 
• Participants will fast overnight for at least 10 hours prior to breakfast. 
• Room temperature water will be provided with dosing (~240 mL, 8 fluid ounces) and 
at all times except 1 hour predose through 2-hours post-dose. The full 240 mL must 
be consumed at dosing. 
• No food is allowed for at least 4 hours post-dose. 
• A standard lunch will be provided approximately 4 hours after dosing. A standard 
dinner will be served approximately 10 hours after dosing. The food content of meals 
must be identical on serial PK sampling days. 
5.3.1.1. 
Fed Conditions 
• Treatments A, B, C, and D will be administered in the fed state.  
• Participants will fast overnight for at least 10 hours prior to breakfast. 
• Treatments A, B, and C will receive a moderate fat and calorie meal. 
• The moderate fat and calorie meal will contain about 600 calories with approximately 
30% of the calories coming from fat [DHHS, 2002]. 
• Treatment D (selected from Part 1) will receive a high fat and calorie meal. 
• The high fat and calorie meal will contain about 800 to 1000 calories with 
approximately 50% of the calories coming from the fat [DHHS, 2002]. 
• Participants will start the meal 30 minutes prior to dosing. Participants will eat this 
meal in 25 minutes or less. Dose administration will occur within 5 minutes of 
completion of meal consumption. 
5.3.1.2. 
Fasted Conditions 
• Treatment E (selected from Part 1) will be administered in the fasted state. 
• Subjects must fast from all food and drink (except water) for 10 hours prior to dosing 
and until 4 hours post-dose. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
• Participants 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 
until after collection of the final PK sample. 
• Participants will abstain from alcohol for 48 hours before the start of dosing until 
after collection of the final PK sample. 
• Use of tobacco and nicotine-containing products will not be allowed from 3 months 
prior to screening until after the final follow-up visit. 


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• Participants must have a negative drug test at screening and on Day -2 and must 
abstain from recreational drug use from screening until after the final visit. 
5.3.3. 
Activity 
• Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests. Participants may participate in light 
recreational activities during studies (e.g., watching television, reading). 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently entered in the study. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, any protocol deviations and any SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may not be rescreened. 
5.5. 
Criteria for Temporarily Delaying 
Not applicable. 
6. 
STUDY INTERVENTIONS AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Interventions Administered 
In Part 1, all 3 treatments will be administered as per randomized treatment sequence. 
Based on Part 1 interim analysis, a treatment will be selected for administration in Part 2. 
Treatment 
A 
A 
B 
C 
Intervention 
Name 
GSK3640254 
DTG 
GSK3640254 / 
DTG 
(GSK4107821) 
GSK3640254 / 
DTG 
(GSK4107821) 
Type  
Drug 
Drug 
Drug 
Drug 
Dose 
Formulation 
Tablet 
Tablet 
Tablet 
Tablet 


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Treatment 
A 
A 
B 
C 
Unit Dose 
Strength(s)  
GSK3640254 
25mg, 100 mg 
 
DTG 50 mg 
GSK3640254 / 
DTG, 
150 mg/50 mg 
GSK3640254 / 
DTG,  
150 mg/50 mg 
Dosage 
Level(s) 
Single dose of 2 x 
GSK3640254 
25mg Tablets + 1 x 
GSK3640254 
100mg Tablet  
DTG 50 mg 
Single dose of 1 x 
GSK3640254 / 
DTG Tablet 
Single dose of 1 x 
GSK3640254 / 
DTG Tablet 
Administered together as a single dose 
Route of 
Administration 
Oral 
Oral 
Oral 
Oral 
Use 
Experimental 
Experimental 
Experimental 
Experimental 
IMP and NIMP 
IMP 
IMP 
IMP 
IMP 
Sourcing 
GSK3640254 
Sourced by 
Sponsor 
 
DTG Sourced 
Locally 
GSK3640254 / 
DTG Sourced by 
Sponsor 
GSK3640254 / 
DTG Sourced by 
Sponsor 
Packaging and 
Labeling 
 
Provided in bulk by 
GSK. The 
investigator will 
package in high 
density 
polyethylene 
bottles. Each bottle 
will be labeled as 
required per 
country 
requirement. 
30 tablets in a 
HDPE bottle 
labelled per 
country 
requirement 
Provided in bulk by 
GSK. The 
investigator will 
package in high 
density 
polyethylene 
bottles. Each bottle 
will be labeled as 
required per 
country 
requirement. 
Provided in bulk by 
GSK. The 
investigator will 
package in high 
density 
polyethylene 
bottles. Each bottle 
will be labeled as 
required per 
country 
requirement. 
DTG = dolutegravir; FDC = fixed-dose combination; IMP = investigational medicinal product; NIMP = non 
investigational medicinal product. 
6.2. 
Preparation/Handling/Storage/Accountability 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 


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(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study 
intervention are provided in the Study Reference Manual (SRM). 
5. Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. In the case of unintentional 
occupational exposure notify the monitor, medical monitor, and/or VH/GSK study 
contact. 
6. A Material Safety Data Sheet/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 VH/GSK. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study. Study participants will be randomly assigned to a treatment 
sequence in accordance with the randomization schedule generated by PPD prior to the 
start of the study and using validated software. 
6.4. 
Study Intervention Compliance 
• When the individual dose for a participant is prepared from a bulk supply, the 
preparation of the dose will be confirmed by a second member of the study site staff.  
• When participants are dosed at the site, they will receive study intervention directly 
from the investigator or designee, under medical supervision. The date and time of 
each dose administered in the clinic will be recorded in the source documents. The 
dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering 
the study intervention. Study site staff will examine each participant’s mouth to 
ensure that the study intervention was ingested. 
6.5. 
Dose Modification 
Not applicable. 
6.6. 
Continued Access to Study Intervention after the End of the 
Study 
Participants will not receive any additional treatment from VH/GSK or with 
GSK3640254 or DTG after the completion of the study because only healthy participants 
are eligible for study participation. 


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6.7. 
Treatment of Overdose 
For this study, any dose of GSK3640254 or DTG greater than the planned dose within a 
24-hour time period (±2 hours) will be considered an overdose. 
VH/GSK does not recommend specific treatment for an overdose. The investigator will 
use clinical judgment to treat an overdose. 
In the event of an overdose, the investigator should: 
1. Contact the medical monitor immediately. 
2. Closely monitor the participant for AE or SAE and laboratory abnormalities until 
GSK3640254 or DTG can no longer be detected systemically (at least 5 days). 
3. Obtain a plasma sample for PK analysis immediately and through 7 days after the 
last dose of study intervention 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 electronic case report form (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 
participant. 
6.8. 
Concomitant Therapy 
Participants must abstain from taking prescription (i.e. dofetilide) or non-prescription 
drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 
7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is 
longer) before the start of study intervention until completion of the follow-up visit, 
unless, in the opinion of the investigator and sponsor, the medication will not interfere 
with the study. 
Acetaminophen/paracetamol, at doses of ≤2 grams/day and topical hydrocortisone cream 
1% are permitted for use any time during the study and their use should be documented in 
the eCRF. Other medications are not permitted without prior discussion with the 
VH/GSK medical monitor. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention. If study intervention is permanently discontinued, the participant will 
remain in the study to be evaluated for safety. See the SoA (Section 1.3) for data to be 
collected at the time of discontinuation of study intervention and follow-up and for any 
further evaluations that need to be completed. 


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7.1.4. 
Columbia-Suicide Severity Rating Scale Criteria 
Emergence of any positive (abnormal) response confirmed by the investigator on a 
clinician (or qualified designee) administered C-SSRS during the treatment phase of the 
study will be cause for immediate clinical assessment of suicidality (by the investigator 
or a consulting psychiatrist). Emergence of new onset suicidal ideation or a DAIDS 
Grade 3 or higher psychiatric AE will result in immediate discontinuation and urgent 
specialist psychiatric evaluation and management. 
See the SoA (Section 1.3) for data to be collected at the time of intervention 
discontinuation and follow-up and for any further evaluations that need to be completed. 
7.1.5. 
Individual Participant Laboratory Abnormality and Adverse Event 
Stopping Criteria 
Investigators should make every effort to have a discussion with the medical monitor 
before the next dose to help assess if the study intervention should be stopped.  
• Any clinically significant AE or abnormalities in vital sign measurements, laboratory 
results or ECGs deemed to require discontinuation of study intervention; however, 
participants will continue to be clinically evaluated as necessary to ensure their safety 
• DAIDS Grade 3 or higher rash or DAIDS Grade 2 rash with evidence of systemic 
involvement  
• Any allergic or hypersensitivity reactions to study intervention 
• Any DAIDS Grade 3 or higher psychiatric AE 
• New onset suicidal ideation 
• Any DAIDS Grade 3 or higher AE related to study intervention 
• Any DAIDS Grade 4 AE 
• DAIDS Grade 3 or higher laboratory abnormalities 
• A participant must permanently discontinue study intervention and be discontinued 
from the study if they have COVID-19 infection as clinically determined by the 
investigator (suspect, probable, or confirmed using the most recent version of the 
WHO case definition) (Appendix 6) or by laboratory testing. Note: if this occurs, all 
other participants within the same cohort as the participant who developed COVID-
19 infection will be discharged from the site regardless of whether or not they are 
• symptomatic. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the study at any time at his or her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, or compliance reasons. This is expected to be uncommon. 


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• A participant who is withdrawn from the study for any reason related to safety (listed 
in Section 7.1.5 or otherwise) will be continued to be followed to assess the outcome 
of the safety event that triggered discontinuation of study intervention. 
• At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted, as shown in the SoA. See SoA (Section 1.3) for data to be 
collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 
• The participant will be permanently discontinued both from the study intervention 
and from the study at that time. 
• If the participant withdraws consent for disclosure of future information, the sponsor 
may retain and continue to use any data collected before such a withdrawal of 
consent. 
• If a participant withdraws from the study, he or she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site study 
records. 
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• Should the participant continue to be unreachable, he or she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.3). 
• Protocol waivers or exemptions are not allowed. 


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• Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.  
• Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA. 
• The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will not exceed 
500 mL. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
8.1. 
Efficacy Assessments 
Not applicable. 
8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations 
• A full physical examination will include, at a minimum, assessments of the skin, 
cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and 
weight will also be measured and recorded. 
• A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses.  
8.2.2. 
Vital Signs 
• Oral temperature, pulse rate, respiratory rate, and blood pressure will be assessed. 
• Blood pressure and pulse measurements will be assessed in a supine position with a 
completely automated device. Manual techniques will be used only if an automated 
device is not available. The site will follow their standard process for repeating vital 
signs, as needed. 


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• Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the participant in a quiet setting without distractions (e.g., television, cell 
phones). 
• At each time point at which triplicate measurements are required, 3 consecutive blood 
pressure and pulse readings will be recorded at intervals of at least 1 minute. Each 
measurement will be recorded in the eCRF. 
• When vital signs are scheduled at the same time as blood collections for laboratory 
assessments, vital signs are to be taken first. 
8.2.3. 
Electrocardiograms 
• Twelve-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and QTcF intervals. Refer to Section 7.1.2 for QTcF withdrawal criteria and 
additional QTcF readings that may be necessary. 
• The ECGs taken on Day -1 will be a single reading to confirm eligibility. 
• The pre-dose time point ECGs will generate a triplicate averaged QTcF. This pre dose 
triplicate averaged QTcF value will serve as the baseline for the applicable study 
period. 
o At each time point at which triplicate ECG are required, 3 individual ECG 
tracings should be obtained as closely as possible in succession, but no more than 
2 minutes apart. The full set of triplicates should be completed over a brief (e.g., 
5 to 10 minutes) recording period. Each measurement will be recorded in the 
eCRF. 
• Post-dose ECGs otherwise are single assessments. 
• Twelve-lead ECGs will be performed with the participant in a supine position after a 
rest of at least 10 minutes. 
8.2.4. 
Clinical Safety Laboratory Assessments 
• See Appendix 2 for the list of clinical laboratory tests to be performed and to the SoA 
(Section 1.3) for the timing and frequency.  
• The investigator must review the laboratory report, document this review, and record 
any clinically significant changes occurring during the study as an AE. The laboratory 
reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the participant’s 
condition. 
• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 7 days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered significantly abnormal by the investigator or medical monitor.  


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o If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
• All protocol-required laboratory tests, as defined in Appendix 2, must be conducted in 
accordance with the laboratory manual and the SoA (Section 1.3). 
8.2.5. 
Pregnancy Testing 
• Refer to Section 5.1 for pregnancy testing entry criteria. 
• Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the absence 
of pregnancy at any time during the participant’s participation in the study. 
8.2.6. 
Suicidal Ideation and Behaviour Risk Monitoring 
GSK3640254 is not a central nervous system active drug nor is it being developed for a 
neurologic or psychiatric condition. However, given the risk of suicidal ideation 
identified with a previous MI compound, GSK3532795, all participants will undergo 
screening using the C-SSRS administered by a clinician (or qualified designee); any 
positive (abnormal) response confirmed by the investigator will exclude them from 
participating. A repeat assessment will be done during the treatment phase of the study. 
In case of positive (abnormal) response confirmed by the investigator, the participant will 
undergo immediate clinical assessment of suicidality (by the investigator or a consulting 
psychiatrist). Emergence of new onset suicidal ideation or a DAIDS Grade 3 or higher 
psychiatric AE will result in immediate discontinuation and urgent specialist psychiatric 
evaluation and management. 
The definitions of behavioral suicidal events used in this scale are based on those used in 
the Columbia-Suicide History Form [Posner, 2007]. Questions are asked on suicidal 
behavior, suicidal ideation, and intensity of ideation. Screening visit questions will be in 
relation to lifetime experiences and current experiences (within the past 2 months) and all 
subsequent questioning in relation to the last assessment. 
Emergent non-suicidal psychiatric AE evaluation and management: 
• Any DAIDS Grade 1 or 2 psychiatric AE: A DAIDS Grade 1 or 2 psychiatric AE 
may result in additional unscheduled visits (in-clinic or at home) as clinically 
indicated. This may include a more in-depth assessment of the AE through interview, 
additional unscheduled clinical laboratory tests, and/or imaging. Psychiatric 
consultation may be required at the discretion of the investigator. Any 
pharmacotherapy should be discussed with the medical monitor. 
• Any DAIDS Grade 3 or 4 psychiatric AE: As described in Section 7.1.5, a DAIDS 
Grade 3 or 4 psychiatric AE will result in discontinuation from the study and 
emergency psychiatric evaluation (including potential hospitalization and 
pharmacotherapy as indicated). 


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8.2.7. 
Gastrointestinal Intolerability Evaluation and Monitoring Plan 
(with Stopping Criteria) 
Preclinical toxicology studies in animals have suggested a potential for GI-related 
toxicity with GSK3640254. Prior clinical studies have not evaluated for the presence of 
gastric toxicity in humans. Thus, it is unclear if any of the GI AEs observed in any 
clinical studies were representative of, associated with, or resulted from gastric toxicity 
(if present). Thus, in a clinically conservative fashion this section provides general 
guidance to the investigator on the evaluation and management of primarily upper GI 
symptoms (Table 1). The investigator may contact the VH/GSK medical monitor to 
discuss evaluation and management (including discontinuation of a participant) of any GI 
symptoms throughout the study. 
For any DAIDS Grade 4 or related DAIDS Grade 3 AE, the investigator will discontinue 
the participant from the study and may perform an evaluation/management plan 
incorporating the elements in Table 1. 
Table 1 
Gastrointestinal Toxicity Evaluation and Management 
HISTORY 
For symptoms of all grades, a thorough history forms the foundation of 
proper evaluation and management. The following are potential 
manifestations of some GI clinical syndromes that may occur (possibly 
in combination) during the clinical study.  
Abdominal Pain 
The investigator should obtain information on chronology, location, 
intensity/character, aggravating and alleviating factors, and associated 
symptoms in the context of the participants relevant past medical history 
[Millham, 2016]. With chronic symptoms, factors suggestive of an organic 
process include: fever, night sweats, loss of appetite, weight loss, and 
nocturnal awakening [Yarze, 2016]. The historical and physical examination 
should be efficient and lead to an accurate diagnosis soon after presentation. 
Nausea and Vomiting 
The investigator should attempt to identify the etiology of these symptoms (and 
whether it is intraperitoneal, extraperitoneal, medication related, infection 
related, or due to a metabolic disorder [Hasler, 2012]). Medications can cause 
nausea and vomiting acutely.  
Dyspepsia 
The investigator should identify the presence of red flags (odynophagia, 
unexplained weight loss, recurrent vomiting, GI bleeding, jaundice, palpable 
mass or adenopathy, or family history of GI malignancy). Symptoms of 
dyspepsia could include early satiety, bloating, or belching. Additionally, 
atypical symptoms of dyspepsia could include pharyngitis, asthma, bronchitis, 
hoarseness, chest pain, or abdominal pain.  
Diarrhea 
Similar to other GI symptoms, important historical assessment includes 
duration, onset, pattern, epidemiology (e.g. travel and diet), aggravating or 
iatrogenic factors, alleviating factors, stool appearance, presence of other 
symptoms (e.g. abdominal pain), or weight loss. The differential can be 
narrowed if there are clear watery, inflammatory, or fatty manifestations 
[Schiller, 2016]. 
Other Clinical 
Syndromes 
Additional diagnostic criteria for other GI disorders potentially encountered in 
the clinical study are available elsewhere [Rome Foundation 2019]. 
PHYSICAL 
EXAMINATION 
Physical examination should complement elements obtained from the 
history [Hasler 2012]. The examination elements may include: 
auscultation for bowel sounds (up to 2 minutes if necessary) and 


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palpation (including assessment for rebound, guarding, and muscular 
rigidity) [Millham, 2016]. Acutely, the investigator may assess for signs 
of intravascular volume depletion (e.g., orthostasis) and/or aspiration of 
vomitus as appropriate. Abdominal tenderness and guarding may 
indicate inflammation. The presence of fecal blood can indicate mucosal 
damage (e.g., from an ulcer). Complete evaluation of dyspepsia should 
include an oral examination (poor dentition or pharyngeal erythema) and 
lungs for wheezing.  
DIAGNOSTIC 
EVALUATION AND 
MANAGEMENT 
A major goal in the diagnostic evaluation of a participant with upper GI 
symptoms is to quickly arrive at a final diagnosis without exposing the 
participant to unnecessary (invasive) testing; investigators should 
exercise good clinical judgment in this regard [Soll, 2009]. A major goal 
of therapy is directed at correcting the underlying identifiable medical or 
surgical abnormalities (e.g., preformation or infarction) 
[Malagelada, 2016]. Consultation (e.g., gastroenterologist) is 
recommended as clinically indicated. Emergent action should be taken 
as necessary: correction of hypovolemia or electrolyte abnormalities. 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.


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• All SAEs will be recorded and reported to the sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• Investigators are not obligated to actively seek information on AEs or SAEs after the 
conclusion of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, 
and he or she considers the event to be reasonably related to the study intervention or 
study participation, the investigator must promptly notify the sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and non-serious AEs of special 
interest (as defined in Section 8.3.6)], will be followed until the event is resolved, 
stabilized, otherwise explained, or the participant is lost to follow-up (as defined in 
Section 7.3). Further information on follow-up procedures is given in Appendix 3. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met.  
• The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB/IEC, and investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
• An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the CIB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
8.3.5. 
Pregnancy 
• Details of all pregnancies in female participants and, if indicated, female partners of 
male participants will be collected after the start of study intervention and through the 
end of pregnancy. 


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• If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to VH/GSK within 24 hours of learning of the female 
participant or female partner of male participant (after obtaining the necessary signed 
informed consent from the female partner) pregnancy. While pregnancy itself is not 
considered to be an AE or SAE, any pregnancy complication or elective termination 
of a pregnancy for medical reasons will be reported as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• The participant/pregnant female partner will be followed to determine the outcome of 
the pregnancy. The investigator will collect follow-up information on the 
participant/pregnant female partner and the neonate and the information will be 
forwarded to the sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.3.4. While the investigator is not obligated to actively seek this information 
in former study participants/pregnant female partner, he or she may learn of an SAE 
through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention or be withdrawn from the study. 
8.3.6. 
Adverse Events of Special Interest 
Adverse events of special interest include all AEs classified in the cardiovascular (per the 
Medical Dictionary for Regulatory Activities) system organ class, seizure, and syncope. 
Additional AEs of special interest within other system organ classes (e.g., GI, neurologic, 
or psychiatric and skin disorders) may be defined in the reporting and analysis plan. 
8.4. 
Pharmacokinetics 
• Whole blood samples of approximately 4 mL will be collected for measurement of 
plasma concentrations of GSK3640254 and DTG as specified in the SoA 
(Section 1.3). 
• A maximum of 10 samples may be collected at additional time points during the 
study if warranted and agreed upon between the investigator and the sponsor. 
• Instructions for the collection and handling of biological samples will be provided by 
the sponsor. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• Samples will be used to evaluate the PK of GSK3640254 and DTG. Samples 
collected for analyses of plasma concentration may also be used to evaluate safety or 
efficacy aspects related to concerns arising during or after the study. 
8.5. 
Genetics 
Genetics are not evaluated in this study. 


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8.6. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.7. 
Immunogenicity Assessments 
Immunogenicity is not evaluated in the study. 
8.8. 
Medical Resource Utilization and Health Economics 
Medical resource utilization and health economics parameters are not evaluated in this 
study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
There is no formal hypothesis that will be statistically tested in this study. 
9.2. 
Sample Size Determination 
As there is no formal research hypothesis being statistically tested in this study, the 
sample size was not selected based on statistical considerations but determined using 
feasibility. For each part, approximately 18 participants will be enrolled to ensure that 
14 evaluable participants complete the study. If participants prematurely discontinue the 
study, additional participants may be enrolled after consultation with the sponsor to 
ensure that the required number of evaluable participants complete the study. 
Note: "Enrolled" means a participant's, or their legally acceptable representative’s, 
agreement has been obtained to participate in a clinical study following completion of the 
informed consent process and screening. Potential participants who are screened for the 
purpose of determining eligibility for the study, but do not participate in the study, are not 
considered enrolled, unless otherwise specified by the protocol.  
9.2.1. 
Sample Size Assumptions 
Based on the results from a previous study ING113674 the intersubject coefficient of 
variation (CVb) for DTG was 27-34% and 30-35%, respectively, for AUC(0-∞) and 
Cmax in the fasted state  and 31-35% and 19-24%, respectively in the fed state. Based on 
the results from a previous study 213567 the intersubject coefficient of variation (CVb) 
for GSK3640254 was 40.3% and 45.3%, respectively, for AUC(0-τ) and Cmax in the 
fasted state, and 42.2% and 35.6%, respectively in the fed state.  
It was assumed that intrasubject coefficient of variation (CVw) was approximately 60% 
of the calculated CVb. Thus, it was decided that a conservative CVw estimate of 21% 
would be used for the sample size calculation for DTG and 27.2% would be a 
conservative estimate to use for the sample size calculation of GSK3640254. 


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Since it was expected that coadministration of GSK3640254 and DTG would increase the 
exposure of DTG, a range for point estimate for a ratio of 1.0, 1.1, and 1.2 were explored. 
It was expected that coadministration of GSK3640254 with DTG would have no 
significant impact on the exposure of GSK3640254, thus a range for point estimate for a 
ratio of 0.9, 1.0, and 1.1 were explored. 
For DTG, with a sample size of 14, 16 and 18 evaluable participants, it was estimated 
that the precision (i.e., half-width of the 90% confidence interval [CI] on the log and ratio 
scale) and CI on the original scale for each point estimate would be as follows: 
N 
Drug 
CVw 
(%) 
Half-Width 
(log scale) 
Half-Width 
(original 
scale) 
Point Estimate 
90% CI 
14 
DTG 
21 
0.139 
0.149 
1.0 
(0.87, 1.15) 
1.1 
(0.96, 1.26) 
1.2 
(1.04, 1.38) 
16 
DTG 
21 
0.128 
0.137 
1.0 
(0.88, 1.14) 
1.1 
(0.97, 1.25) 
1.2 
(1.06, 1.36) 
18 
DTG 
21 
0.120 
0.127 
1.0 
(0.89, 1.13) 
1.1 
(0.98, 1.24) 
1.2 
(1.06, 1.35) 
 
For GSK3640254, with a sample size of 14, 16 and 18 evaluable participants, it was 
estimated that the precision (i.e., half-width of the 90% CI on the log and ratio scale) and 
CI on the original scale for each point estimate would be as follows: 
N 
Drug 
CVw 
(%) 
Half-Width 
(log scale) 
Half-Width 
(original 
scale) 
Point 
Estimate 
90% CI 
14 
GSK3640254 
27.2 
0.179 
0.196 
0.9 
(0.75, 1.08) 
1.0 
(0.84, 1.20) 
1.1 
(0.92, 1.32) 
16 
GSK3640254 
27.2 
0.166 
0.181 
0.9 
(0.76, 1.06) 
1.0 
(0.85, 1.18) 
1.1 
(0.93, 1.30) 
18 
GSK3640254 
27.2 
0.155 
0.168 
0.9 
(0.77, 1.05) 
1.0 
(0.86, 1.17) 
1.1 
(0.94, 1.28) 
 


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9.2.2. 
Sample Size Sensitivity 
For a sensitivity analysis, assuming a range of within-participant variability, a sample 
size of 14, 16 and 18 evaluable participants, it was estimated that the precision (i.e., half-
width of the 90% CI on the log and ratio scale) and CI on the original scale for each point 
estimate would be as follows: 
N 
Drug 
CVw 
(%) 
Half-Width 
(log scale) 
Half-Width 
(original 
scale) 
Point 
Estimate 
90% CI 
14 
Dolutegravir 
or 
GSK3640254 
30 
0.196 
0.217 
0.9 
(0.74, 1.09) 
1.0 
(0.82, 1.22) 
1.1 
(0.90, 1.34) 
1.2 
(0.99, 1.46) 
35 
0.228 
0.256 
0.9 
(0.72, 1.13) 
1.0 
(0.80, 1.26) 
1.1 
(0.88, 1.38) 
1.2 
(0.96, 1.51) 
16 
Dolutegravir 
or 
GSK3640254 
30 
0.182 
0.200 
0.9 
(0.75, 1.08) 
1.0 
(0.83, 1.20) 
1.1 
(0.92, 1.32) 
1.2 
(1.00, 1.44) 
35 
0.211 
0.235 
0.9 
(0.73, 1.11) 
1.0 
(0.81, 1.23) 
1.1 
(0.89, 1.36) 
1.2 
(0.97, 1.48) 
18 
Dolutegravir 
or 
GSK3640254 
30 
0.170 
0.185 
0.9 
(0.76, 1.07) 
1.0 
(0.84, 1.19) 
1.1 
(0.93, 1.30) 
1.2 
(1.01, 1.42) 
35 
0.197 
0.218 
0.9 
(0.74, 1.10) 
1.0 
(0.82, 1.22) 
1.1 
(0.90, 1.34) 
1.2 
(0.99, 1.46) 
Approximately 18 participants were planned to be treated to ensure that 14 evaluable 
participants completed the study. 


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9.3. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Population 
Description 
Screened 
All participants who sign the ICF. 
Randomized 
All participants who are randomly assigned to a treatment 
sequence. 
Safety 
All participants who receive at least 1 dose of study 
intervention. This population will be used for all demographic 
and safety summaries. 
Pharmacokinetic Concentration 
The PK Concentration Population will include all participants 
who undergo plasma PK sampling and have evaluable PK 
assay results. This population will be used for the PK 
concentration listings, summary tables, and plotting of 
concentration/time data. 
Pharmacokinetic Parameter 
The PK Parameter Population will include all participants who 
undergo plasma PK sampling and have evaluable PK 
parameters estimated. This population will be used for PK 
parameter listings, PK parameter summary tables, statistical 
analysis tables. 
9.4. 
Statistical Analyses 
The statistical analysis plan will be finalized prior to database lock and it will include a 
more technical and detailed description of the statistical analyses described in this 
section. This section is a summary of the planned statistical analyses of the most 
important endpoints including primary and key secondary endpoints. 
9.4.1. 
Pharmacokinetic Analyses 
Plasma GSK3640254 and DTG concentration-time data will be analyzed by PPD, under 
the oversight of the Clinical Pharmacology Modeling & Simulation Department within 
VH/GSK, using noncompartmental methods with Phoenix WinNonlin Version 8.0 or 
higher. Statistical analysis will be performed by PPD, under the oversight of Clinical 
Statistics, VH/GSK. Calculations will be based on the actual sampling times recorded 
during the study. 
Endpoint 
Statistical Analysis Methods 
Primary 
• The primary endpoints of this study are PK-related. The analysis for the 
primary PK endpoints will be performed for the PK Parameter 


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Endpoint 
Statistical Analysis Methods 
Population. Plasma concentrations of GSK3640254 and DTG will be 
subjected to PK analyses using noncompartmental methods. 
• Based on the individual concentration-time data the following primary 
plasma PK parameters will be estimated: 
o AUC(0-), AUC(0-t), and Cmax 
• Analysis will be performed to compare the relative BA of 2 FDCs of 
GSK3640254 and DTG with GSK3640254 and DTG administered 
together as single agents. Analyses will be performed on the natural 
logarithms of AUC(0-), AUC(0-t), and Cmax using linear mixed-effect 
models with treatment, period, and sequence as fixed effects and 
participant as a random effect. Effects will be estimated, and CIs will be 
constructed for the following treatment comparison: 
o Treatment B versus Treatment A 
o Treatment C versus Treatment A 
Point estimates and 90% CIs for treatment differences on the log scale 
derived from the model will be exponentiated to obtain estimates for 
geometric mean ratios and CIs on the original scale. 
• The effect of food (moderate fat and calorie meal) on the PK of the select 
FDC of GSK3640254 + DTG will be similarly analyzed for the following 
treatment comparisons: 
o Treatment D versus Treatment E 
• Summary statistics (arithmetic mean, geometric mean, median, standard 
deviation, minimum, maximum, and coefficient of variation) for plasma 
GSK3640254 and DTG primary PK parameter values will be 
summarized by treatment. 
Secondary 
• Based on the individual concentration-actual time data the following 
secondary plasma PK parameters will be estimated: 
o Tmax, tlag, t1/2, and CL/F 
• Summary statistics (arithmetic mean, geometric mean, median, standard 
deviation, minimum, maximum, and coefficient of variation) for plasma 
GSK3640254 and DTG secondary PK parameter values will be 
summarized by treatment.  
• Summary statistics (arithmetic mean, median, standard deviation, 
minimum, maximum, and coefficient of variation) for plasma 
GSK3640254 and DTG PK concentrations will be summarized by 
treatment using the PK Concentration Population. 


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9.4.2. 
Safety Analyses 
All safety analyses will be performed on the Safety Population.  
Safety data will be presented in tabular format and summarized descriptively according to 
VH/GSK’s Integrated Data Standards Library standards. No formal statistical analysis of 
the safety data will be conducted. 
The details of the statistical analyses of safety data will be provided in the reporting and 
analysis plan. 
9.4.3. 
Other Analysis 
Additionally, special statistical and data analysis considerations may be warranted in the 
event that COVID-19 or related epidemics or natural disasters may affect the study and 
data integrity. To the extent possible, these will be described in the main study reporting 
and analysis plan; alternatively, a separate reporting and analysis plan focusing on 
modified data handling rules (e.g., changes to analysis populations, visit windows and 
endpoints) and analyses (e.g., sensitivity analyses to assess impact of and account for 
missing data) may be prepared, taking into account applicable regulatory guidance and 
industry best practices for handling such situations [DHHS, 2002; EMA, Mar 2020; 
EMA, Apr 2020]. 
9.5. 
Interim Analysis 
There will be no formal interim analysis. An analysis is planned after completion of 
Part 1 and will inform FDC formulation to include in Part 2. Preliminary safety & PK 
data will be analyzed by PPD under the oversight of Clinical Pharmacology Modeling & 
Simulation within VH/GSK. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines 
o Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines 
o Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants.  
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), ), European Medical Device 
Regulation 2017/745 for clinical device research (if applicable), and all other 
applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 


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Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
• The investigator or his or her representative will explain the nature of the study to the 
participant or their legally authorized representative and answer all questions 
regarding the study. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
Health Insurance Portability and Accountability Act requirements (HIPAA), where 
applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study.  
• A copy of the ICF(s) must be provided to the participant or their legally authorized 
representative.  
• Participants who are rescreened are required to sign a new ICF. 
VH/GSK (alone or working with others) may use participant’s coded study data and 
samples and other information to carry out this study; understand the results of this study; 
learn more about GSK3640254 or DTG or about the study disease; publish the results of 
these research efforts; work with government agencies or insurers to have the 
GSK3640254 or DTG approved for medical use or approved for payment coverage.  
The ICF may contain a separate section that addresses the use of participant data and 
remaining samples for optional further research. The investigator or authorised designee 
will inform each participant of the possibility of further research not related to the 
study/disease. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period. A 
separate signature will be required to document a participant's agreement to allow any 
participant data and/or remaining leftover samples to be used for further research not 
related to the study/disease. Participants who decline further research will tick the 
corresponding “No” box. 
10.1.4. 
 Data Protection 
• Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable 
will not be transferred.  


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• The participant must be informed that his or her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent.  
• The participant must be informed that his or her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities.  
10.1.5. 
Committees Structure 
Not applicable. 
10.1.6. 
Dissemination of Clinical Study Data 
• Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report. The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a VH/GSK site or other 
mutually-agreeable location. 
• VH/GSK will also provide all investigators who participated in the study with a 
summary of the study results and will tell the investigators what treatment their 
participants’ received. The investigator(s) is/are encouraged to share the summary 
results with the study participants, as appropriate. 
• Under the framework of the SHARE initiative, VH/GSK intends to make anonymized 
participant-level data from this study available to external researchers for scientific 
analyses or to conduct further research that can help advance medical science or 
improve patient care. This helps ensure the data provided by study participants are 
used to maximum effect in the creation of knowledge and understanding. Requests 
for access may be made through www.clinicalstudydatarequest.com. 
• VH/GSK intends to make anonymized patient-level data from this study available to 
external researchers for scientific analyses or to conduct further research that can help 
advance medical science or improve patient care. This helps ensure the data provided 
by study participants are used to maximum effect in the creation of knowledge and 
understanding 
• A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or eCRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF.  
• Guidance on completion of eCRFs will be provided in electronic CRF Completion 
Guidelines. 


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• Quality tolerance limits (QTLs) will be pre-defined in the QTL report to identify 
systematic issues that can impact participant safety and/or reliability of study results. 
These pre-defined parameters will be monitored during and at the end of the study 
and all deviations from the QTLs and remedial actions taken will be summarized in 
the clinical study report. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• Monitoring details describing strategy including definition of study critical data items 
and processes (e.g., risk-based initiatives in operations and quality such as Risk 
Management and Mitigation Strategies and Analytical Risk-Based Monitoring), 
methods, responsibilities and requirements, including handling of noncompliance 
issues and monitoring techniques (central, remote, or on-site monitoring) are provided 
in the Monitoring Plan. 
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process including systems used can be found in the study 
Data Management Plan. 
• The sponsor assumes accountability for actions delegated to other individuals (e.g., 
Contract Research Organizations). 
• Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years from the issue of the final clinical 
study report or equivalent summary unless local regulations or institutional policies 
require a longer retention period. No records may be destroyed during the retention 
period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor.  
10.1.8. 
Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
• Definition of what constitutes source data and its origin can be found in the SRM. 
• The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
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10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first participant screened and will be the study start 
date. 
Study/Site Termination 
VH/GSK or designee reserves the right to close the study site or terminate the study at 
any time for any reason at the sole discretion of VH/GSK. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and 
study supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• Discontinuation of further study intervention development 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate or no recruitment of participants (evaluated after a reasonable amount of 
time) by the investigator 
• If the study is prematurely terminated or suspended, the sponsor shall promptly 
inform the investigators, the IECs/IRBs, the regulatory authorities, and any contract 
research organization(s) used in the study of the reason for termination or suspension, 
as specified by the applicable regulatory requirements. The investigator shall 
promptly inform the participant and should assure appropriate participant therapy 
and/or follow-up. 
10.1.10. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If this 
is foreseen, the investigator agrees to submit all manuscripts or abstracts to the 
sponsor before submission. This allows the sponsor to protect proprietary information 
and to provide comments.  
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual 


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site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
• The tests detailed in Table 2 will be performed by the local laboratory. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
• Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
Table 2 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
Red Blood Cell Indices: 
White blood cell count 
with differential: 
 
Red Blood Cell 
Count 
Mean corpuscular volume 
Neutrophils 
 
Hemoglobin 
Mean corpuscular hemoglobin  Lymphocytes 
 
Hematocrit 
 
Monocytes 
 
 
 
Eosinophils 
 
 
 
Basophils 
 
 
 
Absolute neutrophil count 
Clinical Chemistry1 
Blood urea nitrogen 
Carbon dioxide 
Total protein 
 
Creatinine 
Aspartate 
aminotransferase (AST) 
Albumin 
 
Glucose (fasting) 
ALT 
Globulin 
 
Potassium 
Gamma-glutamyl transferase 
Anion gap 
 
Sodium 
Total and direct bilirubin 
Alkaline phosphatase2 
 
Calcium 
Lactate dehydrogenase 
Uric acid 
 
Chloride 
Total cholesterol 
Creatine phosphokinase 
 
Phosphorus 
Triglycerides 
Serum lipase 
 
 
 
Serum amylase 
Routine Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, nitrite, and leukocyte esterase 
by dipstick 
• 
Microscopic examination (if blood, leukocyte esterase, or protein is abnormal) 
Pregnancy testing 
• 
Highly sensitive human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)3 


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Laboratory 
Assessments 
Parameters 
Other Screening 
Tests 
• 
Molecular test for SARS-CoV-2 (Two consecutive approved molecular tests 
[polymerase chain reaction or antigen test]. The first test should be performed 
≥7 days prior to admission and the second test will be performed on Day -2 
after admission to the clinic. 
• 
Follicle-stimulating hormone (FSH) (as needed in women of non-childbearing 
potential only) 
• 
Serology: HIV-1 and -2 antigen/antibody immunoassay, hepatitis B surface 
antigen, hepatitis C antibody 
• 
Alcohol, cotinine, and drug screen (to include at minimum amphetamines, 
barbiturates, cannabinoids, cocaine, or phencyclidine, or nonprescribed 
opiates, oxycodone, benzodiazepines, methadone, or tricyclic 
antidepressants) 
1. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 7.1 and Appendix 5. 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). 
2. 
If alkaline phosphatase is elevated, consider fractionating. 
3. 
Local urine pregnancy testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/IEC. 


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10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting 
10.3.1. 
Definition of Adverse Event 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 


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Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
10.3.2. 
Definition of Serious Adverse Event 
An SAE is defined as any serious adverse event that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
• This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 


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interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• Possible Hy’s Law case: ALT ≥3 × ULN AND total bilirubin ≥2 × ULN (>35% 
direct bilirubin) or INR >1.5 must be reported as an SAE. 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, 
intensive treatment for allergic bronchospasm, blood dyscrasias, 
convulsions, or development of intervention dependency or intervention 
abuse. 
 
10.3.3. 
Recording and Follow-Up of Adverse Events and Serious 
Adverse Events 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• The investigator will then record all relevant AE/SAE information. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to VH/GSK in lieu of completion of the VH/GSK required form. 
• There may be instances when copies of medical records for certain cases are 
requested by VH/GSK. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to VH/GSK. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
 


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Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study using the latest version of DAIDS grading table (Appendix 7) and 
assign it to 1 of the following categories:  
• Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AE and SAE can be assessed as severe. 
• Life-Threatening: Inability to perform basic self-care functions. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the CIB and/or Product Information, for marketed 
products, in his or her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he or 
she has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to VH/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 VH/GSK. 
• The investigator may change his or her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
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• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 
VH/GSK to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals. 
• If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide VH/GSK with a copy of any post-mortem 
findings including histopathology. 
• New or updated information will be recorded in the originally submitted 
documents. 
• 
The investigator will submit any updated SAE data to VH/GSK within 24 hours of 
receipt of the information. 
10.3.4. 
Reporting of Serious Adverse Events to VH/GSK 
SAE Reporting to VH/GSK via Electronic Data Collection Tool 
• The primary mechanism for reporting SAE to VH/GSK will be the electronic data 
collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• The investigator or medically-qualified sub-investigator must show evidence within 
the eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to study intervention/study participation (causality) 
within 72 hours of SAE entry into the eCRF. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the medical monitor by telephone. 
• 
Contacts for SAE reporting can be found in SRM. 
 


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


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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming post-menopausal unless permanently 
sterile (see below) 
Notes: 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with more than one FSH measurement 
(>40 IU/L or mIU/mL) is required.  
o Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 


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10.4.2. 
Contraception Guidance: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsa That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
• Intrauterine device 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a to medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole 
sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used. Spermatogenesis cycle 
is approximately 90 days. 
Note: documentation of azoospermia for a male participant can come from the site 
personnel’s review of the participant’s medical records, medical examination, or medical 
history interview.. 
Highly Effective Methodsa That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly. 
• Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Male condom 
and female condom should not be used together (due to risk of failure from friction). 


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10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments 
Liver Chemistry Stopping Criteria  
 
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  
Actions 
Follow-up Assessments 
• Immediately discontinue study intervention 
• Report the event to VH/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 participant 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 INR) 
and perform liver event follow-up 
assessments within 24 hours 
• Monitor participant 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 INR) 
and perform liver event follow-up 
• Viral hepatitis serology3 
• Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminase values show downward 
trend 
• Obtain blood sample for PK analysis, 
obtained within 48 hours 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 eCRF 
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 


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Liver Chemistry Stopping Criteria  
assessments within 24-72 hours 
• Monitor participant weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
total immunoglobulin G or gamma 
globulins. 
• Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and /or liver biopsy to evaluate liver 
disease; complete liver imaging and/or 
liver biopsy eCRF. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT 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, which 
may indicate severe liver injury (possible “Hy’s Law”), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving anticoagulants. 
3. 
Includes: hepatitis A immunoglobulin (IgM) antibody, hepatitis B surface antigen, and hepatitis B core antibody; 
hepatitis C RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
obtain heterophile antibody or monospot testing) and hepatitis E IgM antibody. 
4. 
Pharmacokinetic sample may not be required for participants known to be receiving placebo or non-GSK 
comparator interventions. Record the date/time of the PK blood sample draw and the date/time of the last dose of 
study intervention prior to PK blood sample draw on the eCRF. If the date or time of the last dose is unclear, 
provide the participant’s best approximation. If the date/time of the last dose cannot be approximated OR a PK 
sample cannot be collected in the time period indicated above, do not obtain a PK sample. Instructions for sample 
handling and shipping are in the SRM. 


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10.6. 
Appendix 6: COVID-19 Pandemic and Clinical Study 
Continuity 
The COVID-19 pandemic may impact the conduct of clinical studies. Significant 
logistical challenges may arise from quarantines, variable restrictions on site resources 
and operations, site closures, travel limitations and the inability of an individual 
participant to attend clinic visits, interruptions to the supply chain for the investigational 
product, or other considerations if site personnel or study participants become infected 
with COVID-19. These challenges may lead to difficulties in meeting protocol-specified 
procedures, including dispensation of the investigational product to the participant or 
adhering to protocol-mandated visits and laboratory/diagnostic testing. 
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in study 
treatment for participants enrolled in this clinical study. 
In order to maintain the scientific integrity of the study and adhere to updated guidance 
from regulators, procedures have also been put into place to ensure that the actions taken 
to mitigate against any impact of COVID-19 are well documented in the study database. 
This appendix outlines the measures which are approved for implementation within this 
clinical study, to protect participant safety, welfare, and rights, and to ensure data 
integrity and the integrity of the clinical study, as a result of COVID-19 only. These 
measures may be implemented in accordance with any requirements and expectations set 
out by local IRBs/IECs and National Competent Authorities, as necessary. 
This appendix does not apply to participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19.  
10.6.1. 
Changes to Study Visits and Study Procedures 
• There may be cases where the current principal investigator of a site is indisposed for 
a period and may need to delegate parts of his or her duties temporarily, e.g., to a sub-
investigator. Any such changes should be documented in the site’s source records. 
Any permanent changes in principal investigator should be communicated to the 
sponsor. 
• There may also be circumstances where immediate actions are required by the 
sponsor and/or investigator, outside of what is contemplated in the protocol, in order 
to protect a study participant from immediate hazard. Any such measures will be 
carefully documented and conducted in accordance with the National Competent 
Authority/IRB/IEC regulations. 
10.6.2. 
COVID-19 Specific Data Capture 
10.6.2.1. 
Capturing COVID-19 Specific Protocol Deviations 
Please refer to the SRM for specific details on capturing protocol deviations as a result of 
COVID-19. 


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10.6.2.2. 
Capturing COVID-19 Specific Adverse Events and Serious Adverse 
Events 
ViiV Healthcare is monitoring the evolving situation with respect to COVID-19 carefully 
and the impact this may have on ongoing or planned clinical studies. It is important for 
the study team to describe COVID-19 related AEs/SAEs and their impact on study data 
and outcomes. Standardization of case definitions will facilitate future data analyses. 
Please use the following guidance: 
1. Adverse events should continue to be evaluated as to whether they meet SAE criteria 
as defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. Serious AEs and AEs should be submitted following usual 
study procedures and timelines. 
2. Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released March 20, 2020, represents a time point for standardized 
collection. We recognize definitions are likely to continue to evolve; the most recent 
definitions should be consulted for each case (WHO). When reporting both serious 
and non-serious AEs (related to COVID-19 infection), investigators should use the 
following verbatim terms: 
a. Suspected COVID-19 infection; or 
b. Probable COVID-19 infection; or 
c. Confirmed COVID-19 infection  
3. Sites should contact the study medical monitor for questions related to definitions, 
reporting, and decisions around the impact to study drug continuation in the setting 
of clinically defined mild COVID-19 infection. 
4. A new COVID-19 infection eCRF will be included to collect additional details about 
the reported COVID-19 AE or SAE data. It is important that the correct information 
is collected from each participant reporting a COVID-19 AE or SAE. Therefore, 
please use the eCRF templates to help you collect this information for all COVID-19 
related AEs/SAEs. 
10.6.2.2.1. World Health Organization Case Definition (December 16, 2020 Version) 
Please see the WHO Case Definition for Suspected, Probable, or Confirmed case of 
SARS-CoV-2 infection: https://www.who.int/publications/i/item/WHO-2019-nCoV-
Surveillance_Case_Definition-2020.2 
A. A participant with acute respiratory illness (fever and at least one sign/symptom 
of respiratory disease, e.g., cough, shortness of breath) AND a history of travel to 
or residence in a location reporting community transmission of COVID-19 
disease during the 14 days prior to symptom onset; 
OR 
B. A participant with any acute respiratory illness AND having been in contact (see 
definition of “COVID-19 contact” below) with a confirmed or probable 


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COVID-19 case (see definition of “contact”) in the last 14 days prior to symptom 
onset; 
OR 
C. A participant with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation. 
Probable case:  
A. A suspect case for whom testing for the COVID-19 virus is inconclusive 
(inconclusive being the result of the test reported by the laboratory). 
OR  
B. A suspect case for whom testing could not be performed for any reason. 
Confirmed case: 
A person with laboratory confirmation of COVID-19 infection, irrespective of clinical 
signs and symptoms. 
COVID-19 Contact: 
A contact is a person who experienced any one of the following exposures during the 
2 days before and the 14 days after the onset of symptoms of a probable or confirmed 
case: 
1. Face-to-face contact with a probable or confirmed case within 1 meter and for more 
than 15 minutes; 
2. Direct physical contact with a probable or confirmed case; 
3. Direct care for a patient with probable or confirmed COVID-19 disease without 
using proper personal protective equipment; OR 
4. Other situations as indicated by local risk assessments. 
Note: For confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken which led to 
confirmation. 
 
 


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10.8. 
Appendix 8: Abbreviations and Trademarks 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ART 
Antiretroviral therapy 
AST 
Aspartate aminotransferase 
AUC 
Area under the plasma concentration-time curve 
AUC(0-t) 
Area under the plasma concentration-time curve from 
time zero to time t 
AUC(0-∞) 
Area under the plasma concentration-time curve from 
time zero extrapolated to infinity 
BA 
Bioavailability  
bpm 
Beats per minute 
CI 
Confidence interval 
CIB 
Clinical Investigator’s Brochure  
Cmax 
Maximum observed concentration  
Cτ 
Trough concentration 
C-QTc 
Concentration-corrected QT interval 
CL/F 
Apparent oral clearance 
COVID-19 
Coronavirus disease 
CPK 
Creatinine phosphokinase 
CRF 
Case report form 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
CVb 
Intersubject coefficient of variation 
CVw 
Intrasubject coefficient of variation 
D 
Day 
DAIDS 
Division of AIDS 
DILI 
Drug induced liver injury 
DTG 
Dolutegravir 
ECG 
Electrocardiogram  
FDA 
Food and Drug Administration 
FDC 
Fixed-dose combination 
FSH 
Follicle-stimulating hormone 
FTIH 
First time in human 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
GSK 
GlaxoSmithKline  
HBV 
Hepatitis B virus 


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HBsAg 
Hepatitis B virus surface antigen 
HCV 
Hepatitis C virus 
hCG 
Human chorionic gonadotropin 
hERG/Ikr 
Human Ether-a-go-go-Related Gene/Rapid Delayed 
rectifier 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus-1 
HRT 
Hormonal replacement therapy 
ICF 
Informed consent form  
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee  
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional Review Board  
IU 
International unit 
kg 
Kilogram 
mIU 
milli-international units 
mg 
Milligram 
MI 
Maturation inhibitor 
mL 
millilitre 
msec 
Millisecond 
ng 
Nanogram 
NIMP 
Non-investigational medicinal product 
PD 
Pharmacodynamics 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
QD 
Once daily 
QTc 
Corrected QT interval 
QTcF 
Corrected QT interval using the Fridericia formula 
SAD 
Single ascending dose 
SAE 
Serious adverse event  
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SoA 
Schedule of activities 
SRM 
Study Reference Manual  
SCN5A 
Sodium Voltage-Gated Channel Alpha Subunit 5 
t1/2 
Apparent terminal phase half-life 
tlag 
Lag time for absorption 
Tmax 
Time of maximum observed concentration  


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TQT 
Thorough QT 
ULN 
Upper limit of normal  
VH 
ViiV Healthcare 
Vz/F 
Apparent volume of distribution 
WHO 
World Health Organization 
WOCBP 
Woman of childbearing potential  
 
Trademark Information 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by ViiV 
Healthcare 
Portia 
 
DAIDS 
Tivicay 
 
SAS 
 
 
WinNonlin 
 


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11. 
REFERENCES 
Bristol-Myers Squibb Document Number 930109388, 1.0; BMS-TMF-3548385 1.0. 
Clinical Study Report: A Randomized, Double-Blind, Double-Dummy, Positive- 
Controlled, Crossover Study to Determine Electrocardiographic Effects of BMS-955176 
in Healthy Subjects, 13-JAN-2017 
Buzzi M, Wandeler G, Anderegg N et al. Dolutegravir-based maintenance therapy in 
HIV-infected patients: systematic review and meta-analysis. 16 European AIDS 
Conference - European AIDS Clinical Society (EACS). 2017; Accessed at: 
http://natap.org/2017/EACS/EACS_41.htm 
Clotet B, Feinberg J, Van Lunzen J, et al. Once−daily dolutegravir versus darunavir plus 
ritonavir in antiretroviral−naïve adults with HIV−1 infection (FLAMINGO): 48 week 
results from the randomised open−label phase 3b study. Lancet. 2014;383:2222−2231. 
Department of Health and Human Services (DHHS), Food and Drug Administration, 
Center for Drug Evaluation and Research, Center for Drug Evaluation and Research 
(US). Guidance for Industry: Food-effect bioavailability and fed bioequivalence studies. 
December 2002. Available from: https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/food-effect-bioavailability-and-fed-bioequivalence-studies. 
Department of Health and Human Services (DHHS), National Institutes of Health, 
National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of 
AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Corrected Version 2.1. July 2017. Available from: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.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, Investigators, and Institutional Review Boards. FDA 
Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 
Public Health Emergency. April 2020. Available from: https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-
medical-products-during-covid-19-public-health-emergency 
European Medicines Agency (EMA). Science Medicines Health, Committee for Human 
Medicinal Products. Points to Consider on Implications of Coronavirus (COVID-19) on 
methodological Aspects of Ongoing Clinical Trials. March 2020. Available from: 
https://www.ema.europa.eu/en/documents/scientific-guideline/points-consider-
implications-coronavirus-disease-covid-19-methodological-aspects-ongoing-
clinical_en.pdf. 
European Medicines Agency (EMA). Science Medicines Health, Heads of Medicines 
Agencies. Guidance on the Management of Clinical Trials During the COVID-19 
(Coronavirus) Pandemic. April 2020. Available from: 
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/guidanceclinicaltrials_covid19_en.pdf. 


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GSK Document Number 2018N379610_02. Clinical Investigator's Brochure for 
GSK3640254, November 2020 
GSK Document Number RM2007/00683/14. Clinical Investigator’s Brochure for 
GSK1349572, September 2020 
GSK Document Number 2019N399207_03. Clinical Protocol 208379, Phase IIb, 
randomized, partially blind, active controlled, dose-range finding study of GSK3640254 
compared to a reference arm of dolutegravir, each in combination with nucleoside reverse 
transcriptase inhibitors, in HIV-1 infected antiretroviral treatment-naive adults 25-SEP- 
2020 
GSK Document Number 2019N399318_00. Clinical Protocol 209712, An Open Label 
Two-way Interaction Clinical Trial to Evaluate the Pharmacokinetic Interactions Between 
GSK3640254 and Dolutegravir in Healthy Subjects 12-DEC-2018 
GSK Document Number 2020N430256_00. A Double-Blind (Sponsor Unblinded), 
Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to 
Investigate the Safety, Tolerability and Pharmacokinetics of GSK3640254 in Healthy 
Participants, 09 Sept 2018. 
GSK Document Number 2010N105142_00. Clinical Protocol ING113674, Relative 
bioavailability study of three different tablet formulations of GSK1349572 50 mg and the 
Dose Proportionality of and Effect of Food on the Selected Formulation in healthy male 
and female volunteers 
Hasler WL. Nausea, Vomiting, and Indigestion: Introduction. Chapter 39. Harrison’s 
Principles of Internal Medicine 18th edition. 2012. McGraw Hill. 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, et al. 
Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen 
overdose and acute liver failure. Drug Metab Dispos. 2009;37:1779-84. 
Malagelada JR and Malagelada C. Nausea and Vomitting. Chapter 15. Sleisenger and 
Fordtran's Gastrointestinal and Liver Disease 10th edition. 2016. Elsevier. 
Millham FH Acute Abdominal Pain. Chapter 11. Sleisenger and Fordtran's 
Gastrointestinal and Liver Disease 10th edition. 2016. Elsevier. 
Morales-Ramirez J, Bogner JR, Molina JM, et al. Safety, efficacy, and dose response of 
the maturation inhibitor GSK3532795 (formerly known as BMS-955176) plus 
tenofovir/emtricitabine once daily in treatment-naive HIV-1-infected adults: Week 24 
primary analysis from a randomized Phase IIb trial. PLoS ONE. 2018; 13(10): e0205368. 
Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification 
Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the 
FDA’s pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 
2007;164:1035–1043. 


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Raffi F, Jaeger H, Quiros-Roldan E, et al.; extended SPRING-2 Study Group. Once-daily 
dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 
infection (SPRING-2 study): 96 week results from a randomised, double-blind, 
noninferiority trial. Lancet Infect Dis. 2013;13(11):927-935. 
Rome Foundation. Rome IV Diagnostic Criteria for Functional Gastrointestinal 
Disorders. 2019. Available from: https://romeonline.org/?product=rome-iv-diagnostic-
algorithms-for-common-gi-symptoms-second-edition. Accessed 19 January 2021. 
Schiller LR and Sellin J. Diarrhea. Chapter 16. Sleisenger and Fordtran's Gastrointestinal 
and Liver Disease 10th edition. 2016. Elsevier. 
Soll AH, Graham DY. Peptic Ulcer Disease. Chapter 40. Textbook of Gastroenterology. 
5th edition. 2009. Blackwell Publishing. 
Tivicay Prescribing Information. ViiV Healthcare, June 2020. Available at: 
https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_In
formation/Tivicay/pdf/TIVICAY-PI-PIL-IFU.PDF. Accessed 19 January 2021.  
Walmsley SL, Antela A, Clumeck N, et al; SINGLE Investigators. Dolutegravir plus 
abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 
2013;369(19):1807-1818. 
Yarze JC and Friedman LS Chronic Abdominal Pain. Chapter 12. Sleisenger and 
Fordtran's Gastrointestinal and Liver Disease 10th edition. 2016. Elsevier. 

SAP_001.pdf: 
 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
213055 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for A Two-Part, Randomized, 
Open-Label, Single Dose, Crossover Clinical Study to 
Assess the Relative Bioavailability of Fixed-Dose 
Combinations of GSK3640254 and Dolutegravir and to 
Assess the Effect of Food on the Select Fixed Dose 
Combination of GSK3640254 and Dolutegravir in Healthy 
Participants 
Compound Number  : GSK3640254, GSK4107821 
Clinical Study 
Identifier 
: GSK 213055 
Effective Date  
: 22/06/2021 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report (CSR) for Protocol 213055. 
• 
This RAP is intended to describe the full analyses required for the study.  
• 
This RAP will be provided to the study team members to convey the content of 
the Statistical Analysis Complete (SAC) deliverable. 


 
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TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 4 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 5 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 5 
2.2. 
Study Objective(s) and Endpoint(s)............................................................... 5 
2.3. 
Study Design ................................................................................................ 6 
2.4. 
Statistical Hypotheses................................................................................... 7 
2.5. 
Sample Size ................................................................................................. 7 
2.6. 
Study Blinding ............................................................................................... 7 
3. 
PLANNED ANALYSES ............................................................................................ 8 
3.1. 
Interim Analyses ........................................................................................... 8 
3.2. 
Final Analyses .............................................................................................. 8 
4. 
ANALYSIS POPULATIONS ..................................................................................... 9 
4.1. 
Protocol Deviations ..................................................................................... 10 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 11 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 11 
5.2. 
Baseline Definitions .................................................................................... 11 
5.3. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 12 
6. 
STUDY POPULATION ANALYSES ....................................................................... 13 
6.1. 
Overview of Planned Study Population Analyses ........................................ 13 
7. 
PHARMACOKINETIC ANALYSES ......................................................................... 14 
7.1. 
Primary Pharmacokinetic Analyses ............................................................. 14 
7.1.1. 
Endpoint / Variables ..................................................................... 14 
7.1.1.1. 
Drug Concentration Measures .................................... 14 
7.1.1.2. 
Derived Pharmacokinetic Parameters......................... 14 
7.1.2. 
Summary Measure ...................................................................... 14 
7.1.3. 
Population of Interest ................................................................... 14 
7.1.4. 
Statistical Analyses / Methods ..................................................... 15 
7.1.4.1. 
Statistical Methodology Specification .......................... 15 
7.2. 
Secondary Pharmacokinetic Analyses ........................................................ 16 
7.2.1. 
Endpoint / Variables ..................................................................... 16 
7.2.1.1. 
Drug Concentration Measures .................................... 16 
7.2.1.2. 
Derived Pharmacokinetic Parameters......................... 16 
7.2.2. 
Summary Measure ...................................................................... 17 
7.2.3. 
Population of Interest ................................................................... 17 
7.2.4. 
Statistical Analyses / Methods ..................................................... 17 
8. 
SAFETY ANALYSES ............................................................................................. 18 
8.1. 
Adverse Events Analyses ........................................................................... 18 
8.2. 
Clinical Laboratory Analyses ....................................................................... 18 
8.3. 
Adverse Events of Special Interest ............................................................. 18 
8.4. 
Other Safety Analyses ................................................................................ 19 


 
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9. 
ADDITIONAL ANALYSES DUE TO THE COVID-19 PANDEMIC ........................... 20 
9.1. 
Study Population ......................................................................................... 20 
9.1.1. 
Additional Displays for Participants with a COVID-19 
Infection ....................................................................................... 20 
9.2. 
Safety ......................................................................................................... 20 
9.2.1. 
Assessment of COVID-19 AEs .................................................... 20 
10. REFERENCES ....................................................................................................... 21 
11. APPENDICES ........................................................................................................ 22 
11.1. 
Appendix 1: Schedule of Activities .............................................................. 22 
11.1.1. 
Protocol Defined Schedule of Events ........................................... 22 
11.2. 
Appendix 2: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 27 
11.2.1. 
Study Phases .............................................................................. 27 
11.2.1.1. Study Phases for Concomitant Medication ................. 27 
11.2.2. 
Treatment Emergent Flag for Adverse Events ............................. 27 
11.3. 
Appendix 3: Data Display Standards & Handling Conventions .................... 28 
11.3.1. 
Reporting Process ....................................................................... 28 
11.3.2. 
Reporting Standards .................................................................... 28 
11.3.3. 
Reporting Standards for Pharmacokinetics .................................. 29 
11.4. 
Appendix 4: Derived and Transformed Data ............................................... 31 
11.4.1. 
General ........................................................................................ 31 
11.4.2. 
Study Population .......................................................................... 31 
11.5. 
Appendix 5: Reporting Standards for Missing Data ..................................... 32 
11.5.1. 
Premature Withdrawals ................................................................ 32 
11.5.2. 
Handling of Missing Data ............................................................. 32 
11.5.2.1. Handling of Missing and Partial Dates ........................ 32 
11.6. 
Appendix 6: Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events .......................................... 33 
11.6.1. 
Laboratory Values ........................................................................ 33 
11.7. 
Appendix 7: Values of Potential Clinical Importance ................................... 35 
11.7.1. 
ECG ............................................................................................. 35 
11.7.2. 
Vital Signs .................................................................................... 35 
11.8. 
Appendix 8: Abbreviations & Trademarks ................................................... 36 
11.8.1. 
Abbreviations ............................................................................... 36 
11.8.2. 
Trademarks ................................................................................. 37 
11.9. 
Appendix 9: List of Data Displays ............................................................... 38 
11.9.1. 
Data Display Numbering .............................................................. 38 
11.9.2. 
Mock Example Shell Referencing ................................................ 38 
11.9.3. 
Deliverables ................................................................................. 38 
11.9.4. 
Study Population Tables .............................................................. 39 
11.9.5. 
Safety Tables ............................................................................... 40 
11.9.6. 
Safety Figures ............................................................................. 45 
11.9.7. 
Pharmacokinetic Tables ............................................................... 46 
11.9.8. 
Pharmacokinetic Figures ............................................................. 48 
11.9.9. 
ICH Listings ................................................................................. 50 
11.9.10. Non-ICH Listings .......................................................................... 55 
 


 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the CSR for Protocol: 213055. 
Revision Chronology: 
Original Protocol 
213055 
25-MAR-2021 
Original 
Amendment 1 
05-MAY -2021 
 


 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
This study will compare the relative bioavailability (BA) of 2 Fixed-Dose Combinations 
(FDCs) of GSK3640254 / Dolutegravir (DTG) with GSK3640254 and DTG administered 
together as single agents (Part 1). In addition, this study will investigate the effect of food 
on the pharmacokinetics (PK) of the selected FDC of GSK3640254 / DTG. This study 
will investigate the effect of a high fat and calorie meal on the PK, safety, and tolerability 
of the FDC of GSK3640254 + DTG, in comparison with administration under fasting 
conditions (Part 2). 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1. 
Table 1 
Changes to Protocol Defined Analysis Plan 
Protocol 
Reporting & Analysis Plan 
Statistical Analysis Plan 
Statistical Analysis Plan 
Rationale for Changes 
• 
This is an open-label study 
• 
Biostatistics and 
Programming teams from 
both GSK and PPD will 
remain blinded to the 
actual randomization 
schedule. Other teams 
including PPD Clinical 
Pharmacology team will 
remain open-label 
• 
Biostatistics and 
Programming teams 
remain blinded following 
GSK’s requirement 
 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary 
Part 1 
• To assess the relative BA of FDCs of 
GSK3640254 / DTG compared with 
GSK3640254 / DTG administered together as 
single agents when administered with a 
moderate fat and calorie meal 
Part 2 
• To assess the effect of food on the PK of the 
selected FDC of GSK3640254 / DTG when 
administered with a high fat and calorie meal 
compared to fasted conditions 
Parts 1 and 2 
• Plasma AUC(0-∞), AUC(0-t), and Cmax for 
GSK3640254 and DTG 
Secondary 
Secondary  
Part 1 
• 
To assess the safety and tolerability of FDCs 
of GSK3640254 / DTG compared with 
GSK3640254 and DTG administered 
together as single agents  
Parts 1 and 2 
• 
Safety and tolerability parameters for AEs or 
SAEs, observed and change from baseline 
clinical laboratory assessments, ECGs, and 
vital sign measurements 


 
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Objectives 
Endpoints 
Part 2 
• 
To assess the safety and tolerability of 
selected FDC of GSK3640254 / DTG 
following single oral administration to healthy 
participants under fasted or fed conditions 
2.3. 
Study Design 
 Overview of Study Design and Key Features 
Figure 1 Study Design Schematic 
 
Design 
Features 
A Phase 1, 2-part, randomized, open-label, crossover study. 
The study will consist of a screening period and a treatment period. 
• 
Screening Period: within 28 days before the first dose of study intervention 
o Part 1: 3-period, 3-treatment, crossover design, with a washout period of at least 
7 days (-4 hours) between doses 
o Part 2: 2-period, 2-treatment crossover design, with a washout period of at least 
7 days (-4 hours) between doses 
Dosing 
• 
Part 1: 
o Treatment A = A single oral dose of GSK3640254 25 mg (2 x tablets), 
GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered 
together under moderate fat and calorie conditions 
o Treatment B = A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg 
(1 x monolayer tablet) FDC administered under moderate fat and calorie 
conditions. 
o Treatment C = A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg 
(1 x bilayer tablet) FDC administered under moderate fat and calorie 
conditions. 
 
• 
Part 2: 
o Treatment D = A single oral dose of selected FDC of GSK3640254 / DTG, 
150 mg /50 mg administered under high fat and calorie conditions 
o Treatment E = A single oral dose of selected FDC of GSK3640254 / DTG, 
150 mg / 50 mg administered under fasted conditions 
Time & 
Events 
• 
Refer to Appendix 1: Schedule of Activities 
Treatment 
Assignment 
• 
This is a randomized study. Biostatistics and Programming teams from both GSK 
and PPD will remain blinded to the actual randomization schedule. Other teams 
including PPD Clinical Pharmacology team will remain open-label. 


 
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 Overview of Study Design and Key Features 
• 
In Part 1, participants will be randomly assigned to 1 of 3 treatment sequences in 
1:1:1 ratio; in Part 2, participants will be randomly assigned to 1 of 2 treatment 
sequences in 1:1 ratio. 
• 
Site pharmacy group will use a computer-generated randomization schedule for 
treatment assignments. 
• 
The computer-generated randomization schedule will be produced by SAS software 
(Version 9.4). 
Interim 
Analysis 
• 
After completion of Part 1 the study, preliminary safety & PK data will be analyzed 
by PPD under the oversight of Clinical Pharmacology Modeling & Simulation within 
VH/GSK to determine the formulation to be used in Part 2.  
• 
GSK Clinical Pharmacology Modeling and Simulation and the study team will inform 
the principal investigator of the formulation decision. 
• 
The interim outputs will be produced by WinNonlin (8.0 or higher). 
 
2.4. 
Statistical Hypotheses 
There is no formal research hypothesis that will be statistically tested in this study. 
2.5. 
Sample Size 
As there is no formal research hypothesis being statistically tested in this study, the 
sample size was not selected based on statistical considerations but determined using 
feasibility. For each part, approximately 18 participants will be enrolled to ensure that 
14 evaluable participants complete the study. If participants prematurely discontinue the 
study, additional participants may be enrolled after consultation with the sponsor to 
ensure that the required number of evaluable participants complete the study.  
Since it was expected that coadministration of GSK3640254 and DTG would increase the 
exposure of DTG, ranges for point estimate for a ratio of 1.0, 1.1, and 1.2 were explored. 
It was expected that coadministration of GSK3640254 with DTG would have no 
significant impact on the exposure of GSK3640254, thus ranges for point estimate for a 
ratio of 0.9, 1.0, and 1.1 were explored. The details of the results of these analyses can be 
found in the protocol Section 9.2.  
2.6. 
Study Blinding 
The Biostatistics and Programming teams for GSK will be blinded during this study. PPD 
will work with ADaM datasets and table, listing, and figures (TLFs) based on the 
surrogate randomization schedule, and not having access to the actual randomization 
schedule until unblinding process in the final analysis. 
Once Medidata RaveDatabase Hard Lock occurs, Source Data Lock is achieved, at which 
point the PPD team will switch from surrogate to actual randomization. The unblinded 
SDTM datasets will be transferred to the GSK Data Management team, who will 
authorize Database Freeze (DBF). At this point the entire GSK study team is officially 
unblinded. 


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
There is no formal interim analysis planned but an analysis using preliminary PK data 
from Part 1 will be used to determine the formulation to be used for Part 2.  
GSK Clinical Pharmacology Modeling and Simulation and the study team will inform the 
principal investigator of the formulation decision. 
The interim outputs will be produced by WinNonlin (8.0 or higher). 
3.2. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the 
following sequential steps: 
1. All participants have completed the study as defined in the protocol. 
2. All required database cleaning activities have been completed and final database 
release (DBR). 
3. All criteria for unblinding the randomization codes have been met.  
4. Randomization codes have been distributed by the PPD Randomization Team to 
PPD Biostatistics and Programming team. 
5. Database freeze has been declared by GSK Data Management after reviewing the 
unblinded SDTM datasets. 
6. Only after DBF has been declared by GSK Data Management can GSK Biostatistics 
and Programming be unblinded. 


 
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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened  
• 
All participants who signed the informed consent 
form 
• 
This population will be used for screen failure 
listing and summary. 
• 
Study Population 
Enrolled 
• 
All participants who passed screening and 
entered the study. 
• 
This population will be used for summary of 
enrolled participants 
• 
Study Population 
Randomized  
• 
All participants who were randomly assigned to 
a treatment sequence. 
• 
This population will be used for listing of 
randomization schedule. 
• 
Study Population 
Safety 
• 
All participants who received at least one dose 
of study intervention. 
• 
This population will be used for the safety 
displays and baseline/demographic 
characteristics. 
• 
Study Population 
• 
Safety 
Pharmacokinetic 
Concentration  
• 
All participants who underwent plasma PK 
sampling and had evaluable PK assay results. 
• 
This population will be used for the PK 
concentration listings, summary tables, and 
plotting of concentration-time data. 
• 
PK Concentration 
Pharmacokinetic 
Parameter  
• 
All participants who underwent plasma PK 
sampling and had evaluable PK parameters 
estimated. 
• 
This population will be used for PK parameter 
listings, PK parameter summary tables, and 
statistical analysis tables. 
• 
PK Parameter 
• 
PK statistical analysis 
Refer to Appendix 9: List of Data Displays which details the population used for each display. 


 
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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 
summarized 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. The “significant” protocol 
deviation in the Protocol Deviation Management Plan is equivalent to “important” 
protocol deviations. 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
significant deviations [and deviations which may lead to exclusion from the 
analysis populations] are captured and categorized on the protocol deviations 
dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
A separate listing of all inclusion/exclusion criteria deviations will also be provided. This 
listing will be based on data as recorded on the inclusion/exclusion page of the electronic 
case report form (eCRF). 


 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
Data Displays for Reporting – Part 1 
By Treatment 
Description 
Code 
Order in TLF  
A single oral dose of GSK3640254 25 mg (2 x tablets), 
GSK3640254 100 mg (1 x tablet) / DTG 50 mg (1 x tablet) 
administered together under moderate fat and calorie 
conditions (reference) 
Treatment A 
1 
A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg 
(1 x monolayer tablet) FDC administered under moderate fat 
and calorie conditions 
Treatment B 
2 
A single oral dose of GSK3640254 / DTG, 150 mg / 50 mg 
(1 x  bilayer tablet) FDC administered under moderate fat 
and calorie conditions 
Treatment C 
3 
By Sequence 
Description 
Code 
Order in TLF  
Sequence 1 
ABC 
1 
Sequence 2 
BCA 
2 
Sequence 3 
CAB 
3 
Data Displays for Reporting – Part 2 
By Treatment 
Description 
Code 
Order in TLF 
A single oral dose of selected FDC from Part 1 of 
GSK3640254 / DTG, 150 mg / 50 mg administered under 
high fat and calorie conditions 
Treatment D 
1 
A single oral dose of selected FDC from Part 1 of 
GSK3640254 / DTG, 150 mg / 50 mg administered under 
fasted conditions 
Treatment E 
2 
By Sequence 
Description 
Code 
Order in TLF  
Sequence 1 
DE 
1 
Sequence 2 
ED 
2 
5.2. 
Baseline Definitions 
For 12-lead ECGs and vital signs, the baseline value will be the average (for quantitative 
assessments) or the worst case (for interpretation) of the triplicate pre-dose assessments 
within each period. For clinical laboratory parameters, the baseline value will be the 
latest pre-dose assessment with a non-missing value, including those from unscheduled 


 
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visits, prior to the first study drug administration in each treatment period. If there is no 
non-missing value prior to the first study drug administration in each treatment period, 
the last non-missing value in the previous treatment period will be defined as baseline.. 
Parameter 
Study Assessments Considered as 
Baseline 
Baseline Used in Data Display 
 
Screening 
Day -1 
Day 1 (Pre-Dose) 
Safety 
 
Vital Signs 
X 
X 
X 
Day 1 (Pre-Dose) [1] for each period 
12-Lead ECG 
X 
X 
X 
Day 1 (Pre-Dose) [1] for each period  
Hematology 
X 
X 
 
Day -1 for each period[2] 
Clinical Chemistry 
X 
X 
 
Day -1 for each period[2] 
Urinalysis 
X 
X 
 
Day -1 for each period[2] 
ECG = electrocardiogram. 
[1] The average (for quantitative assessments) or the worst case (for interpretation) of the pre-dose triplicate 
assessments will be used as the baseline. 
[2] Day -1 in periods 2 and 3 refers to the Day 7 of the previous period. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
5.3. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 
Section 
Component 
11.1 
Appendix 1: Schedule of Activities  
11.2 
Appendix 2: Study Phases and Treatment Emergent Adverse Events 
11.3 
Appendix 3: Data Display Standards & Handling Conventions 
11.3.3 
Appendix 4: Derived and Transformed Data 
11.5 
Appendix 5: Reporting Standards for Missing Data 
11.6 
Appendix 6: Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events 
11.7 
Appendix 7: Values of Potential Clinical Importance 
11.8 
Appendix 8: Abbreviations & Trade Marks 
11.9 
Appendix 9: List of Data Displays 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the Screened, Randomized, or Safety 
population, unless otherwise specified.  
Study population analyses including analyses of participant’s disposition, protocol 
deviations (including inclusion/exclusion criteria deviations), demographic and baseline 
characteristics, prior and concomitant medications, and exposure and treatment 
compliance will be based on VH/GSK’s Integrated Data Standards Library standards. 
Details of the planned displays are presented in Appendix 9: List of Data Displays. 


 
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7. 
PHARMACOKINETIC ANALYSES 
7.1. 
Primary Pharmacokinetic Analyses 
7.1.1. 
Endpoint / Variables 
7.1.1.1. 
Drug Concentration Measures 
Refer to Appendix 3: Data Display Standards & Handling Conventions (Section 11.3.3 
Reporting Standards for PK). Plasma concentrations of GSK3640254 and DTG will be 
measured and presented in tabular form and will be summarized descriptively. Plasma 
GSK3640254 and DTG concentration-time data will be listed by participant, treatment 
group, and sampling time for each study part and summarized by treatment group and 
sampling time for each study part. 
7.1.1.2. 
Derived Pharmacokinetic Parameters 
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin (8.0 or higher). All calculations of non-compartmental parameters will be 
based on actual sampling times. Pharmacokinetic parameters listed will be determined 
from the plasma concentration-time data, as data permit. Participants who experience 
emesis at or before 2 times median Tmax or participants whose pre-dose concentrations 
are >5% of their Cmax value for the given treatment will be excluded from the 
calculation of summary statistics and statistical analysis for the respective treatment. 
Parameter 
Parameter Description 
AUC(0-) 
Area under the plasma concentration-time curve from time 0 extrapolated to infinity, to be 
calculated using the linear trapezoidal rule for each incremental trapezoid and the log 
trapezoidal rule for each decremental trapezoid. 
AUC(0-t) 
Area under the plasma concentration-time curve from time 0 to the last quantifiable 
concentration, to be calculated using the linear trapezoidal rule for each incremental 
trapezoid and the log trapezoidal rule for each decremental trapezoid. 
Cmax 
Maximum observed concentration, determined directly from the concentration-time data. 
NOTES: 
• 
Additional parameters may be included as required. 
7.1.2. 
Summary Measure 
Pharmacokinetic parameters AUC(0-), AUC(0-t), and Cmax of GSK3640254 and DTG 
following single dose administration of GSK3640254 and DTG administered together as 
single agents and following single dose administration of FDC tablet formulations of 
GSK3640254 / DTG to healthy participants. 
7.1.3. 
Population of Interest  
The primary PK analyses will be based on the PK concentration population for plasma 
PK concentrations and the PK parameter population for plasma PK parameters and 
statistical analysis. 


 
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7.1.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 9: List of Data Displays and 
will be based on GSK Data Standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarized using descriptive statistics and listed. 
Primary plasma PK parameters (AUC[0-], AUC[0-t], and Cmax) will be estimated for 
GSK3640254 and DTG. Summary statistics (arithmetic mean, geometric mean, median, 
standard deviation [SD], coefficient of variation [CV], minimum, maximum, 
between-subject coefficient of variation [CVb], and 95% confidence interval [CI]) for 
plasma GSK3640254 and DTG PK parameter values will be summarized by treatment for 
each study part. 
Summary statistics (arithmetic mean, 95% CI, SD, median, minimum, and maximum) for 
plasma GSK3640254 and DTG PK concentrations will be summarized by treatment 
using the PK Concentration Population. 
7.1.4.1. 
Statistical Methodology Specification 
The following PK statistical analyses will only be performed if sufficient data are 
available (i.e., if participants have well defined plasma profiles). 
Endpoint / Variables 
• Plasma primary PK endpoints include AUC(0-), AUC(0-t), and Cmax for GSK3640254 and 
DTG as data permit. 
Model Specification 
Part 1 
• Analysis will be performed to compare the relative BA of 2 FDCs of GSK3640254 and DTG 
with GSK3640254 and DTG administered together as single agents. Analyses will be 
performed on the natural logarithms of AUC(0-), AUC(0-t), and Cmax using linear -mixed 
effect models with treatment, period, and sequence as fixed effects and participant nested 
within a sequence as a random effect. Effects will be estimated, and CIs will be constructed 
for the following treatment comparisons: 
o Treatment B (test) versus Treatment A (reference) 
o Treatment C (test) versus Treatment A (reference) 
o Point estimates, 90% CIs, and intra-subject CV% for treatment differences on the 
log scale derived from the model will be exponentiated to obtain estimates for 
geometric mean ratios and CIs on the original scale. 
Part 2 
• Analysis will be performed to compare the effect of food (-high fat and calorie meal) on the 
PK of GSK3640254 and DTG following administration of the selected FDC tablet formulation 
from Part 1. Analyses will be performed on the natural logarithms of AUC(0-), AUC(0-t), 
and Cmax using linear mixed-effect models with treatment, period, and sequence as fixed 


 
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effects and participant nested within a sequence as a random effect. Effects will be 
estimated, and CIs will be constructed for the following treatment comparisons: 
o Treatment D (test) versus Treatment E (reference) 
o Point estimates, 90% CIs, and intra-subject CV% for treatment differences on the 
log scale derived from the model will be exponentiated to obtain estimates for 
geometric mean ratios and CIs on the original scale 
Model Checking & Diagnostics 
• Model assumptions will be applied, but appropriate adjustments may be made based on the 
data. 
Model Results Presentation 
Part 1 
• Statistical analysis for comparison of GSK3640254 and DTG relative BA by analysis of 
variance (ANOVA) will be presented in tabular format with geometric mean ratios for the 
following treatment comparison: 
o Treatment B (test) versus Treatment A (reference) 
o Treatment C (test) versus Treatment A (reference) 
Part 2 
• Statistical analysis for the effect of food (high fat high calorie meal) by ANOVA will be 
presented in tabular format with geometric mean ratios for the following treatment 
comparisons: 
o Treatment D (test) versus Treatment E (reference) 
 
7.2. 
Secondary Pharmacokinetic Analyses 
7.2.1. 
Endpoint / Variables 
7.2.1.1. 
Drug Concentration Measures  
Refer to Appendix 3: Data Display Standards & Handling Conventions (Section 11.3.3 
Reporting Standards for Pharmacokinetic). 
7.2.1.2. 
Derived Pharmacokinetic Parameters 
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin (8.0 or higher). All calculations of non-compartmental parameters will be 
based on actual sampling times. Participants who experience emesis at or before 2 times 
median Tmax or participants whose pre-dose concentrations are >5% of their Cmax value 
for the given treatment will be excluded from the calculation of summary statistics for the 
respective treatment. 


 
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Plasma PK parameters listed below will be determined from the plasma 
concentration-time data, as data permits: 
Parameter 
Parameter Description 
Tmax 
Time of maximum observed concentration 
Tlag 
Lag time for absorption 
t1/2 
Apparent terminal phase half-life 
CL/F 
Apparent clearance following extravascular administration 
NOTES: 
• 
Additional parameters may be included as required. 
7.2.2. 
Summary Measure 
Pharmacokinetic parameters Tmax, Tlag, t1/2, and CL/F following single dose 
administration of GSK3640254 and DTG administered together as single agents and 
following single dose administration of FDC tablet formulations of GSK3640254 / DTG 
to healthy participants. 
7.2.3. 
Population of Interest  
The secondary PK analyses will be based on the PK parameter population for plasma PK 
parameters, unless otherwise specified. 
7.2.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 9: List of Data Displays and 
statistical principles. 
Unless otherwise specified, endpoints/variables defined in Section 7.2.1 will be 
summarized using descriptive statistics and listed. 
Secondary plasma PK parameters Tmax, Tlag, t1/2, and CL/F will be estimated for 
GSK3640254 and DTG. Summary statistics (arithmetic mean, geometric mean, median, 
CV, SD, minimum, maximum, CVb, and 95% CI) for secondary plasma PK parameters 
of GSK3640254 and DTG will be summarized by treatment. 


 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety population, unless otherwise specified. 
8.1. 
Adverse Events Analyses 
Adverse events (AEs) analyses including the analysis of AEs, serious (SAEs), and other 
significant AEs will be based on VH/GSK’s Integrated Data Standards Library standards. 
The details of the planned displays are provided in Appendix 9: List of Data Displays. 
Adverse events will be assigned to the last treatment received prior to start date/time of 
the AE. If no time was reported for an AE and the date is the same as date of dosing, the 
AE will be assigned to the treatment dosed on that day. Adverse events occurring after 
the last dose date and time + 5 days (Day 6 and beyond for each treatment period) and 
before the dose date and time of the next treatment will not be summarized but will be 
listed. 
8.2. 
Clinical Laboratory Analyses 
Laboratory evaluations including the analyses of chemistry laboratory tests, hematology 
laboratory tests, urinalysis, pregnancy tests, and other screening tests will be based on 
VH/GSK’s Integrated Data Standards Library standards and will be graded using the 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events (Version 2.1, July 2017). The details of the planned displays are in 
Appendix 9: List of Data Displays. 
8.3. 
Adverse Events of Special Interest 
.At the end of the study, QT prolongation, gastrointestinal intolerability, gastric toxicity, 
psychiatric events, nervous system disorders, and skin and subcutaneous tissue disorders 
will be summarized by treatment. A listing will also be provided accordingly. 
The AESI of QT prolongation will be defined as cardiac disorders system organ class 
(SOC) plus preferred terms (PTs) using the Medical Dictionary for Regulatory Activities 
(MedDRA) Standardized MedDRA Query (SMQ) “Torsade de pointes/QT Prolongation” 
(narrow and broad terms) plus seizure. 
Gastrointestinal intolerability and gastric toxicity AESIs will be defined within three 
narrow sub-SMQs [Gastrointestinal nonspecific symptoms and therapeutic procedures 
SMQ; Gastrointestinal nonspecific dysfunction SMQ; Gastrointestinal nonspecific 
inflammation (SMQ)] plus a selection of relevant broad PTs from the Gastrointestinal 
non-specific symptoms and therapeutic procedures SMQ.  
Psychiatric AESI will be defined within the following:  
• Sub-SMQ “Suicide/self-injury” (SMQ) from parent SMQ of “Depression and 
Suicide/Self Injury”. Only narrow terms from the sub-SMQ will be selected. 


 
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• Sub-SMQ “Depression (excluding suicide and self-injury)” (SMQ) from parent SMQ 
of “Depression and Suicide/Self Injury”. Only narrow terms from the sub-SMQ will 
be selected. 
• All PTs from high level group term (HLGT) “Manic and Bipolar Mood Disorders and 
Disturbances” under SOC “Psychiatric Disorders”. 
• Narrow terms from SMQ “Psychosis and Psychotic Disorders” selected. 
• All PTs from HLGT “Anxiety Disorders and Symptoms”, under SOC “Psychiatric 
disorders”. 
• All PTs from HLGT “Sleep Disorders and Disturbances” and HLGT “Sleep 
disturbances (include subtypes)”. 
Nervous system disorders AESIs will be defined within the following:  
• Four HLGTs under Nervous System Disorders SOC: “Headaches”; “Mental 
impairment disorders (excluding dementia)”; “Disturbance in consciousness” and 
“Seizures and seizure disorder” 
Skin and subcutaneous tissue disorder AESIs will be defined with the following PTs:  
Skin and subcutaneous tissue disorders term to be provided when the final analyis is 
carried out(term will include rash, maculopapular rash, urticaria etc).  
8.4. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs, vital signs, pregnancy, 
and Columbia-Suicide Severity Rating Scale (CSSR-S) questionnaire will be based on 
VH/GSK’s Integrated Data Standards Library standards, unless otherwise specified. A 
figure of mean change from baseline in QTc using the Fridericia formula (QTcF) interval 
along with the 2-sided 95% CI using Student’s t distribution will be presented by 
treatment and visit. The details of the planned displays are presented in Appendix 9: List 
of Data Displays. 
 


 
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9. 
ADDITIONAL ANALYSES DUE TO THE COVID-19 
PANDEMIC 
9.1. 
Study Population 
9.1.1. 
Additional Displays for Participants with a COVID-19 Infection 
A participant is defined as having a suspected, probable, or confirmed COVID-19 
infection during the study if the answer is “Confirmed”, “Probable”, or “Suspected” to 
the case diagnosis question from the COVID-19 coronavirus infection assessment eCRF. 
Summaries and listings of the numbers of participants with a suspected, probable, or 
confirmed COVID-19 infection, and of COVID-19 test results will be based on 
VH/GSK’s Integrated Data Standards Library standards. The details of the planned 
displays are provided in Appendix 9: List of Data Displays. 
9.2. 
Safety 
9.2.1. 
Assessment of COVID-19 AEs 
A Standardised MedDRA Query (SMQ) will be used to identify all COVID-19 AEs. 
The incidence of AEs and SAEs (Fatal and Non-Fatal) of COVID-19, COVID-19 AEs 
leading to study drug discontinuation, COVID-19 AEs leading to study withdrawal, and 
COVID-19 AEs by severity, will be obtained from standard AE and SAE summaries. 


 
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10. 
REFERENCES 
• Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse. Version 2.1. July 2017. Division of AIDS National Institute of Allergy and 
Infectious Diseases National Institutes of Health US Department of Health and 
Human Services Events. Retrieved on 28/04/2021 at : 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
• ViiV Healthcare Study number 213055. A Relative Bioavailability and Food-Effect 
Study of the Fixed Dose Combination of GSK3640254 and Dolutegravir in Healthy 
Participants. ClinicalTrials.gov Identifier: IND139,838. 25 March 2021. 


 
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11. 
APPENDICES 
11.1. 
Appendix 1: Schedule of Activities 
11.1.1. 
Protocol Defined Schedule of Events 
Screening Visit (Part 1 and Part 2) 
Visit Window (relative to Day 1) 
Screening 
(up to 35 days before Day 1) 
Outpatient Visit 
X 
Informed Consent 
X 
Inclusion and exclusion criteria 
X 
Demography 
X 
Full physical examination including height and weight1 
X 
Laboratory assessments (hematology, clinical chemistry, urinalysis) 
X 
12-lead electrocardiogram 
X 
Vital sign measurements 
X 
Medication/drug/alcohol history 
X 
Past and current medical conditions 
X 
Columbia-Suicide Severity Rating Scale 
X 
Serum pregnancy test 
X 
Follicle-stimulating hormone (as needed, to confirm postmenopausal status) 
X 
Drug, alcohol, and cotinine screen 
X 
Human immunodeficiency virus, hepatitis B and C screening 
X 
Molecular test for SARS-CoV-22 
X 
1. A full physical examination will include at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal, and neurological 
systems. 
2. Two consecutive approved molecular tests (polymerase chain reaction or antigen test). The first test should be performed ≥7 days prior to 
admission. 
 


 
 
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Time and Events (Part 1) 
Procedure 
Check-in 
Baseline1 
Period 1 & 2 
Period 3 
Notes 
Day -2 
Day  
–1 
Day 1 
Washout 
Day 1 
Day 2 
Days 3-4 
Day 52 
 
Day 2 
Days 3-5 Days 6-7 
Admit to clinic 
X 
 
 
 
 
 
 
 
 
 
 
Discharge from clinic 
 
 
 
 
 
 
 
 
 
X 
Discharge from clinic following completion of the last study procedure on 
Day 5 of Period 3. 
Brief physical examination 
 
X 
 
 
 
D7 
 
 
 
X 
Interim or symptom-targeted physical examination will be performed at the 
discretion of the investigator. See Section 8.2.1 of the protocol for 
description of brief physical examination. 
Vital signs 
 
X 
X 
X 
D3 
D7 
X 
X 
X 
X 
Blood pressure and pulse will be measured in triplicate at predose on 
Day 1 in all periods. Single blood pressure and pulse will be measured on 
other study days. 
Temperature check 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG 
 
X 
X 
 
 
 
X 
 
 
X 
The ECGs on Day 1 in all periods will be taken at predose, and post-dose 
at 2, 4, and 6 hours. The predose ECGs will be taken in triplicate to 
establish a baseline QTcF. The post-dose ECGs are single ECGs. 
Drug, alcohol, and cotinine screen 
X 
 
 
 
 
 
 
 
 
 
See Appendix 2 of the protocol for specific tests to be performed. 
Molecular test for SARS-CoV-2 
X* 
 
 
 
D5 
 
 
 
 
X 
* The second test will be performed on Day -2 after admission to the clinic. 
Participants will be quarantined within the clinic until the second test result 
is negative. Once the second test result is confirmed negative, participants 
can be released into the study unit and will follow infection control 
practices. 
Laboratory assessments 
(hematology, chemistry, urinalysis) 
 
X3 
 
X 
 
D7 
 
X 
 
X 
See Appendix 2 of the protocol for specific tests to be performed. Day 2 
samples in each period to be collected 24 hours after dosing. 
Pregnancy test 
X 
 
 
 
 
 
 
 
 
X 
Serum testing on Day –2 
Columbia-Suicide Severity Rating 
Scale 
 
X 
 
 
 
D7 
 
 
 
X 
 
Study intervention: GSK3640254 
25 mg, 100 mg or GSK3640254 / 
DTG 150 mg / 50 mg fixed-dose 
combination Or DTG 50 mg 
 
 
X 
 
 
 
X 
 
 
 
See Section 4.1. of the protocol 
GSK3640254 PK sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
X 
Blood for PK analysis of GSK3640254 will be collected within 40 minutes 
prior to dosing and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 
and 96 hours post-dose in all periods. 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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AE = adverse event; D = day; ECG = electrocardiogram; PK = pharmacokinetic; QTcF = QT interval corrected using Fridericia’s formula; SAE = serious adverse event. 
1 Baseline assessments will be collected on Day -1 before Period 1. 
2 Evaluations scheduled for Day 5 in Period 3 will also be performed for participants who discontinue early. 
3 Review and approval prior to dosing on Day 1 in Periods 1, 2 and 3.. 
 
Procedure 
Check-in 
Baseline1 
Period 1 & 2 
Period 3 
Notes 
Day -2 
Day  
–1 
Day 1 
Washout 
Day 1 
Day 2 
Days 3-4 
Day 52 
 
Day 2 
Days 3-5 Days 6-7 
Dolutegravir PK sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
X 
Blood for PK analysis of dolutegravir will be collected within 40 minutes 
prior to dosing and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 
and 96 hours post-dose in all periods. 
AE review 
 
 
======================X=========================➔ 
 
SAE review 
================================X===============================➔  
Concomitant medications 
================================X===============================➔  


 
 
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Time and Events (Part 2) 
Procedure 
Check-
in 
Baseline1 
Period 1 
Period 2 
Notes 
Day -2 
Day  
–1 
Day 1 
Washout 
Day 1 
Day 2 
Days 3-4 
Day 52 
 
Day 2 
Days 3-5 Days 6-7 
Admit to clinic 
X 
 
 
 
 
 
 
 
 
 
 
Discharge from clinic 
 
 
 
 
 
 
 
 
 
X 
Discharge from clinic following completion of the last study procedure on 
Day 5 of Period 2. 
Brief physical examination 
 
X 
 
 
 
D7 
 
 
 
X 
Interim or symptom-targeted physical examination will be performed at the 
discretion of the investigator. See Section 8.2.1 of the protocol for 
description of brief physical examination. 
Vital signs 
 
X 
X 
X 
D3 
D7 
X 
X 
X 
X 
Blood pressure and pulse will be measured in triplicate at predose on Day 
1 in both periods. Single blood pressure and pulse will be measured on 
other study days. 
Temperature check 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG 
 
X 
X 
 
 
D7 
X 
 
 
X 
The ECGs on Day 1 in all periods will be taken at predose, and post-dose 
at 2, 4, and 6 hours. The predose ECGs will be taken in triplicate to 
establish a baseline QTcF. The post-dose ECGs are single ECGs. 
Drug, alcohol, and cotinine screen 
X 
 
 
 
 
 
 
 
 
 
See Appendix 2 of the protocol for specific tests to be performed. 
Molecular test for SARS-CoV-2 
X* 
 
 
 
D5 
 
 
 
 
X 
* The second test will be performed on Day -2 after admission to the clinic. 
Participants will be quarantined within the clinic until the second test result 
is negative. Once the second test result is confirmed negative, participants 
can be released into the study unit and will follow infection control 
practices. 
Laboratory assessments 
(hematology, chemistry, urinalysis) 
 
X3 
 
X 
 
D7 
 
X 
 
X 
See Appendix 2 of the protocol for specific tests to be performed. Day 2 
samples in each period to be collected 24 hours after dosing. 
Pregnancy test 
X 
 
 
 
 
 
 
 
 
X 
Serum testing on Day –2 
Columbia-Suicide Severity Rating 
Scale 
 
X 
 
 
 
D7 
 
 
 
X 
 
Study intervention: GSK3640254 
25 mg, 100 mg or GSK3640254 / 
DTG 150 mg / 50 mg fixed-dose 
combination Or DTG 50 mg 
 
 
X 
 
 
 
X 
 
 
 
See Section 4.1. of the protocol 
 


 
 
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AE = adverse event; D = day; ECG = electrocardiogram; PK = pharmacokinetic; QTcF = QT interval corrected using Fridericia’s formula; SAE = serious adverse event. 
1 Baseline assessments will be collected on Day -1 before Period 1. 
2 Evaluations scheduled for Day 5 in Period 2 will also be performed for participants who discontinue early. 
3 Review and approval prior to dosing on Day 1 of Periods 1, 2 and 3. 
The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data review (e.g., to obtain data closer to the time of peak plasma concentrations) to ensure appropriate 
monitoring. Any changes in the timing of time points for any planned study assessments as the result of emerging PK data from this study must be documented and approved by the relevant study team member and then archived 
in the sponsor and site study files but will not constitute a protocol amendment. The Institutional Review Board (IRB) or Independent Ethics Committee (IEC) will be informed of any safety issues that constitute a substantial 
amendment and require alteration of the safety monitoring scheme or amendment of the informed consent form (ICF). The changes will be approved by the healthy authority and the ethics committee before implementation. 
 
 
 
 
 
 
Procedure 
Check-
in 
Baseline1 
Period 1 
Period 2 
Notes 
Day -2 
Day  
–1 
Day 1 
Washout 
Day 1 
Day 2 
Days 3-4 
Day 52 
 
Day 2 
Days 3-5 Days 6-7 
GSK3640254 PK sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
X 
Blood for PK analysis of GSK3640254 will be collected within 40 minutes 
prior to dosing and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 
and 96 hours post-dose in both periods. 
Dolutegravir PK sampling 
 
 
X 
X 
D3, D4, 
D5 
 
X 
X 
X 
X 
Blood for PK analysis of dolutegravir will be collected within 40 minutes 
prior to dosing and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 
and 96 hours post-dose in both periods. 
AE review 
 
 
==============X=================➔ 
 
SAE review 
======================X======================➔ 
 
Concomitant medications 
======================X======================➔ 
 


 
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11.2. 
Appendix 2: Study Phases and Treatment Emergent 
Adverse Events 
11.2.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
study treatment start date(/time) and stop date(/time). 
Study Phase 
Definition 
Pre-Treatment  
Date and Time ≤ Study Treatment Start Date and Time 
On-Treatment 
Study Treatment Start Date and Time < Date and Time ≤ Study Treatment Stop 
Date and Time + 5 days the Date and Time of Early Withdrawal Visit whichever is 
later. 
Post-Treatment  
Date and Time > Study Treatment Stop Date and Time + 5 days or the Date and 
Time of Early Withdrawal Visit whichever is later 
 
11.2.1.1. 
Study Phases for Concomitant Medication 
Study Phase 
Definition 
Prior 
If medication end date is not missing and is before Day -1 
Concomitant 
Any medication that is not a prior 
NOTES:  
• 
Please refer to Appendix 5: Reporting Standards for Missing Data for handling of missing and partial dates for 
concomitant medication. Use the rules in this table if concomitant medication date is completely missing. 
 
 
11.2.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
If AE onset date and time is on or after treatment start date and time & on or 
before treatment stop date and time + 5 days within each treatment period.  
• 
Study Treatment Start Date and Time ≤ AE Start Date and Time ≤ Study 
Treatment Stop Date and Time + 5 days within each treatment period. 
• 
If the AE onset date is completely missing, the AE is considered as treatment 
emergent. 
NOTES:  
• 
If the study treatment stop date is missing, then the AE will be considered to be On-Treatment. 
• 
Please refer to Appendix 5: Reporting Standards for Missing Data for handling of missing and partial dates for 
AEs. Use the rules in this table if the AE onset date is completely missing. 
 


 
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11.3. 
Appendix 3: Data Display Standards & Handling 
Conventions 
11.3.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software (9.4) will be used. 
Reporting Area 
HARP Server 
\\us1salx00259.corpnet2.com 
HARP Compound 
GSK3640254 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.1).  
• 
For creation of ADaM datasets (ADC1/ADCM/ADAE), the same version of dictionary datasets will be 
implemented as those being used for conversion from SI to SDTM. 
Generation of RTF Files 
• 
RTF files will be generated for all reporting efforts described in the RAP. 
11.3.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include participant level listings in the main body of the GSK CSR. All participant level 
listings should be located in the modular appendices as ICH or non-ICH listings. 
• 
MedDRA version 24.0 will be applied for reporting, unless otherwise stated. 
Formats 
• 
All data will be presented by study part separately. 
• 
All data will be reported according to the actual treatment the participant received unless otherwise 
stated. 
• 
GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s. 
Planned and Actual Time 
• 
Reporting for tables, figures, and formal statistical analyses: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. For procedures without predose 
assessment within period, the baseline planned time will be the Day 7 of the previous period. 
• 
The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 


 
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• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings.  
• 
Visits outside the protocol defined time-windows (i.e. recorded as protocol deviations) will be 
included in listings but omitted from figures (mean figures only for PK concentrations), 
summaries, and statistical analyses (excluding statistical analyses of PK parameters). 
Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables except for determining baseline and the 
worst-case values. 
• 
Unscheduled visits will not be included in figures. 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
 
11.3.3. 
Reporting Standards for Pharmacokinetics 
Pharmacokinetic Concentration Data 
Descriptive 
Summary Statistics, 
Graphical Displays 
and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical Principle 6.06.1. 
For continuous data: 
• 
NQs at the beginning of a participant profile (i.e., before the first incidence of 
a measurable concentration) are deemed to be 0 as it is assumed that in this 
circumstance no drug is yet measurable in the blood. 
• 
For NQs at the end of the participant profile (i.e., after the last incidence of a 
measurable concentration): 
• 
For individual plots and PK analyses these are dropped (set to missing) 
as they do not provide any useful information (and can erroneously 
indicate that absolutely no drug is present) 
• 
For summary statistics, these are set to 0 (to avoid skewing of the 
summary statistics) 
• 
Individual NQs which fall between two measurable concentrations are set to 
missing (individual values of this nature are assumed to be an anomaly). 
If two or more NQ values occur in succession between measurable 
concentrations, the profile will be deemed to have terminated at the last 
measurable concentration prior to these NQs. For the purpose of individual 
participant plots, these NQs will be set to 0, and the subsequent measurable 
concentrations will be retained. For the derivation of PK parameters, these NQs 
and any subsequent measurable concentrations will be omitted (set to missing). 
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only. 


 
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Pharmacokinetic Parameter Data 
Descriptive 
Summary Statistics, 
Graphical Displays, 
and Listings 
N, n, arithmetic mean, 95% CI of arithmetic mean, geometric mean, 95% CI of 
geometric mean, SD, SD of logged data CV (%), and between-subject geometric 
CVb (%) will be reported. 
CVb (%) = √ (exp(SD2) - 1) * 100 
(SD = SD of Ln-Transformed data) 
Parameters Not 
Being 
Ln-Transformed 
Tmax, λz, λz lower, λz upper, and λz no. of points. 
Parameters Not 
Being Summarized 
λz, λz lower, λz upper, and λz no. of points. 
Listings 
Include the first point, last point and number of points used in the determination 
of λz and Rsq_adjusted for listings. 
 


 
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11.4. 
Appendix 4: Derived and Transformed Data 
11.4.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
Mean of the measurements will be calculated and used in any derivation of summary statistics but if 
listed, all data will be presented. 
• 
The worst finding/interpretation associated with multiple measurements as the finding/interpretation 
for that time point. 
• 
Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance 
summary tables. 
Study Day 
• 
Calculated as the number of days from Dose Date on Period 1 Day 1: 
• 
Assessment Date = Missing  
  → Study Day = Missing  
• 
Assessment Date < Dose Date on Period 1 Day 1  
  → Study Day = Assessment Date –Dose Date on Period 1 Day 1 
• 
Assessment Date >= Dose Date on Period 1 Day 1  
  → Study Day = Assessment Date – Dose Date on Period 1 Day 1 + 1 
Period Day 
• 
Calculated as the number of days from First Dose Date for the respective period: 
• 
Assessment Date = Missing  
  → Period Day = Missing  
• 
Assessment Date < Dose Date on Period 1 Day 1 
  → Period Day = Assessment Date – Dose Date on Period 1 Day 1 
• 
Dose Date on Period 1 Day 1 <= Assessment Date < Dose Date on Period 2 Day 1 
  → Period Day = Assessment Date – Dose Date on Period 1 Day 1 + 1 
• 
Dose Date on Period 2 Day 1 <= Assessment Date < Dose Date on Period 3 Day 1 
  → Period Day = Assessment Date – Dose Date on Period 2 Day 1 + 1 
• 
Assessment Date >= Dose Date on Period 3 Day 1  
  → Period Day = Assessment Date – Dose Date on Period 3 Day 1 + 1 
 
11.4.2. 
Study Population 
Age 
• 
GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed as 
follows: 
o Any participant with a missing day will have this imputed as day ‘15’. 
o Any participant with a missing day and month will have this imputed as ‘30th June’. 
• 
Birth date will be presented in listings as ‘YYYY’. 
Body Mass Index (BMI) 
• 
Calculated as Weight (kg) / [Height (m)2] 
 


 
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11.5. 
Appendix 5: Reporting Standards for Missing Data 
11.5.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Participant study completion (i.e., as specified in the protocol) was defined as the 
participant had completed all phases of the study including the final date on which 
data were or are expected to be collected.  
• 
Withdrawn participants were not replaced in the study. 
• 
All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified. 
11.5.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank fields 
on the collection instrument:  
o These data will be indicated by the use of a “blank” in participant listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Outliers 
• 
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
11.5.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays.  
Adverse Events 
• 
The eCRF allows for the possibility of partial dates (i.e., only month and year) 
to be recorded for AE start and end dates; that is, the day of the month may 
be missing. In such a case, the following conventions will be applied for 
calculating the time to onset and the duration of the event: 
o Missing Start Day: First of the month will be used unless this is before 
the start date of study treatment; in this case the study treatment start 
date will be used and hence the event is considered On-treatment as per 
Appendix 2: Study Phases and Treatment Emergent Adverse Events. 
o Missing Stop Day: Last day of the month will be used, unless this is after 
the stop date of study treatment; in this case the study treatment stop 
date will be used. 
• 
Completely missing start or end dates will remain missing, with no imputation 
applied. Consequently, time to onset and duration of such events will be 
missing. 
Concomitant 
Medications/Medical 
History 
• 
Partial dates for any concomitant medications recorded in the eCRF will be 
imputed using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' 
will be used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. 
• 
The recorded partial date will be displayed in listings. 


 
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11.6. 
Appendix 6: Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events 
11.6.1. 
Laboratory Values 
The Division of AIDS (DAIDS) grading for severity of laboratory toxicities and clinical 
AEs, version 2.1, July 2017 (2) will be used to assign grades to laboratory values. 
Laboratory results are converted to use SI units; only the numeric part of the criteria will 
be used. If for a laboratory parameter there are multiple grades sharing the same criteria, 
the maximum grade will be used. The table below outlines the planned laboratory 
assessments to be done in the study. 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
RBC Indices: 
Mean corpuscular volume 
 
Mean corpuscular 
hemoglobin 
 
 
WBC count with Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Absolute neutrophil count 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical Chemistry BUN 
Glucose (fasting) 
Creatinine 
Potassium 
Sodium 
Calcium 
Chloride 
Phosphorus 
Carbon dioxide 
Aspartate  
Aminotransferase 
Alanine Aminotransferase  
Gamma-glutamyl 
transferase 
Total and direct bilirubin 
Lactate dehydrogenase 
Total cholesterol 
Triglycerides 
Alkaline phosphatase2 
Total Protein 
Albumin 
Globulin 
Anion gap 
Uric acid 
Creatine phosphokinase 
Serum lipase 
Serum amylase 
Routine Urinalysis • Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase 
by dipstick 
• Microscopic examination (if blood, leukocyte esterase, or protein is abnormal) 
Pregnancy testing • Highly sensitive human chorionic gonadotropin (hCG) pregnancy test (as needed for 
women of childbearing potential)3 
Other Screening 
Tests 
•  Molecular test for SARS-CoV-2 (Two consecutive approved molecular tests 
[polymerase chain reaction or antigen test]. The first test should be performed ≥7 days 
prior to admission and the second test will be performed on Day -2 after admission to 
the clinic. 
•  Follicle-stimulating hormone (as needed in women of non-childbearing potential 
only) 
•  Serology: HIV-1 and -2 antigen/antibody immunoassay, hepatitis B surface antigen, 
hepatitis C antibody 
•  Alcohol, cotinine, and drug screen (to include at minimum amphetamines, 
barbiturates, cannabinoids, cocaine, or phencyclidine, or nonprescribed opiates, 
oxycodone, benzodiazepines, methadone, or tricyclic antidepressants) 


 
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1. Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 7.1 and Appendix 5. 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). 
2. If alkaline phosphatase is elevated, consider fractionating. 
3. Local urine pregnancy testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/IEC. 
 


 
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11.7. 
Appendix 7: Values of Potential Clinical Importance 
11.7.1. 
ECG 
ECG Parameter 
Units 
Potential Clinically Important Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
< 320 
> 450* 
Absolute PR Interval 
msec 
< 110 
> 220 
Absolute QRS Interval 
msec 
< 75 
> 110 
Change from Baseline 
Increase from Baseline QTc 
msec 
 
> 60 
* Exclusion criteria: Confirmed QTcF value >450 msec at screening or Day 1. 
 
 
11.7.2. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Potential Clinically Important Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
bpm 
< 40 
> 110 
 


 
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11.8. 
Appendix 8: Abbreviations & Trademarks 
11.8.1. 
Abbreviations 
Abbreviation 
Description 
AE  
Adverse Event 
ANOVA 
Analysis of Variance 
AUC  
Area under the plasma concentration-time curve 
AUC(0-∞)  
AUC from time 0 extrapolated to infinity 
AUC(0-t) 
AUC from Time 0 to Time t 
BA  
Bioavailability 
BMI 
Body Mass Index 
bpm  
Beats per minute 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence interval 
CL/F  
Apparent oral clearance 
Cmax  
Maximum observed concentration 
COVID-19 
Coronavirus disease 
CRF  
Case report form 
CSR  
Clinical Study Report 
C-SSRS  
Columbia-Suicide Severity Rating Scale 
CV 
Coefficient of variation 
CVb  
Coefficient of variation (Between)  
DAIDS 
Division of AIDS 
DBF 
Database Freeze 
DBR 
Database Release 
DP 
Decimal Places 
ECG  
Electrocardiogram 
FDA  
Food and Drug Administration 
GSK  
GlaxoSmithKline 
hCG 
Human Chorionic Gonadotropin 
HIV 
Human Immunodeficiency Virus 
ICH  
International Council On Harmonisation 
IDSL 
Integrated Data Standards Library 
IRB  
Institutional Review Board 
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
PI  
Principal Investigator 
PK 
Pharmacokinetic 
PT 
Preferred Term 
QTcF 
QTc using the Fridericia formula 
RAP 
Reporting & Analysis Plan 
SAC 
Statistical Analysis Complete 
SAE 
Serious Adverse Event 
SARS-CoV2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SMQ 
Standardized MedDRA Query 
SOC 
System Organ Class 
t1/2 
Apparent Terminal Phase Half-life 


 
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Abbreviation 
Description 
Tmax 
Time of Maximum Observed Concentration 
TLF 
Tables, listings, figures 
ULN  
Upper Limit of Normal 
VH  
ViiV Healthcare 
11.8.2. 
Trademarks 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by ViiV 
Healthcare 
Tivicay 
 
DAIDS 
 
 
SAS 
 
 
WinNonlin 
 
 


 
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11.9. 
Appendix 9: List of Data Displays 
11.9.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.14 
 
Safety 
2.1 to 2.56 
2.1 to 2.2 
Pharmacokinetic 
3.1 to 3.14 
3.1 to 3.18 
Section 
Listings 
ICH Listings 
1 to 72 
Other Listings 
73 to 80 
 
11.9.2. 
Mock Example Shell Referencing 
Non-IDSL specifications will be referenced as indicated and if required example 
mock-up displays provided in the Table/Listing/Figure Shells. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’ 
 
11.9.3. 
Deliverables 
Delivery  
Description 
SAC 
Final Statistical Analysis Complete 
 
 


 
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11.9.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
Enrolled 
NS1 
Summary of Number of Subjects Enrolled 
 
SAC 
1.2. 
Safety 
ES1 
Summary of Subject Disposition for the Subject Conclusion 
Record – Part 1 
 
SAC 
1.3. 
Safety 
ES1 
Summary of Subject Disposition for the Subject Conclusion 
Record – Part 2 
 
SAC 
1.4. 
Screened 
SD1 
Summary of Screening Status and Reasons for Screen Failures   
SAC 
1.5. 
Randomized 
SP1 
Summary of Study Populations – Part 1 
 
SAC 
1.6. 
Randomized 
SP1 
Summary of Study Populations – Part 2 
 
SAC 
Protocol Deviations 
1.7. 
Safety 
DV1 
Summary of Important Protocol Deviations – Part 1 
 
SAC 
1.8. 
Safety 
DV1 
Summary of Important Protocol Deviations – Part 2 
 
SAC 
Demographic and Baseline Characteristics 
1.9. 
Safety 
DM1 
Summary of Demographic Characteristics – Part 1 
 
SAC 
1.10. 
Safety 
DM1 
Summary of Demographic Characteristics – Part 2 
 
SAC 
1.11. 
Safety 
DM5 
Summary of Race and Racial Combinations – Part 1 
 
SAC 
1.12. 
Safety 
DM5 
Summary of Race and Racial Combinations – Part 2 
 
SAC 
1.13. 
Safety 
DM11 
Summary of Age Ranges – Part 1 
 
SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.14. 
Safety 
DM11 
Summary of Age Ranges – Part 2 
 
SAC 
 
11.9.5. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
2.1.  
Safety 
AE1xo 
Summary of Adverse Events by System Organ Class and 
Preferred Term – Part 1 
 
SAC 
2.2.  
Safety 
AE1xo 
Summary of Adverse Events by System Organ Class and 
Preferred Term – Part 2 
 
SAC 
2.3.  
Safety 
AE1xo 
Summary of Drug-Related Adverse Events by System Organ 
Class and Preferred Term – Part 1 
 
SAC 
2.4.  
Safety 
AE1xo 
Summary of Drug-Related Adverse Events by System Organ 
Class and Preferred Term – Part 2 
 
SAC 
2.5.  
Safety 
AE3 
Summary of Common (>=5%) Adverse Events by Overall 
Frequency – Part 1 
 
SAC 
2.6.  
Safety 
AE3 
Summary of Common (>=5%) Adverse Events by Overall 
Frequency – Part 2 
 
SAC 
2.7.  
Safety 
AE15 
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term – Part 1 
(Number of Subjects and Occurrences) 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.8.  
Safety 
AE15 
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term – Part 2 
(Number of Subjects and Occurrences) 
 
SAC 
2.9.  
Safety 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term – Part 1 
(Number of Subjects and Occurrences) 
 
SAC 
2.10. 
Safety 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term – Part 2 
(Number of Subjects and Occurrences) 
 
SAC 
2.11. 
Safety 
AE5A 
Summary of Adverse Events by System Organ Class and 
Preferred Term and Maximum Intensity – Part 1 
 
SAC 
2.12. 
Safety 
AE5A 
Summary of Adverse Events by System Organ Class and 
Preferred Term and Maximum Intensity – Part 2 
 
SAC 
2.13. 
Safety 
AE1xo 
Summary of Adverse Events of Special Interest by System 
Organ Class and Preferred Term – Part 1 
 
SAC 
2.14. 
Safety 
AE1xo 
Summary of Adverse Events of Special Interest by System 
Organ Class and Preferred Term – Part 2 
 
SAC 
Laboratory: Chemistry  
2.15. 
Safety 
LB1 
Summary of Clinical Chemistry Data – Part 1 
 
SAC 
2.16. 
Safety 
LB1 
Summary of Clinical Chemistry Data – Part 2 
 
SAC 
2.17. 
Safety 
LB1 
Summary of Clinical Chemistry Changes from Baseline – Part 1 
 
SAC 
2.18. 
Safety 
LB1 
Summary of Clinical Chemistry Changes from Baseline – Part 2 
 
SAC 
2.19. 
Safety 
LB16 
Summary of Clinical Chemistry Results by Maximum Grade 
Increase Post-Baseline Relative to Baseline – Part 1 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.20. 
Safety 
LB16 
Summary of Clinical Chemistry Results by Maximum Grade 
Increase Post-Baseline Relative to Baseline – Part 2 
 
SAC 
Laboratory: Hematology 
2.21. 
Safety 
LB1 
Summary of Hematology Data – Part 1 
 
SAC 
2.22. 
Safety 
LB1 
Summary of Hematology Data – Part 2 
 
SAC 
2.23. 
Safety 
LB1 
Summary of Hematology Changes from Baseline – Part 1 
 
SAC 
2.24. 
Safety 
LB1 
Summary of Hematology Changes from Baseline – Part 2 
 
SAC 
2.25. 
Safety 
LB16 
Summary of Hematology Results by Maximum Grade Increase 
Post-Baseline Relative to Baseline – Part 1 
 
SAC 
2.26. 
Safety 
LB16 
Summary of Hematology Results by Maximum Grade Increase 
Post-Baseline Relative to Baseline – Part 2 
 
SAC 
Laboratory: Urinalysis 
2.27. 
Safety 
LB1 
Summary of Urine Concentration – Part 1 
 
SAC 
2.28. 
Safety 
LB1 
Summary of Urine Concentration – Part 2 
 
SAC 
2.29. 
Safety 
LB1 
Summary of Urine Concentration Changes from Baseline – Part 
1 
 
SAC 
2.30. 
Safety 
LB1 
Summary of Urine Concentration Changes from Baseline – Part 
2 
 
SAC 
2.31. 
Safety 
UR3 
Summary of Urinalysis Dipstick Results – Part 1 
 
SAC 
2.32. 
Safety 
UR3 
Summary of Urinalysis Dipstick Results – Part 2 
 
SAC 
2.33. 
Safety 
LB16 
Summary of Urinalysis by Maximum Grade Increase Post-
Baseline Relative to Baseline – Part 1 
 
SAC 
2.34. 
Safety 
LB16 
Summary of Urinalysis by Maximum Grade Increase Post-
Baseline Relative to Baseline – Part 2 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
ECG 
2.35. 
Safety 
SAFE_T1 
Summary of ECG Findings – Part 1 
 
SAC 
2.36. 
Safety 
SAFE_T1 
Summary of ECG Findings – Part 2 
 
SAC 
2.37. 
Safety 
EG2 
Summary of ECG Values – Part 1 
 
SAC 
2.38. 
Safety 
EG2 
Summary of ECG Values – Part 2 
 
SAC 
2.39. 
Safety 
EG2 
Summary of ECG Changes from Baseline – Part 1 
 
SAC 
2.40. 
Safety 
EG2 
Summary of ECG Changes from Baseline – Part 2 
 
SAC 
2.41. 
Safety 
EG10 
Summary of Maximum QTc Values Post-Baseline Relative to 
Baseline by Category – Part 1 
 
SAC 
2.42. 
Safety 
EG10 
Summary of Maximum QTc Values Post-Baseline Relative to 
Baseline by Category – Part 2 
 
SAC 
2.43. 
Safety 
EG11 
Summary of Maximum Increase in QTc Values Post-Baseline 
Relative to Baseline by Category – Part 1 
 
SAC 
2.44. 
Safety 
EG11 
Summary of Maximum Increase in QTc Values Post-Baseline 
Relative to Baseline by Category – Part 2 
 
SAC 
Vital Signs 
2.45. 
Safety 
VS1 
Summary of Vital Signs – Part 1 
 
SAC 
2.46. 
Safety 
VS1 
Summary of Vital Signs – Part 2 
 
SAC 
2.47. 
Safety 
VS1 
Summary of Vital Sign Changes from Baseline – Part 1 
 
SAC 
2.48. 
Safety 
VS1 
Summary of Vital Sign Changes from Baseline – Part 2 
 
SAC 
C-SSRS 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.49 
Safety 
CSSRS4 
Listing of C-SSRS Suicidal Ideation and Behavior Data – Part 1 
 
SAC 
2.50 
Safety 
CSSRS4 
Listing of C-SSRS Suicidal Ideation and Behavior Data – Part 2 
 
SAC 
SARS-CoV-2 
2.51 
Safety 
PAN1 
Summary of COVID-19 Assessments – Part 1 
 
SAC 
2.52 
Safety 
PAN1 
Summary of COVID-19 Assessments – Part 2 
 
SAC 
2.53 
Safety 
SAFE_T2 
Summary of COVID-19 Adverse Event Summary – Part 1 
 
SAC 
2.54 
Safety 
SAFE_T2 
Summary of COVID-19 Adverse Event Summary – Part 2 
 
SAC 
2.55 
Safety 
PAN3 
Summary of COVID-19 Symptoms for Subjects with Adverse 
Event – Part 1 
 
SAC 
2.56 
Safety 
PAN3 
Summary of COVID-19 Symptoms for Subjects with Adverse 
Event – Part 2 
 
SAC 
 


 
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11.9.6. 
Safety Figures 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
ECG 
2.1.  
Safety 
EG9 
Mean (95% CI) Change from Baseline in QTcF Interval by 
Timepoint and Treatment – Part 1 
 
SAC 
2.2.  
Safety 
EG9 
Mean (95% CI) Change from Baseline in QTcF Interval by 
Timepoint and Treatment – Part 2 
 
SAC 
 


 
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11.9.7. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
PK Concentration Data 
3.1.  
PK 
Concentration 
PK01 
Summary of GSK3640254 Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – Part 1 
Part 1 
SAC 
3.2.  
PK 
Concentration 
PK01 
Summary of Dolutegravir Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – Part 1 
Part 1 
SAC 
3.3.  
PK 
Concentration 
PK01 
Summary of GSK3640254 Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – Part 2 
Part 2 
SAC 
3.4.  
PK 
Concentration 
PK01 
Summary of Dolutegravir Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – Part 2 
Part 2 
SAC 
PK Derived Parameters 
3.5.  
PK 
Parameter 
PK04 
Summary Statistics of Derived GSK3640254 Plasma 
Pharmacokinetic Parameters (Non-Transformed) Based on 
Actual Time by Treatment – Part 1 
Part 1 Parameters with units 
SAC 
3.6.  
PK 
Parameter 
PK04 
Summary Statistics of Derived GSK3640254 Plasma 
Pharmacokinetic Parameters (Ln-Transformed) Based on 
Actual Time by Treatment – Part 1 
Part 1 Parameters with units 
SAC 
3.7.  
PK 
Parameter 
PK04 
Summary Statistics of Derived Dolutegravir Plasma 
Pharmacokinetic Parameters (Non-Transformed) Based on 
Actual Time by Treatment – Part 1 
Part 1 Parameters with units 
SAC 
3.8.  
PK 
Parameter 
PK04 
Summary Statistics of Derived Dolutegravir Plasma 
Pharmacokinetic Parameters (Ln-Transformed) Based on 
Actual Time by Treatment – Part 1 
Part 1 Parameters with units 
SAC 
3.9.  
PK 
Parameter 
PK04 
Summary Statistics of Derived GSK3640254 Plasma 
Pharmacokinetic Parameters (Non-Transformed) Based on 
Actual Time by Treatment – Part 2 
Part 2 Parameters with units 
SAC 


 
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3.10. 
PK 
Parameter 
PK04 
Summary Statistics of Derived GSK3640254 Plasma 
Pharmacokinetic Parameters (Ln-Transformed) Based on 
Actual Time by Treatment – Part 2 
Part 2 Parameters with units 
SAC 
3.11. 
PK 
Parameter 
PK04 
Summary Statistics of Derived Dolutegravir Plasma 
Pharmacokinetic Parameters (Non-Transformed) Based on 
Actual Time by Treatment – Part 2 
Part 2 Parameters with units 
SAC 
3.12. 
PK 
Parameter 
PK04 
Summary Statistics of Derived Dolutegravir Plasma 
Pharmacokinetic Parameters (Ln-Transformed) Based on 
Actual Time by Treatment – Part 2 
Part 2 Parameters with units 
SAC 
PK Analysis Tables 
3.13. 
PK 
Parameter 
PK05 
Statistical Analysis of Plasma Pharmacokinetic Parameters: 
Analysis of Variance (ANOVA) – Part 1 
Part 1 AUC(0-), AUC(0-t) and 
Cmax for GSK3640254 and 
Dolutegravir 
SAC 
3.14. 
PK 
Parameter 
PK05 
Statistical Analysis of Plasma Pharmacokinetic Parameters: 
Analysis of Variance (ANOVA) – Part 2 
Part 2 AUC(0-), AUC(0-t) and 
Cmax for GSK3640254 and 
Dolutegravir 
SAC 


 
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11.9.8. 
Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
Individual Concentration Plots 
3.1.  
PK 
Concentration 
PK16A 
Individual GSK3640254 Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – Part 1 
Part 1, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.2.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – Part 1 
Part 1, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.3.  
PK 
Concentration 
PK16A 
Individual GSK3640254 Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – Part 2 
Part 2, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.4.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – Part 2 
Part 2 Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
3.5.  
PK 
Concentration 
PK16A 
Individual GSK3640254 Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – Part 1 
Part 1 Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
3.6.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – Part 1 
Part 1 Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
3.7.  
PK 
Concentration 
PK16A 
Individual GSK3640254 Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – Part 2 
Part 2 Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 


 
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3.8.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – Part 2 
Part 2 Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
Mean / Median Concentration Plots 
3.9.  
PK 
Concentration 
PK17 
Mean (Standard Deviation) GSK3640254 Plasma 
Concentration-Time Plots by Treatment - Part 1 (Linear and 
Semi-Logarithmic) 
Treatments (A, B, and C) 
Overlaid 
SAC 
3.10. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) Dolutegravir Plasma 
Concentration-Time Plots by Treatment - Part 1 (Linear and 
Semi-Logarithmic) 
Treatments (A, B, and C) 
Overlaid 
SAC 
3.11. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) GSK3640254 Plasma 
Concentration-Time Plots by Treatment - Part 2 (Linear and 
Semi-Logarithmic) 
Treatments (D and E) Overlaid 
SAC 
3.12. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) Dolutegravir Plasma 
Concentration-Time Plots by Treatment - Part 2 (Linear and 
Semi-Logarithmic) 
Treatments (D and E) Overlaid 
SAC 
3.13. 
PK 
Concentration 
PK18 
Median (Range) GSK3640254 Plasma Concentration-Time 
Plots by Treatment - Part 1 (Linear and Semi-Logarithmic) 
Treatments (A, B, and C) 
Overlaid 
SAC 
3.14. 
PK 
Concentration 
PK18 
Median (Range) Dolutegravir Plasma Concentration-Time Plots 
by Treatment - Part 1 (Linear and Semi-Logarithmic) 
Treatments (A, B, and C) 
Overlaid 
SAC 
3.15. 
PK 
Concentration 
PK18 
Median (Range) GSK3640254 Plasma Concentration-Time 
Plots by Treatment - Part 2 (Linear and Semi-Logarithmic) 
Treatments (D and E) Overlaid 
SAC 
3.16. 
PK 
Concentration 
PK18 
Median (Range) Dolutegravir Plasma Concentration-Time Plots 
by Treatment - Part 2 (Linear and Semi-Logarithmic) 
Treatments (D and E) Overlaid 
SAC 
3.17. 
PK 
Parameter 
EFF_F3 
Forest Plot for Plasma Pharmacokinetic Parameters - Part 1 
ANOVA for GSK3640254 and 
Dolutegravir; AUC0-inf, AUC0-t, 
Cmax 
SAC 
3.18. 
PK 
Parameter 
EFF_F3 
Forest Plot for Plasma Pharmacokinetic Parameters -  Part 2 
ANOVA for GSK3640254 and 
Dolutegravir; AUC0-inf, AUC0-t, 
Cmax 
SAC 


 
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11.9.9. 
ICH Listings 
ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
Randomized 
POP_L1 
Listing of Randomization Schedule – Part 1 
 
SAC 
2.  
Randomized 
POP_L1 
Listing of Randomization Schedule – Part 2 
 
SAC 
3.  
Safety 
ES3 
Listing of Reasons for Study Withdrawal – Part 1 
 
SAC 
4.  
Safety 
ES3 
Listing of Reasons for Study Withdrawal – Part 2 
 
SAC 
5.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
 
SAC 
Protocol Deviations 
6.  
Safety 
DV2 
Listing of Important Protocol Deviations – Part 1 
 
SAC 
7.  
Safety 
DV2 
Listing of Important Protocol Deviations – Part 2 
 
SAC 
8.  
Safety 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
– Part 1 
 
SAC 
9.  
Safety 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
– Part 2 
 
SAC 
Populations Analyzed 
10.  
Safety 
SP3A 
Listing of Subjects Excluded from Any Population – Part 1 
 
SAC 
11.  
Safety 
SP3A 
Listing of Subjects Excluded from Any Population – Part 2 
 
SAC 
Demographic and Baseline Characteristics 
12.  
Safety 
DM2 
Listing of Demographic Characteristics – Part 1 
 
SAC 
13.  
Safety 
DM2 
Listing of Demographic Characteristics – Part 2 
 
SAC 
14.  
Safety 
DM9 
Listing of Race – Part 1 
 
SAC 
15.  
Safety 
DM9 
Listing of Race – Part 2 
 
SAC 


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
Prior and Concomitant Medications 
16.  
Safety 
CM5 
Listing of Concomitant Medications – Part 1 
Based on GSK Drug Dictionary 
SAC 
17.  
Safety 
CM5 
Listing of Concomitant Medications – Part 2 
Based on GSK Drug Dictionary 
SAC 
Exposure and Treatment Compliance 
18.  
Safety 
EX4 
Listing of Exposure Data – Part 1 
 
SAC 
19.  
Safety 
EX4 
Listing of Exposure Data – Part 2 
 
SAC 
20.  
Safety 
POP_L2 
Listing of Meal Data – Part 1 
 
SAC 
21.  
Safety 
POP_L2 
Listing of Meal Data – Part 2 
 
SAC 
22.  
Safety 
SU2 
Listing of Substance Use History – Part 1 
 
SAC 
23.  
Safety 
SU2 
Listing of Substance Use History – Part 2 
 
SAC 
Adverse Events 
24.  
Safety 
AE2 
Listing of Relationship Between System Organ Class and 
Verbatim Text – Part 1 
 
SAC 
25.  
Safety 
AE2 
Listing of Relationship Between System Organ Class and 
Verbatim Text – Part 2 
 
SAC 
26.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events – 
Part 1 
 
SAC 
27.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events – 
Part 2 
 
SAC 
28.  
Safety 
AE8xo 
Listing of All Adverse Events – Part 1 
 
SAC 
29.  
Safety 
AE8xo 
Listing of All Adverse Events – Part 2 
 
SAC 
Serious and Other Significant Adverse Events 
30.  
Safety 
AE8xo 
Listing of Study Drug Related Adverse Events – Part 1 
 
SAC 


 
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No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
31.  
Safety 
AE8xo 
Listing of Study Drug Related Adverse Events – Part 2 
 
SAC 
32.  
Safety 
AE8xo 
Listing of Serious Adverse Events (Fatal & Non-Fatal) – Part 1 
 
SAC 
33.  
Safety 
AE8xo 
Listing of Serious Adverse Events (Fatal & Non-Fatal) – Part 2 
 
SAC 
34.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event 
– Part 1 
 
SAC 
35.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event 
– Part 2 
 
SAC 
36.  
Safety 
PSRAE2-5 
Listing of Possible Suicidality-Related Adverse Event Data: 
Event and Description – Part 1 
 
SAC 
37.  
Safety 
PSRAE2-5 
Listing of Possible Suicidality-Related Adverse Event Data: 
Event and Description – Part 2 
 
SAC 
38.  
Safety 
AE8xo 
Listing of Adverse Events Leading to Withdrawal from Study – 
Part 1 
 
SAC 
39.  
Safety 
AE8xo 
Listing of Adverse Events Leading to Withdrawal from Study – 
Part 2 
 
SAC 
40.  
Safety 
AE8xo 
Listing of Adverse Events of Special Interest – Part 1 
 
SAC 
41.  
Safety 
AE8xo 
Listing of Adverse Events of Special Interest – Part 2 
 
SAC 
Hepatobiliary (Liver) 
42.  
Safety 
MH2 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events – Part 1 
 
SAC 
43.  
Safety 
MH2 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events – Part 2 
 
SAC 
44.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events – Part 1 
 
SAC 


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
45.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events – Part 2 
 
SAC 
46.  
Safety 
LIVER15 
Listing of Liver Stopping Event Profile for Subjects with Liver 
Stopping Criteria Met 
 
SAC 
All Laboratory 
47.  
Safety 
LB5A 
Listing of Clinical Chemistry with any Toxicities – Part 1 
 
SAC 
48.  
Safety 
LB5A 
Listing of Clinical Chemistry with any Toxicities – Part 2 
 
SAC 
49.  
Safety 
LB5A 
Listing of All Clinical Chemistry Data for Subjects with any 
Toxicities – Part 1 
 
SAC 
50.  
Safety 
LB5A 
Listing of All Clinical Chemistry Data for Subjects with any 
Toxicities – Part 2 
 
SAC 
51.  
Safety 
LB5A 
Listing of Hematology with any Toxicities – Part 1 
 
SAC 
52.  
Safety 
LB5A 
Listing of Hematology with any Toxicities – Part 2 
 
SAC 
53.  
Safety 
LB5A 
Listing of All Hematology Data for Subjects with any Toxicities 
– Part 1 
 
SAC 
54.  
Safety 
LB5A 
Listing of All Hematology Data for Subjects with any Toxicities 
– Part 2 
 
SAC 
55.  
Safety 
LB5A 
Listing of Urinalysis with any Toxicities – Part 1 
 
SAC 
56.  
Safety 
LB5A 
Listing of Urinalysis with any Toxicities – Part 2 
 
SAC 
57.  
Safety 
LB5A 
Listing of All Urinalysis Data for Subjects with any Toxicities – 
Part 1 
 
SAC 
58.  
Safety 
LB5A 
Listing of All Urinalysis Data for Subjects with any Toxicities – 
Part 2 
 
SAC 
ECG 


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
59.  
Safety 
EG6 
Listing of All ECG Findings – Part 1 
 
SAC 
60.  
Safety 
EG6 
Listing of All ECG Findings – Part 2 
 
SAC 
61.  
Safety 
EG6 
Listing of All Abnormal ECG Findings – Part 1 
 
SAC 
62.  
Safety 
EG6 
Listing of All Abnormal ECG Findings – Part 2 
 
SAC 
63.  
Safety 
EG4 
Listing of All ECG Values – Part 1 
 
SAC 
64.  
Safety 
EG4 
Listing of All ECG Values – Part 2 
 
SAC 
Vital Signs 
65.  
Safety 
VS5 
Listing of All Vital Signs of Potential Clinical Importance – Part 
1 
 
SAC 
66.  
Safety 
VS5 
Listing of All Vital Signs of Potential Clinical Importance – Part 
2 
 
SAC 
67.  
Safety 
VS5 
Listing of All Vital Signs for Subjects with any Value of Potential 
Clinical Importance – Part 1 
 
SAC 
68.  
Safety 
VS5 
Listing of All Vital Signs for Subjects with any Value of Potential 
Clinical Importance – Part 2 
 
SAC 
Other Safety 
69.  
Safety 
PAN12 
Listing of COVID-19 Assessments and Symptom Assessments 
– Part 1 
 
SAC 
70.  
Safety 
PAN12 
Listing of COVID-19 Assessments and Symptom Assessments 
– Part 2 
 
SAC 
71.  
Safety 
AE8xo 
Listing of Adverse Events of COVID-19 – Part 1 
 
SAC  
72.  
Safety 
AE8xo 
Listing of Adverse Events of COVID-19 – Part 2 
 
SAC  
 


 
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11.9.10. 
Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
Pharmacokinetics 
73.  
PK 
Concentration 
PK07xo 
Listing of GSK3640254 Plasma Concentration-Time Data by 
Treatment – Part 1 
Part 1 
SAC 
74.  
PK 
Concentration 
PK07xo 
Listing of Dolutegravir Plasma Concentration-Time Data by 
Treatment – Part 1 
Part 1 
SAC 
75.  
PK 
Concentration 
PK07xo 
Listing of GSK3640254 Plasma Concentration-Time Data by 
Treatment – Part 2 
Part 2 
SAC 
76.  
PK 
Concentration 
PK07xo 
Listing of Dolutegravir Plasma Concentration-Time Data by 
Treatment – Part 2 
Part 2 
SAC 
77.  
PK 
Parameter 
PK13xo 
Listing of GSK3640254 Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – Part 1 
Part 1 
SAC 
78.  
PK 
Parameter 
PK13xo 
Listing of Dolutegravir Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – Part 1 
Part 1 
SAC 
79.  
PK 
Parameter 
PK13xo 
Listing of GSK3640254 Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – Part 2 
Part 2 
SAC 
80.  
PK 
Parameter 
PK13xo 
Listing of Dolutegravir Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – Part 2 
Part 2 
SAC