A Randomized, 2-Cohort, 2-Period, Single Dose, Crossover Clinical Study to Assess the Effect of Food on the Pediatric Dispersible Tablet Formulations of TRIUMEQ (Dolutegravir/Abacavir/Lamivudine) and DOVATO (Dolutegravir/Lamivudine) in Healthy Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: ViiV Healthcare

 
 
Protocol 
 
Study ID:  216149 
 
Official Title of Study: A Randomized, 2-Cohort, 2-Period, Single Dose, Crossover 
Clinical Study to Assess the Effect of Food on the Pediatric Dispersible Tablet 
Formulations of TRIUMEQ (Dolutegravir/Abacavir/Lamivudine) and DOVATO 
(Dolutegravir/Lamivudine) in Healthy Adult Participants 
 
Date of Document: 04-MAR-2021 
 
 

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SPONSOR SIGNATORY: 
Protocol Title: A Randomized, 2-Cohort, 2-Period, Single Dose, Crossover Clinical 
Study to Assess the Effect of Food on the Pediatric Dispersible Tablet Formulations of 
TRIUMEQ (Dolutegravir/Abacavir/Lamivudine) and DOVATO 
(Dolutegravir/Lamivudine) in Healthy Adult Participants 
Protocol Number: 216149 
Compound Number 
or Name: 
GSK2619619 (Dolutegravir/Abacavir/Lamivudine ) and 
GSK3515864 (Dolutegravir/Lamivudine) 
 
 
 
Sherene Min MD,  
Vice President, 
Head of Development 
 
Date 
The signed page is a separate document 
 
 
 
 
 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual

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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY: ............................................................................................... 2 
TABLE OF CONTENTS .................................................................................................. 3 
1. 
PROTOCOL SUMMARY .......................................................................................... 6 
1.1. 
Synopsis ....................................................................................................... 6 
1.2. 
Schema ........................................................................................................ 9 
1.3. 
Schedule of Activities .................................................................................. 10 
2. 
INTRODUCTION .................................................................................................... 13 
2.1. 
Study Rationale .......................................................................................... 13 
2.2. 
Background ................................................................................................ 13 
2.3. 
Benefit/Risk Assessment ............................................................................ 14 
2.3.1. 
Risk Assessment ......................................................................... 15 
2.3.2. 
Benefit Assessment ..................................................................... 18 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 18 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 18 
4. 
STUDY DESIGN .................................................................................................... 19 
4.1. 
Overall Design ............................................................................................ 19 
4.2. 
Scientific Rationale for Study Design .......................................................... 20 
4.3. 
Justification for Dose .................................................................................. 20 
4.4. 
End of Study Definition ............................................................................... 21 
5. 
STUDY POPULATION ........................................................................................... 21 
5.1. 
Inclusion Criteria ......................................................................................... 21 
5.2. 
Exclusion Criteria ........................................................................................ 23 
5.3. 
Lifestyle Considerations .............................................................................. 25 
5.3.1. 
Meals and Dietary Restrictions .................................................... 25 
5.3.2. 
Caffeine, Alcohol, and Tobacco ................................................... 25 
5.3.3. 
Activity ......................................................................................... 26 
5.4. 
Screen Failures........................................................................................... 26 
5.5. 
Criteria for Temporarily Delaying ................................................................ 26 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 27 
6.1. 
Study Interventions Administered ............................................................... 27 
6.1.1. 
Dosing Instructions for TRIUMEQ and DOVATO 
Dispersible Tablets ...................................................................... 27 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 28 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 28 
6.4. 
Study Intervention Compliance ................................................................... 28 
6.5. 
Dose Modification ....................................................................................... 29 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 29 
6.7. 
Treatment of Overdose ............................................................................... 29 
6.8. 
Concomitant Therapy.................................................................................. 29 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 30 
7.1. 
Discontinuation of Study Intervention .......................................................... 30 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 30 
7.1.2. 
QTc Stopping Criteria .................................................................. 31 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 31 
7.3. 
Lost to Follow-up ........................................................................................ 32 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 32 
8.1. 
Efficacy Assessments ................................................................................. 33 
8.2. 
Safety Assessments ................................................................................... 33 
8.2.1. 
Physical Examinations ................................................................. 33 
8.2.2. 
Vital Signs .................................................................................... 33 
8.2.3. 
Electrocardiograms ...................................................................... 33 
8.2.4. 
Clinical Safety Laboratory Assessments ...................................... 34 
8.2.5. 
Pregnancy Testing ....................................................................... 34 
8.2.6. 
Palatability Assessment ............................................................... 34 
8.2.7. 
Toxicity Management ................................................................... 34 
8.2.8. 
COVID-19 Measures ................................................................... 35 
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting .................................................................................................... 35 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 35 
8.3.2. 
Method of Detecting AEs and SAEs ............................................. 36 
8.3.3. 
Follow-up of AEs and SAEs ......................................................... 36 
8.3.4. 
Regulatory Reporting Requirements for SAEs ............................. 36 
8.3.5. 
Pregnancy ................................................................................... 36 
8.4. 
Pharmacokinetics ....................................................................................... 37 
8.5. 
Genetics and/or Pharmacogenomics .......................................................... 37 
8.6. 
Biomarkers ................................................................................................. 37 
8.7. 
Immunogenicity Assessments ..................................................................... 37 
8.8. 
Medical Resource Utilization and Health Economics .................................. 37 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 37 
9.1. 
Statistical Hypotheses................................................................................. 37 
9.2. 
Sample Size Determination ........................................................................ 38 
9.2.1. 
Sample Size Assumption ............................................................. 38 
9.2.2. 
Sample Size Sensitivity ................................................................ 38 
9.3. 
Analysis Sets .............................................................................................. 38 
9.4. 
Statistical Analyses ..................................................................................... 39 
9.4.1. 
Pharmacokinetic Analysis ............................................................ 39 
9.4.2. 
Safety Analysis ............................................................................ 41 
9.4.3. 
Other Analysis ............................................................................. 41 
9.5. 
Interim Analysis .......................................................................................... 41 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 42 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 42 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 42 
10.1.2. 
Financial Disclosure ..................................................................... 42 
10.1.3. 
Informed Consent Process .......................................................... 43 

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10.1.4. 
Data Protection ............................................................................ 43 
10.1.5. 
Committees Structure .................................................................. 44 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 44 
10.1.7. 
Data Quality Assurance ............................................................... 44 
10.1.8. 
Source Documents ...................................................................... 45 
10.1.9. 
Study and Site Start and Closure ................................................. 46 
10.1.10. Publication Policy ......................................................................... 46 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 48 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting ............................................................................................. 50 
10.3.1. 
Definition of AE ............................................................................ 50 
10.3.2. 
Definition of SAE .......................................................................... 51 
10.3.3. 
Recording and Follow-up of AE and SAE..................................... 52 
10.3.4. 
Reporting of Serious Adverse Events to VH/GSK ........................ 54 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 56 
10.4.1. 
Definitions: ................................................................................... 56 
10.4.2. 
Contraception Guidance: ............................................................. 57 
10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 59 
10.6. 
Appendix 6: Clinical Protocol COVID-19: Recommended Measures 
Pandemic and Clinical Trial Continuity ........................................................ 61 
10.6.1. 
Study Procedures During COVID-19 Pandemic ........................... 61 
10.7. 
Appendix 7: Toxicity Management .............................................................. 62 
10.7.1. 
Specific Toxicities/Adverse Event Management ........................... 63 
10.8. 
Appendix 8: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Corrected Version 2.1, July 2017 ................. 67 
10.9. 
Appendix 9: Abbreviations and Trademarks ................................................ 68 
11. REFERENCES ....................................................................................................... 70 
 

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Brief Summary: The purpose of this study is to assess the effect of food on the PK of the 
pediatric formulations of TRIUMEQ or DOVATO in normal healthy adult participants. 
Study details include: 
• Total study duration for each cohort: 51 days (including screening) 
• Treatment duration: 2 days (Day 1 of each period) 
• Visit frequency: Follow-up visit 7 to 14 days after the last dose of study 
intervention in Period 2. 
Number of Participants: Per cohort, approximately 16 participants will be randomized 
to receive and be treated with study intervention to ensure that 14 evaluable participants 
complete the study in each cohort. 
Intervention Groups and Duration: In each cohort, participants will receive a single 
dose of each of the following study interventions, administered as 1 treatment per period, 
according to their assigned sequence: 
• 
Cohort 1:  
• Treatment A: Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 6 dispersible 
tablets) administered as a dispersion and taken immediately under fed conditions. 
• Treatment B: Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 6 dispersible 
tablets) administered as a dispersion and taken immediately under fasted conditions. 
Cohort 2: 
• Treatment C: Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 6 dispersible tablets) 
administered as a dispersion and taken immediately under fed conditions. 
• Treatment D: Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 6 dispersible tablet) 
administered as a dispersion and taken immediately under fasted conditions. 
• 
Participants administered Treatments A and C will fast overnight for at least 
10 hours prior to dosing and will receive a high-fat (approximately 50 percent of 
total caloric content of the meal) and high-calorie (approximately 800 to 1000 
calories) meal 30 minutes prior to dosing. Dose administration will occur within 
5 minutes of completion of meal consumption. Participants will not receive any 
further food until 4 hours after dosing.  
• 
Participants administered Treatments B and D will fast overnight for at least 
10 hours prior to dosing and until 4 hours after dosing. 
Data Monitoring/ Other Committee: No 

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1.2. 
Schema 
 
3TC = lamivudine; ABC = abacavir; DTG = dolutegravir. 
Washout will be at least 7 days minus 4 hours. 

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1.3. 
Schedule of Activities 
• 
Screening procedures may be done over more than 1 visit but must all be completed 
within 28 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/exclusion criteria. 
Screening Visit 
Procedure 
Screening (Day -28 to -2) 
Informed consent 
X 
Inclusion and exclusion criteria 
X 
Demographics 
X 
Full physical examination including height, weight, and body mass index1 
X 
Laboratory assessments (hematology, chemistry, urinalysis)  
X 
Human leukocyte antigen (HLA)-B*5701 
X 
12-lead electrocardiogram  
X 
Vital sign measurements 
X 
Medication/drug/alcohol history 
X 
Past and current medical conditions 
X 
Pregnancy test 
X 
Follicle-stimulating hormone (as needed, to confirm postmenopausal status) 
X 
Molecular test for SARS-CoV-22 
X 
Drug, alcohol, and cotinine screen 
X 
Human immunodeficiency virus, hepatitis B and hepatitis C screening  
X 
1 
A full physical examination will include at a minimum, assessments of the skin, lungs, cardiovascular system, 
respiratory, gastrointestinal, abdomen (liver and spleen), 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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3TC = lamivudine; ABC = abacavir; AE = adverse event; DTG = dolutegravir; ECG = electrocardiogram; PK = pharmacokinetic; SAE = serious adverse event. 
1. 
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). 
2. 
Participants will be admitted to the study site up to 48 hours prior to dosing. 
3. 
Follow-up visit will occur 7 to 14 days after the last dose of study intervention. 
At follow-up, male participants with no ongoing AEs or vital sign/clinical laboratory results of clinical concern may be followed up virtually by the site via telephone contact. 
Female participants must return for a pregnancy test. 
4. 
Follow-up assessments should be completed in the event of an early participant discontinuation. 
5. 
Clinical laboratory assessment at follow-up is only necessary if a participant had a previous abnormal clinical laboratory value. 
6. 
The first test should be performed ≥7 days prior to admission. The second test should be performed 24 hours prior to admission to the unit. Participants should be 
quarantined within the unit until the second test result is negative. Once the test result is confirmed to be negative, participants can be released into the unit and will follow 
infection control practices. 
7. 
Dosing will occur at Hour 0 on Day 1 of each period. 
Treatment A: Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 6 dispersible tablets) administered as a dispersion and taken immediately under fed conditions. 
Treatment B: Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 6 dispersible tablets) administered as a dispersion and taken immediately under fasted conditions. 
Treatment C: Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 6 dispersible tablets) administered as a dispersion and taken immediately under fed conditions. 
Treatment D: Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 6 dispersible tablets) administered as a dispersion and taken immediately under fasted conditions. 
8. 
Blood collection for PK analysis of DTG, ABC, and/or 3TC will be collected within 60 minutes prior to dosing (0 hour) and 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4 (prior to 
provision of food), 5, 6, 8, 12, 24, 48, and 72 hours post dose in each period. 
9. 
See Section 8.3 for details for AE and SAE time periods and reporting. 
• 
The timing and number of planned study assessments, including safety, PK, or other assessments may be altered during the course of 
the study based on newly available data (e.g., to obtain data closer to the time of peak plasma concentrations) to ensure appropriate 
monitoring.  
• 
Any changes in the timing or addition 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/Independent Ethics Committee 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. The changes will be 
approved by the competent authorities and the ethics committee before implementation. 

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2. 
INTRODUCTION 
TRIUMEQ™ (GSK2619619) is a fixed-combination (FDC) that contains the integrase 
inhibitor (INI) dolutegravir (DTG) (TIVICAY™, [GSK Document Number 
RM2007/00683/14]) and 2 nucleoside reverse transcriptase inhibitors, abacavir (ABC) 
and lamivudine (3TC) first approved in the US in 2014 [TRIUMEQ, 2014]. 
DOVATOTM (GSK3515864) is a fixed-dose combination (FDC) 2-drug regimen that 
contains the INI DTG [TIVICAY, [GSK Document Number RM2007/00683/14]) and 
the nucleoside reverse transcriptase inhibitor 3TC first approved in the US in 2019 
[DOVATO, 2019]. 
2.1. 
Study Rationale 
A dispersible tablet formulation (5-mg tablet for oral suspension) of TIVICAY has been 
developed and approved for administration in the younger pediatric populations aged 
4 weeks and weighing at least 3 kg. 
Both TRIUMEQ and DOVATO are FDC tablets and cannot be adjusted. The 
development of a pediatric dispersible tablet formulation of the 2-drug and 3-drug 
regimen, respectively, which achieves drug exposures similar to that of approved adult 
formulations, would be beneficial to patients weighing less than 25 kg who are not able to 
swallow tablet formulations. Both TRIUMEQ and DOVATO dispersible table 
formulations have been developed, including use of the TRIUMEQ dispersible 
formulation in a current clinical study. 
This study will assess the effect of food on the pharmacokinetics (PK) of TRIUMEQ 
(DTG 5 mg/abacavir [ABC] 60 mg/3TC 30 mg) dispersible tablets (6 dispersible tablets 
to achieve DTG 30 mg/ABC 360 mg/3TC 180 mg) and DOVATO (DTG 5 mg/3TC 
30 mg) dispersible tablets (6 dispersible tablets to achieve DTG 30 mg/3TC 180 mg), 
both being developed for pediatric populations. In addition, this study will assess the 
safety and tolerability of DOVATO (DTG 5 mg/3TC 30 mg) (6 dispersible tablets to 
achieve DTG 30 mg/3TC 180 mg) dispersible tablets and TRIUMEQ (DTG 5 mg/ABC 
60 mg/3TC 30 mg) (6 dispersible tablets to achieve DTG 30 mg/ABC 360 mg/3TC 
180 mg) dispersible tablets. 
This study will be conducted in accordance with the Food and Drug Administration 
(FDA) guidance for industry on food-effect bioavailability and fed bioequivalence studies 
[Department of Health and Human Services [DHHS, 2002]. 
2.2. 
Background 
TIVICAY, as a DTG single-drug entity, is a next generation INI with low to moderate 
inter-participant PK variability, a predictable exposure-response relationship, and a 
14-hour plasma half-life that supports once-daily dosing without the need for PK 
boosters.  
Fixed-dose combinations have greatly simplified the treatment of patients with human 
immunodeficiency virus (HIV). The promise of improved adherence is important; FDCs 

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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 (ART) 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. To 
achieve successful long-term treatment, the prevention of drug resistance has become the 
most significant challenge. 
DOVATO is a two-drug, FDC tablet. The combination of DTG, with its high barrier to 
resistance and ability to confer a rapid decline in HIV-1 ribonucleic acid (RNA), with the 
nucleoside reverse transcriptase inhibitor 3TC, has shown a low frequency of virologic 
failure and emergent resistance comparable with other currently available three-drug 
regimens. The efficacy and safety of the two-drug FDC of DOVATO makes it suitable 
for both treatment-naïve individuals, and as a replacement treatment for three-drug ART 
in virologically suppressed (“switch”) patients [DOVATO, 2019]. 
TRIUMEQ is a three-drug FDC tablet developed to address the need for a FDC with an 
integrase strand transfer inhibitor paired with a dual nucleoside reverse transcriptase 
inhibitor backbone (ABC/3TC) and is now approved for the treatment of HIV in adults 
and pediatric patients weighing at least 40 kg as a single-tablet regimen with or without 
food to achieve convenient dosing and improve patient compliance.  
Alternate formulations (e.g., dispersible tablets) and dosing strategies for both DOVATO 
and TRIUMEQ have been developed for pediatric patients less than 12 years old who 
may have difficulty swallowing conventional tablet formulations. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of DTG as a 
single entity, in combination with ABC/3TC as TRIUMEQ, and in combination with 3TC 
as DOVATO, is provided in the Clinical Investigator’s Brochure (CIB) [GSK Document 
Number RM2007/00683/14]  and the prescribing information TIVICAY, 2013; 
DOVATO, 2019;TRIUMEQ, 2014]. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events (AEs) of DTG, ABC, and 3TC may be found in the 
CIB [GSK Document Number RM2007/00683/14] and the prescribing information 
[DOVATO, 2019; TRIUMEQ, 2014]. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy1 
Gastrointestinal (GI) 
intolerance 
Nonclinical studies showed upper and lower GI toxicity, including vomiting, 
diarrhea, and gastric erosions observed in monkey toxicology studies 
(thought to be related to local and not systemic toxicity).  
Mild to moderate GI intolerance (mainly diarrhea and nausea) is 
associated with DTG treatment in a small proportion of participants; 
however, there were no indications of an increased risk for peptic ulcers or 
serious erosions. 
Routine monitoring of GI symptoms will be performed (Section 8.3 
and Appendix 3). 
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 
OCT-2 receptor. DTG has been shown to have no significant effect on 
glomerular filtration rate (GFR) or effective renal plasma flow. 
Measurement of albumin/creatinine ratio confirmed there was no 
difference in the effect of DTG on albumin excretion compared with EFV or 
Raltegravir (RAL). 3TC is eliminated by renal excretion and exposure 
increases in patients with renal dysfunction. 
Due to requirements for dose reduction of 3TC in patients with renal 
dysfunction, participants with a creatinine clearance <90 mL/min are 
excluded (Section 5.2). 
Specific/detailed toxicity management guidance is provided for 
participants who develop a decline in renal function (Appendix 5). 
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 suicide ideation and behaviors are common 
in HIV-infected patients. The psychiatric profile for DTG (including 
suicidality, depression, bipolar and hypomania, anxiety, and abnormal 
dreams) was similar or favorable compared with other ARVs. 
The reporting rate for insomnia was statistically higher for blinded 
DTG+ABC/3TC compared with EFV/TDF/FTC in ING114467; however, 
this was not duplicated in any other Phase IIb/III study conducted with 
DTG. 
 This study is limited to healthy volunteers only (Section 5.1). 
Creatine phosphokinase 
(CPK) elevations 
Asymptomatic CPK elevations mainly in association with exercise have 
been reported with DTG therapy. 
Specific detailed toxicity management guidance is provided for 
participants who develop Grade 3 to 4 CPK elevations (Appendix 5). 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy1 
Use in pregnancy 
The safe use of DTG in human pregnancy has not been established. DTG 
has been shown to cross the placenta in reproductive toxicity studies in 
animals. DTG has not been associated with findings in animal 
reproductive studies. 
Women who are pregnant will be excluded from the study 
(Section 5.2). 
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. 
1. 
Careful monitoring of events will be conducted using serious adverse event (SAE) reports and alerts for Grade 3/4 laboratory toxicities (per Division of Acquired Immune 
Deficiency Syndrome [DAIDS] toxicity grading for HIV-infected patients [Appendix 8]). Serious/severe events will be managed appropriately including, but not limited to, 
withdrawal of study intervention and will be followed to resolution as per sponsor’s standard medical monitoring practices.  

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quantifiable concentration; DTG = dolutegravir; ECG = electrocardiogram; PK = pharmacokinetics; SAE = serious 
adverse event; t1/2 = terminal elimination phase half-life; tlag = lag time for absorption; Tmax = time of maximum 
observed concentration; Vz/F = apparent volume of distribution. 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a 2-cohort, single-center, randomized, open-label, single-dose, crossover study to 
assess the effect of food on the PK of the pediatric formulations of TRIUMEQ 
(DTG/ABC/3TC) dispersible tablets and DOVATO (DTG/3TC) dispersible tablets in 
healthy adult participants. 
The study will consist of a screening period, 2 treatment periods with a single dose of 
study intervention per treatment period in each cohort, a washout period, and a follow-up 
visit. Participants will have a screening visit within 28 days before the first dose of study 
intervention. 
In each cohort, prior to dosing on Day 1 of Period 1, participants will be randomly 
assigned to 1 of 2 treatment sequences (AB or BA in Cohort 1 and CD or DC in 
Cohort 2). Cohorts are independent of one another and may run in parallel. 
Cohort 1: 
• Treatment A: Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 6 dispersible 
tablets) administered as a dispersion and taken immediately under fed conditions. 
• Treatment B: Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 6 dispersible 
tablets) administered as a dispersion and taken immediately under fasted conditions. 
Cohort 2: 
• Treatment C: Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 6 dispersible tablets) 
administered as a dispersion and taken immediately under fed conditions. 
• Treatment D: Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 6 dispersible tablets) 
administered as a dispersion and taken immediately 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.  
Participants administered Treatments A and C will fast overnight for at least 10 hours 
prior to dosing and will receive a high-fat (approximately 50 percent of total caloric 
content of the meal) and high-calorie (approximately 800 to 1000 calories) meal 
30 minutes prior to dosing (Section 6.1.1) per the Food and Drug Administration (FDA) 
guidance for industry on food-effect bioavailability and fed bioequivalence studies 
[DHHS, 2002]. Dose administration will occur within 5 minutes of completion of meal 
consumption. Participants will not receive any further food until 4 hours after dosing.  

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Participants administered Treatments B and D will fast overnight for at least 10 hours 
prior to dosing and until 4 hours after dosing. 
Pharmacokinetic blood samples for the analysis of DTG, ABC, and 3TC will be collected 
prior to dosing (0 hour) on Day 1 and up to 72 hours postdose in Periods 1 and 2. 
Safety and tolerability will be assessed by monitoring and recording of AEs, 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). In each of the 2 treatment periods, participants will be admitted to the study 
site up to 48 hours prior to dosing and will be discharged following completion of the last 
study procedure on Day 4 of each period. Participants will return to the study site for a 
follow-up visit 7 to 14 days after the last dose of study intervention in Period 2. The total 
duration of the study, including screening, is approximately 51 days. 
4.2. 
Scientific Rationale for Study Design 
This is an open-label, single-dose, 2-cohort, 2-period, single-center, crossover study to 
investigate the effect of food on the PK of the pediatric formulations of TRIUMEQ and 
DOVATO dispersible tablets.  
The study will investigate the effect of a high-fat and high-calorie meal on the PK, safety, 
and tolerability of the pediatric formulations of TRIUMEQ and DOVATO dispersible 
tablets compared to administration under fasting conditions in accordance with the Food 
and Drug Administration (FDA) guidance for industry on food-effect bioavailability and 
fed bioequivalence studies [DHHS, 2002]. 
 
TRIUMEQ dispersible tablet is a bilayer tablet with DTG and 3TC in one layer and ABC 
in the other layer. DOVATO dispersible tablet formulation is a monolayer tablet. DTG 
and 3TC are common both in TRIUMEQ and DOVATO dispersible tablet formulations. 
Since both formulations are not identical, the impact of food on each of the components 
may be different; thus, both formulations are included in the study. 
The open-label crossover design of this study is well-established for studying the effect 
of food. 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 subject to the appropriate regulatory and ethics committee approval and will 
be listed on the website ClinicalTrials.gov. No placebo control will be used, as this is not 
necessary for the purposes of this study. 
4.3. 
Justification for Dose 
The US FDA-approved dose of TRIUMEQ for the treatment of HIV infection in adults 
and pediatric patients weighing at least 40 kg is 1 oral tablet, once daily, with or without 

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food. TRIUMEQ is an FDC product containing 600 mg of ABC, 50 mg of DTG, and 
300 mg of 3TC.  
The US FDA-approved dose of DOVATO for the treatment of HIV infection in adults is 
1 oral tablet, once daily, with or without food. DOVATO is an FDC product containing 
50 mg of DTG and 300 mg of 3TC.  
The US FDA has approved TIVICAY tablets and tablets for suspension for the treatment 
of HIV-1 infection in pediatric patients as young as 4 weeks of age and weighing at least 
3 kg in combination with other ART.  
The highest approved TIVICAY dose with the dispersible tablet formulation is 30 mg. 
The pediatric TRIUMEQ dispersible tablet dose of 30 mg DTG, 360 mg ABC, and 
180 mg 3TC (6 tablets each consisting of DTG 5 mg, ABC 60 mg, and 3TC 30 mg) and 
the pediatric DOVATO dispersible tablet dose of 30 mg DTG and 180 3TC (6 tablets 
each consisting of DTG 5 mg and 3TC 30 mg) were selected for this study as these will 
be the highest marketed doses for the pediatric population. 
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 final date on which data were or are expected to be 
collected. 
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 
Age 
1. Participant must be 18 to 50 years of age inclusive, at the time of signing the 
informed consent. 
Type of Participant and Disease Characteristics 
2. Participants who are healthy as determined by the investigator or medically qualified 
designee based on a medical evaluation including medical history, physical 
examination, laboratory tests, and cardiac monitoring (history and electrocardiogram 
[ECG]).  

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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 31.0 kg/m2 (inclusive). 
Sex 
Sex and Contraceptive/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: 
1. A male participant must agree to use contraception as detailed in Appendix 4 
during the treatment period and for at least 2 weeks plus an additional 90 days 
(a spermatogenesis cycle) after the last dose of study intervention and refrain 
from donating sperm during this period. 
b. Female Participants:  
1. 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: 
o Is not a woman of childbearing potential (WOCBP) as defined in 
Appendix 4. 
OR 
o 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 30 days (i.e., 5 half-lives) 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. 
• A WOCBP must have a negative highly sensitive serum pregnancy test (Appendix 2) 
at screening and check-in (Day -1). 
• 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 informed 
consent form (ICF) and in this protocol. 

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History/Diagnostic 
6. Documentation that the participant is negative for the human leukocyte antigen 
(HLA)-B*5701 allele. 
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. 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. 
3. A pre-existing condition interfering with normal gastrointestinal anatomy or motility 
(e.g., gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal 
function, that could interfere with the absorption, metabolism, and/or excretion of the 
study intervention. 
4. QTcF >450 msec 
NOTES:  
o The QTc is the QT interval corrected for heart rate according to Fridericia’s 
formula (QTcF) machine-read or manually over-read. 
o QTcF will be used to determine eligibility and discontinuation for an 
individual participant in this trial. 
5. A participant with known or suspected active coronavirus disease (COVID-19) 
infection OR contact with an individual with known COVID-19, within 14 days of 
study enrollment. 
Laboratory Assessments 
6. Presence of hepatitis B surface antigen at screening or within 3 months prior to 
starting study intervention. 
7. Positive hepatitis C antibody test result at screening or within 3 months prior to 
starting study intervention AND positive on reflex to hepatitis C RNA. 
8. Positive HIV-1 and -2 antigen/antibody immunoassay at screening. 
9. 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. 
10. 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. 
11. Any acute laboratory abnormality at screening which, in the opinion of the 
investigator, should preclude participation in the study of an investigational 
compound. 

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12. Any Grade 2 to 4 laboratory abnormality at screening, with the exception of creatine 
phosphokinase (CPK) and 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 laboratory abnormality is allowed 
within a single screening period to determine eligibility. 
13. A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine 
(indicating active current smoking) at screening or before the first dose of study 
intervention. 
Prior/Concomitant Therapy 
14. Unable to refrain from the use of prescription or non-prescription drugs including 
vitamins, herbal and dietary supplements (including St John’s wort) within 7 days (or 
14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) 
prior to the first dose of study intervention and for the duration of the study until 
completion of the follow-up visit, unless, in the opinion of the investigator and ViiV 
Healthcare (VH)/GSK medical monitor, the medication will not interfere with the 
study procedures or compromise participant safety. (Note: acetaminophen at doses of 
2 grams/day is permitted for use any time during the study.) 
15. 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/Concurrent Clinical Study Experience 
16. Participation in another concurrent clinical study or prior clinical study (with the 
exception of imaging trials) prior to Day 1 of Period 1 in the current study: 30 days, 
5 half-lives, or twice the duration of the biological effect of the study intervention 
(whichever is longer). 
 
17. Where participation in the study would result in donation of blood or blood products 
in excess of 500 mL within 60 days. 
Diagnostic assessments 
18. Estimated serum creatinine clearance (CKD-EPI) <90 mL/min. 
 
Other Exclusions 
19. History of regular alcohol consumption within 6 months of the study, defined as an 
average weekly intake of >14 units for males or >7 drinks for females. One unit is 
equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of 
wine, or 1.5 ounces (45 mL) of 80 proof distilled spirits. 
20. Unable to refrain from tobacco or nicotine-containing products within 1 month prior 
to screening. 

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21. History of sensitivity, prior intolerance or hypersensitivity 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 one glass of wine or juice or one of these fruits per day, in 
combination. 
• Participants will refrain from chewing or ingesting sugar-free gums, candies or other 
processed food/drink products that contain sugar alcohols (e.g., sorbitol, mannitol, 
xylitol, maltitol, isomalt) during the inpatient period of each dosing session (i.e., 
Day 1 through 96 hours post dose in each period). 
• Once in the clinical unit, participants will not be allowed to eat anything other than 
the food provided by the study center. 
• No water is allowed from 1 hour prior to dosing until 2 hour after dosing except for 
the glass of water needed to administer the study intervention (Section 6.1.1). Water 
is allowed ad libitum at all other times. 
• The food content of meals must be identical on the Day 1 serial PK sampling for 
Periods 1 and 2. 
5.3.1.1. 
Fed Conditions 
• 
Treatments A and C will be administered in the fed state. Participants will fast 
overnight for at least 10 hours prior to dosing and will receive a high-fat and 
high-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 on serial PK sampling days (i.e., Day 1 of Periods 1 
and 2). A high-fat (approximately 50 percent of total caloric content of the meal) 
and high-calorie (approximately 800 to 1000 calories) meal is recommended as 
a test meal which should derive approximately 150, 250, and 500 to 600 calories 
from protein, carbohydrate, and fat, respectively, per FDA guidance [DHHS, 
2002]. 
5.3.1.2. 
Fasted Conditions 
• 
Treatments B and D will be administered in the fasted state. Participants will 
fast overnight for at least 10 hours prior to dosing until 4 hours after dosing. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
• During each dosing session, participants will abstain from ingesting caffeine- or 
xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 

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24 hours before the start of dosing until after collection of the final PK sample at 
72 hours postdose. 
• During each dosing session, participants will abstain from alcohol for 24 hours before 
the start of dosing until after collection of the final PK sample at 72 hours post dose.  
• Use of tobacco- and nicotine-containing products will not be allowed from 1 month 
prior to screening until after the final visit. 
• Participants must have a negative drug test at screening and Day -1 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 48 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 (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations, and any 
serious AEs (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. 

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6. 
STUDY INTERVENTION 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 
Intervention Name 
TRIUMEQ (DTG/ABC/3TC) 
DOVATO (DTG/3TC) 
Type  
Drug 
Drug 
Dose Formulation  
Dispersible Tablet 
Dispersible Tablet 
Unit Dose 
Strengths  
Single dose, FDC tablet - DTG 
5 mg/ABC 60 mg/3TC 30 mg 
Single dose, FDC tablet - DTG 
5 mg/3TC 30 mg 
Dosage Level 
6 dispersible tablets of DTG 
5 mg/ABC 60 mg/3TC 30 mg for a 
total dose of 30 mg/360 mg/180 mg 
6 dispersible tables of DTG 5 mg/3TC 
30 mg for a total dose of 
30 mg/180 mg 
Route of 
Administration 
Oral 
Oral 
IMP and NIMP 
IMP 
IMP 
Sourcing 
Sourced by sponsor 
Sourced by sponsor 
Packaging and 
Labelling 
Study Intervention will be provided 
in high-density polyethylene 
bottles. Each bottle will be labelled 
as required per country 
requirement. 
Study Intervention will be provided in 
high-density polyethylene bottles. 
Each bottle will be labelled as 
required per country requirement. 
• 
3TC = lamivudine; ABC, abacavir; DTG = dolutegravir; FDC = fixed-dose combination; IMP = investigational 
medicinal product 
6.1.1. 
Dosing Instructions for TRIUMEQ and DOVATO Dispersible 
Tablets 
• Each dispersible tablet for TRIUMEQ contains DTG 5 mg/ABC 60 mg/3TC 30 mg. 
Six dispersible tablets will be needed to achieve the total dose (DTG 30 mg/ABC 
360 mg/3TC 180 mg). 
• Each dispersible tablet for DOVATO contains DTG 5 mg/3TC 30 mg. Six dispersible 
tablets will be needed to achieve the total dose (DTG 30 mg/3TC 180 mg). 
1. Place 20 mL of clean drinking water in a 60 mL dosing cup. A syringe is appropriate 
to measure this volume to ensure accuracy. 

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2. Place 6 tablets into the container and swirl gently for 1 to 2 minutes to disperse the 
tablets. Ensure the tablets have fully dispersed before moving to the next step. 
3. Have the participant swallow the dispersion as swiftly as they can, preferably in 1 to 
2 swallows. 
4. Rinse the container with 15 mL of water (a syringe is appropriate to measure this 
volume to ensure accuracy) and have the participant swallow the rinse as swiftly as 
they can, preferably in 1 to 2 swallows. 
5. Give the participant an additional 205 mL of water to swallow (Note: total volume of 
water given in steps 1 through 5 should be 240 mL and will be documented). Note: 
the words “immediately dose” in the protocol mean within 30 minutes after 
completion of the preparation. 
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 study site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff. 
3. The investigator, study site, 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. 
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, single-center study. Within each cohort, study participants will be 
randomly assigned to 1 of 2 treatment sequences in accordance to the randomization 
scheduled 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 study site, they will receive study intervention 
directly from the investigator or designee, under medical supervision. The date and 

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time of each dose administered in the study site 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 after completion of 
the study because only healthy participants are eligible for study participation. 
6.7. 
Treatment of Overdose 
For this study, any dose of TRIUMEQ greater than DTG 30 mg/ABC 360 mg/3TC 
180 mg (6 tablets of DTG 5 mg/ABC 60 mg/3TC 30 mg) or DOVATO greater than DTG 
30 mg/3TC 180 mg (6 tablets of DTG 5 mg/3TC 30 mg) within a 24-hour time period, 
will be considered an overdose. 
VH/GSK does not recommend specific treatment for an overdose of TRIUMEQ or 
DOVATO. The investigator will use clinical judgement 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/SAE and laboratory abnormalities until 
TRIUMEQ or DOVATO can no longer be detected systemically (at least 7 days). 
3. Obtain a plasma sample for PK analysis within 2 days from the date of 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 
on the printed case report form (CRF) or electronic CRF (eCRF). 
Decisions regarding dose interruptions will be made by the investigator in consultation 
with the medical monitor based on the clinical evaluation of the participant. 
6.8. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
• reason for use 
• dates of administration including start and end dates 

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• dosage information including dose and frequency 
The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Participants must abstain from taking prescription or non-prescription drugs including 
vitamins, herbal and dietary or herbal 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 until 
completion of the follow-up visit, unless, in the opinion of the investigator and VH/GSK 
medical monitor, the medication will not interfere with the study procedures or 
compromise participant safety. 
Acetaminophen at doses of 2 grams/day is permitted for use any time during the study. 
Other concomitant medications may be considered on a case-by-case basis by the 
investigator in consultation 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 not 
remain in the study to be evaluated for PK. 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. 
7.1.1. 
Liver Chemistry Stopping Criteria 
Study intervention will be discontinued for a participant if liver chemistry stopping 
criteria are met: 

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Figure 1 
Phase 1 Liver Chemistry Stopping Criteria – Liver Stopping Event 
Algorithm 
 
ALT = alanine transaminase; INR = international normalized ratio; SAE = serious adverse event; ULN = upper limit of 
normal. 
Refer to Appendix 5 for required Liver Safety Actions and Follow-up Assessments. 
7.1.2. 
QTc Stopping Criteria 
The same correction formula (QTcF) must be used for each individual participant to 
determine eligibility for and discontinuation from the study. This formula may not be 
changed or substituted once the participant has been enrolled. 
• An enrolled participant that develops an on-treatment QTcF >500 msec or an increase 
from baseline QTcF >60 ms should have 2 repeat unscheduled ECGs within 
10 minutes. Using these triplicate ECGs, if the average QTcF >500 ms or an increase 
from baseline QTcF >60 ms, the participant will be withdrawn from the study. 
• 
See the SoA (Section 1.3) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that need to be 
completed. 
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. 
• At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted, as shown in the SoA (Section 1.3). See SoA for data to be 
collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 

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• 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 study site for a 
required study visit: 
• The study 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. 
• 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 
(Section 1.3), 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 
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• Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA (Section 1.3). 
• 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 timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations 
• A brief physical examination (screening and Day -1 of each period) 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 or semi-supine  
position with a completely automated device. Manual techniques will be used only if 
an automated device is not available.  
• Blood pressure and pulse measurements should be preceeded by at least 5 minutes of 
rest for the participant in a quiet setting without distractions (e.g., television, cell 
phones. 
8.2.3. 
Electrocardiograms 
• 12-lead ECGs will be performed with the participant in a supine position having 
rested in this position for at least 10 minutes beforehand. 
• Single 12-lead ECGs will be obtained at screening and Day -1 of each period using an 
ECG machine that automatically calculates the pulse rate and measures PR, QRS, 
QT, and QTcF intervals. Refer to Section 7.1.2 for QTc withdrawal criteria and 
additional QTc readings that may be necessary. 

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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.  
• Clinical laboratory assessments at follow-up are only necessary if a participant had a 
previous abnormal laboratory value. 
• All laboratory tests with values considered clinically significantly abnormal on 
Day -1, Day 4 of each period, or at the follow-up visit (if applicable) should be 
repeated until the values return to normal or baseline or are no longer considered 
significantly abnormal by the investigator or medical monitor. 
o If clinically significant values do not return to normal/baseline within a period 
of time judged reasonable by the investigator, the etiology should be identified 
and the sponsor notified. 
• All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
• If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded. 
8.2.5. 
Pregnancy Testing 
• 
Refer to Section 5.1 Inclusion Criteria 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 involvement in the study. 
8.2.6. 
Palatability Assessment 
A palatability questionnaire will be administered to each participant within 10 minutes 
following dosing of dispersion treatments, as indicated in the SoA (Section 1.3). 
Participants will be given the questionnaire to read prior to receiving each unique 
dispersion dose. Details for the palatability questionnaire will be included in the SRM. 
8.2.7. 
Toxicity Management 
Both ABC and DTG are associated with a risk for hypersensitivity reactions, which were 
observed more commonly with ABC. Hypersensitivity reactions observed for each of 
these study intervention share some common features such as fever and/or rash with other 
symptoms indicating multiorgan involvement. Time to onset was typically 10 to 14 days 
for both ABC and DTG-associated reactions, although reactions to ABC may occur at 
any time during therapy. Additional information on toxicity management is outlined in 
Appendix 7. 

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8.2.8. 
COVID-19 Measures 
The measures approved for implementation within this clinical trial to protect participant 
safety, welfare, and rights, and to ensure data integrity and the integrity of the clinical 
trial, as a result of COVID-19 only, are outlined in Appendix 6. 
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting 
The definitions of AEs or SAEs can be found in Appendix 3. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up all AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study intervention (see Section 7).  
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All AEs and SAEs will be collected from the start of study intervention until the 
follow-up visit at the time points specified in the SoA (Section 1.3). However, any 
SAEs assessed as related to study participation (e.g., study intervention, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or 
related to a VH/GSK product will be recorded from the time a participant consents to 
participate in the study. 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be considered medical history, not an AE, and will 
be recorded in the source documents. 
• All SAEs will be recorded and reported to the sponsor or designee immediately, and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• Investigators are not obligated to actively seek AEs or SAEs after the conclusion of 
the study participation. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has been discharged from the study, and he or 
she considers the event to be reasonably related to the study intervention or study 
participation, the investigator must promptly notify the sponsor. 

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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 nonleading 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 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, Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC), and investigators. 
• 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 investigator’s brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
• 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. 
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 the pregnancy (termination or delivery).  
• 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. 

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• 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 poststudy pregnancy-related SAEs 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. 
8.4. 
Pharmacokinetics 
• Whole blood samples of approximately 2 mL will be collected for measurement of 
plasma concentrations of DTG, ABC, and 3TC, as specified in the SoA (Section 1.3). 
• Instructions for the collection and handling of biological samples will be provided in 
the SRM. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• Samples will be used to evaluate the PK of DTG, ABC, 3TC. 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 and/or Pharmacogenomics 
A sample for HLA-B*5701 allele will be drawn at screening for qualitative 
inclusion/exclusion only. There will be no quantitative analysis of these samples and they 
will not be stored. 
8.6. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.7. 
Immunogenicity Assessments 
Immunogenicity is not evaluated in this 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. An estimation 
approach will be used to evaluate the effect of food on the PK of FDC dispersible tablets. 

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9.2. 
Sample Size Determination 
9.2.1. 
Sample Size Assumption 
A maximum of 16 participants per cohort will be enrolled to study intervention such that 
approximately 14 evaluable participants per cohort complete the study. 
Note: “Enrolled” means a participant’s, or their legally acceptable representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process. 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. 
Based on the results from a previous PK study of DTG granules administered to healthy 
participants [GSK Document Number 2017N330422_00], the within participant 
variability (CVw%) of DTG/ABC/3TC and DTG/3TC area under the plasma 
concentration-time curve (AUC) from time zero extrapolated to infinity (AUC[0-inf]), 
AUC from time zero to time of last observed quantifiable concentration calculated using 
the linear trapezoidal method when concentrations are increasing and the logarithmic 
trapezoidal method when concentrations are decreasing AUC(0-t), and maximum 
observed plasma concentration (Cmax) ranged from 4.8% and 21.4%. Therefore, it was 
decided that 21.4% would be a conservative estimate on which the sample size 
calculation is based. 
For each study cohort, with a sample size of 14 evaluable participants, it is estimated that 
the precision (i.e., half-width of the 90% confidence interval (CI) on the ratio scale) for 
the test:reference comparison will be within 15.3% of the point estimate for AUC(0-inf), 
AUC(0-t), and Cmax. Hence, if the point estimate of the ratio of geometric means is 
1, then the 90% CI will be approximately (0.87, 1.15). 
9.2.2. 
Sample Size Sensitivity 
For the sensitivity analysis, assuming a higher %CVw (30%) and a sample size of 
14 evaluable participants in each study cohort, it was estimated that the half-width of the 
90% CI for the ratio of treatment comparison (test:reference) would be within 21.7% of 
the point estimate for AUC(0-inf), AUC(0-t), and Cmax. Hence, if the point estimate of 
the ratio of geometric means is 1, then the 90% CI will be approximately (0.82, 1.22). 
9.3. 
Analysis Sets 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Screened 
The Screened Population will include all participants who sign the ICF. 
This population will be used to present the date of first subject first 
screened, and numbers of subjects screened and enrolled. 

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Population 
Description 
Safety 
The Safety Population will include 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, summary tables, 
and statistical analysis tables. 
9.4. 
Statistical Analyses 
The statistical analysis plan will be finalized prior to first patient first visit 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 Analysis 
Plasma DTG, ABC, and 3TC concentration-time data will be analyzed by PPD, under the 
oversight of Clinical Pharmacology Modelling & 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 Biostatistics, 
VH/GSK. Calculations will be based on the actual sampling times recorded during the 
study. From the plasma DTG, ABC, and 3TC concentration-time data, the following 
primary pharmacokinetic parameters will be determined and analysed: Cmax, AUC(0-t), 
AUC(0-inf).  The following secondary PK parameters will be summarized: AUC(0-24), 
t1/2,  tmax, tlag, C24, and Ct.  Additional PK parameters may also be summarized: e.g., 
Vz/F, and CL/F.  
 
 
Endpoint 
Statistical Analysis Methods 
Primary 
Cohort 1 
• The primary endpoints of this study are PK-related. The analysis for the 
primary PK endpoints will be performed for the PK Parameter 
Population. Plasma concentrations of DTG, ABC, and 3TC 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: 
• AUC(0-inf), AUC(0-t) and Cmax 

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Endpoint 
Statistical Analysis Methods 
• Analysis will be performed to compare the effect of food (high-fat meal) 
on the PK of DTG, ABC, and 3TC following administration of TRIUMEQ 
dispersible tablets compared to the PK of DTG, ABC, and 3TC following 
administration of TRIUMEQ dispersible tablets under fasted conditions. 
Analyses will be performed on the natural logarithms of AUC(0-inf), 
AUC(0-t), and Cmax using linear mixed effect models with treatment, 
sequence, and period as fixed effects and subject nested within 
sequence as a random effect. Effects will be estimated, and confidence 
intervals (CIs) will be constructed for the following treatment comparison: 
• Treatment A (test) versus Treatment B (reference) 
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. 
• Summary statistics (arithmetic mean, geometric mean, median, standard 
deviation, minimum, maximum, and coefficient of variation) for plasma 
DTG, ABC, and 3TC primary PK parameter values will be summarized 
by treatment. 
Cohort 2 
• The primary endpoints of this study are PK-related. The analysis for the 
primary PK endpoints will be performed for the PK Parameter 
Population. Plasma concentrations of DTG and 3TC 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: 
• AUC(0-inf), AUC(0-t) and Cmax 
• Analysis will be performed to compare the effect of food (high-fat meal) 
on the PK of DTG and 3TC following administration of DOVATO 
dispersible tablets compared to the PK of DTG and 3TC following 
administration of DOVATO dispersible tablets under fasted conditions. 
Analyses will be performed on the natural logarithms of AUC(0-inf), 
AUC(0-t), and Cmax using linear mixed effect models with treatment, 
sequence, and period as fixed effects and subject nested within 
sequence as a random effect. Effects will be estimated, and confidence 
intervals (CIs) will be constructed for the following treatment comparison: 
• Treatment C (test) versus Treatment D (reference) 
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. 
• Summary statistics (arithmetic mean, geometric mean, median, standard 
deviation, minimum, maximum, and coefficient of variation) for plasma 
DTG and 3TC primary PK parameter values will be summarized by 
treatment. 

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Endpoint 
Statistical Analysis Methods 
Secondary 
Cohort 1 and 
Cohort 2 
• 
Based on the individual concentration-actual time data the following 
secondary plasma PK parameters will be estimated: 
• tmax, tlag, t1/2, AUC(0-24), Ct, and C24 
• 
Summary statistics (arithmetic mean, geometric mean, median, 
standard deviation, minimum, maximum, and coefficient of variation) for 
plasma DTG, ABC, and 3TC secondary PK parameter values will be 
summarized by treatment.  
• 
Summary statistics (arithmetic mean, median, standard deviation, 
minimum, maximum, and coefficient of variation) for plasma DTG, ABC, 
and 3TC PK concentrations will be summarized by treatment using the 
PK Concentration Population. 
9.4.2. 
Safety Analysis 
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 (RAP). 
9.4.3. 
Other Analysis 
Palatability questionnaire variables will be summarized descriptively. Further details will 
be provided in the RAP. 
 
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 RAP; 
alternatively, a separate RAP 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, 2020; EMA, 2020]. 
  
9.5. 
Interim Analysis 
No interim analysis is planned. 

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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, CIB, 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 and 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/her representative will explain the nature of the study to the 
participant or his or her legally authorized representative and answer all questions 
regarding the study. 
• Participants must be informed that their participation is voluntary. Participants or his 
or her 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, 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 his or her 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 TRIUMEQ and DOVATO or about the study disease; publish the 
results of these research efforts; work with government agencies or insurers to have the 
TRIUMEQ and DOVATO 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 authorized 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 investigator who participated in the study with a 
summary of the study results . The investigator is encouraged to share the summary 
results with the study participant, as appropriate. 
• The procedures and timing for public disclosure of the protocol and results summary 
and for development of a manuscript for publication for this study will be in 
accordance with VH/GSK Policy. 
• VH/GSK intends to make anonymized patient-level data from this trial available to 
external researchers for scientific analyses or to conduct further research that can help 
advance medical science or improve patient care. This helps ensure the data provided 
by trial participants are used to maximum effect in the creation of knowledge and 
understanding. 
• 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 eCRFs 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 the eCRF Completion 
Guidelines. 
• Quality tolerance limits (QTL) will be predefined in the QTL report to identify 
systematic issues that can impact participant safety and/or reliability of study results. 
These predefined parameters will be monitored during and at the end of the study and 

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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 ICFs, 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/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 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 
regulatory requirements. 

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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 subject 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 

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

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2. 
If alkaline phosphatase is elevated, consider fractionating .A new 5 mL SST blood sample will need to be 
drawn. 
3. 
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 

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• 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 the 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 postmenopausal 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 Methodsb That Have Low User Dependency Failure rate of <1% per 
year when used consistently and correctly. 
• Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
• Intrauterine device 
• Intrauterine hormone-releasing systemc 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a medical cause) 
• 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole 
sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 90 days. 
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 Methodsb That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly. 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
• oral 
• intravaginal 
• transdermal 
• injectable 
• Progestogen-only hormone contraception associated with inhibition of ovulationc 
• oral 
• injectable 
• Sexual abstinence 
• 
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. 

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c. 
Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with 
Clinical Trial Facilitation Group guidelines, acceptable contraceptive methods are limited to those which inhibit 
ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, symptothermal, post ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method are not acceptable methods of contraception for this study. 
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 
Table 2 
Phase 1 Liver Chemistry Stopping Criteria and Required Follow-Up 
Assessments 
Phase 1 Liver chemistry stopping criteria have been designed to assure subject safety and 
to evaluate liver event etiology  
Liver Chemistry Stopping Criteria  
 
ALT-absolute 
 
ALT≥3 × ULN 
If ALT≥3 × ULN AND total bilirubin 2 × ULN (>35% direct bilirubin) or INR >1.5, report to 
VH/GSK as an SAE1,2. 
See additional Actions and Follow-Up Assessments listed below. 
Required Actions, Monitoring and Follow-Up Assessments  
Actions 
Follow-Up Assessments 
• 
Report the event to VH/GSK within 24 hours 
• 
Complete the liver event form 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, stabilise, or return to within baseline (see 
MONITORING below) 
MONITORING: 
If ALT ≥3 × ULN AND total bilirubin ≥2 × ULN or 
INR >1.5 
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin, and INR) and 
perform liver event follow-up assessments within 
24 hours 
• 
Monitor participant twice weekly until liver 
chemistries resolve, stabilise or return to within 
baseline 
• 
A specialist or hepatology consultation is 
recommended 
If ALT≥3 × ULN AND total bilirubin <2 × ULN and 
INR ≤1.5: 
• 
Perform liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin, and INR) and 
perform liver event follow-up assessments within 
24-72 hours 
• 
Monitor participant weekly until liver chemistries 
• 
Viral hepatitis serology3 
• 
Obtain INR and recheck with each liver chemistry 
assessment until the aminotransferase values show 
downward trend 
• 
Obtain 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 event form 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, and other 
over-the-counter medications. 
• 
Record alcohol use on the liver event alcohol intake 
in the eCRF 
 
If ALT≥3 × ULN AND total bilirubin 2 × ULN or INR 
>1.5 obtain the following in addition to the assessments 
listed above: 
• 
Anti-nuclear antibody, anti-smooth muscle antibody, 
Type 1 anti-liver kidney microsomal antibodies, and 
quantitative total immunoglobulin G or gamma 
globulins. 
• 
 Liver imaging (ultrasound, magnetic resonance, or 
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Liver Chemistry Stopping Criteria  
resolve, stabilize, or return to within baseline 
evaluate liver disease; complete liver imaging and/or 
liver biopsy CRF. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation testing is 
not immediately available, discontinue study intervention for that participant if ALT 3 x 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 total 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 to VH/GSK as an SAE (excluding 
studies of hepatic impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving 
anticoagulants. 
3. Includes: hepatitis A immunoglobulin (IgM) antibody; HBsAg and HBcAb; hepatitis C RNA; cytomegalovirus IgM 
antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or monospot 
testing) and hepatitis E IgM antibody. 

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10.6. 
Appendix 6: Clinical Protocol COVID-19: Recommended 
Measures Pandemic and Clinical Trial Continuity 
COVID-19 pandemic may impact the conduct of clinical studies. Challenges may arise 
from quarantines, site closures, travel limitations, 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 administering or using the investigational 
product 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 trial database. 
This appendix outlines measures that may be applicable for any site impacted by the 
COVID-19 pandemic. The purpose of the appendix is to provide information on the 
measures to be taken to protect participants’ safety, welfare and rights, and promote data 
integrity. 
These measures will remain in place until the site is able to resume normal working 
activities OR until study completion/other time period. 
10.6.1. 
Study Procedures During COVID-19 Pandemic 
During the special circumstances caused by the current COVID-19 pandemic, you should 
consider specific public health guidance, the impact of any travel restrictions 
implemented by local/regional health authorities and local institutions, and individual 
benefit/risk when making enrollment and treatment decisions for trial participants. 
Every effort should be made to adhere to protocol-specified assessments for participants 
on study intervention, including follow-up; however when not possible, for the duration 
of these special circumstances, the following measures may be implemented for enrolled 
participants.  
• 
Investigators should document in site files and in participant source documents how 
restrictions related to COVID-19 led to the changes in study conduct and duration of 
those changes and indicate which study participants were impacted and how those 
trial participants were impacted (as per the current local COVID-19 related 
regulatory guidance). 
• 
Missing protocol-required data/visits due to COVID-19 should be noted in 
participant notes and recorded as a COVID-19 protocol deviation. 

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10.7. 
Appendix 7: Toxicity Management 
Adverse events that occur during the trial should be evaluated by the investigator and 
graded according to the DAIDS toxicity scales (see Appendix 8). Additional information 
regarding detecting, documenting and reporting AEs and SAEs are available in 
Appendix 3. 
Study drug may be stopped at the discretion of the investigator and according to the 
severity of the AE. 
No toxicity-related dose reductions of study drugs will be allowed. Guidance is provided 
below on participant management. All changes in study intervention must be accurately 
recorded in the participant’s eCRF. 
NOTE: In the event of a discontinuation of DTG/ABC/3TC FDC for any reason, the 
investigator must obtain a complete history of the events surrounding the discontinuation 
of DTG/ABC/3TC FDC, evaluate for the possibility of a clinically suspected 
hypersensitivity reaction, and initiate participant management as outlined in the DTG 
CIB, regardless of a subject’s HLA-B*5701 status. 
Grade 1 or Grade 2 Toxicity/Adverse Event 
Participants who develop a Grade 1 or Grade 2 AE or toxicity may continue study 
intervention at the discretion of the investigator. Participants who choose to withdraw 
from the study due to a Grade 1 or 2 AE should have study withdrawal and follow-up 
evaluations completed. 
Grade 3 Toxicity/Adverse Event 
Participants who develop a Grade 3 AE or toxicity should be managed as follows: 
If the investigator has compelling evidence that the Grade 3 AE or toxicity has not been 
caused by study intervention, dosing may continue after discussion with the medical 
monitor. 
Participants who develop a Grade 3 AE or toxicity that the investigator considers related 
or possibly related to the study intervention should have study intervention permanently 
discontinued. 
Participants with asymptomatic Grade 3 laboratory abnormalities require permanent 
discontinuation and study drug and should be investigated for all potential non-drug 
related causes.  
Exceptions are noted for rash and hypersensitivity reactions in Section 10.7.1.3. 
Grade 4 Toxicity/Adverse Event 
Participants who develop a Grade 4 AE or toxicity should have study intervention 
discontinued.  

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Participants experiencing Grade 4 AEs requiring permanent discontinuation of study 
intervention should be followed weekly until resolution of the AE and encouraged to 
complete the withdrawal and follow-up study evaluations as noted above. 
Participants with asymptomatic Grade 4 laboratory abnormalities require permanent 
discontinuation of study drug and should be investigated for all potential non-drug related 
causes. An in-clinic follow-up visit will be conducted approximately 4 weeks after the 
last dose of study medication for subjects with ongoing AEs and SAEs and also any 
laboratory abnormalities that are considered to be AEs or potentially harmful to the 
subject, at the last on-study visit. 
10.7.1. 
Specific Toxicities/Adverse Event Management 
General guidelines for the management of specific toxicities that are considered to be 
related or possibly related to study treatment are provided below. 
Participants who permanently discontinue study intervention for reasons of toxicity 
should be followed weekly until resolution of the AE and encouraged to complete the 
withdrawal and follow-up study evaluations (Section 8.3.3). 
10.7.1.1. 
Liver Chemistry Stopping and Follow-up Criteria 
Liver chemistry threshold stopping criteria have been designed to assure subject safety 
and to evaluate liver event aetiology during administration of study drug and the follow-
up period. For a complete listing of stopping and follow-up criteria refer to Appendix 5. 
10.7.1.2. 
Decline in Renal Function  
Participants who experience an increase in serum creatinine from baseline of 
45 micromoles/liter (Mol/L) (or 0.5 milligrams/deciliter [mg/dL]) should return for a 
confirmatory assessment within 2 to 4 weeks. A urinalysis and urine albumin/creatinine 
and urine protein/creatinine ratios, serum cystatin C, and an estimated GFR using the 
CKD-EPI cystatin C method [Inker, 2012] should also be done at this confirmatory visit 
(refer to the SRM for details on the collection and processing of these urine samples). If 
the creatinine increase is confirmed, the investigator should contact the study medical 
monitor to discuss additional follow-up and medical management. 
10.7.1.3. 
Hypersensitivity reaction  
Both ABC and DTG are associated with a risk for hypersensitivity reactions and share 
some common features such as fever and/or rash with other symptoms indicating 
multiorgan involvement. Clinically it is not possible to determine whether a 
hypersensitivity reaction with DTG/ABC/3TC FDC is caused by ABC or DTG. 
Hypersensitivity reactions have been observed more commonly with ABC, some of 
which have been life-threatening, and in rare cases fatal, when not managed 
appropriately. More detailed clinical descriptions of these reactions are included in the 
DTG/ABC/3TC CIB [GSK Document Number RM2007/00683/14]. 

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The risk for ABC hypersensitivity reactions to occur is significantly increased for patients 
who test positive for the HLA-B*5701 allele. However, ABC hypersensitivity reactions 
have been reported at a lower frequency in patients who do not carry this allele. In the 
prospective study CNA106030 (PREDICT-1), the use of pre-therapy screening for the 
presence of HLA-B*5701 and subsequently avoiding ABC in HLA-B*5701 positive 
patients, significantly reduced the incidence of clinically suspected ABC hypersensitivity 
reactions from 7.8% (66 of 847) to 3.4% (27 of 803) (p<0.0001) [Mallal, 2008]. In 
clinical studies EPZ108859 (ARIES) and CNA109586 (ASSERT), 0.8% (4/515) and 
3.1% (6/192) of subjects who were HLA-B*5701 negative and who received ABC 
developed a clinically suspected ABC hypersensitivity reaction, respectively [Post, 2010; 
Squires, 2010]. 
With reference to the DTG/ABC/3TC CIB and the ‘Subject Information and Consent 
Form’, investigators must ensure that participants are fully informed regarding the risk of 
hypersensitivity reactions prior to commencing ABC therapy. Each participant should 
also be reminded of the importance of reading the Alert Card accompanying their study 
medication and keeping it with them at all times. 
The following should be adhered to in the management of participants presenting 
with signs and symptoms suggesting a possible hypersensitivity reaction: 
• 
In any participant treated with DTG/ABC/3TC, the clinical diagnosis of suspected 
hypersensitivity reaction must remain the basis of clinical decision making. 
• 
DTG/ABC/3TC must be stopped without delay, even in the absence of the 
HLA-B*5701 allele, if a hypersensitivity reaction is suspected. Delay in stopping 
treatment with after the onset of hypersensitivity may result in a 
life-threatening reaction. Clinical status including liver aminotransferases and 
bilirubin should be monitored.  
• 
Subjects who have experienced a hypersensitivity reaction should not restart ABC. 
• 
After stopping treatment with DTG/ABC/3TC for reasons of a suspected 
hypersensitivity reaction, DTG/ABC/3TC or any other medicinal product 
containing ABC or DTG must never be reinitiated. 
• 
Restarting ABC-containing products following a suspected ABC 
hypersensitivity reaction can result in a prompt return of symptoms within 
hours and may include life-threatening hypotension and death. 
10.7.1.3.1. Reporting of Hypersensitivity Reactions 
If a clinically suspected case of hypersensitivity reaction to ABC meets one of the 
ICH-E2A definitions of seriousness listed in Appendix 3 then, in addition to reporting the 
case as an SAE, the ABC hypersensitivity reactions printed or eCRF should also be 
completed within one week of the onset of the hypersensitivity reaction. 

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10.7.1.4. 
Skin Reactions without Other Symptoms that are Typical of Abacavir 
Hypersensitivity Reactions 
Including serious skin reactions such as Stevens-Johnson Syndrome, Toxic 
Epidermal Necrolysis, Erythema Multiforme or rash with significant liver 
dysfunction  
Participants should be instructed to contact the investigator as soon as possible if they 
develop a rash while on study. 
Subjects who develop rash of any grade should be evaluated for the possibility of an 
ABC hypersensitivity reaction or a serious skin reaction such as Stevens-Johnson 
syndrome, toxic epidermal necrolysis, or erythema multiforme. Stevens-Johnson 
syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported very 
rarely in patients taking ABC-containing products. These patients generally do not have 
the cluster of additional symptoms (e.g., gastrointestinal and respiratory) that characterize 
the ABC hypersensitivity reaction, but they do have features typical of these serious skin 
reactions. 
If a serious skin reaction develops, ABC should be discontinued, and the subject should 
not be re-challenged with any ABC-containing medicinal product (i.e., TRIUMEQ, 
ZIAGENTM, TRIZIVIRTM, EPZICOM, or KIVEXA). 
Mild to moderate rash is an expected adverse reaction for DTG-containing ART. 
Episodes generally occur within the first 10 weeks of treatment, rarely require 
interruptions or discontinuations of therapy and tend to resolve within 2 to 3 weeks. The 
index case of hypersensitivity with DTG involved a profuse, purpuric, and coalescing 
leukocytoclastic vasculitis as well as clinically significant liver chemistry elevations. 
Other than this case, no other instances of serious skin reaction, including 
Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme, have 
been reported for DTG in clinical trials. 
The following guidance is provided for clinical management of participants who 
experience rash alone in the absence of accompanying diagnosis of ABC hypersensitivity 
reaction, systemic or allergic symptoms or signs of mucosal, or target lesions. 
Participants with an isolated Grade 1 rash may take the second dose of study drug at the 
investigator’s discretion. The participant should be advised to contact the investigator 
immediately if there is any worsening of the rash, if any systemic signs or symptoms 
worsen, or if mucosal involvement develops. 
Participants may take the second dose of study drug for an isolated Grade 2 rash. 
However, study drug should be permanently discontinued for any Grade ≥2 rash that is 
associated with an increase in ALT (Section 7.1.1). The participant should be advised to 
contact the physician immediately if a rash fails to resolve (after more than 2 weeks), if 
there is any worsening of the rash, if any systemic signs or allergic symptoms develop, or 
if mucosal involvement develops. 

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Participants should permanently discontinue study drug for an isolated Grade 3 or 4 rash, 
and the participant should be withdrawn from the study. Participants should be treated as 
clinically appropriate and followed until resolution of the AE. 
The rash and any associated symptoms should be reported as AEs (Section 8.3) and 
appropriate toxicity ratings should be used to grade the events (based on DAIDS toxicity 
gradings). 
If the etiology of the rash can be definitely diagnosed as being unrelated to the study 
intervention and due to a specific medical event or a concomitant  
10.7.1.5. 
Creatine Phosphokinase Elevation 
A Grade 3 or higher elevation in CPK should result in a repeat assessment within 2 to 
4 weeks to ensure the result is transient or due to exercise and will not require a change in 
study intervention. A history regarding use of drugs known to cause increase of CPK 
(such as statins), physical activity, or exercise preceding the CPK evaluation should be 
obtained. Grade 4 elevations in CPK should have a repeat assessment after the participant 
has abstained from exercise for >24 hours.  
 
 

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by third party copyright laws and therefore have been excluded.

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10.9. 
Appendix 9: Abbreviations and Trademarks 
3TC 
Lamivudine 
ABC 
Abacavir 
AE 
Adverse event 
AIDS 
Acquired immune deficiency syndrome 
ALT 
Alanine transaminase 
ART 
Antiretroviral therapy 
AST 
Aspartate aminotransferase 
AUC 
Area under the plasma concentration-time curve 
AUC(0-
24) 
Area under the plasma concentration-time curve from time zero to twenty-four hours 
AUC(0-
inf) 
Area under the plasma concentration-time curve from time zero extrapolated to 
infinity 
AUC(0-t) Area under the concentration-time curve from time zero to time of last observed 
quantifiable concentration 
C24 
Concentration at twenty-four hours post-dose 
CI 
Confidence interval 
CIB 
Clinical Investigator Brochure 
CL/F 
Apparent oral clearance 
Cmax 
Maximum observed plasma concentration 
CONSO
RT 
Consolidated Standards of Reporting Trials 
CPK 
Creatine phosphokinase 
CRF 
Case report form 
CVw% 
Within participant variability 
DAIDS 
Division of AIDS 
DHHS 
Department of Health and Human Services 
DTG 
Dolutegravir 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EU 
European Union 
FDA 
Food and Drug Administration 
FDC 
Fixed-dose combination 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GSK 
GlaxoSmithKline 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
HRT 
Hormone replacement therapy 
ICF 
Informed consent form 
IEC 
Independent Ethics Committee 

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INI 
Integrase inhibitor 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
PK 
Pharmacokinetic(s) 
QTc 
Corrected QT interval 
QTcF 
Corrected QT interval according to Fridericia’s formula 
QTL 
Quality tolerance limit 
RAP 
Reporting and analysis plan 
RNA 
Ribonucleic Acid 
SAE 
Serious adverse event 
SoA 
Schedule of Activities 
SRM 
Study reference manual 
SUSAR 
Serious Unexpected Serious Adverse Reactions 
t1/2 
Terminal elimination phase half-life 
tlag 
Lag time for absorption 
Tmax 
Time to maximum observed concentration taken directly from the concentration-time 
profile 
ULN 
Upper limit of normal 
US 
United States 
VH 
ViiV Healthcare 
Vz/F 
Apparent volume of distribution 
WOCBP 
Women of child bearing potential 
 
Trademark Information 
Trademarks of the ViiV Healthcare and 
GlaxoSmithKline group of companies 
 
Trademarks not owned by the ViiV 
Healthcare and GlaxoSmithKline group 
of companies 
DOVATO 
 
WinNonlin 
KIVEXA/EPZICOM 
 
TIVICAY 
 
TRIUMEQ 
 
TRIZIVIR 
 
ZIAGEN 
 
 
 

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