Conditions: HIV Infections
Keywords: TRIUMEQ DOVATO Pharmacokinetics Food effect Dolutegravir Abacavir Lamivudine
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 33
Healthy volunteers: yes

Brief summary:
This study will assess the effect of food on the pharmacokinetics (PK) of pediatric formulations of TRIUMEQ (dolutegravir \[DTG\] 5 milligrams \[mg\]/abacavir \[ABC\] 60 mg/lamivudine \[3TC\] 30 mg) dispersible tablets and DOVATO (DTG 5 mg/3TC 30 mg) dispersible tablets in healthy adult participants. Additionally, safety and tolerability of these formulations will also be assessed. TRIUMEQ and DOVATO are registered trademarks of GlaxoSmithKline group of companies.

Detailed description:

Arms:
arm 1: Participants received TRIUMEQ (dolutegravir \[DTG\] 5 milligram \[mg\]/abacavir \[ABC\] 60 mg/lamivudine \[3TC\] 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment A) in treatment period 1 followed by TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment B) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2. arm 2: Participants received TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment B) in treatment period 1 followed by TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment A) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2. arm 3: Participants received DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment C) in treatment period 1 followed by DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment D) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2. arm 4: Participants received DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment D) in treatment period 1 followed by DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment C) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2.

Interventions: intervention 1: TRIUMEQ intervention 2: DOVATO
Intervention descriptions: intervention 1: TRIUMEQ will be available as fixed dose combination (FDC) dispersible tablets to be administered orally as a dispersion. intervention 2: DOVATO will be available as FDC dispersible tablets to be administered orally as a dispersion.

Protocol document:
Prot_000.pdf: 
 
 
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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TMF-11803454 
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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 
reasons for screening failure, as applicable. 


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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 
computerized tomography) and/or liver biopsy to 


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


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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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11. 
REFERENCES 
Department of Health and Human Services (DHHS), Food and Drug Administration, 
Center for Drug Evaluation and Research, Center for Drug Evaluation and Research 
(US). Guidance for Industry: Food-effect bioavailability and fed bioequivalence studies. 
December 2002. Available from: https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/food-effect-bioavailability-and-fed-bioequivalence-studies 
Department of Health and Human Services (DHHS), Food and Drug Administration, 
Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research 
(US). Guidance for Industry, Investigators, and Institutional Review Boards. Conduct of 
clinical trials of medical products during the COVID-19 public health emergency. 
December 2020. Available from: https://www.fda.gov/regulatoryinformation/search-fda-
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-
guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-
emergency 
Department of Health and Human Services (DHHS), National Institutes of Health, 
National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of 
AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events, 
Corrected Version 2.1. July 2017. Available from: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
DOVATO Prescribing Information (dolutegravir, and lamivudine tablets), for oral use. 
August, 2019. 
European Medicines Agency (EMA). Science Medicines Health, Committee for Human 
Medicinal Products. Points to consider on implications of coronavirus disease 
(COVID-19) on methodological aspects of ongoing clinical trials. June 2020. Available 
from: https://www.ema.europa.eu/en/documents/scientific-guideline/points-consider-
implications-coronavirus-disease-covid-19-methodological-aspects-ongoing-clinical_en-
0.pdf. 
GlaxoSmithKline Document Number 2017N330422_00. Study 205894A 2-Part, Phase I, 
Single-Dose, 3-Period Crossover Relative Bioavailability Study of a Pediatric TRIUMEQ 
Dispersible Tablet and Pediatric Dolutegravir and Lamivudine (DTG/3TC) Fixed Dose 
Combination Dispersible Tablet Formulations as Compared With Adult Tablets in 
Healthy Volunteers. 2018. 
GlaxoSmithKline Document Number RM2007/00683/14: GSK1349572 Clinical 
Investigator's Brochure, version 14. September 2020. 
Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. 
Estimating glomerular filtration rate from serum creatinine and cystatin c. N Engl J Med. 
2012;367(1):20-9. 
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 
screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568-79. 


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Post FA, Moyle GJ, Stellbrink HJ, Domingo P, Podzamczer D, Fisher M, et al. 
Randomized comparison of renal effects, efficacy, and safety with once-daily 
abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in 
antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. 
J Acquir Immune Defic Syndr. 2010;55(1):49-57. 
Squires KE, Young B, DeJesus E, Bellos N, Murphy D, Sutherland-Phillips DH, et al. 
Safety and efficacy of a 36-week induction regimen of abacavir/lamivudine and 
ritonavir-boosted atazanavir in HIV-infected patients. HIV Clin Trials. 2010;11(2):69-79.  
TIVICAY Prescribing Information (dolutegravir), or oral use. August 2013. 
TRIUMEQ Prescribing Information (abacavir, dolutegravir, and lamivudine tablets), for 
oral use. August, 2014. 

SAP_001.pdf: 
 
 
Reporting and Analysis Plan Amendment 1. 
 
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: 07-JUN-2021 
 
 


 
CONFIDENTIAL 
 
ViiV Healthcare group of companies 
 
216149 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for 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 
Compound Number  : GSK2619619 (Dolutegravir/Abacavir/Lamivudine ) and 
GSK3515864 (Dolutegravir/Lamivudine) 
Clinical Study 
Identifier 
: GSK216149 
Effective Date  
: Refer to Document Date 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report (CSR) for Protocol 216149. 
• 
This RAP is intended to describe the full analyses required for the study.  
• 
This RAP will be provided to the study team members to convey the content of 
the Statistical Analysis Complete (SAC) deliverable. 
• 
This version of the RAP is amendment 1 to the original RAP dated 20-MAY-2021 
and approved 07-JUN-2021. 
 
 
 
The main changes included in RAP Amendment 1 are as follows: 
1. Planned changes to deliveries due to need to report Cohort 1 separately following 
recruitment issues (Section 3.2). 
2. Removal of reference to analysis of human leukocyte antigen (HLA) B*5701 which 
is only collected at the screening visit (Section 8.3). 
 
Copyright 2021 the ViiV Healthcare group of companies. All rights reserved. 
Unauthorised copying or use of this information is prohibited. 


 
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TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 4 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 5 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 5 
2.2. 
Study Objective(s) and Endpoint(s)............................................................... 5 
2.3. 
Study Design ................................................................................................ 7 
2.4. 
Statistical Hypotheses................................................................................... 8 
2.5. 
Sample Size ................................................................................................. 8 
2.5.1. 
Sample Size Assumption ............................................................... 8 
2.5.2. 
Sample Size Sensitivity .................................................................. 8 
2.6. 
Study Blinding ............................................................................................... 9 
3. 
PLANNED ANALYSES .......................................................................................... 10 
3.1. 
Interim Analyses ......................................................................................... 10 
3.2. 
Final Analyses ............................................................................................ 10 
4. 
ANALYSIS POPULATIONS ................................................................................... 11 
4.1. 
Protocol Deviations ..................................................................................... 12 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 13 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 13 
5.2. 
Baseline Definitions .................................................................................... 13 
5.3. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 13 
6. 
STUDY POPULATION ANALYSES ....................................................................... 15 
6.1. 
Overview of Planned Study Population Analyses ........................................ 15 
7. 
PHARMACOKINETIC ANALYSES ......................................................................... 16 
7.1. 
Primary Pharmacokinetic Analyses ............................................................. 16 
7.1.1. 
Endpoint / Variables ..................................................................... 16 
7.1.1.1. 
Drug Concentration Measures .................................... 16 
7.1.1.2. 
Derived Pharmacokinetic Parameters......................... 16 
7.1.2. 
Summary Measure ...................................................................... 16 
7.1.3. 
Population of Interest ................................................................... 16 
7.1.4. 
Statistical Analyses / Methods ..................................................... 17 
7.1.4.1. 
Statistical Methodology Specification .......................... 17 
7.2. 
Secondary Pharmacokinetic Analyses ........................................................ 18 
7.2.1. 
Endpoint / Variables ..................................................................... 18 
7.2.1.1. 
Drug Concentration Measures .................................... 18 
7.2.1.2. 
Derived Pharmacokinetic Parameters......................... 18 
7.2.2. 
Summary Measure ...................................................................... 19 
7.2.3. 
Population of Interest ................................................................... 19 
7.2.4. 
Statistical Analyses / Methods ..................................................... 19 
8. 
SAFETY ANALYSES ............................................................................................. 20 
8.1. 
Adverse Events Analyses ........................................................................... 20 
8.2. 
Clinical Laboratory Analyses ....................................................................... 20 


 
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8.3. 
Other Safety Analyses ................................................................................ 20 
8.4. 
COVID 19 Related Analyses ....................................................................... 20 
9. 
OTHER ANALYSES ............................................................................................... 21 
10. REFERENCES ....................................................................................................... 22 
11. APPENDICES ........................................................................................................ 23 
11.1. 
Appendix 1: Schedule of Activities .............................................................. 23 
11.1.1. 
Protocol Defined Schedule of Events ........................................... 23 
11.2. 
Appendix 2: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 27 
11.2.1. 
Study Phases .............................................................................. 27 
11.2.2. 
Study Phases for Lab, Electrocardiograms, and Vital 
Signs ........................................................................................... 27 
11.2.3. 
Study Phases for Concomitant Medication ................................... 27 
11.2.4. 
Treatment Emergent Flag for Adverse Events ............................. 27 
11.3. 
Appendix 3: Data Display Standards & Handling Conventions .................... 28 
11.3.1. 
Reporting Process ....................................................................... 28 
11.3.2. 
Reporting Standards .................................................................... 28 
11.3.3. 
Reporting Standards for Pharmacokinetics .................................. 30 
11.4. 
Appendix 4: Derived and Transformed Data ............................................... 31 
11.4.1. 
General ........................................................................................ 31 
11.4.2. 
Study Population .......................................................................... 31 
11.4.3. 
Safety .......................................................................................... 32 
11.5. 
Appendix 5: Reporting Standards for Missing Data ..................................... 33 
11.5.1. 
Premature Withdrawals ................................................................ 33 
11.5.2. 
Handling of Missing Data ............................................................. 33 
11.5.2.1. Handling of Missing and Partial Dates ........................ 33 
11.6. 
Appendix 6: Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events .......................................... 34 
11.6.1. 
Laboratory Values ........................................................................ 34 
11.7. 
Appendix 7: Values of Potential Clinical Importance ................................... 37 
11.7.1. 
ECG ............................................................................................. 37 
11.7.2. 
Vital Signs .................................................................................... 37 
11.8. 
Appendix 8: Abbreviations & Trademarks ................................................... 38 
11.8.1. 
Abbreviations ............................................................................... 38 
11.8.2. 
Trademarks ................................................................................. 39 
11.9. 
Appendix 9: List of Data Displays ............................................................... 40 
11.9.1. 
Data Display Numbering .............................................................. 40 
11.9.2. 
Mock Example Shell Referencing ................................................ 40 
11.9.3. 
Deliverables ................................................................................. 40 
11.9.4. 
Study Population Tables .............................................................. 41 
11.9.5. 
Safety Tables ............................................................................... 43 
11.9.6. 
Safety Figures ............................................................................. 47 
11.9.7. 
Pharmacokinetic Tables ............................................................... 48 
11.9.8. 
Pharmacokinetic Figures ............................................................. 50 
11.9.9. 
Other Tables ................................................................................ 53 
11.9.10. ICH Listings ................................................................................. 54 
11.9.11. Non-ICH Listings .......................................................................... 59 
 


 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report (CSR) for Protocol: 216149, sponsored by ViiV 
Healthcare group of companies. 
Revision Chronology: 
Original Protocol 
216149 
04-MAR-2021 
Original 


 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
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. 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There are no changes from the originally planned statistical analysis specified in the 
protocol. 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary 
Primary  
• 
To assess the effect of food 
(fasted and high-fat meal) on the 
PK of TRIUMEQ (DTG/ABC/3TC) 
dispersible tablets. 
• 
AUC(0-inf), AUC(0-t) and Cmax for TRIUMEQ 
(DTG/ABC/3TC) 
• 
To assess the effect of food 
(fasted and high-fat meal) on the 
PK of DOVATO (DTG/3TC) 
dispersible tablets 
• 
AUC(0-inf), AUC(0-t) and Cmax for DOVATO 
(DTG/3TC) 
Secondary 
Secondary  
• 
To assess the effect of food 
(fasted and high-fat meal) on the 
secondary PK parameters of 
TRIUMEQ (DTG/ABC/3TC) 
dispersible tablets. 
• 
tlag, t1/2, AUC(0-24), Ct, C24, CL/F, Vz/F, and Tmax 
for TRIUMEQ (DTG/ABC/3TC) 
• 
To assess the effect of food 
(fasted and high-fat meal) on the 
secondary PK parameters of 
DOVATO (DTG/3TC) dispersible 
tablets. 
• 
tlag, t1/2, AUC(0-24), Ct, C24, CL/F, Vz/F, and Tmax 
for DOVATO (DTG/3TC) 
• 
To assess the safety and 
tolerability of TRIUMEQ 
(DTG/ABC/3TC) dispersible 
tablets under fasted or fed (high-
fat) conditions. 
• 
Safety and tolerability endpoints include incidence of 
AEs and SAEs, observed and change from baseline 
in clinical laboratory assessments, ECGs, and vital 
sign measurements (blood pressure and pulse rate) 
• 
To assess the safety and 
tolerability of DOVATO 
(DTG/3TC) dispersible tablets 
under fasted or fed (high-fat) 
conditions 
Exploratory 
Exploratory 
• 
To evaluate the palatability of the 
dispersible tablets 
• 
Palatability questionnaire scores 
3TC = lamivudine; ABC = abacavir; AE = adverse event; AUC(0-24) = area under the plasma 
concentration-time curve from time zero to 24 hours; AUC(0-inf) = area under the plasma 


 
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concentration-time curve from time zero extrapolated to infinity; AUC0-t = area under the plasma 
concentration-time curve from time zero to time of last quantifiable concentration; C24 = 
concentration at 24 hours postdose; Cmax = maximum observed plasma concentration; Ct = last 
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 


 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
3TC = lamivudine; ABC = abacavir; DTG = dolutegravir, 
Washout will be at least 7 days minus 4 hours. 
Design 
Features 
• Phase I, 2-cohort, single-center, randomized, open-label, single-dose, 
crossover study. 
• 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. 
Dosing 
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. 


 
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Overview of Study Design and Key Features 
Treatment 
Assignment 
• 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. 
Interim 
Analysis 
• There will be no interim analysis. 
 
2.4. 
Statistical Hypotheses 
There is no formal research hypothesis that will be statistically tested in this study. 
2.5. 
Sample Size 
2.5.1. 
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 his or her 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). 
2.5.2. 
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 


 
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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). 
2.6. 
Study Blinding 
While this is an open label study, the following measures will be taken to restrict 
information that may lead to unblinding, where feasible. PPD will work with ADaM 
datasets and TLFs based on the surrogate randomization schedule, and not have access to 
the actual randomization schedule. While the source data can still reveal the actual 
treatment, this data will be concealed to the Biostatistics and Programming teams for 
GSK during the course of the study. 
Once RAVE Database Hard Lock occurs, Source Data Lock is achieved, at which point 
the PPD team will switch from surrogate to actual randomization. The unblinded SDTM 
datasets will be transferred to the GSK Data Management team, who will authorize 
Database Freeze. At this point the entire GSK study team is officially unblinded. 
The PPD Clinical Pharmacology and GSK CPMS team will be unblinded throughout the 
study. 


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
There is no formal interim analysis planned. 
3.2. 
Final Analyses 
Due to the recruitment challenges with Cohort 2, Cohort 1 will be reported separately 
prior to full study reporting with the corresponding TLFs included in the CSR. At study 
completion, the CSR will be amended to include all study TLFs, fully covering both 
Cohort 1 and Cohort 2 reporting. For this reporting at study completion, all TLFs for both 
Cohort 1 and Cohort 2 will be produced based on the final database.  
Prior to the initial reporting of Cohort 1 and full reporting at study completion, the 
following sequential steps will be followed: 
1. All participants have completed Cohort 1 / the study as defined in the protocol.  
2. All required database cleaning activities have been completed and final database 
released (DBR). 
3. All criteria for unblinding the randomization codes have been met.  
4. Randomization codes have been distributed by PPD Randomization Team to PPD 
Biostatistics and Programming team. 
5. Database freeze (DBF) has been declared by GSK Data Management after reviewing 
the unblinded SDTM datasets. 
6. Only after DBF has been declared by GSK Data Management can GSK Biostatistics 
and Programming be unblinded. 
7. For the initial reporting of Cohort 1, PPD Randomization Team will only release the 
randomization codes for Cohort 1 to PPD Biostatistics and Programming team upon 
all criteria for unblinding Cohort 1 are met, while PPD Biostatistics and 
Programming team remain blinded for Cohort 2. 
8. For the full reporting at study completion, PPD Randomization Team will release the 
randomization codes for Cohort 2 to PPD Biostatistics and Programming team upon 
all criteria for unblinding Cohort 2 are met. 


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


 
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4.1. 
Protocol Deviations 
• 
Important protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarised and listed. 
• 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Study Deviation Plan. 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations and deviations which may lead to exclusion from the analysis are 
captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
• 
A separate summary and listing of all inclusion/exclusion criteria deviations will also 
be provided. This summary will be based on data as recorded on the 
inclusion/exclusion page of the electronic case report form (eCRF). 


 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
Data Displays for Reporting  
Description 
Code 
Order in 
TLF  
Cohort Used 
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 A 
1 
Cohort 1 
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 B 
2 
Cohort 1 
Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 
6 dispersible tablets) administered as a 
dispersion and taken immediately under fed 
conditions. 
Treatment C 
3 
Cohort 2 
Pediatric DOVATO (DTG 5 mg/3TC 30 mg, 
6 dispersible tablets) administered as a 
dispersion and taken immediately under 
fasted conditions. 
Treatment D 
4 
Cohort 2 
 
5.2. 
Baseline Definitions 
Baseline is defined as the latest pre-dose assessment with a non-missing value for each 
period, including those from unscheduled visits. 
Unless otherwise stated, if baseline data is missing, no derivation will be performed and 
baseline will be set to missing. 
5.3. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 


 
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Section 
Component 
11.1 
Appendix 1: Schedule of Activities  
11.2 
Appendix 2: Study Phases and Treatment Emergent Adverse Events 
11.3 
Appendix 3: Data Display Standards & Handling Conventions 
11.4 
Appendix 4: Derived and Transformed Data 
11.5 
Appendix 5: Reporting Standards for Missing Data 
11.6 
Appendix 6: Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events 
11.7 
Appendix 7: Values of Potential Clinical Importance 
11.8 
Appendix 8: Abbreviations & Trade Marks 
11.9 
Appendix 9: List of Data Displays 
 


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


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


 
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7.1.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 9: List of Data Displays and 
will be based on GSK Data Standards and statistical principles. 
Unless otherwise specified, endpoints/variables defined in Section 7.1.1 will be 
summarized using descriptive statistics and listed. 
Primary plasma PK parameters (AUC[0-inf], AUC[0-t], and Cmax) will be estimated for 
DTG, ABC, and 3TC. Summary statistics [arithmetic mean, geometric mean, median, 
standard deviation (SD), percent coefficient of variation (CV%), minimum, maximum, 
between-subject percent coefficient of variation (CVb%), and 95% confidence interval 
(CI)] for plasma DTG, ABC, and 3TC PK parameter values will be summarized by 
treatment using PK Parameter Population. 
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. 
7.1.4.1. 
Statistical Methodology Specification 
The following PK statistical analyses will only be performed if sufficient data are 
available (i.e. if participants have well defined plasma profiles). 
Endpoint / Variables 
• Plasma primary PK endpoints include AUC(0-inf), AUC(0-t), and Cmax, for DTG, ABC, and 
3TC as data permit. 
Model Specification 
Cohort 1 
• 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, period, and sequence 
as fixed effects and participant nested within a sequence (participant(sequence)) as a 
random effect. Effects will be estimated, and CIs will be constructed for the following 
treatment comparisons: 
o Treatment A (test) versus Treatment B (reference) 
o Point estimates, 90% CIs [estimate ± SE*tinv(0.95, df)], and intra-subject CV% [sqrt 
(exp (variance for ln-transformed data)-1)*100]. 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. 
Cohort 2 
• 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), 


 
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and Cmax using linear mixed-effect models with treatment, period, and sequence as fixed 
effects and participant nested within a sequence [participant(sequence)] as a random effect. 
Effects will be estimated, and CIs will be constructed for the following treatment 
comparisons: 
o Treatment C (test) versus Treatment D (reference) 
o Point estimates, 90% CIs [estimate ± SE*tinv(0.95, df)], and intra-subject CV% [sqrt 
(exp (variance for ln-transformed data)-1)*100] for treatment differences on the log 
scale derived from the model will be exponentiated to obtain estimates for geometric 
mean ratios and CIs on the original scale. 
Model Checking & Diagnostics 
• Model assumptions will be applied, but appropriate adjustments may be made based on the 
data. 
Model Results Presentation 
• Statistical analysis for the effect of food (high fat high calorie meal) by ANOVA will be 
presented in tabular format with geometric mean ratios for the following treatment 
comparisons: 
o Treatment A (test) versus Treatment B (reference) 
o Treatment C (test) versus Treatment D (reference) 
7.2. 
Secondary Pharmacokinetic Analyses 
7.2.1. 
Endpoint / Variables 
7.2.1.1. 
Drug Concentration Measures  
Refer to Appendix 3: Data Display Standards & Handling Conventions (Section 11.3.3 
Reporting Standards for Pharmacokinetic). 
7.2.1.2. 
Derived Pharmacokinetic Parameters 
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin (8.0 or higher). All calculations of non-compartmental parameters will be 
based on actual sampling times. Pharmacokinetic parameters listed will be determined 
from the plasma concentration-time data, as data permit. Participants who experience 
emesis at or before 2 times median Tmax or participants whose predose concentrations are 
>5% of their Cmax value for the given treatment will be excluded from the calculation of 
summary statistics and statistical analysis for the respective treatment. 
Secondary plasma pharmacokinetic parameters listed below will be determined from the 
plasma concentration-time data, as data permits: 
Parameter 
Parameter Description 
AUC(0-24) 
Area under the plasma concentration-time curve from time 0 to 24 hours postdose, to be 
calculated using the linear trapezoidal rule for each incremental trapezoid and the log 
trapezoidal rule for each decremental trapezoid. 


 
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Parameter 
Parameter Description 
Tmax 
Time of maximum observed concentration 
Tlag 
Lag time for absorption 
t1/2 
Apparent terminal phase half-life 
C24 
Plasma concentration at 24 hours postdose 
Ct 
Last quantifiable plasma concentration 
NOTES: 
• 
Additional parameters including CL/F and Vz/F may be included as required. 
7.2.2. 
Summary Measure 
Secondary pharmacokinetic parameters: AUC(0-24), Tmax, tlag, t1/2, C24, and Ct of 
DTG, ABC, and 3TC following single dose administration of pediatric TRIUMEQ and 
AUC(0-24), Tmax, tlag, t1/2, C24, and Ct of DTG and 3TC following single dose 
administration of pediatric DOVATO formulations under fed or fasted conditions to 
healthy participants. 
7.2.3. 
Population of Interest  
The secondary PK analyses will be based on the PK concentration population for plasma 
PK concentrations, and the PK parameter population for plasma PK parameters, unless 
otherwise specified. 
7.2.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 9: List of Data Displays and 
will be based on GSK Data Standard and statistical principles. 
Unless otherwise specified, endpoints/variables defined in Section 7.2.1 will be 
summarized using descriptive statistics and listed. 
Secondary plasma PK parameters [AUC(0-24), Tmax, tlag, t1/2, C24, and Ct] will be 
estimated for DTG, ABC, and 3TC. Summary statistics (arithmetic mean, geometric 
mean, median, SD, CV%, minimum, maximum, CVb%, and 95% CI) for secondary 
plasma PK parameters of DTG, ABC, and 3TC will be summarized by treatment using 
PK Parameter Population. 
Summary statistics (arithmetic mean, median, SD, minimum, maximum, and CV%) for 
plasma DTG, ABC, and 3TC PK concentrations will be summarized by treatment using 
the PK Concentration Population. 


 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety population unless otherwise specified. 
8.1. 
Adverse Events Analyses 
Adverse events (AEs) analyses including the analysis of AEs, serious AEs (SAEs), and 
other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 9: List of Data Displays. 
For studies with greater than one treatment period (e.g., crossover study), if AE onset is 
during one period and worsens in severity during a later period, it will be counted in both 
periods. For the later period the onset date of AE with the elevated grade will be the first 
dose date of the later treatment period. 
8.2. 
Clinical Laboratory Analyses 
Laboratory evaluations including the analyses of chemistry laboratory tests, hematology 
laboratory tests, urinalysis, and pregnancy test will be based on GSK Core Data 
Standards and will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events (Version 2.1, July 2017). The details of 
the planned displays are in Appendix 9: List of Data Displays. 
8.3. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs, vital signs, liver 
events, and pregnancy will be based on GSK Core Data Standards, unless otherwise 
specified. The details of the planned displays are presented in Appendix 9: List of Data 
Displays. 
8.4. 
COVID 19 Related Analyses 
Based on GSK’s “Impact of COVID-19 on Assessment of Safety in Clinical Trials Points 
to Consider”, it is GSK’s recommendation that study teams should capture COVID-19 
cases based on the WHO criteria using the categories of: suspected, probable, and 
confirmed cases. COVID-19 eCRF pages are used in the study for data collection and 
analysis purposes. After a discussion with the study team, the following analyses will be 
included:  
• Number of subjects with suspected, probable, or confirmed COVID-19 infection 
• Number of subjects who had a COVID-19 diagnosis test performed and the 
number of subjects with positive, negative, or indeterminate results. 
 
Further display details are provided in Appendix 9: List of Data Displays. 


 
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9. 
OTHER ANALYSES 
Palatability Assessment results will be based on GSK Core Data Standards, unless 
otherwise specified. The details of the planned displays are presented in Appendix 9: List 
of Data Displays. 


 
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10. 
REFERENCES 
 
• Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events. Version 2.1. July 2017. Division of AIDS National Institute of 
Allergy and Infectious Diseases National Institutes of Health US Department of 
Health and Human Services Events. Retrieved on 12/3/2021 at : 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
 
 


 
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11. 
APPENDICES 
11.1. 
Appendix 1: Schedule of Activities 
11.1.1. 
Protocol Defined Schedule of Events 
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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Treatment Period Assessment – Cohort 1 and Cohort 2 
Procedure 
All Study Periods 
Follow-up/Early 
Discontinuation3 
Notes 
Assessments 
Day –2 or 
Day –12 
Day 1 
Washout1 
Day 2 
Day 3 
Day 4 
Admit to clinic 
X 
 
 
 
 
 
Day -1 of Period 2 may be the same day as Day 6 of Period 1. 
Discharge from clinic 
 
 
 
 
X 
 
Discharge from the study site following completion of the last study procedure 
on Day 4 of each period.  
Outpatient visit4 
 
 
 
 
 
X 
 
Brief physical examination 
X 
 
 
 
 
 
Brief physical examinations may be completed as a full physical examinations 
at the discretion of the investigator. See Protocol Section 8.2.1 for description of 
brief physical examination.  
Vital signs 
X 
 
 
 
X 
X 
Single vital sign measurements at all time points (Protocol Section 8.2.2). 
12-lead ECG 
X 
 
 
 
X 
 
Single ECG measurements. Additional ECGs may be performed at the 
discretion of the investigator.  
Urine drug, alcohol, and  
cotinine screen 
X 
 
 
 
 
 
See Protocol Appendix 2 for specific tests to be performed. 
Clinical laboratory assessments5 
X 
 
 
 
X 
X 
See Protocol Section 8.2.4 for additional information and Protocol Appendix 2 
for specific tests to be performed.  
Molecular test for SARs-CoV-26 
X 
 
 
 
 
 
Polymerase Chain Reaction (PCR) or Antigen test. 
Pregnancy test 
X 
 
 
 
 
X 
Pregnancy test will be performed as per the standard practice of the study site. 
Dosing with study intervention7 
 
X 
 
 
 
 
 
Palatability assessment 
 
X 
 
 
 
 
To be completed within 10 minutes following dosing (see Protocol  
Section 8.2.6 ) 
Meals 
 
Standard for the study site 
 
 
See Protocol Section 4.1 for specific information on meals.  
Serial PK sampling8 
 
X 
X 
X 
X 
 
 
AE and SAE review9 
==========================X==========================➔  


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Procedure 
All Study Periods 
Follow-up/Early 
Discontinuation3 
Notes 
Assessments 
Day –2 or 
Day –12 
Day 1 
Washout1 
Day 2 
Day 3 
Day 4 
Concomitant medications 
==========================X==========================➔  
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 Protocol 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. 


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• 
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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11.2. 
Appendix 2: Study Phases and Treatment Emergent 
Adverse Events 
11.2.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
study treatment start date(/time) and stop date(/time). 
11.2.2. 
Study Phases for Lab, Electrocardiograms, and Vital Signs 
Assessments and events will be classified according to the time of occurrence relative to 
study treatment start date(/time) and stop date(/time). 
Study Phase 
Definition 
Pre-Treatment  
Date and Time ≤Study Treatment Start Date and Time 
On-Treatment 
Study Treatment Start Date and Time <Date and Time ≤Study Treatment Stop Date 
and Time + 6 days 
Post-Treatment  
Date and Time >Study Treatment Stop Date and Time + 6 days 
 
11.2.3. 
Study Phases for Concomitant Medication 
Study Phase 
Study Phase 
Prior 
End Date and Time < Study First Dosing Start Date and Time 
Concomitant 
End Date and Time > = Study First Dosing Start Date and Time and Start Date 
<= Study Treatment Stop Date and Time + 6 days  
NOTES:  
Please refer to Appendix 5: Reporting Standards for Missing Data for handling of missing and partial dates for 
concomitant medication. Use the rules in this table if concomitant medication date is completely missing. 
 
 
11.2.4. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
If AE onset date and time is on or after treatment start date and time & on or 
before treatment stop date and time + 6 days.  
• 
Study Treatment Start Date and Time ≤AE Start Date and Time ≤Study 
Treatment Stop Date and Time + 6 days. 
• 
If the AE onset date is completely missing, the AE is considered as treatment 
emergent. 
NOTES:  
• 
If the study treatment stop date is missing, then the AE will be considered to be On-Treatment. 
• 
Please refer to Appendix 5: Reporting Standards for Missing Data for handling of missing and partial dates for 
AEs. Use the rules in this table if the AE onset date is completely missing. 
 


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11.3. 
Appendix 3: Data Display Standards & Handling 
Conventions 
11.3.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software (9.4) will be used. 
Reporting Area 
HARP Server 
US1SALX00259.corpnet2.com 
HARP Compound 
gsk1349572 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.1).  
• 
For creation of ADaM datasets (ADC1/ADCM/ADAE), the same version of dictionary datasets will be 
implemented for conversion from SI to SDTM. 
Generation of RTF Files 
• 
RTF files will be generated for all reporting efforts described in the RAP. 
11.3.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include participant level listings in the main body of the GSK Clinical Study Report. All 
participant level listings should be located in the modular appendices as ICH or non-ICH listings. 
Formats 
• 
All data will be reported according to the actual treatment the participant received unless otherwise 
stated. 
• 
GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DPs) will be rounded to integer, 
unless otherwise specified.  
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DPs. 


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Planned and Actual Time 
• 
Reporting for tables, figures, and formal statistical analyses: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses, and 
calculation of any derived parameters, unless otherwise stated. 
• 
The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings.  
• 
Visits outside the protocol defined time-windows (i.e. recorded as protocol deviations) will be 
included in listings but omitted from figures (mean figures only for PK concentrations), 
summaries, and statistical analyses (excluding statistical analyses of PK parameters). 
Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables except for determining the worst-case 
values. 
• 
Unscheduled visits will not be included in figures. 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
 
 
 


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11.3.3. 
Reporting Standards for Pharmacokinetics 
Pharmacokinetic Concentration Data 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical Principle 6.06.1. 
For continuous data: 
• 
NQs at the beginning of a participant profile (i.e. before the first incidence of a 
measurable concentration) are deemed to be zero as it is assumed that in this 
circumstance no drug is yet measurable in the blood. 
• 
For NQs at the end of the participant profile (i.e. after the last incidence of a 
measurable concentration); 
• 
for individual plots and pharmacokinetic analyses these are dropped (set 
to missing) as they do not provide any useful information (and can 
erroneously indicate that absolutely no drug is present) 
• 
for summary statistics, these are set to 0 (to avoid skewing of the 
summary statistics). 
• 
Individual NQs which fall between two measurable concentrations are set to 
missing (individual values of this nature are assumed to be an anomaly). 
If two or more NQ values occur in succession between measurable concentrations, 
the profile will be deemed to have terminated at the last measurable concentration 
prior to these NQs. For the purpose of individual participant plots, these NQs will be 
set to 0, and the subsequent measurable concentrations will be retained. For the 
derivation of pharmacokinetic parameters, these NQs and any subsequent 
measurable concentrations will be omitted (set to missing). 
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only. 
Pharmacokinetic Parameter Data 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
N, n, arithmetic mean, 95% CI of arithmetic mean, geometric mean, 95% CI of 
geometric mean, SD, SD of logged data CV (%), and between-subject geometric 
coefficient of variation (CVb (%)) will be reported. 
CVb (%) = √ (exp(SD2) - 1) * 100 
(SD = SD of Ln-Transformed data) 
Parameters Not 
Being Ln-
Transformed 
Tmax, λz, λz lower, λz upper, and λz no. of points. 
Parameters Not 
Being Summarized 
λz, λz lower, λz upper, and λz no. of points. 
Listings 
Include the first point, last point and number of points used in the determination of 
λz and Rsq_adjusted for listings. 
 


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


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11.4.3. 
Safety 
12-Lead Electrocardiograms 
QTcB Interval 
• 
QTcB interval in msec will be calculated using QT interval (msec) and RR interval (msec) as 
 
𝑄𝑇𝑐𝐵= 
𝑄𝑇
√𝑅𝑅
1000
 
where RR interval in msec is calculated using QT interval (msec) and QTcF interval (msec) 
as 
𝑅𝑅= ( 𝑄𝑇
𝑄𝑇𝑐𝐹)3 × 1000 
 


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


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11.6. 
Appendix 6: Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events 
11.6.1. 
Laboratory Values 
Laboratory abnormalities will be graded according to the DAIDS grading table Version 2.1, July 2017. Laboratory results are converted to 
use SI units; only the numeric part of the criteria will be used. If for a laboratory parameter there are multiple grades sharing the same 
criteria, the maximum grade will be used. 
Hematology 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Absolute Lymphocyte Count, Low 
(cell/mm3; cells/L) 
>5 years of age (not HIV infected) 
600 to <650 
0.600 × 109 to <0.650 × 109 
500 to <600 
0.500 × 109 to <0.600 × 109 
350 to <500 
0.350 × 109 to <0.500 × 109 
<350 
<0.350 × 109 
Absolute Neutrophil Count, Low 
(cells/mm3; cells/L) 
>7 days of age 
800 to 1,000 
0.800 × 109 to 1.000 × 109 
600 to 799 
0.600 × 109 to 0.799 × 109 
400 to 599 
0.400 × 109 to 0.599 × 109 
<400 
<0.400 × 109 
Hemoglobin, Low (g/dL; mmol/L) 
≥13 years of age (male only) 
10.0 to 10.9 
6.19 to 6.76 
9.0 to <10.0 
5.57 to <6.19 
7.0 to <9.0 
4.34 to <5.57 
<7.0 
<4.34 
Hemoglobin, Low (g/dL; mmol/L) 
≥13 years of age (female only) 
9.5 to 10.4 
5.88 to 6.48 
8.5 to <9.5 
5.25 to <5.88 
6.5 to <8.5 
4.03 to <5.25 
<6.5 
<4.03 
Platelets, Decreased (cells/mm3; 
cells/L) 
100,000 to <125,000 
100.000 × 109 to <125.000 × 
109 
50,000 to <100,000 
50.000 × 109 to <100.000 × 109 
25,000 to <50,000 
25.000 × 109 to <50.000 × 
109 
<25,000 
<25.000 × 109 
White Blood Cell, Decreased 
(cells/mm3; cells/L) 
>7 days of age 
2,000 to 2,499 
2.000 × 109 to 2.499 × 109 
1,500 to 1,999 
1.500 × 109 to 1.999 × 109 
1,000 to 1,499 
1.000 × 109 to 1.499 × 109 
<1,000 
<1.000 × 109 
 
 
 


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Clinical Chemistry 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Albumin, Low (g/dL; g/L) 
3.0 to <LLN 
30 to <LLN 
≥2.0 to <3.0 
≥20 to <30 
<2.0 
<20 
NA 
Alkaline Phosphatase, High 
1.25 to <2.5 × ULN 
2.5 to <5.0 × ULN 
5.0 to <10.0 × ULN 
≥10.0 × ULN 
Alanine Aminotransferase, High 
1.25 to <2.5 × ULN 
2.5 to <5.0 × ULN 
5.0 to <10.0 × ULN 
≥10.0 ULN 
Amylase (Total), High 
1.1 to <1.5 × ULN 
1.5 to <3.0 × ULN 
3.0 to <5.0 × ULN 
≥5.0 × ULN 
Aspartate Aminotransferase, High 
1.25 to <2.5 × ULN 
2.5 to <5.0 × ULN 
5.0 to <10.0 × ULN 
≥10.0 × ULN 
Bicarbonate, Low (mEq/L; mmol/L) 
16.0 to <LLN 
16.0 to <LLN 
11.0 to <16.0 
11.0 to <16.0 
8.0 to <11.0 
8.0 to <110. 
<8.0 
<8.0 
Direct Bilirubin, High 
>28 days of age 
NA 
NA 
>ULN with other signs and 
symptoms of hepatotoxicity 
>ULN with life-
threatening 
consequences (e.g., 
signs and symptoms of 
liver failure) 
Total Bilirubin, High 
>28 days of age 
1.1 to <1.6 × ULN 
1.6 to <2.6 × ULN 
2.6 to <5.0 × ULN 
≥5.0 × ULN 
Calcium, High (mg/dL; mmol/L) 
≥7 days of age 
10.6 to <11.5 
2.65 to <2.88 
11.5 to <12.5 
2.88 to <3.13 
12.5 to <13.5 
3.13 to <3.38 
≥13.5 
≥3.38 
Calcium, Low (mg/dL; mmol/L) 
≥7 days of age 
7.8 to <8.4 
1.95 to <2.10 
7.0 to <7.8 
1.75 to <1.95 
6.1 to <7.0 
1.53 to <1.75 
<6.1 
<1.53 
Creatine Kinase, High 
3 to <6 × ULN 
6 to <10 × ULN 
10 to <20 × ULN 
≥20 × ULN 
Creatinine, High 
Choose the method that selects for 
the higher grade 
1.1 to 1.3 × ULN 
>1.3 to 1.8 × ULN OR Increase to 
1.3 to <1.5 × participant’s baseline 
>1.8 to <3.5 ULN OR 
Increase to 1.5 to <2.0 × 
participant’s baseline 
≥3.5 × ULN OR Increase 
of ≥2.0 × participant’s 
baseline 
Glucose Fasting, High (mg/dL; 
mmol/L) 
110 to 125 
6.11 to <6.95 
>125 to 250 
6.95 to <13.89 
>250 to 500 
13.89 to <27.75 
≥500 
≥27.75 
Glucose, Low (mg/dL; mmol/L) 
≥1 month of age 
55 to 64 
3.05 to <3.55 
40 to <55 
2.22 to <3.05 
30 to <40 
1.67 to <2.22 
<30 
<1.67 
Lipase, High 
1.1 to <1.5 × ULN 
1.5 to <3.0 × ULN 
3.0 to <5.0 × ULN 
≥5.0 × ULN 


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Cholesterol, Fasting, High (mg/dL; 
mmol/L) 
≥18 years of age 
200 to <240 
5.18 to <6.19 
240 to <300 
6.19 to <7.77 
≥300 
≥7.77 
NA 
Triglycerides, Fasting, High (mg/dL; 
mmol/L) 
150 to 300 
1.71 to 3.42 
>300 to 500 
>3.42 to 5.7 
>500 to <1.000 
>5.7 to 11.4 
>1,000 
>11.4 
Phosphate, Low (mg/dL; mmol/L) 
>14 years of age 
2.0 to <LLN 
0.65 to <LLN 
1.4 to <2.0 
0.45 to <0.65 
1.0 to <1.4 
0.32 to <0.45 
<1.0 
<0.32 
Potassium, High (mEq/L; mmol/L) 
5.6 to <6.0 
5.6 to <6.0 
6.0 to <6.5 
6.0 to <6.5 
6.5 to <7.0 
6.5 to <7.0 
≥7.0 
≥7.0 
Potassium, Low (mEq/L; mmol/L) 
3.0 to <3.4 
3.0 to <3.4 
2.5 to <3.0 
2.5 to <3.0 
2.0 to <2.5 
2.0 to <2.5 
<2.0 
<2.0 
Sodium, High (mEq/L; mmol/L) 
146 to <150 
146 to <150 
150 to <154 
150 to <154 
154 to <160 
154 to <160 
≥160 
≥160 
Sodium, Low (mEq/L; mmol/L) 
130 to <135 
130 to <135 
125 to <130 
125 to <130 
121 to <125 
121 to <125 
≤ 120 
≤ 120 
Uric Acid, High (mEq/L; mmol/L) 
7.5 to <10.0 
0.45 to <0.59 
10.0 to <12.0 
0.59 to <0.71 
12.0 to <15.0 
0.71 to <0.89 
≥15.0 
≥0.89 
NA=not applicable; LLN = lower limit of normal; ULN=upper limit of normal. 
 
Urinalysis 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Glucose/Glycosuria (random 
collection tested by dipstick) 
Trace to 1+ or ≤ 250 mg 
2+ or >250 to ≤ 500 mg 
>2+ or >500 mg 
NA 
Protein/Proteinuria (random 
collection tested by dipstick) 
1+ 
2+ 
3+ or higher 
NA 
Red Blood Cells (RBCs)/Hematuria 
(not to be reported based on dipstick 
findings or on blood believed to be of 
menstrual origin) 
6 to <10 RBCs per high 
power field 
≥10 RBCs per high power field 
Gross, with or without clots 
OR with RBC casts OR 
intervention indicated 
Life-threatening 
consequences 
NA=not applicable 
 


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11.7. 
Appendix 7: Values of Potential Clinical Importance 
11.7.1. 
ECG 
ECG Parameter 
Units 
Potential Clinically Important Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
<320 
>450 
Absolute PR Interval 
msec 
<120 
>200 
Absolute QRS Complex 
msec 
<75 
>110 
Change from Baseline 
Increase from Baseline QTc 
msec 
 
>60 
 
11.7.2. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Potential Clinically Important Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
<85 
>140 
Diastolic Blood Pressure 
mmHg 
<45 
>90 
Heart Rate 
Beats per 
minute 
<40 
>100 
 


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11.8. 
Appendix 8: Abbreviations & Trademarks 
11.8.1. 
Abbreviations 
Abbreviation 
Description 
3TC 
Lamivudine 
ABC 
Abacavir 
AE 
Adverse Event 
ANOVA 
Analysis of Variance 
ARV  
Antiretroviral therapy 
AUC  
Area under the Plasma Concentration-Time Curve 
AUC(0-inf)  
AUC from Time 0 Extrapolated to Infinity 
AUC(0-t) 
AUC from Time 0 to Time t 
BMI 
Body Mass Index 
C24 
Plasma Concentration at 24 hours postdose 
CDISC 
Clinical Data Interchange Standards Consortium 
CI  
Confidence Interval 
CIOMS  
Council for International Organizations of Medical Sciences 
CL/F  
Apparent Oral Clearance 
Cmax  
Cmax Maximum Observed Plasma Concentration 
CRF 
Case Report Form 
CSR  
Clinical Study Report 
Ct 
Last quantifiable concentration 
CV 
Coefficient of Variation 
CVb  
Coefficient of Variation (Between)  
CVw 
Within participant variability 
DAIDS 
Division of AIDS 
DBF 
Database Freeze 
DBR 
Database Release 
DP 
Decimal Places 
DTG 
Dolutegravir 
ECG  
Electrocardiogram 
ER  
Extended Release 
EU  
European Union 
FDA  
Food and Drug Administration 
FSH  
Follicle Stimulating Hormone 
GSK  
GlaxoSmithKline 
hCG 
Human Chorionic Gonadotropin 
HLGT 
High Level Group Term 
HIV 
Human Immunodeficiency Virus 
ICH  
International Council On Harmonisation 
IDSL 
Integrated Data Standards Library 
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
NQ 
Not quantifiable 
PK 
Pharmacokinetic 


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Abbreviation 
Description 
PT 
Preferred Term 
QTcF 
QTc using the Fridericia formula 
RAP 
Reporting & Analysis Plan 
SAC 
Statistical Analysis Complete 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SMQ 
Standardized MedDRA Query 
SOC 
System Organ Class 
t1/2 
Apparent Terminal Phase Half-life 
Tlag 
lag time for absorption 
Tmax 
Time of Maximum Observed Concentration 
TLF 
Tables, listings, figures 
ULN  
Upper Limit of Normal 
Vz/F  
Apparent Oral Volume of Distribution 
11.8.2. 
Trademarks 
Trademarks of the ViiV Healthcare 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
DOVATO 
 
SAS  
TRIUMEQ 
 
WinNonlin 
 
 
 


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11.9. 
Appendix 9: List of Data Displays 
11.9.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.14 
 
Safety 
2.1 to 2.48 
2.1 to 2.2 
Pharmacokinetic 
3.1 to 3.17 
3.1 to 3.22 
Other 
4.1 to 4.2 
 
Section 
Listings 
ICH Listings 
1 to 67 
Other Listings 
68 to 83 
 
11.9.2. 
Mock Example Shell Referencing 
Non-IDSL specifications will be referenced as indicated and if required example 
mock-up displays provided in the Table/Listing/Figure Shells. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
Other 
OTHER_Fn 
OTHER_Tn 
OTHER_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’ 
 
11.9.3. 
Deliverables 
Delivery  
Description 
SAC  
Final Statistical Analysis Complete 


 
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11.9.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
Enrolled 
NS1 
Summary of Number of Subjects Enrolled by Country and Site 
ID 
 
SAC 
1.2. 
Safety 
ES1xo 
Summary of Subject Disposition for the Subject Conclusion 
Record – TRIUMEQ 
 
SAC 
1.3. 
Safety 
ES1xo 
Summary of Subject Disposition for the Subject Conclusion 
Record – DOVATO 
 
SAC 
1.4. 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failures   
SAC 
1.5. 
Screened 
SP1 
Summary of Study Populations – TRIUMEQ 
 
SAC 
1.6. 
Screened 
SP1 
Summary of Study Populations – DOVATO 
 
SAC 
Protocol Deviations 
1.7. 
Safety 
DV1 
Summary of Important Protocol Deviations – TRIUMEQ 
 
SAC 
1.8. 
Safety 
DV1 
Summary of Important Protocol Deviations – DOVATO 
 
SAC 
Demographic and Baseline Characteristics 
1.9. 
Safety 
DM1xo 
Summary of Demographic Characteristics – TRIUMEQ 
 
SAC 
1.10. 
Safety 
DM1xo 
Summary of Demographic Characteristics – DOVATO 
 
SAC 
1.11. 
Safety 
DM6xo 
Summary of Race and Racial Combinations – TRIUMEQ 
 
SAC 
1.12. 
Safety 
DM6xo 
Summary of Race and Racial Combinations – DOVATO 
 
SAC 
1.13. 
Safety 
DM11xo 
Summary of Age Ranges – TRIUMEQ 
 
SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.14. 
Safety 
DM11xo 
Summary of Age Ranges – DOVATO 
 
SAC 


 
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11.9.5. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
2.1.  
Safety 
AE1xo 
Summary of Adverse Events by System Organ Class and 
Preferred Term – TRIUMEQ 
 
SAC 
2.2.  
Safety 
AE1xo 
Summary of Adverse Events by System Organ Class and 
Preferred Term – DOVATO 
 
SAC 
2.3.  
Safety 
AE1xo 
Summary of Drug-Related Adverse Events by System Organ 
Class and Preferred Term – TRIUMEQ 
 
SAC 
2.4.  
Safety 
AE1xo 
Summary of Drug-Related Adverse Events by System Organ 
Class and Preferred Term – DOVATO 
 
SAC 
2.5.  
Safety 
AE3 
Summary of Common (>=2 subjects) Adverse Events by Overall 
Frequency – TRIUMEQ 
 
SAC 
2.6.  
Safety 
AE3 
Summary of Common (>=2 subjects) Adverse Events by Overall 
Frequency – DOVATO 
 
SAC 
2.7.  
Safety 
AE15 
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term – TRIUMEQ 
(Number of Subjects and Occurrences) 
 
SAC 
2.8.  
Safety 
AE15 
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term – DOVATO 
(Number of Subjects and Occurrences) 
 
SAC 
2.9.  
Safety 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term – TRIUMEQ 
(Number of Subjects and Occurrences) 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.10. 
Safety 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term – DOVATO 
(Number of Subjects and Occurrences) 
 
SAC 
2.11. 
Safety 
AE5B 
Summary of Adverse Events by System Organ Class and 
Preferred Term and Maximum Intensity – TRIUMEQ 
 
SAC 
2.12. 
Safety 
AE5B 
Summary of Adverse Events by System Organ Class and 
Preferred Term and Maximum Intensity – DOVATO 
 
SAC 
Laboratory: Chemistry  
2.13. 
Safety 
LB1 
Summary of Clinical Chemistry Data – TRIUMEQ 
 
SAC 
2.14. 
Safety 
LB1 
Summary of Clinical Chemistry Data – DOVATO 
 
SAC 
2.15. 
Safety 
LB1 
Summary of Clinical Chemistry Changes from Baseline – 
TRIUMEQ 
 
SAC 
2.16. 
Safety 
LB1 
Summary of Clinical Chemistry Changes from Baseline – 
DOVATO 
 
SAC 
2.17. 
Safety 
LB16 
Summary of Clinical Chemistry Results by Maximum Grade 
Increase Post-Baseline Relative to Baseline – TRIUMEQ 
 
SAC 
2.18. 
Safety 
LB16 
Summary of Clinical Chemistry Results by Maximum Grade 
Increase Post-Baseline Relative to Baseline – DOVATO 
 
SAC 
Laboratory: Hematology 
2.19. 
Safety 
LB1 
Summary of Hematology Data – TRIUMEQ 
 
SAC 
2.20. 
Safety 
LB1 
Summary of Hematology Data – DOVATO 
 
SAC 
2.21. 
Safety 
LB1 
Summary of Hematology Changes from Baseline – TRIUMEQ 
 
SAC 
2.22. 
Safety 
LB1 
Summary of Hematology Changes from Baseline – DOVATO 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.23. 
Safety 
LB16 
Summary of Hematology Results by Maximum Grade Increase 
Post-Baseline Relative to Baseline – TRIUMEQ 
 
SAC 
2.24. 
Safety 
LB16 
Summary of Hematology Results by Maximum Grade Increase 
Post-Baseline Relative to Baseline – DOVATO 
 
SAC 
Laboratory: Urinalysis 
2.25. 
Safety 
LB1 
Summary of Urine Concentration – TRIUMEQ 
 
SAC 
2.26. 
Safety 
LB1 
Summary of Urine Concentration – DOVATO 
 
SAC 
2.27. 
Safety 
LB1 
Summary of Urine Concentration Changes from Baseline – 
TRIUMEQ 
 
SAC 
2.28. 
Safety 
LB1 
Summary of Urine Concentration Changes from Baseline – 
DOVATO 
 
SAC 
2.29. 
Safety 
SAFE_T1 
Summary of Urinalysis Dipstick Results – TRIUMEQ 
 
SAC 
2.30. 
Safety 
SAFE_T1 
Summary of Urinalysis Dipstick Results – DOVATO 
 
SAC 
2.31. 
Safety 
LB16 
Summary of Urinalysis by Maximum Grade Increase Post-
Baseline Relative to Baseline – TRIUMEQ 
 
SAC 
2.32. 
Safety 
LB16 
Summary of Urinalysis by Maximum Grade Increase Post-
Baseline Relative to Baseline – DOVATO 
 
SAC 
ECG 
2.33. 
Safety 
EG1 
Summary of ECG Findings – TRIUMEQ 
 
SAC 
2.34. 
Safety 
EG1 
Summary of ECG Findings – DOVATO 
 
SAC 
2.35. 
Safety 
EG2 
Summary of ECG Values – TRIUMEQ 
 
SAC 
2.36. 
Safety 
EG2 
Summary of ECG Values – DOVATO 
 
SAC 
2.37. 
Safety 
EG2 
Summary of ECG Changes from Baseline – TRIUMEQ 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.38. 
Safety 
EG2 
Summary of ECG Changes from Baseline – DOVATO 
 
SAC 
2.39. 
Safety 
EG10 
Summary of Maximum QTc Values Post-Baseline Relative to 
Baseline by Category – TRIUMEQ 
 
SAC 
2.40. 
Safety 
EG10 
Summary of Maximum QTc Values Post-Baseline Relative to 
Baseline by Category – DOVATO 
 
SAC 
2.41. 
Safety 
EG11 
Summary of Maximum Increase in QTc Values Post-Baseline 
Relative to Baseline by Category – TRIUMEQ 
 
SAC 
2.42. 
Safety 
EG11 
Summary of Maximum Increase in QTc Values Post-Baseline 
Relative to Baseline by Category – DOVATO 
 
SAC 
Vital Signs 
2.43. 
Safety 
VS1 
Summary of Vital Signs – TRIUMEQ 
 
SAC 
2.44. 
Safety 
VS1 
Summary of Vital Signs – DOVATO 
 
SAC 
2.45. 
Safety 
VS1 
Summary of Vital Sign Changes from Baseline – TRIUMEQ 
 
SAC 
2.46. 
Safety 
VS1 
Summary of Vital Sign Changes from Baseline – DOVATO 
 
SAC 
COVID-19 
2.47. 
Safety 
PAN1 
Summary of COVID-19 Assessment – TRIUMEQ 
 
SAC 
2.48. 
Safety 
PAN1 
Summary of COVID-19 Assessment – DOVATO 
 
SAC 


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


 
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11.9.7. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
PK Concentration Data 
3.1.  
PK 
Concentration 
PK01 
Summary of Dolutegravir Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – TRIUMEQ 
DTG for TRIUMEQ 
SAC 
3.2.  
PK 
Concentration 
PK01 
Summary of Abacavir Plasma Pharmacokinetic Concentration-
Time Data (units) by Treatment – TRIUMEQ 
ABC for TRIUMEQ 
SAC 
3.3.  
PK 
Concentration 
PK01 
Summary of Lamivudine Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – TRIUMEQ 
3TC for TRIUMEQ 
SAC 
3.4.  
PK 
Concentration 
PK01 
Summary of Dolutegravir Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – DOVATO 
DTG for DOVATO 
SAC 
3.5.  
PK 
Concentration 
PK01 
Summary of Lamivudine Plasma Pharmacokinetic 
Concentration-Time Data (units) by Treatment – DOVATO 
3TC for DOVATO 
SAC 
PK Derived Parameters 
3.6.  
PK 
Parameter 
PK06 
Summary Statistics of Derived Dolutegravir Plasma 
Pharmacokinetic Parameters (Non-Transformed and Ln-
Transformed) Based on Actual Time by Treatment – TRIUMEQ 
Parameters with units for 
TRIUMEQ 
SAC 
3.7.  
PK 
Parameter 
PK06 
Summary Statistics of Derived Abacavir Plasma 
Pharmacokinetic Parameters (Non-Transformed and Ln-
Transformed) Based on Actual Time by Treatment – TRIUMEQ 
Parameters with units for 
TRIUMEQ 
SAC 
3.8.  
PK 
Parameter 
PK06 
Summary Statistics of Derived Lamivudine Plasma 
Pharmacokinetic Parameters (Non-Transformed and Ln-
Transformed) Based on Actual Time by Treatment – TRIUMEQ 
Parameters with units for 
TRIUMEQ 
SAC 
3.9.  
PK 
Parameter 
PK06 
Summary Statistics of Derived Dolutegravir Plasma 
Pharmacokinetic Parameters (Non-Transformed and Ln-
Transformed) Based on Actual Time by Treatment – DOVATO 
Parameters with units DOVATO 
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3.10. 
PK 
Parameter 
PK06 
Summary Statistics of Derived Lamivudine Plasma 
Pharmacokinetic Parameters (Non-Transformed and Ln-
Transformed) Based on Actual Time by Treatment – DOVATO 
Parameters with units DOVATO 
SAC 
PK Analysis Tables 
3.11. 
PK 
Parameter 
PK05 
Statistical Analysis of Plasma Pharmacokinetic Parameters: 
Analysis of Variance (ANOVA) – TRIUMEQ 
TRIUMEQ AUC(0-inf), AUC(0-t) 
and Cmax for each analyte 
SAC 
3.12. 
PK 
Parameter 
PK05 
Statistical Analysis of Plasma Pharmacokinetic Parameters: 
Analysis of Variance (ANOVA) – DOVATO 
DOVATO AUC(0-inf), AUC(0-t) 
and Cmax for each analyte 
SAC 


 
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11.9.8. 
Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
Individual Concentration Plots 
3.1.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – TRIUMEQ 
TRIUMEQ, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.2.  
PK 
Concentration 
PK16A 
Individual Abacavir Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – TRIUMEQ 
TRIUMEQ, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.3.  
PK 
Concentration 
PK16A 
Individual Lamivudine Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – TRIUMEQ 
TRIUMEQ, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.4.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – DOVATO 
DOVATO, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.5.  
PK 
Concentration 
PK16A 
Individual Lamivudine Plasma Concentration-Time Plots by 
Participant (Linear and Semi-Logarithmic) – DOVATO 
DOVATO, Paginate by Participant 
Dashed line represents the LLQ 
Treatments Overlaid 
SAC 
3.6.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – TRIUMEQ 
TRIUMEQ Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
3.7.  
PK 
Concentration 
PK16A 
Individual Abacavir Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – TRIUMEQ 
TRIUMEQ Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
3.8.  
PK 
Concentration 
PK16A 
Individual Lamivudine Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – TRIUMEQ 
TRIUMEQ Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
3.9.  
PK 
Concentration 
PK16A 
Individual Dolutegravir Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – DOVATO 
DOVATO Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
3.10. 
PK 
Concentration 
PK16A 
Individual Lamivudine Plasma Concentration-Time Plots by 
Treatment (Linear and Semi-Logarithmic) – DOVATO 
DOVATO Paginate by Treatment 
Dashed line represents the LLQ 
Individuals Overlaid 
SAC 
Mean / Median Concentration Plots 
3.11. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) Dolutegravir Plasma 
Concentration-Time Plots by Treatment - TRIUMEQ (Linear 
and Semi-Logarithmic) 
Treatments (A and B) Overlaid 
SAC 
3.12. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) Abacavir Plasma Concentration-
Time Plots by Treatment - TRIUMEQ (Linear and Semi-
Logarithmic) 
Treatments (A and B) Overlaid 
SAC 
3.13. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) Lamivudine Plasma Concentration-
Time Plots by Treatment - TRIUMEQ (Linear and Semi-
Logarithmic) 
Treatments (A and B) Overlaid 
SAC 
3.14. 
PK 
Concentration 
PK18 
Median (Range) Dolutegravir Plasma Concentration-Time Plots 
by Treatment - TRIUMEQ (Linear and Semi-Logarithmic) 
Treatments (A and B) Overlaid 
SAC 
3.15. 
PK 
Concentration 
PK18 
Median (Range) Abacavir Plasma Concentration-Time Plots by 
Treatment - TRIUMEQ (Linear and Semi-Logarithmic) 
Treatments (A and B) Overlaid 
SAC 
3.16. 
PK 
Concentration 
PK18 
Median (Range) Lamivudine Plasma Concentration-Time Plots 
by Treatment - TRIUMEQ (Linear and Semi-Logarithmic) 
Treatments (A and B) Overlaid 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
3.17. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) Dolutegravir Plasma 
Concentration-Time Plots by Treatment - DOVATO (Linear and 
Semi-Logarithmic) 
Treatments (C and D) Overlaid 
SAC 
3.18. 
PK 
Concentration 
PK17 
Mean (Standard Deviation) Lamivudine Plasma Concentration-
Time Plots by Treatment - DOVATO (Linear and Semi-
Logarithmic) 
Treatments (C and D) Overlaid 
SAC 
3.19. 
PK 
Concentration 
PK18 
Median (Range) Dolutegravir Plasma Concentration-Time Plots 
by Treatment - DOVATO (Linear and Semi-Logarithmic) 
Treatments (C and D) Overlaid 
SAC 
3.20. 
PK 
Concentration 
PK18 
Median (Range) Lamivudine Plasma Concentration-Time Plots 
by Treatment - DOVATO (Linear and Semi-Logarithmic) 
Treatments (C and D) Overlaid 
SAC 
3.21. 
PK 
Parameter 
PK_F1 
Forest Plot for Plasma Pharmacokinetic Parameters – 
TRIUMEQ 
TRIUMEQ ANOVA AUC(0-inf), 
AUC(0-t) and Cmax for each 
analyte 
SAC 
3.22. 
PK 
Parameter 
PK_F1 
Forest Plot for Plasma Pharmacokinetic Parameters -  
DOVATO 
DOVATO ANOVA  AUC(0-inf), 
AUC(0-t) and Cmax for each 
analyte 
SAC 
 


 
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11.9.9. 
Other Tables 
Palatability Assessment 
4.1.  
Safety 
OTHER_T1 
Summary of Palatability Assessment – TRIUMEQ 
 
SAC 
4.2.  
Safety 
OTHER_T1 
Summary of Palatability Assessment – DOVATO 
 
SAC 
 


 
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11.9.10. 
ICH Listings 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
Randomized 
POP_L1 
Listing of Randomization Schedule – TRIUMEQ 
 
SAC 
2.  
Randomized 
POP_L1 
Listing of Randomization Schedule – DOVATO 
 
SAC 
3.  
Safety 
ES2xo 
Listing of Reasons for Study Withdrawal – TRIUMEQ 
 
SAC 
4.  
Safety 
ES2xo 
Listing of Reasons for Study Withdrawal – DOVATO 
 
SAC 
5.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
 
SAC 
Protocol Deviations 
6.  
Safety 
DV2xo 
Listing of Important Protocol Deviations – TRIUMEQ 
 
SAC 
7.  
Safety 
DV2xo 
Listing of Important Protocol Deviations – DOVATO 
 
SAC 
8.  
Safety 
IE3xo 
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations – TRIUMEQ 
 
SAC 
9.  
Safety 
IE3xo 
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations – DOVATO 
 
SAC 
Populations Analyzed 
10.  
Safety 
SP3xo 
Listing of Subjects Excluded from Any Population – 
TRIUMEQ 
 
SAC 
11.  
Safety 
SP3xo 
Listing of Subjects Excluded from Any Population – 
DOVATO 
 
SAC 
Demographic and Baseline Characteristics 
12.  
Safety 
DM2xo 
Listing of Demographic Characteristics – TRIUMEQ 
 
SAC 
13.  
Safety 
DM2xo 
Listing of Demographic Characteristics – DOVATO 
 
SAC 


 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
14.  
Safety 
DM9xo 
Listing of Race – TRIUMEQ 
 
SAC 
15.  
Safety 
DM9xo 
Listing of Race – DOVATO 
 
SAC 
Prior and Concomitant Medications 
16.  
Safety 
CM3xo 
Listing of Concomitant Medications – TRIUMEQ 
Based on GSK Drug Dictionary 
SAC 
17.  
Safety 
CM3xo 
Listing of Concomitant Medications – DOVATO 
Based on GSK Drug Dictionary 
SAC 
Exposure and Treatment Compliance 
18.  
Safety 
EX3xo 
Listing of Exposure Data – TRIUMEQ 
 
SAC 
19.  
Safety 
EX3xo 
Listing of Exposure Data – DOVATO 
 
SAC 
20.  
Safety 
SAFE_L1 
Listing of Meal Data – TRIUMEQ 
 
SAC 
21.  
Safety 
SAFE_L1 
Listing of Meal Data – DOVATO 
 
SAC 
Adverse Events 
22.  
Safety 
AE2 
Listing of Relationship Between System Organ Class and 
Verbatim Text – TRIUMEQ 
 
SAC 
23.  
Safety 
AE2 
Listing of Relationship Between System Organ Class and 
Verbatim Text – DOVATO 
 
SAC 
24.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events – 
TRIUMEQ 
 
SAC 
25.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events – 
DOVATO 
 
SAC 
26.  
Safety 
AE8CPxo 
Listing of All Adverse Events – TRIUMEQ 
 
SAC 
27.  
Safety 
AE8CPxo 
Listing of All Adverse Events – DOVATO 
 
SAC 
Serious and Other Significant Adverse Events 
28.  
Safety 
AE8CPxo 
Listing of Study Drug Related Adverse Events – TRIUMEQ 
 
SAC 


 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
29.  
Safety 
AE8CPxo 
Listing of Study Drug Related Adverse Events – DOVATO 
 
SAC 
30.  
Safety 
AE8CPxo 
Listing of Serious Adverse Events (Fatal & Non-Fatal) – 
TRIUMEQ 
 
SAC 
31.  
Safety 
AE8CPxo 
Listing of Serious Adverse Events (Fatal & Non-Fatal) – 
DOVATO 
 
SAC 
32.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse 
Event – TRIUMEQ 
 
SAC 
33.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse 
Event – DOVATO 
 
SAC 
34.  
Safety 
AE8CPxo 
Listing of Adverse Events Leading to Withdrawal from Study 
– TRIUMEQ 
 
SAC 
35.  
Safety 
AE8CPxo 
Listing of Adverse Events Leading to Withdrawal from Study 
– DOVATO 
 
SAC 
36.   
Safety 
AE8CPxo 
Listing of Adverse Events With Grade 3 or Higher – 
TRIUMEQ 
 
SAC 
37.  
Safety 
AE8CPxo 
Listing of Adverse Events With Grade 3 or Higher – 
DOVATO 
 
SAC 
Hepatobiliary (Liver) 
38.  
Safety 
MH2xo 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events – TRIUMEQ 
 
SAC 
39.  
Safety 
MH2xo 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events – DOVATO 
 
SAC 
40.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events – TRIUMEQ 
 
SAC 


 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
41.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events – DOVATO 
 
SAC 
All Laboratory 
42.  
Safety 
LB5Axo 
Listing of Clinical Chemistry with any Toxicities – TRIUMEQ 
 
SAC 
43.  
Safety 
LB5Axo 
Listing of Clinical Chemistry with any Toxicities – DOVATO 
 
SAC 
44.  
Safety 
LB5Axo 
Listing of All Clinical Chemistry Data for Subjects with any 
Toxicities – TRIUMEQ 
 
SAC 
45.  
Safety 
LB5Axo 
Listing of All Clinical Chemistry Data for Subjects with any 
Toxicities – DOVATO 
 
SAC 
46.  
Safety 
LB5Axo 
Listing of Hematology with any Toxicities – TRIUMEQ 
 
SAC 
47.  
Safety 
LB5Axo 
Listing of Hematology with any Toxicities – DOVATO 
 
SAC 
48.  
Safety 
LB5Axo 
Listing of All Hematology Data for Subjects with any 
Toxicities – TRIUMEQ 
 
SAC 
49.  
Safety 
LB5Axo 
Listing of All Hematology Data for Subjects with any 
Toxicities – DOVATO 
 
SAC 
50.  
Safety 
LB5Axo 
Listing of Urinalysis with any Toxicities – TRIUMEQ 
 
SAC 
51.  
Safety 
LB5Axo 
Listing of Urinalysis with any Toxicities – DOVATO 
 
SAC 
52.  
Safety 
LB5Axo 
Listing of All Urinalysis Data for Subjects with any Toxicities 
– TRIUMEQ 
 
SAC 
53.  
Safety 
LB5Axo 
Listing of All Urinalysis Data for Subjects with any Toxicities 
– DOVATO 
 
SAC 
ECG 
54.  
Safety 
EG5xo 
Listing of All ECG Findings – TRIUMEQ 
 
SAC 
55.  
Safety 
EG5xo 
Listing of All ECG Findings – DOVATO 
 
SAC 


 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
56.  
Safety 
EG5xo 
Listing of All Abnormal ECG Findings – TRIUMEQ 
 
SAC 
57.  
Safety 
EG5xo 
Listing of All Abnormal ECG Findings – DOVATO 
 
SAC 
58.  
Safety 
EG3xo 
Listing of All ECG Values – TRIUMEQ 
 
SAC 
59.  
Safety 
EG3xo 
Listing of All ECG Values – DOVATO 
 
SAC 
Vital Signs 
60.  
Safety 
VS4xo 
Listing of All Vital Signs of Potential Clinical Importance – 
TRIUMEQ 
 
SAC 
61.  
Safety 
VS4xo 
Listing of All Vital Signs of Potential Clinical Importance – 
DOVATO 
 
SAC 
62.  
Safety 
VS4xo 
Listing of All Vital Signs for Subjects with any Value of 
Potential Clinical Importance – TRIUMEQ 
 
SAC 
63.  
Safety 
VS4xo 
Listing of All Vital Signs for Subjects with any Value of 
Potential Clinical Importance – DOVATO 
 
SAC 
Human Leukocyte Antigen – B 
64.  
Safety 
SAFE_L2 
Listing of Human leukocyte antigen B*5701– TRIUMEQ 
 
SAC 
65.  
Safety 
SAFE_L2 
Listing of Human leukocyte antigen B*5701– DOVATO 
 
SAC 
COVID-19 
66.  
Safety 
PAN12 
Listing of COVID-19 Assessments and Symptom 
Assessment – TRIUMEQ 
 
SAC 
67.  
Safety 
PAN12 
Listing of COVID-19 Assessments and Symptom 
Assessment – DOVATO 
 
SAC 
 
 


 
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11.9.11. 
Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
Palatability Assessment 
68.  
Safety 
OTHER_L1 
Listing of Palatability Assessment – TRIUMEQ 
 
SAC 
69.  
Safety 
OTHER_L1 
Listing of Palatability Assessment – DOVATO 
 
SAC 
Pharmacokinetics 
70.  
PK 
Concentration 
PK07xo 
Listing of Dolutegravir Plasma Concentration-Time Data by 
Treatment – TRIUMEQ 
DTG for TRIUMEQ 
SAC 
71.  
PK 
Concentration 
PK07xo 
Listing of Abacavir Plasma Concentration-Time Data by 
Treatment – TRIUMEQ 
ABC for TRIUMEQ 
SAC 
72.  
PK 
Concentration 
PK07xo 
Listing of Lamivudine Plasma Concentration-Time Data by 
Treatment – TRIUMEQ 
3TC for TRIUMEQ 
SAC 
73.  
PK 
Concentration 
PK07xo 
Listing of Dolutegravir Plasma Concentration-Time Data by 
Treatment – DOVATO 
DTG for DOVATO 
SAC 
74.  
PK 
Concentration 
PK07xo 
Listing of Lamivudine Plasma Concentration-Time Data by 
Treatment – DOVATO 
3TC for DOVATO 
SAC 
75.  
PK 
Parameter 
PK13xo 
Listing of Dolutegravir Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – TRIUMEQ 
DTG for TRIUMEQ 
SAC 
76.  
PK 
Parameter 
PK13xo 
Listing of Abacavir Plasma Pharmacokinetic Parameters Based 
on Actual Time by Treatment – TRIUMEQ 
ABC for TRIUMEQ 
SAC 
77.  
PK 
Parameter 
PK13xo 
Listing of Lamivudine Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – TRIUMEQ 
3TC for TRIUMEQ 
SAC 
78.  
PK 
Parameter 
PK13xo 
Listing of Dolutegravir Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – DOVATO 
DTG for DOVATO 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
79.  
PK 
Parameter 
PK13xo 
Listing of Lamivudine Plasma Pharmacokinetic Parameters 
Based on Actual Time by Treatment – DOVATO 
3TC for DOVATO 
SAC 
Pregnancy 
82. 
Safety 
SAFE_L3 
Listing of Pregnancy – TRIUMEQ 
 
 
83. 
Safety 
SAFE_L3 
Listing of Pregnancy – DOVATO