A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics and Tolerability of Cabotegravir and Rilpivirine Long-Acting Injections Following Intramuscular Administration in the Vastus Lateralis Muscle of Healthy Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: ViiV Healthcare

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

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

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

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

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

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

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

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

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1.2.
Schema

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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12.
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Clinical Investigator's Brochure, Version 09, December 2019.
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Durability of CAB and RPV as Two Drug Oral Maintenance Therapy – LATTE Week 
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Margolis DA, Gonzalez Garcia J, Stellbrink H-J, et al. Safety, efficacy and durability of 
long-acting CAB and RPV as two drug IM maintenance therapy for HIV-1 infection:  
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Swindells S, Andrade-Villanueva J-F, Richmond G, et al. Long-acting cabotegravir + 
rilpivirine as maintenance therapy: ATLAS week 48 results. Published at: Conference on 
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https://www.who.int/publications-detail/global-surveillance-for-human-infection-with-
novel-coronavirus-(2019-ncov). Accessed 18 June 2020.