Trial Outcomes & Findings for Study to Evaluate the Safety Tolerability and Acceptability of Long Acting Injections of the Human Immunodeficiency Virus (HIV) Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ECLAIR) (NCT NCT02076178)

NCT ID: NCT02076178

Last Updated: 2017-12-15

Results Overview

Clinical adverse event (AE) were graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The grades were: 1 (mild)=Symptoms causing no or minimal interference with usual social and functional activities; 2 (moderate)= Symptoms causing greater than minimal interference with usual social and functional activities; 3 (severe)= Symptoms causing inability to perform usual social and functional activities; 4 (potentially life threatening): Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data has been presented for any Grade 2 or higher event in the injection phase for injection phase (Week 5- Week 41).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

127 participants

Primary outcome timeframe

Up to Week 41

Results posted on

2017-12-15

Participant Flow

This study was conducted at 10 centers in United states. Participants who received study medication are being followed for 52 Weeks following their last injection while those in placebo group were followed until all participants completed Week 41. The first subject's first visit was 27-Mar-2014 and the last subject's last visit was 15-May-2015.

A total of 205 participants were screened of which 78 participants were not randomized. The remaining 127 participants were randomized to the study treatment who entered the oral and injection phase. Out of this, one participant randomized but withdrawn consent prior to treatment.

Participant milestones

Participant milestones
Measure	Placebo Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received intramuscular (IM) injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 milligrams (mg) tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Oral Phase STARTED	21	106
Oral Phase COMPLETED	21	94
Oral Phase NOT COMPLETED	0	12
Injection Phase STARTED	21	94
Injection Phase COMPLETED	20	87
Injection Phase NOT COMPLETED	1	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received intramuscular (IM) injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 milligrams (mg) tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Oral Phase Adverse Event	0	7
Oral Phase Withdrawal by Subject	0	4
Oral Phase Physician Decision	0	1
Injection Phase Protocol defined stopping criteria	1	0
Injection Phase Withdrawal by Subject	0	3
Injection Phase Physician Decision	0	3
Injection Phase Lost to Follow-up	0	1

Baseline Characteristics

One participant randomized but withdrawn consent prior to treatment and not included in analysis for Age, continuous.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=106 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.	Total n=127 Participants Total of all reporting groups
Age, Continuous	33.7 Years STANDARD_DEVIATION 11.56 • n=21 Participants • One participant randomized but withdrawn consent prior to treatment and not included in analysis for Age, continuous.	35.1 Years STANDARD_DEVIATION 11.75 • n=105 Participants • One participant randomized but withdrawn consent prior to treatment and not included in analysis for Age, continuous.	34.9 Years STANDARD_DEVIATION 11.68 • n=126 Participants • One participant randomized but withdrawn consent prior to treatment and not included in analysis for Age, continuous.
Sex: Female, Male Female	0 Participants n=21 Participants	0 Participants n=106 Participants	0 Participants n=127 Participants
Sex: Female, Male Male	21 Participants n=21 Participants	106 Participants n=106 Participants	127 Participants n=127 Participants
Race/Ethnicity, Customized African American/African Heritage	7 Participants n=21 Participants	33 Participants n=106 Participants	40 Participants n=127 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=21 Participants	3 Participants n=106 Participants	3 Participants n=127 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=21 Participants	2 Participants n=106 Participants	3 Participants n=127 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=21 Participants	2 Participants n=106 Participants	3 Participants n=127 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=21 Participants	1 Participants n=106 Participants	1 Participants n=127 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=21 Participants	1 Participants n=106 Participants	1 Participants n=127 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=21 Participants	3 Participants n=106 Participants	3 Participants n=127 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	12 Participants n=21 Participants	59 Participants n=106 Participants	71 Participants n=127 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=21 Participants	2 Participants n=106 Participants	2 Participants n=127 Participants

PRIMARY outcome

Timeframe: Up to Week 41

Population: Safety Injection population was defined as all participants enrolled in the study who received at least one injection of study medication.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=94 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants With Any Grade 2 or Higher Event in the Injection Phase	10 Participants	75 Participants

PRIMARY outcome

Timeframe: Up to Week 41

Population: The randomized population was defined as all participants who met the study criteria and were randomly assigned to treatment in the study.

The concurrent medications that were consumed by participants during the injection phase were of the class nervous system, musculo-skeletal system, genito urinary systems and sex hormones, various, respiratory system, dermatologicals, alimentary tract and metabolism, sensory organs, systemic hormonal preparations, excluding sex hormones, blood and blood forming organs, cardiovascular system. The participants who took medication from any of the above class of during the injection phase (Week 5-Week 41) have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=106 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants Who Recieved Injection Site Reaction (ISR) Related Concomitant Medication in the Injection Phase	5 Participants	55 Participants

PRIMARY outcome

Timeframe: Up to Week 41

Population: Safety Injection population.

The severity of laboratory results was graded according to the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening. Data for Number of participants who experienced grade 2 or higher laboratory results in the injection phase (Week 5-Week 14) have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=94 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Activated prothrombin time/standard	1 Participants	0 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Activated partial thromboplastin time	1 Participants	0 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Alanine aminotransferase	0 Participants	2 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Aspartate aminotransferase	0 Participants	2 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Bilirubin	0 Participants	4 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Carbon dioxide	0 Participants	1 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Cholesterol	1 Participants	4 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Creatine kinase	3 Participants	6 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Glucose	2 Participants	7 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Leukocytes	0 Participants	2 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Lipase	1 Participants	10 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Neutrophils	0 Participants	3 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Prothrombin time	1 Participants	0 Participants
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Urate	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Week 41

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Full 12-lead ECGs included heart rate, PR, QRS, QT and QTc intervals. Measurements were taken from the participant following 5 minutes of rest in a semi-supine position. ECGs were performed at Week 5, Week 17, Week 29 and Week 41 in the injection phase (Week 5-Week 41). ECG abnormalities characterized as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS) upto Week 41 have been presented. There were no A-CS findings for ECG in the injection phase.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=105 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase Week 5, A-NCS	6 Participants	30 Participants
Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase Week 17, A-NCS	9 Participants	34 Participants
Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase Week 29, A-NCS	7 Participants	27 Participants
Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase Week 41, A-NCS	5 Participants	23 Participants

PRIMARY outcome

Timeframe: Baseline (Week 5) to Week 41

Population: Safety population. Only those participants available at the specified time points were analyzed.

Vital signs measurements were performed for SBP and DBP following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=105 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase Week 17, DBP	-3.10 millimeters of mercury Standard Deviation 11.541	-0.74 millimeters of mercury Standard Deviation 7.214
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase Week 29, DBP	-3.75 millimeters of mercury Standard Deviation 12.781	0.32 millimeters of mercury Standard Deviation 8.283
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase Week 41, DBP	-1.19 millimeters of mercury Standard Deviation 13.692	0.01 millimeters of mercury Standard Deviation 9.286
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase Week 17, SBP	-1.52 millimeters of mercury Standard Deviation 14.041	-0.66 millimeters of mercury Standard Deviation 9.237
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase Week 29, SBP	2.80 millimeters of mercury Standard Deviation 10.904	2.62 millimeters of mercury Standard Deviation 10.868
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase Week 41, SBP,	-1.38 millimeters of mercury Standard Deviation 14.044	1.64 millimeters of mercury Standard Deviation 12.012

PRIMARY outcome

Timeframe: Baseline (Week 5) to Week 41

Population: Safety population. Only those participants available at the specified time points were analyzed.

Vital signs measurements were performed for HR following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=105 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase Week 17, HR	1.19 beats per minute Standard Deviation 11.021	3.26 beats per minute Standard Deviation 11.684
Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase Week 29, HR	1.55 beats per minute Standard Deviation 10.149	4.06 beats per minute Standard Deviation 10.740
Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase Week 41, HR	1.43 beats per minute Standard Deviation 10.181	2.73 beats per minute Standard Deviation 11.752

PRIMARY outcome

Timeframe: Up to Week 41

Population: Safety Injection population.

Common ISR included pain, erythema, nodules and any other ISR with greater or equal to 5 participants. The number of participants who experienced pain events by needle length, swelling events by needle length, bump events by needle length for injection phase by maximum grades have been presented for the injection phase (Week 5-Week 41).

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=94 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR swelling, Grade 4	0 Participants	0 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR pain, Grade 1	11 Participants	31 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR pain, Grade 2	1 Participants	37 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR pain, Grade 3	0 Participants	18 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR pain, Grade 4	0 Participants	0 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR swelling, Grade 1	0 Participants	11 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR swelling, Grade 2	0 Participants	4 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR swelling, Grade 3	0 Participants	0 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR Bump, Grade 1	0 Participants	9 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR Bump, Grade 2	0 Participants	3 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR Bump, Grade 3	0 Participants	0 Participants
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades ISR Bump, Grade 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 41

Population: The pharmacokinetic parameter population comprised of all participants who underwent plasma pharmacokinetic sampling and have evaluable cabotegravir parameters estimated. Only those participants available at the specified time points were analyzed.

Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for AUC(0-tau) a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (i.e.12 hours).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase Injection 1	3414.71 hour*microgram per milliliter Geometric Coefficient of Variation 42.5	—
Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase Injection 2	3873.25 hour*microgram per milliliter Geometric Coefficient of Variation 44.3	—
Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase Injection 3	4020.89 hour*microgram per milliliter Geometric Coefficient of Variation 36.2	—

SECONDARY outcome

Timeframe: Up to Week 41

Population: Pharmacokinetic parameter population. Only those participants available at the specified time points were analyzed.

Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for Ctau defined as the concentration at the end of the dosing interval and Cmax defined as the maximum observed plasma concentration.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase Cmax, Injection 3	4.91 micrograms per milliliter Geometric Coefficient of Variation 66.6	—
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase Cmax, Injection 1	4.26 micrograms per milliliter Geometric Coefficient of Variation 88.6	—
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase Cmax, Injection 2	5.22 micrograms per milliliter Geometric Coefficient of Variation 78.0	—
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase Ctau, Injection 1	0.302 micrograms per milliliter Geometric Coefficient of Variation 157.1	—
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase Ctau, Injection 2	0.331 micrograms per milliliter Geometric Coefficient of Variation 164.5	—
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase Ctau, Injection 3	0.387 micrograms per milliliter Geometric Coefficient of Variation 149.6	—

SECONDARY outcome

Timeframe: Up to Week 41

Population: Pharmacokinetic parameter population. Only those participants available at the specified time points were analyzed.

Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for tmax defined as the time to the maximum observed plasma concentration and t½ defined as the time taken for the concentration of drug in the blood to decrease by half of the original amount.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase tmax, Injection 1	13.14 days Standard Deviation 11.503	—
Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase tmax, Injection 2	8.91 days Standard Deviation 9.311	—
Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase tmax, Injection 3	9.25 days Standard Deviation 7.579	—
Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase t½ , Injection 1	20.54 days Standard Deviation 10.690	—

SECONDARY outcome

Timeframe: Up to Week 41

Population: Pharmacokinetic parameter population. Only those participants available at the specified time point were analyzed.

The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for AUC (0-tau) by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI). Assessments was also performed for AUC (0-tau) by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 50 percent BMI lower, Injection 1	4103.71 hour*microgram per milliter Geometric Coefficient of Variation 28.4	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 50 percent BMI lower, Injection 2	4250.82 hour*microgram per milliter Geometric Coefficient of Variation 49.6	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 50 percent BMI lower, Injection 3	4847.07 hour*microgram per milliter Geometric Coefficient of Variation 26.1	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 50 percent BMI upper, Injection 1	2830.06 hour*microgram per milliter Geometric Coefficient of Variation 45.6	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 50 percent BMI upper, Injection 2	3536.52 hour*microgram per milliter Geometric Coefficient of Variation 36.7	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 50 percent BMI upper, Injection 3	3405.52 hour*microgram per milliter Geometric Coefficient of Variation 35.2	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 1.5 inch Injection 1	3666.95 hour*microgram per milliter Geometric Coefficient of Variation 40.0	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 1.5 inch Injection 2	4177.42 hour*microgram per milliter Geometric Coefficient of Variation 44.0	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 1.5 inch Injection 3	4263.31 hour*microgram per milliter Geometric Coefficient of Variation 38.9	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 2 inch Injection 1	2782.06 hour*microgram per milliter Geometric Coefficient of Variation 42.6	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 2 inch Injection 2	3191.72 hour*microgram per milliter Geometric Coefficient of Variation 38.5	—
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase 2 inch Injection 3	3493.85 hour*microgram per milliter Geometric Coefficient of Variation 24.1	—

SECONDARY outcome

Timeframe: Up to Week 41

Population: Pharmacokinetic parameter population. Only those participants available at the specified time point were analyzed.

The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for Ctau and Cmax by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI. ). Assessments was also performed for Ctau and Cmax by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for Ctau, Injection 2	0.312 micrograms per milliter Geometric Coefficient of Variation 152.4	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for Ctau, Injection 3	0.372 micrograms per milliter Geometric Coefficient of Variation 150.7	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for Cmax, Injection 1	2.78 micrograms per milliter Geometric Coefficient of Variation 92.8	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for Cmax, Injection 2	3.52 micrograms per milliter Geometric Coefficient of Variation 92.7	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for Cmax, Injection 1	6.02 micrograms per milliter Geometric Coefficient of Variation 51.3	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for Cmax, Injection 2	6.65 micrograms per milliter Geometric Coefficient of Variation 54.8	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for Cmax, Injection 3	6.99 micrograms per milliter Geometric Coefficient of Variation 35.9	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for Ctau, Injection 1	0.226 micrograms per milliter Geometric Coefficient of Variation 159.9	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for Ctau, Injection 2	0.312 micrograms per milliter Geometric Coefficient of Variation 138.3	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for Ctau, Injection 3	0.334 micrograms per milliter Geometric Coefficient of Variation 102.2	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for Cmax, Injection 1	2.99 micrograms per milliter Geometric Coefficient of Variation 100.0	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for Cmax, Injection 2	4.12 micrograms per milliter Geometric Coefficient of Variation 88.4	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for Cmax, Injection 3	3.59 micrograms per milliter Geometric Coefficient of Variation 68.0	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for Ctau, Injection 1	0.394 micrograms per milliter Geometric Coefficient of Variation 141.7	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for Ctau, Injection 2	0.350 micrograms per milliter Geometric Coefficient of Variation 193.8	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for Ctau, Injection 3	0.437 micrograms per milliter Geometric Coefficient of Variation 193.3	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for Cmax, Injection 1	4.94 micrograms per milliter Geometric Coefficient of Variation 79.3	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for Cmax, Injection 2	6.09 micrograms per milliter Geometric Coefficient of Variation 63.7	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for Cmax, Injection 3	5.56 micrograms per milliter Geometric Coefficient of Variation 65.0	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for Ctau, Injection 1	0.270 micrograms per milliter Geometric Coefficient of Variation 177.7	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for Cmax, Injection 3	3.65 micrograms per milliter Geometric Coefficient of Variation 57.6	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for Ctau, Injection 1	0.418 micrograms per milliter Geometric Coefficient of Variation 93.7	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for Ctau, Injection 2	0.381 micrograms per milliter Geometric Coefficient of Variation 200.3	—
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for Ctau, Injection 3	0.426 micrograms per milliter Geometric Coefficient of Variation 152.1	—

SECONDARY outcome

Timeframe: Up to Week 41

Population: Pharmacokinetic parameter population. Only those participants available at the specified time point were analyzed.

The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for tmax and t½ by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI). Assessments was also performed for tmax and t½ by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for tmax, Injection 1	8.55 Days Standard Deviation 5.402	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for tmax, Injection 2	8.62 Days Standard Deviation 7.378	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for tmax, Injection 3	7.75 Days Standard Deviation 1.845	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI lower for t½, Injection 1	19.54 Days Standard Deviation 10.384	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for tmax, Injection 1	17.83 Days Standard Deviation 14.008	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for tmax, Injection 2	9.20 Days Standard Deviation 10.955	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for tmax, Injection 3	10.58 Days Standard Deviation 10.139	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 50 percent BMI upper for t½, Injection 1	22.32 Days Standard Deviation 11.234	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for tmax, Injection 1	11.33 Days Standard Deviation 9.497	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for tmax, Injection 2	9.10 Days Standard Deviation 10.408	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for tmax, Injection 3	9.53 Days Standard Deviation 7.774	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 1.5 inch for t½, Injection 1	21.26 Days Standard Deviation 11.506	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for tmax, Injection 1	18.34 Days Standard Deviation 14.987	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for tmax, Injection 2	8.42 Days Standard Deviation 5.757	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for tmax, Injection 3	8.57 Days Standard Deviation 7.196	—
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase 2 inch for t½, Injection 1	17.27 Days Standard Deviation 4.747	—

SECONDARY outcome

Timeframe: Up to Week 41

Population: Safety injection population.

Acceptability of cabetogravir injections was assessed number of participants who had severe ISRs and ISR symptom. ISR examination for severity included an assessment of pain, pruritis, warm to touch, bruising, discoloration, erythema, swelling, induration and bump events. Common ISR Symptoms for Injection Phase included pain, erythema, nodules and any other ISRs with greater or equal to five participants. Data has been presented for the injection phase (W5-W41) by grades and needle length.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=94 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pain, Grade 1,	11 Participants	63 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pain, Grade 2	1 Participants	51 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pain, Grade 3	0 Participants	18 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pain, Grade 4	0 Participants	0 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pruritis, Grade 1	3 Participants	15 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pruritis, Grade 2	0 Participants	6 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pruritis, Grade 3	0 Participants	0 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Pruritis, Grade 4	0 Participants	0 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Bruising	1 Participants	11 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Discolouration	0 Participants	4 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Erythema	0 Participants	6 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Haemorrhage	1 Participants	0 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Induration	0 Participants	10 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Swelling	0 Participants	15 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Bump	0 Participants	12 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR, needle any length, Warm to touch	0 Participants	12 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR symptoms, needle any length, Mild or Grade 1	11 Participants	12 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR symptoms,needle any length,Moderate or Grade2	1 Participants	8 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR symptoms, needle any length, Severe or Grade 3	0 Participants	2 Participants
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length ISR symptoms, needle any length, Grade 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 4

Population: Safety population.

Clinical AE were graded using the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The grades were: 1 (mild)=Symptoms causing no or minimal interference with usual social and functional activities; 2 (moderate)= Symptoms causing greater than minimal interference with usual social and functional activities; 3 (severe)= Symptoms causing inability to perform usual social and functional activities; 4 (potentially life threatening): Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data has been presented for any Grade 2 or higher event in the injection phase for injection phase (Week 5- Week 41).

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=105 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase Any AE	8 Participants	56 Participants
Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase Grade 2-4 AE	4 Participants	24 Participants
Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase Any SAE	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 41

Population: The Randomized Population comprised of all participants who met study criteria were randomly assigned to treatment in the study with the exception of any participants with documented evidence of not having consumed any amount of study medication.

The concurrent medications that were consumed by participants during the injection phase were of the class nervous system, musculo-skeletal system, genito-urinary systems and sex hormones, various, respiratory system, dermatologicals, alimentary tract and metabolism, anti-infectives for systemic use, sensory organs, systemic hormonal preparations excluding sex hormones, blood and blood forming organs, cardiovascular system, anti-neoplastic and immunomodulating agents, anti-parasitic products, insecticides and repellents . The participants who took medication from any of the above class of during the during the overall study duration injection phase (Day 1 until Week 41) have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=106 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants Who Received Concurrent Medication in Overall Study Duration	20 Participants	97 Participants

SECONDARY outcome

Timeframe: Up to Week 4

Population: Safety population.

The severity of clinical chemistry including liver chemistry and hematology toxicities was graded according to the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening. Data for maximum clinical chemistry and hematology toxicities for oral phase (Day 1 upto Week 4) by grades have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=105 Participants Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Clinical chemistry, Grade 1	2 Participants	33 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Clinical chemistry, Grade 2	3 Participants	4 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Clinical chemistry, Grade 3	0 Participants	2 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Clinical chemistry, Grade 4	0 Participants	4 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Liver chemistry, Grade 1	0 Participants	9 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Liver chemistry, Grade 2	0 Participants	2 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Liver chemistry, Grade 3	0 Participants	0 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Liver chemistry, Grade 4	0 Participants	1 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Hematology, Grade 1	0 Participants	4 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Hematology, Grade 3	0 Participants	0 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Hematology, Grade 2	0 Participants	1 Participants
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades Hematology, Grade 4	0 Participants	1 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Cabotegravir

Serious events: 1 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=21 participants at risk Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=105 participants at risk Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
Infections and infestations Appendicitis	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	0.95% 1/105 • Up to Week 41 The safety population was used for analysis.
Vascular disorders Deep vein thrombosis	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	0.00% 0/105 • Up to Week 41 The safety population was used for analysis.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=21 participants at risk Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo.	Cabotegravir n=105 participants at risk Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir.
General disorders Injection site pain	57.1% 12/21 • Up to Week 41 The safety population was used for analysis.	81.9% 86/105 • Up to Week 41 The safety population was used for analysis.
General disorders Injection site pruritus	14.3% 3/21 • Up to Week 41 The safety population was used for analysis.	17.1% 18/105 • Up to Week 41 The safety population was used for analysis.
General disorders Injection site swelling	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	19.0% 20/105 • Up to Week 41 The safety population was used for analysis.
General disorders Pyrexia	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	16.2% 17/105 • Up to Week 41 The safety population was used for analysis.
General disorders Fatigue	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	15.2% 16/105 • Up to Week 41 The safety population was used for analysis.
General disorders Injection site bruising	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	10.5% 11/105 • Up to Week 41 The safety population was used for analysis.
General disorders Injection site warmth	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	11.4% 12/105 • Up to Week 41 The safety population was used for analysis.
General disorders Injection site induration	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	9.5% 10/105 • Up to Week 41 The safety population was used for analysis.
General disorders Chills	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	5.7% 6/105 • Up to Week 41 The safety population was used for analysis.
General disorders Injection site erythema	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	5.7% 6/105 • Up to Week 41 The safety population was used for analysis.
Infections and infestations Upper respiratory tract infection	28.6% 6/21 • Up to Week 41 The safety population was used for analysis.	19.0% 20/105 • Up to Week 41 The safety population was used for analysis.
Infections and infestations Nasopharyngitis	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	12.4% 13/105 • Up to Week 41 The safety population was used for analysis.
Infections and infestations Viral upper respiratory tract infection	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	10.5% 11/105 • Up to Week 41 The safety population was used for analysis.
Infections and infestations Gastroenteritis	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	5.7% 6/105 • Up to Week 41 The safety population was used for analysis.
Infections and infestations Sinusitis	9.5% 2/21 • Up to Week 41 The safety population was used for analysis.	0.95% 1/105 • Up to Week 41 The safety population was used for analysis.
Nervous system disorders Headache	19.0% 4/21 • Up to Week 41 The safety population was used for analysis.	24.8% 26/105 • Up to Week 41 The safety population was used for analysis.
Nervous system disorders Dizziness	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	5.7% 6/105 • Up to Week 41 The safety population was used for analysis.
Gastrointestinal disorders Diarrhoea	14.3% 3/21 • Up to Week 41 The safety population was used for analysis.	15.2% 16/105 • Up to Week 41 The safety population was used for analysis.
Gastrointestinal disorders Nausea	9.5% 2/21 • Up to Week 41 The safety population was used for analysis.	6.7% 7/105 • Up to Week 41 The safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 3/21 • Up to Week 41 The safety population was used for analysis.	3.8% 4/105 • Up to Week 41 The safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	5.7% 6/105 • Up to Week 41 The safety population was used for analysis.
Musculoskeletal and connective tissue disorders Myalgia	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	9.5% 10/105 • Up to Week 41 The safety population was used for analysis.
Investigations Blood creatine phosphokinase increased	9.5% 2/21 • Up to Week 41 The safety population was used for analysis.	7.6% 8/105 • Up to Week 41 The safety population was used for analysis.
Blood and lymphatic system disorders Neutropenia	0.00% 0/21 • Up to Week 41 The safety population was used for analysis.	7.6% 8/105 • Up to Week 41 The safety population was used for analysis.
Immune system disorders Seasonal allergy	4.8% 1/21 • Up to Week 41 The safety population was used for analysis.	6.7% 7/105 • Up to Week 41 The safety population was used for analysis.
Psychiatric disorders Insomnia	9.5% 2/21 • Up to Week 41 The safety population was used for analysis.	0.00% 0/105 • Up to Week 41 The safety population was used for analysis.