Trial Outcomes & Findings for Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Bictegravir (GS-9883) in Human Immunodeficiency Virus (HIV)-1 Infected Participants (NCT NCT02275065)

NCT ID: NCT02275065

Last Updated: 2020-11-09

Results Overview

DAVG11 was defined as the time-weighted average between the first postbaseline value through the last available on-treatment (ie, the last dose date + 1) value up to Day 11 minus the baseline value in plasma HIV-1 RNA (log10 copies/mL). All HIV-1 RNA data up to Day 11 were used for this analysis. DAVG11 was calculated using the trapezoidal rule and the area-under-the-curve concept.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 23 participants
• Primary outcome timeframe: Baseline up to Day 11
• Results posted on: 2020-11-09

Participant Flow

Participants were enrolled at study sites in United States. The first participant was screened on 24 October 2014. The last study visit occurred on 29 January 2015.

33 participants were screened.

Participant milestones

Measure	Bictegravir 5 mg Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
Overall Study STARTED	5	4	5	5	4
Overall Study COMPLETED	4	4	4	4	4
Overall Study NOT COMPLETED	1	0	1	1	0

Reasons for withdrawal

Measure	Bictegravir 5 mg Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
Overall Study Randomized but not treated	1	0	1	1	0

Baseline Characteristics

Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Bictegravir (GS-9883) in Human Immunodeficiency Virus (HIV)-1 Infected Participants

Baseline characteristics by cohort

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 Participants Placebo matched to bictegravir tablet administered orally once daily for 10 days	Total n=20 Participants Total of all reporting groups
Age, Continuous	29 years STANDARD_DEVIATION 4.0 • n=5 Participants	44 years STANDARD_DEVIATION 16.5 • n=7 Participants	34 years STANDARD_DEVIATION 11.5 • n=5 Participants	36 years STANDARD_DEVIATION 11.2 • n=4 Participants	24 years STANDARD_DEVIATION 3.2 • n=21 Participants	33 years STANDARD_DEVIATION 11.6 • n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	19 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	6 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	3 Participants n=21 Participants	14 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race/Ethnicity, Customized Race · Black	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	6 Participants n=8 Participants
Race/Ethnicity, Customized Race · White	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	13 Participants n=8 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Human Immunodeficiency Virus, Type 1 Ribonucleic Acid (HIV-1 RNA)	3.76 log10 copies/mL STANDARD_DEVIATION 1.020 • n=5 Participants	4.64 log10 copies/mL STANDARD_DEVIATION 0.498 • n=7 Participants	4.42 log10 copies/mL STANDARD_DEVIATION 0.458 • n=5 Participants	4.71 log10 copies/mL STANDARD_DEVIATION 1.040 • n=4 Participants	4.50 log10 copies/mL STANDARD_DEVIATION 0.407 • n=21 Participants	4.40 log10 copies/mL STANDARD_DEVIATION 0.745 • n=8 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 11

Population: The Per-Protocol Analysis Set included all randomized participants who took at least 1 dose of bictegravir with baseline HIV-1 RNA ≥ 1900 copies/mL, which allowed up to 2 log decreases in HIV-1 RNA.

DAVG11 was defined as the time-weighted average between the first postbaseline value through the last available on-treatment (ie, the last dose date + 1) value up to Day 11 minus the baseline value in plasma HIV-1 RNA (log10 copies/mL). All HIV-1 RNA data up to Day 11 were used for this analysis. DAVG11 was calculated using the trapezoidal rule and the area-under-the-curve concept.

Outcome measures

Measure	Bictegravir 5 mg n=3 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 Participants Placebo matched to bictegravir tablet administered orally once daily for 10 days
Time-Weighted Average Change From Baseline up to Day 11 (DAVG11) in Plasma HIV-1 RNA Baseline	4.26 log10 copies/mL Standard Deviation 0.157	4.64 log10 copies/mL Standard Deviation 0.498	4.42 log10 copies/mL Standard Deviation 0.458	4.71 log10 copies/mL Standard Deviation 1.040	4.50 log10 copies/mL Standard Deviation 0.407
Time-Weighted Average Change From Baseline up to Day 11 (DAVG11) in Plasma HIV-1 RNA Change at Day 11	-0.92 log10 copies/mL Standard Deviation 0.104	-1.33 log10 copies/mL Standard Deviation 0.174	-1.37 log10 copies/mL Standard Deviation 0.310	-1.61 log10 copies/mL Standard Deviation 0.256	-0.01 log10 copies/mL Standard Deviation 0.144

SECONDARY outcome

Timeframe: First dose date up to last dose date plus 30 days (Maximum: 40 days)

Population: The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 Participants Placebo matched to bictegravir tablet administered orally once daily for 10 days
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)	75.0 percentage of participants	25.0 percentage of participants	50.0 percentage of participants	50.0 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: First dose date up to last dose date plus 30 days (Maximum: 40 days)

Population: Participants in the Safety Analysis Set were analyzed.

A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 toxicity grade from predose assessment and occurring after the predose visit and on or before the date of the last dose of study drug plus 30 days. If the predose assessment was missing, then any abnormality of at least Grade 1 associated with the study drug was considered a treatment-emergent graded laboratory abnormality. The most severe graded abnormality from all tests was counted for each participant.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 Participants Placebo matched to bictegravir tablet administered orally once daily for 10 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities	75.0 percentage of participants	25.0 percentage of participants	0 percentage of participants	25.0 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Day 17

Population: Participants in the Per-Protocol Analysis Set were analyzed.

Maximum reduction from baseline was defined as the minimum of change from baseline in plasma HIV-1 RNA (i.e. smallest change in HIV-RNA from baseline).

Outcome measures

Measure	Bictegravir 5 mg n=3 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 Participants Placebo matched to bictegravir tablet administered orally once daily for 10 days
Maximum Reduction From Baseline Through Day 17 in Plasma HIV-1 RNA	-1.52 log10 copies/mL Standard Deviation 0.079	-2.18 log10 copies/mL Standard Deviation 0.241	-2.31 log10 copies/mL Standard Deviation 0.191	-2.91 log10 copies/mL Standard Deviation 0.526	-0.12 log10 copies/mL Standard Deviation 0.177

SECONDARY outcome

Timeframe: Baseline up to Day 11

Population: Participants in the Per-Protocol Analysis Set were analyzed.

Viral Decay Slope = (log10 [HIV-1 RNA on Day x] - log10 [HIV-1 RNA on Day 1]) / (x-1), where x is the collection day of the last available on treatment HIV-1 RNA collected up to Day 7.

Outcome measures

Measure	Bictegravir 5 mg n=3 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 Participants Placebo matched to bictegravir tablet administered orally once daily for 10 days
Viral Decay Slope in Plasma HIV-1 RNA	-0.184 log10 copies/mL Standard Deviation 0.0134	-0.252 log10 copies/mL Standard Deviation 0.0277	-0.272 log10 copies/mL Standard Deviation 0.0580	-0.315 log10 copies/mL Standard Deviation 0.0413	-0.011 log10 copies/mL Standard Deviation 0.0200

SECONDARY outcome

Timeframe: Day 17

Population: Participants in the Per-Protocol Analysis Set were analyzed.

Outcome measures

Measure	Bictegravir 5 mg n=3 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 Participants Placebo matched to bictegravir tablet administered orally once daily for 10 days
Percentage of Participants With HIV-1 RNA < 50 Copies/mL	0 percentage of participants	0 percentage of participants	25.0 percentage of participants	50.0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 for single dose and Day 10 for multiple dose

Population: The PK Analysis Set included all participants who were randomized and received at least 1 dose of bictegravir and had at least 1 nonmissing concentration of bictegravir.

Cmax is defined as the maximum concentration of drug.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
Pharmacokinetic (PK) Parameter: Cmax of Bictegravir Following Single-Dose and Multiple-Dose Administration Single-Dose	493.3 ng/mL Standard Deviation 72.12	2565.0 ng/mL Standard Deviation 331.31	4957.5 ng/mL Standard Deviation 667.60	7367.5 ng/mL Standard Deviation 2293.90	—
Pharmacokinetic (PK) Parameter: Cmax of Bictegravir Following Single-Dose and Multiple-Dose Administration Multiple-Dose	741.5 ng/mL Standard Deviation 134.65	3475.0 ng/mL Standard Deviation 712.67	6080.0 ng/mL Standard Deviation 1323.20	12235.0 ng/mL Standard Deviation 3040.98	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 for single dose and Day 10 for multiple dose

Population: Participants in the PK Analysis Set were analyzed.

Tmax is defined as the time (observed time point) of Cmax.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: Tmax of Bictegravir Following Single-Dose and Multiple-Dose Administration Single-Dose	1.00 hours Interval 1.0 to 1.25	1.83 hours Interval 1.33 to 2.5	1.75 hours Interval 1.5 to 2.5	1.50 hours Interval 1.25 to 1.75	—
PK Parameter: Tmax of Bictegravir Following Single-Dose and Multiple-Dose Administration Multiple-Dose	1.50 hours Interval 0.75 to 3.0	1.25 hours Interval 1.0 to 1.5	1.75 hours Interval 1.25 to 2.5	2.74 hours Interval 1.25 to 3.99	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1

Population: Participants in the PK Analysis Set were analyzed.

AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: AUC0-24 of Bictegravir Following Single-Dose Administration	6262.2 ng*hr/mL Standard Deviation 1432.17	31291.8 ng*hr/mL Standard Deviation 3113.91	68476.5 ng*hr/mL Standard Deviation 11667.41	94588.5 ng*hr/mL Standard Deviation 27376.40	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1

Population: Participants in the PK Analysis Set were analyzed.

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: AUClast of Bictegravir Following Single-Dose Administration	6295.5 ng*hr/mL Standard Deviation 1496.59	31401.0 ng*hr/mL Standard Deviation 3123.59	68485.6 ng*hr/mL Standard Deviation 11649.37	94827.0 ng*hr/mL Standard Deviation 27262.26	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10

Population: Participants in the PK Analysis Set were analyzed.

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: AUCtau of Bictegravir Following Multiple-Dose Administration	9983.0 ng*hr/mL Standard Deviation 2664.77	48950.3 ng*hr/mL Standard Deviation 19592.41	87538.4 ng*hr/mL Standard Deviation 28649.77	178901.7 ng*hr/mL Standard Deviation 31865.15	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10

Population: Participants in the PK Analysis Set were analyzed.

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: t1/2 of Bictegravir Following Multiple-Dose Administration	20.79 hours Interval 17.15 to 23.8	15.86 hours Interval 14.07 to 19.37	17.84 hours Interval 15.5 to 20.51	20.88 hours Interval 17.91 to 24.47	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10

Population: Participants in the PK Analysis Set were analyzed.

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: Ctau of Bictegravir Following Multiple-Dose Administration	225.3 ng/mL Standard Deviation 84.57	1052.3 ng/mL Standard Deviation 568.90	2053.0 ng/mL Standard Deviation 977.35	4520.0 ng/mL Standard Deviation 991.90	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10

Population: Participants in the PK Analysis Set were analyzed.

CLss/F is defined as the apparent oral clearance following multiple-dose administration of the drug.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: CLss/F of Bictegravir Following Multiple-Dose Administration	523.8 mL/hr Standard Deviation 115.43	567.3 mL/hr Standard Deviation 196.72	621.9 mL/hr Standard Deviation 211.73	570.6 mL/hr Standard Deviation 87.57	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 and 10

Population: Participants in the PK Analysis Set were analyzed.

Accumulation ratio of AUC (AR_AUC) = AUCtau on Day 10 / AUC0-24 on Day 1. Percentage of accumulation ratio has been reported.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: AR_AUC of Bictegravir Following Multiple-Dose Administration	160.2 percentage of AR_AUC Standard Deviation 25.86	157.4 percentage of AR_AUC Standard Deviation 59.76	125.3 percentage of AR_AUC Standard Deviation 20.92	193.3 percentage of AR_AUC Standard Deviation 22.44	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 and 10

Population: Participants in the PK Analysis Set were analyzed.

Accumulation ratio of Cmax (AR_Cmax) = Cmax on Day 10 / Cmax on Day 1. Percentage of accumulation ratio has been reported.

Outcome measures

Measure	Bictegravir 5 mg n=4 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK Parameter: AR_Cmax of Bictegravir Following Multiple-Dose Administration	149.8 percentage of AR_Cmax Standard Deviation 6.61	138.5 percentage of AR_Cmax Standard Deviation 37.40	122.0 percentage of AR_Cmax Standard Deviation 13.31	168.4 percentage of AR_Cmax Standard Deviation 16.15	—

SECONDARY outcome

Timeframe: 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10

Population: The PK/PD Analysis Set included all participants in PP Analysis Set (all randomized participants who took at least 1 dose of bictegravir with baseline HIV-1 RNA ≥ 1900 copies/mL, which allowed up to 2 log decreases in HIV-1 RNA) and had both nonmissing bictegravir AUCtau on Day 10 and DAVG11 in log10 plasma HIV-1 RNA.

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). DAVG11 was defined as the time-weighted average between the first postbaseline value through the last available on-treatment (ie, the last dose date + 1) value up to Day 11 minus the baseline value in plasma HIV-1 RNA (log10 copies/mL).

Outcome measures

Measure	Bictegravir 5 mg n=3 Participants Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 Participants Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 Participants Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 Participants Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo Placebo matched to bictegravir tablet administered orally once daily for 10 days
PK/Pharmacodynamic (PD) Analysis: Pearson Correlation Between AUCtau of Bictegravir and DAVG11 in Plasma HIV-1 RNA	-1.000 correlation coefficient	0.275 correlation coefficient	-0.940 correlation coefficient	0.713 correlation coefficient	—

Adverse Events

Bictegravir 5 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Bictegravir 25 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Bictegravir 50 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Bictegravir 100 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Bictegravir 5 mg n=4 participants at risk Bictegravir 5 mg (1 × 5 mg tablet) administered orally once daily for 10 days	Bictegravir 25 mg n=4 participants at risk Bictegravir 25 mg (1 × 25 mg tablet) administered orally once daily for 10 days	Bictegravir 50 mg n=4 participants at risk Bictegravir 50 mg (2 × 25 mg tablets) administered orally once daily for 10 days	Bictegravir 100 mg n=4 participants at risk Bictegravir 100 mg (1 × 100 mg tablet) administered orally once daily for 10 days	Placebo n=4 participants at risk Placebo matched to bictegravir tablet administered orally once daily for 10 days
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
General disorders Fatigue	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
Infections and infestations Nasopharyngitis	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
Infections and infestations Upper respiratory tract infection	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
Investigations Blood creatine phosphokinase increased	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
Nervous system disorders Headache	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.
Skin and subcutaneous tissue disorders Papule	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	25.0% 1/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.	0.00% 0/4 • First dose date up to last dose date plus 30 days (Maximum: 40 days) The Safety Analysis Set included participants who were randomized and received at least 1 dose of bictegravir or matched placebo.

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: GileadClinicalTrials@gilead.com

Results disclosure agreements

• Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
• Publication restrictions are in place

Restriction type: OTHER