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

Phase 1

Completed

• Conditions: HIV-1 Infection
• Interventions: Drug: Placebo; Drug: Bictegravir

• Registration Number: NCT02275065
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of the study is to investigate the short-term antiviral potency of bictegravir at multiple doses in antiretroviral (ART) treatment-naive adult participants and participants who are ART-experienced but integrase strand transfer inhibitor (INSTI) naive.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-23
• Study First Submitted QC: 2014-10-23
• Study Start: 2014-10-24
• Study First Posted: 2014-10-27
• Primary Completion: 2015-01-23
• Study Completion: 2015-01-29
• Results First Submitted: 2020-09-08
• Results First Submitted QC: 2020-09-14
• Status Verified: 2020-10
• Results First Posted: 2020-10-08
• Last Update Submitted: 2020-10-16
• Last Update Posted: 2020-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• No current or prior anti-HIV treatment, including ART medications received for prevention (preexposure prophylaxis [PrEP]), or postexposure prophylaxis (PEP) within 12 weeks of screening
• Plasma HIV-1 ribonucleic acid (RNA) ≥ 10,000 copies/mL but ≤ 400,000 copies/mL at screening
• Cluster of differentiation 4+ (CD4+) cell count > 200 cells/mm^3

Key

Exclusion Criteria

• Anticipated to start HIV-1 therapy during the study period
• Active participation in another study of investigational or approved ART agents
• A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
• Participants with positive hepatitis C antibody at screening
• Chronic hepatitis B virus (HBV) infection
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 42 days prior to Day 1 (baseline)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo matched to bictegravir tablet for 10 days
Bictegravir 5 mg	Bictegravir	Bictegravir 5 mg (1 × 5 mg tablet) for 10 days
Bictegravir 25 mg	Bictegravir	Bictegravir 25 mg (1 × 25 mg tablet) for 10 days
Bictegravir 50 mg	Bictegravir	Bictegravir 50 mg (2 × 25 mg tablets) for 10 days
Bictegravir 100 mg	Bictegravir	Bictegravir 100 mg (1 × 100 mg tablet) for 10 days

Primary Outcome Measures

Name	Time	Method
Time-Weighted Average Change From Baseline up to Day 11 (DAVG11) in Plasma HIV-1 RNA	Baseline up to Day 11	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.

Secondary Outcome Measures

Name	Time	Method
Maximum Reduction From Baseline Through Day 17 in Plasma HIV-1 RNA	Baseline to Day 17	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).
Viral Decay Slope in Plasma HIV-1 RNA	Baseline up to Day 11	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.
PK Parameter: CLss/F of Bictegravir Following Multiple-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10	CLss/F is defined as the apparent oral clearance following multiple-dose administration of the drug.
PK/Pharmacodynamic (PD) Analysis: Pearson Correlation Between AUCtau of Bictegravir and DAVG11 in Plasma HIV-1 RNA	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10	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).
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)	First dose date up to last dose date plus 30 days (Maximum: 40 days)
Percentage of Participants With HIV-1 RNA < 50 Copies/mL	Day 17
Pharmacokinetic (PK) Parameter: Cmax of Bictegravir Following Single-Dose and Multiple-Dose Administration	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	Cmax is defined as the maximum concentration of drug.
PK Parameter: Tmax of Bictegravir Following Single-Dose and Multiple-Dose Administration	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	Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: AUC0-24 of Bictegravir Following Single-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1	AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours.
PK Parameter: Ctau of Bictegravir Following Multiple-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10	Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: AR_Cmax of Bictegravir Following Multiple-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 and 10	Accumulation ratio of Cmax (AR_Cmax) = Cmax on Day 10 / Cmax on Day 1. Percentage of accumulation ratio has been reported.
Percentage of Participants Who Experienced Graded Laboratory Abnormalities	First dose date up to last dose date plus 30 days (Maximum: 40 days)	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.
PK Parameter: AUClast of Bictegravir Following Single-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1	AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: AUCtau of Bictegravir Following Multiple-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: t1/2 of Bictegravir Following Multiple-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: AR_AUC of Bictegravir Following Multiple-Dose Administration	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 1 and 10	Accumulation ratio of AUC (AR_AUC) = AUCtau on Day 10 / AUC0-24 on Day 1. Percentage of accumulation ratio has been reported.