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

Gilead Sciences23 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

HIV-1 Infection

Interventions

BictegravirDRUG

Bictegravir tablet(s) administered orally once daily

PlaceboDRUG

Placebo to match bictegravir administered orally once daily

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Key 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.

Locations (16)

Unnamed facility

Berkeley, California, United States

Unnamed facility

Davis, California, United States

Unnamed facility

Long Beach, California, United States

Outcomes

Primary Outcomes

Time-Weighted Average Change From Baseline up to Day 11 (DAVG11) in Plasma 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.

Time frame: Baseline up to Day 11

Secondary Outcomes

Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)

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

Percentage of Participants Who Experienced Graded Laboratory Abnormalities

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.

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

Maximum Reduction From Baseline Through Day 17 in Plasma HIV-1 RNA

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).

Time frame: Baseline to Day 17

Viral Decay Slope in Plasma HIV-1 RNA

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.

Data from ClinicalTrials.gov

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Unnamed facility

Los Angeles, California, United States

Unnamed facility

San Francisco, California, United States

Unnamed facility

Washington D.C., District of Columbia, United States

Unnamed facility

Fort Lauderdale, Florida, United States

Unnamed facility

Orlando, Florida, United States

Unnamed facility

Vero Beach, Florida, United States

Unnamed facility

West Palm Beach, Florida, United States

...and 6 more locations

Time frame: Baseline up to Day 11

Percentage of Participants With HIV-1 RNA < 50 Copies/mL

Time frame: Day 17

Pharmacokinetic (PK) Parameter: Cmax of Bictegravir Following Single-Dose and Multiple-Dose Administration

Cmax is defined as the maximum concentration of drug.

Time frame: 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

PK Parameter: Tmax of Bictegravir Following Single-Dose and Multiple-Dose Administration

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

Time frame: 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

PK Parameter: AUC0-24 of Bictegravir Following Single-Dose Administration

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

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

PK Parameter: AUClast of Bictegravir Following Single-Dose Administration

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

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

PK Parameter: AUCtau of Bictegravir Following Multiple-Dose Administration

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

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

PK Parameter: t1/2 of Bictegravir Following Multiple-Dose Administration

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

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

PK Parameter: Ctau of Bictegravir Following Multiple-Dose Administration

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

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

PK Parameter: CLss/F of Bictegravir Following Multiple-Dose Administration

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

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

PK Parameter: AR_AUC of Bictegravir Following Multiple-Dose Administration

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

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

PK Parameter: AR_Cmax of Bictegravir Following Multiple-Dose Administration

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

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

PK/Pharmacodynamic (PD) Analysis: Pearson Correlation Between AUCtau of Bictegravir and DAVG11 in 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).

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