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

A Phase 1b Randomized, Double-Blinded, Sequential Cohort Placebo-Controlled Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-9883 in HIV-1 Infected Subjects

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 Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Bictegravir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States
    • Davis, California, United States
    • Long Beach, California, United States
    • Los Angeles, California, United States
    • San Francisco, California, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Fort Lauderdale, Florida, United States
    • Orlando, Florida, United States
    • Vero Beach, Florida, United States
    • West Palm Beach, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Michigan
    • Berkley, Michigan, United States
  • New Jersey
    • Newark, New Jersey, United States
  • New Mexico
    • Santa Fe, New Mexico, United States
  • Texas
    • Dallas, Texas, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bictegravir 5 mg; Bictegravir 5 mg (1 × 5 mg tablet) for 10 days	Drug: Bictegravir; Bictegravir tablet(s) administered orally once daily
Experimental: Bictegravir 25 mg; Bictegravir 25 mg (1 × 25 mg tablet) for 10 days	Drug: Bictegravir; Bictegravir tablet(s) administered orally once daily
Experimental: Bictegravir 50 mg; Bictegravir 50 mg (2 × 25 mg tablets) for 10 days	Drug: Bictegravir; Bictegravir tablet(s) administered orally once daily
Experimental: Bictegravir 100 mg; Bictegravir 100 mg (1 × 100 mg tablet) for 10 days	Drug: Bictegravir; Bictegravir tablet(s) administered orally once daily
Placebo Comparator: Placebo; Placebo matched to bictegravir tablet for 10 days	Drug: Placebo; Placebo to match bictegravir administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to Day 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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.	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).	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.	Baseline up to Day 11
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	Cmax is defined as the maximum concentration of drug.	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.	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.	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.	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).	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.	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.	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.	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.	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.	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).	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Day 10

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2014
• Primary Completion (Actual): January 23, 2015
• Study Completion (Actual): January 29, 2015

Study Registration Dates

• First Submitted: October 23, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 27, 2014

Study Record Updates

• Last Update Posted (Actual): November 9, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Adults; Treatment Naive; HIV-1 Infected
• Other Study ID Numbers: GS-US-141-1219

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No