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

• ClinicalTrials.gov Identifier: NCT02275065
• Recruitment Status: Completed
• First Posted: October 27, 2014
• Results First Posted: October 8, 2020
• Last Update Posted: November 9, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: Bictegravir; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 24, 2014
• Actual Primary Completion Date: January 23, 2015
• Actual Study Completion Date: January 29, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

1. 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) ]
2. Percentage of Participants Who Experienced Graded Laboratory Abnormalities [ Time Frame: 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.
3. Maximum Reduction From Baseline Through Day 17 in Plasma HIV-1 RNA [ Time Frame: 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).
4. Viral Decay Slope in Plasma HIV-1 RNA [ Time Frame: 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.
5. Percentage of Participants With HIV-1 RNA < 50 Copies/mL [ Time Frame: Day 17 ]
6. Pharmacokinetic (PK) Parameter: Cmax of Bictegravir Following Single-Dose and Multiple-Dose Administration [ 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 ]
   Cmax is defined as the maximum concentration of drug.
7. PK Parameter: Tmax of Bictegravir Following Single-Dose and Multiple-Dose Administration [ 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 ]
   Tmax is defined as the time (observed time point) of Cmax.
8. PK Parameter: AUC0-24 of Bictegravir Following Single-Dose Administration [ Time Frame: 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.
9. PK Parameter: AUClast of Bictegravir Following Single-Dose Administration [ Time Frame: 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.
10. PK Parameter: AUCtau of Bictegravir Following Multiple-Dose Administration [ Time Frame: 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).
11. PK Parameter: t1/2 of Bictegravir Following Multiple-Dose Administration [ Time Frame: 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.
12. PK Parameter: Ctau of Bictegravir Following Multiple-Dose Administration [ Time Frame: 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.
13. PK Parameter: CLss/F of Bictegravir Following Multiple-Dose Administration [ Time Frame: 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.
14. PK Parameter: AR_AUC of Bictegravir Following Multiple-Dose Administration [ Time Frame: 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.
15. PK Parameter: AR_Cmax of Bictegravir Following Multiple-Dose Administration [ Time Frame: 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.
16. PK/Pharmacodynamic (PD) Analysis: Pearson Correlation Between AUCtau of Bictegravir and DAVG11 in Plasma HIV-1 RNA [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

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

United States, District of Columbia

Washington, District of Columbia, United States

United States, Florida

Fort Lauderdale, Florida, United States

Orlando, Florida, United States

Vero Beach, Florida, United States

West Palm Beach, Florida, United States

United States, Georgia

Atlanta, Georgia, United States

United States, Michigan

Berkley, Michigan, United States

United States, New Jersey

Newark, New Jersey, United States

United States, New Mexico

Santa Fe, New Mexico, United States

United States, Texas

Dallas, Texas, United States

United States, Washington

Seattle, Washington, United States

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02275065
• Other Study ID Numbers: GS-US-141-1219
• First Posted: October 27, 2014
• Results First Posted: October 8, 2020
• Last Update Posted: November 9, 2020
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:

HIV-1 Infected; Adults; Treatment Naive