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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02275065
• Other study ID #: GS-US-141-1219
• Status: Completed
• Phase: Phase 1
• Start date: October 24, 2014
• Est. completion date: January 29, 2015

Study information

• Verified date: October 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: January 29, 2015
• Est. primary completion date: January 23, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Bictegravir
Bictegravir tablet(s) administered orally once daily
• Placebo
Placebo to match bictegravir administered orally once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)		First dose date up to last dose date plus 30 days (Maximum: 40 days)
Secondary	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)
Secondary	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
Secondary	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
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL		Day 17
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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