A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of GS-9350-boosted Atazanavir (ATV/GS-9350) Compared to Ritonavir-boosted Atazanavir (ATV/r) in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Overview
- Phase
- Phase 2
- Intervention
- COBI
- Conditions
- HIV-1 Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 85
- Locations
- 31
- Primary Endpoint
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The objective of this study is to evaluate the safety and efficacy of a regimen containing cobicistat-boosted atazanavir (ATV+COBI) plus emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF in HIV-1 infected, antiretroviral treatment-naive adults.
Participants will be randomized in a 2:1 ratio. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded, at which point all participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive ATV+COBI+FTC/TDF until COBI tablets become commercially available, or until Gilead Sciences elects to terminate the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and sign a written informed consent form
- •Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
- •No prior use of any approved or experimental anti-HIV drug
- •Normal ECG (or if abnormal, determined by the investigator to be not clinically significant)
- •Adequate renal function (estimated glomerular filtration rate ≥ 80 mL/min according to the Cockcroft-Gault formula)
- •Hepatic transaminases ≤ 2.5 × upper limit of normal
- •Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- •Adequate hematologic function (absolute neutrophil count ≥ 1000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
- •Cluster of differentiation 4 (CD4) cell count \> 50 cells/µL
- •Serum amylase ≤ 1.5 × ULN (subjects with serum amylase \>1.5 × ULN remained eligible if serum lipase is ≤ 1.5 × ULN)
Exclusion Criteria
- •New AIDS-defining condition diagnosed within the 30 days prior to screening
- •Documented drug resistance to nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or primary PI resistance mutation(s)
- •Hepatitis B surface antigen positive
- •Hepatitis C antibody positive
- •Participants experiencing cirrhosis
- •Participants experiencing ascites
- •Participants experiencing encephalopathy
- •Females who are breastfeeding
- •Positive serum pregnancy test (female of childbearing potential)
- •Vaccinated within 90 days of study dosing
Arms & Interventions
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
Intervention: COBI
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
Intervention: ATV
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
Intervention: FTC/TDF
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
Intervention: RTV placebo
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
Intervention: RTV
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
Intervention: ATV
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
Intervention: FTC/TDF
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
Intervention: COBI placebo
Outcomes
Primary Outcomes
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
Time Frame: Week 24
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the missing = failure method, where participants with missing data were considered to have failed to achieve the endpoint.
Secondary Outcomes
- Change From Baseline in HIV-1 RNA at Week 48(Baseline to Week 48)
- Change From Baseline in CD4 Cell Count at Week 24(Baseline to Week 24)
- Change From Baseline in CD4 Cell Count at Week 48(Baseline to Week 48)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48(Week 48)
- Change From Baseline in HIV-1 RNA at Week 24(Baseline to Week 24)