Safety and Efficacy of COBI-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: HIV; HIV Infections

Treatments: Drug: RTV placebo; Drug: FTC/TDF; Drug: ATV; Drug: RTV; Drug: COBI placebo; Drug: COBI

Study type: Interventional

Funder types: Industry

Identifiers

NCT01108510

2009-016759-22 (EudraCT Number)

GS-US-216-0114

Details and patient eligibility

About

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) fixed-dose combination (FDC) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF FDC in HIV-1 infected, antiretroviral treatment-naive adults.

Participants will be randomized in a 1:1 ratio. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.

Enrollment: 698 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at screening
• No prior use of any approved or investigational antiretroviral drug for any length of time
• Screening genotype report must show sensitivity to FTC, TDF and ATV
• Normal ECG
• Adequate renal function (eGFR calculated using the Cockcroft-Gault equation ≥ 70 mL/min)
• Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Serum amylase ≤ 5 x ULN
• Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug.
• Age ≥ 18 years
• Life expectancy ≥ 1 year

Exclusion criteria

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Receiving drug treatment for Hepatitis C, or anticipated to receive treatment for Hepatitis C
• Subjects experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Have an implanted defibrillator or pacemaker
• Have an ECG PR interval ≥ 220 msec
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance.
• A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline.
• Medications contraindicated for use with COBI, emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), atazanavir (ATV), ritonavir (RTV) or subjects with any known allergies to the excipients of COBI tablets, Truvada tablets, atazanavir capsules or ritonavir tablets.
• Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial.
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

698 participants in 2 patient groups

ATV+COBI+FTC/TDF

Experimental group

Description:

COBI + RTV placebo + ATV + FTC/TDF once daily

Treatment:

Drug: COBI

Drug: RTV placebo

Drug: ATV

Drug: FTC/TDF

ATV+RTV+FTC/TDF

Active Comparator group

Description:

RTV + COBI placebo + ATV + FTC/TDF once daily

Treatment:

Drug: RTV

Drug: ATV

Drug: COBI placebo

Drug: FTC/TDF