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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01108510
First received: April 20, 2010
Last updated: April 15, 2016
Last verified: April 2016
  Purpose

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.


Condition Intervention Phase
HIV
HIV Infections
Drug: COBI
Drug: RTV
Drug: ATV
Drug: FTC/TDF
Drug: COBI placebo
Drug: RTV placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9350-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the prespecified time point within an allowed window of time, along with study drug discontinuation status.


Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm.

  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 144 was analyzed using the snapshot algorithm.

  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192 [ Time Frame: Week 192 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 192 was analyzed using the snapshot algorithm.

  • Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Change From Baseline in CD4 Cell Count at Week 144 [ Time Frame: Baseline to Week 144 ] [ Designated as safety issue: No ]
  • Change From Baseline in CD4 Cell Count at Week 192 [ Time Frame: Baseline to Week 192 ] [ Designated as safety issue: No ]

Enrollment: 698
Study Start Date: April 2010
Study Completion Date: April 2015
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATV+COBI+FTC/TDF
COBI + RTV placebo + ATV + FTC/TDF once daily
Drug: COBI
Cobicistat (COBI) 150 mg tablet administered orally once daily
Other Names:
  • Tybost®
  • GS-9350
Drug: ATV
Atazanavir (ATV) 300 mg capsule administered orally once daily
Other Name: Reyataz®
Drug: FTC/TDF
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily
Other Name: Truvada®
Drug: RTV placebo
Placebo to match RTV administered orally once daily
Active Comparator: ATV+RTV+FTC/TDF
RTV + COBI placebo + ATV + FTC/TDF once daily
Drug: RTV
Ritonavir (RTV) 100 mg tablet administered orally once daily
Other Name: Norvir®
Drug: ATV
Atazanavir (ATV) 300 mg capsule administered orally once daily
Other Name: Reyataz®
Drug: FTC/TDF
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily
Other Name: Truvada®
Drug: COBI placebo
Placebo to match COBI administered orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01108510

  Show 134 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Huyen Cao, MD Gilead Sciences
  More Information

Publications:
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01108510     History of Changes
Other Study ID Numbers: GS-US-216-0114  2009-016759-22 
Study First Received: April 20, 2010
Results First Received: October 23, 2014
Last Updated: April 15, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Austrian Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
Denmark: Danish Health and Medicines Authority
Dominican Republic: Dirección General de Drogas y Farmacias
Canada: Health Canada
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Medicines Evaluation Board (MEB)
Portugal: INFARMED, National Authority of Medicines and Health Products, IP
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
Thailand: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:
Treatment Naive
HIV 1 Infected

Additional relevant MeSH terms:
HIV Infections
Cobicistat
HIV Protease Inhibitors
Anti-HIV Agents
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Atazanavir Sulfate
Tenofovir
Emtricitabine
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 29, 2016