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A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of GS-9350-boosted Atazanavir Compared to Ritonavir-boosted Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00892437
First received: April 30, 2009
Last updated: October 23, 2014
Last verified: October 2014
  Purpose

The objective of this study is to evaluate the safety and efficacy of a regimen containing cobicistat-boosted atazanavir (ATV/co) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir (RTV)-boosted atazanavir (ATV/r) plus FTC/TDF in HIV-1 infected, antiretroviral treatment-naive adult subjects.

Subjects 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, subjects will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded, at which point all subjects will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive ATV/co+FTC/TDF until COBI tablets become commercially available, or until Gilead Sciences elects to terminate the study.


Condition Intervention Phase
HIV-1 Infection
Drug: Cobicistat
Drug: Ritonavir
Drug: Atazanavir
Drug: FTC/TDF
Drug: Placebo to match COBI
Drug: Placebo to match RTV
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

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 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 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 missing = failure method.

  • Change From Baseline in HIV-1 RNA at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The change from baseline in log_10 HIV-1 RNA at Week 24 was analyzed.

  • Change From Baseline in HIV-1 RNA at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The change from baseline in log_10 HIV-1 RNA at Week 48 was analyzed.

  • Change From Baseline in CD4 Cell Count at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The change from baseline in CD4 cell count at Week 24 was analyzed.

  • Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The change from baseline in CD4 cell count at Week 48 was analyzed.


Enrollment: 85
Study Start Date: May 2009
Estimated Study Completion Date: January 2015
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATV/co+FTC/TDF
Participants will be randomized to receive COBI, plus placebo to match RTV, plus ATV, plus FTC/TDF once daily.
Drug: Cobicistat
Cobicistat (COBI) 150 mg tablet administered orally once daily
Other Names:
  • Tybost®
  • GS-9350
Drug: Atazanavir
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: Placebo to match RTV
Placebo to match RTV administered orally once daily
Active Comparator: ATV/r+FTC/TDF
Participants will be randomized to receive RTV, plus placebo to match COBI, plus ATV, plus FTC/TDF once daily.
Drug: Ritonavir
Ritonavir (RTV) 100 mg soft gelatin capsule administered orally once daily
Other Name: Norvir®
Drug: Atazanavir
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: Placebo to match COBI
Placebo to match COBI administered orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  • Normal thyroid-stimulating hormone
  • Negative serum pregnancy test (females of childbearing potential only)
  • 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 drugs
  • Age ≥ 18 years
  • Life expectancy ≥ 1 year

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
  • History or family history of Long QT Syndrome or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30 years
  • Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
  • Prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) interval at screening (eg, a prolongation of the QTcF interval of greater than 450 msec for males and greater than 470 msec for females)
  • PR interval greater than or equal to 200 msec or less than or equal to 120 msec on ECG at screening
  • QRS greater than or equal to 120 msec on ECG at screening
  • Implanted defibrillator or pacemaker
  • Subjects receiving ongoing therapy with any disallowed medications
  • Current alcohol or substance use judged to potentially interfere with subject study compliance
  • History of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
  • Participation in any other clinical trial without prior approval
  • Medications contraindicated for use with ATV, RTV, FTC, or TDF
  • Any known allergies to the excipients of ATV capsules, RTV capsules, COBI tablets or FTC/TDF tablets
  • Any other clinical condition or prior therapy that 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: NCT00892437

  Show 31 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Chair: Marshall Fordyce, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00892437     History of Changes
Other Study ID Numbers: GS-US-216-0105
Study First Received: April 30, 2009
Results First Received: October 23, 2014
Last Updated: October 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV
HIV-1
Antiretroviral Treatment-Naive

Additional relevant MeSH terms:
Atazanavir
Emtricitabine
Ritonavir
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014