To evaluate the safety and efficacy of a regimen containing GS-9350-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate in HIV 1 infected, antiretroviral treatment-naïve adults. Development of GS-9350 as a "pharmacoenhancer" could provide a beneficial alternative to ritonavir for use in combination with protease inhibitors.

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-Naïve Adults

Conditions

Study Type

Interventional

Study Design

Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Further Details

Primary Outcome Measures:

  • The primary efficacy endpoint is the proportion of subjects that achieve HIV-1 RNA < 50 copies/mL at Week 48
    [ Time Frame: 48 Weeks ]
    [ Designated as safety issue: No ]


Secondary Outcome Measures:

  • The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 96
    [ Time Frame: 96 Weeks ]
    [ Designated as safety issue: No ]
  • The change from baseline in CD4+ cell count at Week 48
    [ Time Frame: 48 Weeks ]
    [ Designated as safety issue: No ]
  • The change from baseline in CD4+ cell count at Week 96
    [ Time Frame: 96 Weeks ]
    [ Designated as safety issue: No ]

 

Arms and Assigned Interventions:

Arms Assigned Interventions

GS-9350 + atazanavir +
emtricitabine/tenofovir
Experimental
DF: GS-9350 + atazanavir +
emtricitabine/tenofovir disoproxil
fumarate + Placebo to match ritonavir 
QD (n = 350)

Drug: GS-9350 + atazanavir +
emtricitabine/tenofovir DF
GS-9350 150 mg + atazanavir 300 mg
+ emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg + Placebo
to match ritonavir 100 mg QD (n = 350)

ritonavir + atazanavir + emtricitabine/
tenofovir DF: Active Comparator
ritonavir + atazanavir + emtricitabine/
tenofovir disoproxil fumarate + Placebo
to match GS-9350 QD (n = 350)
Drug: Comparator: ritonavir + atazanavir +
emtricitabine/tenofovir DF
ritonavir 100 mg + atazanavir 300 mg +
emtricitabine 200 mg/tenofovir disoproxil
fumarate 300 mg + Placebo to match GS-9350
150 mg QD (n = 350)

Study Start

April 2010- December 2012

Eligibility & Criteria

  • Ages Eligible for Study: 18 Years and older
  • Genders Eligible for Study: Both
  • Accepts Healthy Volunteers: No


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
  • 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 day s 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 GS-9350, emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), atazanavir (ATV), ritonavir (RTV) or subjects with any known allergies to the excipients of GS-9350 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.

Total Enrolment

700

Contact Details

Contact: Kitty Yale
650.522-5274

Kitty.Yale@gilead.com