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

• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: April 20, 2010
• First Posted Date: April 22, 2010
• Results First Submitted Date: October 23, 2014
• Results First Posted Date: October 28, 2014
• Last Update Posted Date: May 23, 2016
• Study Start Date: April 2010
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 15, 2016)

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ]

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.

• Original Primary Outcome Measures (submitted: April 20, 2010): The primary efficacy endpoint is the proportion of subjects that achieve HIV-1 RNA < 50 copies/mL at Week 48 [ Time Frame: 48 Weeks ]
• Change History: Complete list of historical versions of study NCT01108510 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: April 15, 2016)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Week 96 ]
  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 ]
  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 ]
  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 ]
• Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline to Week 96 ]
• Change From Baseline in CD4 Cell Count at Week 144 [ Time Frame: Baseline to Week 144 ]
• Change From Baseline in CD4 Cell Count at Week 192 [ Time Frame: Baseline to Week 192 ]

Original Secondary Outcome Measures (submitted: April 20, 2010)

• The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 96 [ Time Frame: 96 Weeks ]
• The change from baseline in CD4+ cell count at Week 48 [ Time Frame: 48 Weeks ]
• The change from baseline in CD4+ cell count at Week 96 [ Time Frame: 96 Weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

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) 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• HIV
• HIV Infections

Intervention

• Drug: COBI
  Cobicistat (COBI) 150 mg tablet administered orally once daily
  Other Names:

  • Tybost®
  • GS-9350
• 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
• Drug: RTV placebo
  Placebo to match RTV administered orally once daily

Study Arms

• Experimental: ATV+COBI+FTC/TDF
  COBI + RTV placebo + ATV + FTC/TDF once daily
  Interventions:

  • Drug: COBI
  • Drug: ATV
  • Drug: FTC/TDF
  • Drug: RTV placebo
• Active Comparator: ATV+RTV+FTC/TDF
  RTV + COBI placebo + ATV + FTC/TDF once daily
  Interventions:

  • Drug: RTV
  • Drug: ATV
  • Drug: FTC/TDF
  • Drug: COBI placebo

Publications *

• Gallant JE, Koenig E, Andrade-Villanueva J, Chetchotisakd P, DeJesus E, Antunes F, Arastéh K, Moyle G, Rizzardini G, Fehr J, Liu Y, Zhong L, Callebaut C, Szwarcberg J, Rhee MS, Cheng AK. Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1-infected patients: week 48 results. J Infect Dis. 2013 Jul;208(1):32-9. doi: 10.1093/infdis/jit122. Epub 2013 Mar 26.
• Gallant JE, Koenig E, Andrade-Villanueva JF, Chetchotisakd P, DeJesus E, Antunes F, Arastéh K, Rizzardini G, Fehr J, Liu HC, Abram ME, Cao H, Szwarcberg J. Brief Report: Cobicistat Compared With Ritonavir as a Pharmacoenhancer for Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate: Week 144 Results. J Acquir Immune Defic Syndr. 2015 Jul 1;69(3):338-40. doi: 10.1097/QAI.0000000000000598.
• Gallant J, Moyle G, Berenguer J, Shalit P, Cao H, Liu YP, Myers J, Rosenblatt L, Yang L, Szwarcberg J. Atazanavir Plus Cobicistat: Week 48 and Week 144 Subgroup Analyses of a Phase 3, Randomized, Double-Blind, Active-Controlled Trial. Curr HIV Res. 2017;15(3):216-224. doi: 10.2174/1570162X14666161021102728.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 23, 2014): 698
• Original Estimated Enrollment (submitted: April 20, 2010): 700
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, Denmark, Dominican Republic, France, Germany, Italy, Mexico, Netherlands, Portugal, Puerto Rico, Spain, Switzerland, Thailand, United Kingdom, United States
• Removed Location Countries: Argentina, Sweden

Administrative Information

• NCT Number: NCT01108510
• Other Study ID Numbers: GS-US-216-0114; 2009-016759-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Huyen Cao, MD; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: April 2016