Study of the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Atripla® (Efavirenz 600 mg/Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

The objective of this double-blinded, multicenter, randomized, active-controlled study is to evaluate the safety and efficacy of Stribild, a single-tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/GS-9350 (cobicistat; COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla) in HIV-1 infected, antiretroviral treatment-naive adult participants. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor (NNRTI)-based STRs.

Participants will be randomized in a 2:1 ratio to receive Stribild or Atripla. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded (Week 60), at which point all participants will attend an Unblinding Visit and be given the option to participate in an open-label rollover extension (the extension is scheduled to be open until Stribild becomes commercially available, or until Gilead Sciences elects to terminate the study).

Study Overview

• Status: Completed
• Conditions: HIV Infections; HIV
• Intervention / Treatment: Drug: Stribild; Drug: Atripla

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health for Life Clinic, PLLC
  • California
    • Long Beach, California, United States, 90813
      • The Living Hope Foundation
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane, MD, Inc.
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Oakland, California, United States, 94609
      • East Bay AIDS Center
    • San Francisco, California, United States, 94115
      • Metropolis Medical
  • Colorado
    • Denver, Colorado, United States, 80220
      • Apex Research Institute
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Whitman Walker Clinic
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physicians Group
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates PC
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary Richmond, MD, PA, Inc.
    • Fort Lauderdale, Florida, United States, 33311
      • Broward Health
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • Infectious Disease of Central Florida
    • Vero Beach, Florida, United States, 32960
      • Treasure Coast Infectious Disease Consultants
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta (IDSA)
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Chase Brexton Health Services, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative of New England
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63139
      • Southampton Healthcare, Inc.
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest C.A.R.E. Center
  • New York
    • New York, New York, United States, 10011
      • Ricky K. Hsu, MD, PC
    • New York, New York, United States, 10011
      • Chelsea Village Medical
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
  • Texas
    • Dallas, Texas, United States, 75215
      • AIDS Arms/ Peabody Health Center
    • Dallas, Texas, United States, 75204
      • Nicholaos Bellos, MD, PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot, MD, PA
  • Washington
    • Seattle, Washington, United States, 98103
      • TribalMed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
• No prior use of any approved or experimental anti-HIV drug
• Normal electrocardiogram (ECG)
• Adequate renal function: estimated glomerular filtration rate ≥ 80 mL/min according to the Cockcroft-Gault formula
• Hepatic transaminases ≤ 2.5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Cluster determinant 4 (CD4) cell count > 50 cells/µL
• Serum amylase ≤ 1.5 x ULN
• Normal thyroid-stimulating hormone
• Negative serum pregnancy test (for 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 12 weeks following the last dose of study drugs
• Life expectancy ≥ 1 year
• Ability to understand and sign a written informed consent form

Exclusion Criteria:

• New acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
• Documented drug resistance to nucleoside reverse transcriptase inhibitors or nonnucleoside reverse transcriptase inhibitors or primary protease inhibitor 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 (for females of childbearing potential)
• Vaccinated within 90 days of study dosing
• History or family history of Long QT Syndrome or family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30
• Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
• Prolonged QTcF interval at screening
• PR interval ≥ 200 msec or ≤ 120 msec on ECG at screening
• QRS ≥ 120 msec on ECG at screening
• Implanted defibrillator or pacemaker
• Participants receiving ongoing therapy with any disallowed medications
• Current alcohol or substance use judged to potentially interfere with participant 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 EFV, EVG, COBI, FTC, or TDF
• Any known allergies to the excipients of Atripla or Stribild tablets
• Any other clinical condition or prior therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Stribild	Drug: Stribild; Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily (QD) + placebo to match Atripla once daily prior to bedtime (QHS)
ACTIVE_COMPARATOR: Atripla	Drug: Atripla; Atripla (EFV 150 mg/FTC 200mg/TDF 300 mg) STR QHS + placebo to match Stribild QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24	The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 24 was summarized.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48	The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 48 was summarized.	Week 48
Change From Baseline in HIV-1 RNA (log_10 Copies/mL)	Change = Week 24 or 48 value minus baseline value	Baseline to Weeks 24 and 48
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24	Change = Week 24 value minus baseline value	Baseline to Week 24
Change From Baseline in CD4 Cell Count at Week 48	Change = Week 48 value minus baseline value	Baseline to Week 48
The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL	The percentage of participants with virologic success at Weeks 24 and 48 assessed using the FDA-defined snapshot analysis for an HIV-1 RNA cutoff of 50 copies/mL was summarized.	Baseline to Weeks 24 and 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Cohen C, Elion R, Ruane P, Shamblaw D, DeJesus E, Rashbaum B, Chuck SL, Yale K, Liu HC, Warren DR, Ramanathan S, Kearney BP. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection. AIDS. 2011 Mar 27;25(6):F7-12. doi: 10.1097/QAD.0b013e328345766f.

Helpful Links

• Gilead Sciences

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): November 1, 2009
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: March 24, 2009
• First Submitted That Met QC Criteria: March 25, 2009
• First Posted (ESTIMATE): March 26, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 4, 2014
• Last Update Submitted That Met QC Criteria: May 22, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: HIV; HIV-1; treatment naive; Antiretroviral Treatment-Naive
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: GS-US-236-0104