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

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI [GS-9350])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla®) in HIV-1 infected, antiretroviral treatment-naive adults. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor-based STRs.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 707
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00731
    • Instituto de Investigacion Clentifica del Sur
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Hope Clinical Research
  • San Juan, Puerto Rico, 00921
    • VA Caribbean Healthcare System
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico, School of Medicine, Proyecto ACTU
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health For Life Clinic Pllc
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Research Center
    • Hayward, California, United States, 94545
      • Kaiser Permanente Hospital
    • Long Beach, California, United States, 90813
      • Living Hope Clinical Foundation
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane, MD, Inc.
    • Los Angeles, California, United States, 90069
      • Anthony Mills, MD, Inc.
    • Los Angeles, California, United States, 90035
      • UCLA Center for Clinical AIDS Research and Education
    • Los Angeles, California, United States, 90028
      • Los Angeles Gay and Lesbian Center DBA Jeffrey Goodman Special Care Clinic
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Oakland, California, United States, 94602
      • Alameda County Medical Center
    • Oakland, California, United States, 94609
      • East Bay AIDS Center
    • Palo Alto, California, United States, 94303
      • Stanford University
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Group
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
    • San Francisco, California, United States, 94115
      • Metropolis Medical
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Center, Clinical Trials Unit
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital, University of California, San Francisco
  • Colorado
    • Denver, Colorado, United States, 80209
      • Apex Research, LLC
  • Connecticut
    • New Haven, Connecticut, United States, 06033
      • Yale University HIV Clinical Trials Program
    • Stamford, Connecticut, United States, 06902
      • The Stamford Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
    • 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, 33308
      • Therafirst Medical Center
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond, MD, PA
    • Fort Lauderdale, Florida, United States, 33311
      • Broward Health/Comprehensive Care Center
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • Idocf/ Valuhealthmd, Llc
    • Tampa, Florida, United States, 33614
      • Infectious Disease Research Institute Inc.
    • Tampa, Florida, United States, 33602
      • University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department
    • Tampa, Florida, United States, 33615
      • St. Joseph's Comprehensive Research Institute
    • Vero Beach, Florida, United States, 32960
      • Treasure Coast Infectious Disease Consultants
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group, PC
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31210
      • Mercer University School of Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • Leahi Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Ruth M. Rothstein CORE Center
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women'S Hospital
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative
    • Springfield, Massachusetts, United States, 01199
      • Baystate Infectious Diseases Clinical Research
    • Springfield, Massachusetts, United States, 01107
      • The Research Institute
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63139
      • Southampton Healthcare
    • St. Louis, Missouri, United States, 63108
      • Central West Clinical Research
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care
    • Newark, New Jersey, United States, 07102
      • Saint Michaels Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
    • Voorhees, New Jersey, United States, 08043
      • Garden State Infectious Diseases Associates, PA
  • New Mexico
    • Sante Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • New York
    • Albany, New York, United States, 12208
      • Upstate ID Association
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - AIDS Center
    • Bronx, New York, United States, 31210
      • Jacobi Medical Center
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Flushing, New York, United States, 11355
      • New York Hospital Queens
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • Mount Vernon, New York, United States, 10550
      • Greiger Clinic
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10011
      • Ricky K. Hsu, MD, PC
    • New York, New York, United States, 10011
      • Chelsea Village Medical, PC
    • New York, New York, United States, 10016
      • The Aaron Diamond AIDS Research Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Clinical and Translational Research Center
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center-Myers Park
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
    • Winston Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44304
      • SUMMA Health System
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75204
      • Southwest Infectious Disease Clinical Research, Inc.
    • Dallas, Texas, United States, 75215
      • Peabody Health Center
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Harlingen, Texas, United States, 78550
      • Valley AIDS Council
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
    • Houston, Texas, United States, 77098
      • Research Access Network
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Clinical Alliance for Research & Education, Infectious Diseases (CARE-ID)
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, MD
    • Spokane, Washington, United States, 99204
      • Rockwood Pulmonary and Critical Care
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

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:

• 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
• 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 EFV
• Normal electrocardiogram (ECG)
• Adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula)
• Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) ≤ 5 x the upper limit of the normal range (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 12 weeks following the last dose of study drug
• Age ≥ 18 years
• Life expectancy ≥ 1 year

Exclusion Criteria:

• A new acquired immunodeficiency syndrome (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)
• Implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
• History of malignancy within the past 5 years or ongoing malignancy 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
• Medications contraindicated for use with EVG, COBI, FTC, EFV, or TDF; or subjects with any known allergies to the excipients of Stribild or Atripla tablets
• Participation in any other clinical trial without prior approval
• 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

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; Stribild plus placebo to match Atripla	Drug: Stribild; Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR administered orally once daily; Drug: Atripla Placebo; Placebo to match Atripla tablet administered orally once daily prior to bedtime
ACTIVE_COMPARATOR: Atripla; Atripla plus placebo to match Stribild	Drug: Atripla; Atripla (EFV 600 mg/FTC 200 mg/TDF 300 mg) tablet administered orally once daily prior to bedtime; Drug: Stribild Placebo; Placebo to match Stribild STR administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96		Week 96
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144		Week 144
The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192		Week 192
The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm		Week 48
The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192	Change = value of the relevant time point minus the baseline value	Baseline; Weeks 48, 96, 144, and 192
The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48		Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, Gallant JE, Liu HC, Zhong L, Yale K, White K, Kearney BP, Szwarcberg J, Quirk E, Cheng AK; GS-US-236-0102 study team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012 Jun 30;379(9835):2439-2448. doi: 10.1016/S0140-6736(12)60917-9. Erratum In: Lancet. 2012 Aug 25;380(9843):730.
• Zolopa A, Sax PE, DeJesus E, Mills A, Cohen C, Wohl D, Gallant JE, Liu HC, Plummer A, White KL, Cheng AK, Rhee MS, Szwarcberg J; GS-US-236-0102 Study Team. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013 May 1;63(1):96-100. doi: 10.1097/QAI.0b013e318289545c.
• Wohl DA, Cohen C, Gallant JE, Mills A, Sax PE, Dejesus E, Zolopa A, Liu HC, Plummer A, White KL, Cheng AK, Rhee MS, Szwarcberg J; GS-US-236-0102 Study Team. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e118-20. doi: 10.1097/QAI.0000000000000057. No abstract available.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: March 17, 2010
• First Submitted That Met QC Criteria: March 26, 2010
• First Posted (ESTIMATE): March 30, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): November 11, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Treatment Naive; HIV 1 Infected
• 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-236-0102