Study to Evaluate the Safety and Efficacy of a Single Tablet Regimen of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Compared With a Single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01309243
First received: March 3, 2011
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

The purpose of the study was to evaluate the safety and efficacy of the emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF) single-tablet regimen (STR) compared with the efavirenz (EFV)/FTC/TDF STR in HIV-1 infected adults who had not previously received treatment with antiretroviral medications. The FTC/RPV/TDF STR offers an alternative treatment option to patients who wish to simplify or improve the tolerability of their treatment regimen.

Participants were randomized in a 1:1 ratio to receive one of the study treatments. Randomization was stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. A treatment duration of 96 weeks was planned, with the option for subjects in FTC/RPV/TDF STR arm to receive treatment following the Week 96 visit until FTC/RPV/TDF STR is commercially available or until Gilead Sciences elects to terminate development in that country.


Condition Intervention Phase
HIV-1 Infection
Drug: FTC/RPV/TDF
Drug: EFV/FTC/TDF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3B, Randomized, Open-label Study to Evaluate the Safety and Efficacy of a Single Tablet Regimen of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Compared With a Single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate 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 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 US FDA snapshot algorithm.


Secondary Outcome Measures:
  • Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting Total Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting Triglycerides at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Development of HIV-1 Genotypic Resistance Through Week 48, All Participants [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    Participants who experienced either suboptimal virologic response or virologic rebound were considered to have virologic failure and were analyzed for resistance. Suboptimal virologic response was assessed at Week 8 and was defined as having HIV-1 RNA ≥ 50 copies/mL and < 1-log10 reduction from baseline at the Week 8 visit, which was confirmed at the subsequent visit. Virologic rebound was defined as having 2 consecutive visits with HIV-1 RNA ≥ 400 copies/mL after achieving HIV-1 RNA < 50 copies/mL, or as having 2 consecutive visits with > 1 log10 increase in HIV-1 RNA from their nadir. In addition, subjects who were on study drugs, had not been analyzed previously, and who had HIV-1 RNA ≥ 400 copies/mL at Week 48 or their last visit (at or after Week 8) were also analyzed for resistance at their last visit. Subsequent to the first resistance testing, subjects experiencing repeated confirmed virologic failure were assessed for resistance retesting on a case-by-case basis.

  • Development of HIV-1 Genotypic Resistance Through Week 48, Participants With Viral Resistance [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    Resistance Analysis Set: participants with either suboptimal virologic response or virologic rebound were considered to have virologic failure and were analyzed. Suboptimal virologic response was assessed at Week 8 and was defined as having HIV-1 RNA ≥ 50 copies/mL and < 1-log10 reduction from baseline at the Week 8 visit, which was confirmed at the subsequent visit. Virologic rebound was defined as having 2 consecutive visits with HIV-1 RNA ≥ 400 copies/mL after achieving HIV-1 RNA < 50 copies/mL, or as having 2 consecutive visits with > 1 log10 increase in HIV-1 RNA from their nadir. In addition, subjects who were on study drugs, had not been analyzed previously, and who had HIV-1 RNA ≥ 400 copies/mL at Week 48, Week 96, or their last visit (at or after Week 8) were also analyzed for resistance at their last visit. Subsequent to the first resistance testing, subjects experiencing repeated confirmed virologic failure were assessed for resistance retesting on a case-by-case basis.


Enrollment: 799
Study Start Date: February 2011
Study Completion Date: February 2014
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FTC/RPV/TDF Drug: FTC/RPV/TDF
Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (TDF) 300 mg single-tablet regimen administered orally once daily with a meal
Other Names:
  • Complera®
  • Eviplera®
Experimental: EFV/FTC/TDF Drug: EFV/FTC/TDF
Efavirenz (EFV) 600 mg/FTC 200 mg/TDF 300 mg single-tablet regimen administered orally once daily on an empty stomach, preferably at bedtime
Other Name: Atripla®

  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 ≥ 2,500 copies/mL at screening
  • No prior use of any approved or experimental anti-HIV drug for any length of time
  • Screening genotype report showing sensitivity to EFV, FTC, TDF, and lack of the RPV mutations K101E/P, E138G/K/Q/R, Y181C/I/V, and H221Y
  • Normal ECG
  • Hepatic transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) ≤ 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 (participants with serum amylase > 5 x ULN remained eligible if serum lipase was ≤ 5 x ULN)
  • Adequate renal function
  • Males and Females of childbearing potential must have agreed to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study period and for 12 weeks following the last dose of study drug.
  • Adult (≥ 18 years) males or non-pregnant females

Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within the 30 days prior to screening
  • Females who were breastfeeding
  • Positive serum pregnancy test (female of childbearing potential)
  • Proven or suspected acute hepatitis in the 30 days prior to study entry
  • Subjects receiving drug treatment for hepatitis C, or subjects who were anticipated to receive treatment for hepatitis C during the course of the study
  • Subjects experiencing decompensated cirrhosis
  • Had an implanted defibrillator or pacemaker
  • Current alcohol or substance abuse
  • A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
  • Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
  • Receiving ongoing therapy or anticipated to need to initiate drugs or herbal/natural supplements during the study that are contraindicated or not recommended for use, including drugs not to be used with FTC, EFV, RPV, or TDF; or subjects with known allergies to the excipients of the FTC/RPV/TDF or EFV/FTC/TDF single-tablet regimens
  • Participation in any other clinical trial without prior approval from the sponsor was prohibited while participating in this trial.
  • Had been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids for immunosuppression during the study (eg, corticosteroids, immunoglobulins, and other immune-based or cytokine-based therapies)
  • Had any other clinical condition or prior therapy that, in the opinion of the Investigator, would have made the participant 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: NCT01309243

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Spectrum Medical Group
Phoenix, Arizona, United States, 85012
United States, California
AHF Research Center
Beverly Hills, California, United States, 90211
Kaiser Permanente Medical Center
Hayward, California, United States, 94545
Living Hope Education and Research Consultants
Long Beach, California, United States, 90813
Jeffrey Goodman Special Care Clinic/Los Angeles Gay and Lesbian Center
Los Angeles, California, United States, 90028
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Oasis Clinic
Los Angeles, California, United States, 90059
Anthony Mills MD Inc
Los Angeles, California, United States, 90069
Lightsource Medical
Los Angeles, California, United States, 90036
Kaiser Permanente Medical Center
Los Angeles, California, United States, 90027
Orange Coast Medical Group
Newport Beach, California, United States, 92663
East Bay AIDS Center
Oakland, California, United States, 94609
Stanford University
Palo Alto, California, United States, 94304
Kaiser Permanente Medical Group
Sacramento, California, United States, 95825
University of California, Davis
Sacramento, California, United States, 95817
La Playa Medical Group and Clinical Research
San Diego, California, United States, 92103
Metropolis Medical/Dr.Fritz
San Francisco, California, United States, 94114
Kaiser Permanente Medical Center, San Francisco
San Francisco, California, United States, 94118
United States, Colorado
Apex Research LLC
Denver, Colorado, United States, 80209
United States, District of Columbia
Whitman-Walker Clinic
Washington, District of Columbia, United States, 20009
Capital Medical Associates, PC
Washington, District of Columbia, United States, 20036
Medical Faculty Associates
Washington, District of Columbia, United States, 20037
Dupont Circle Physician's Group
Washington, District of Columbia, United States, 20009
United States, Florida
Gary J. Richmond, M.D., P.A.
Fort Lauderdale, Florida, United States, 33316
Midway Immunology and Research Center
Fort Pierce, Florida, United States, 34982
Broward General Medical Center
Ft. Lauderdale, Florida, United States, 33311
The Kinder Medical Group
Miami, Florida, United States, 33133
Wohlfeiler, Piperato and Associates, LLC
Miami Beach, Florida, United States, 33139
Orlando Immunology Center
Orlando, Florida, United States, 32803
Valuhealthmd,Llc / Idocf
Orlando, Florida, United States, 32806
Infectious Disease Associates of NW FL
Pensacola, Florida, United States, 32504
AHF Health Positive - Tampa Bay
Safety Harbor, Florida, United States, 34695
St. Joseph's Hospital d/b/a Comprehensive Research Institute
Tampa, Florida, United States, 33614
United States, Georgia
Atlanta ID Group
Atlanta, Georgia, United States, 30309
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
Emory University
Atlanta, Georgia, United States, 30306
Infectious Disease Specialists of America
Decatur, Georgia, United States, 30033
Mercer University School of Medicine
Macon, Georgia, United States, 31201
United States, Hawaii
Clint Spencer Clinic
Honolulu, Hawaii, United States, 96813
United States, Illinois
Northstar Medical Center
Chicago, Illinois, United States, 60657
Howard Brown Health Center
Chicago, Illinois, United States, 60613
Northwestern University
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins Rockland Physicians Practice and Research Group at Greenspring Station
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Community Research Initiative of New England
Boston, Massachusetts, United States, 02111
Claudia T Martorell, MD., LLC dba The Research Institute
Springfield, Massachusetts, United States, 01105
United States, Michigan
Be Well Medical Center
Berkley, Michigan, United States, 48072
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
United States, Missouri
Central West Clinical Research, Inc.
St. Louis, Missouri, United States, 63108
Southampton Healthcare
St. Louis, Missouri, United States, 63139
United States, New Jersey
Saint Michael's Medical Center
Newark, New Jersey, United States, 07102
South Jersey Infectious Disease
Somers Point, New Jersey, United States, 08244
United States, New Mexico
Southwest Care Center
Sante Fe, New Mexico, United States, 87505
United States, New York
Upstate Infectious Disease Associates
Albany, New York, United States, 12208
Montefiore Medical Center
Bronx, New York, United States, 10467
New York Hospital Queens
Flushing, New York, United States, 11355
North Shore University Hospital--Division of Infectious Diseases
Manhasset, New York, United States, 11030
Greiger Clinic
Mount Vernon, New York, United States, 10550
Ricky K. Hsu, Md, Pc
New York, New York, United States, 10011
Beth Israel Medical Center
New York, New York, United States, 10003
United States, North Carolina
Clinical and Translational Research Center - UNC Hospitals
Chapel Hill, North Carolina, United States, 27599
Carolinas Medical Center
Charlotte, North Carolina, United States, 28207
Duke University Medical Center
Durham, North Carolina, United States, 27710
The Brody School of Medicine at East Carolina University
Greenville, North Carolina, United States, 27834
Rosedale Infectious Diseases
Huntersville, North Carolina, United States, 28078
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Summa Health System Care Center
Akron, Ohio, United States, 44203
United States, Pennsylvania
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
University of South Carolina
Columbia, South Carolina, United States, 29223
United States, Texas
Central Texas Clinical Research
Austin, Texas, United States, 78705
Southwest Infectious Disease Associates, Inc.
Dallas, Texas, United States, 75219
Trinity Health and Wellness Center
Dallas, Texas, United States, 75208
Tarrant County Infectious Disease Associates
Fort Worth, Texas, United States, 76104
Garcia Family Health Group
Harlingen, Texas, United States, 78550
Gordon E. Crofoot MD PA
Houston, Texas, United States, 77098
Therapeutic Concepts, P.A.
Houston, Texas, United States, 77004
DCOL Center for Clinical Research
Longview, Texas, United States, 75605
United States, Virginia
CARE-ID
Annandale, Virginia, United States, 22003
United States, Washington
Peter Shalit, M.D.
Seattle, Washington, United States, 98104
Rockwood Pulmonary and Critical Care
Spokane, Washington, United States, 99204
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Holdsworth House Medical Practice
Darlinghurst, New South Wales, Australia, 02010
Australia
St Vincent's Hospital, Sydney
Darlinghurst, Australia, 02010
Taylor Square Private Clinic
Darlinghurst, Australia, 02010
Clinical Research - Infectious Diseases Unit Alfred Hospital
Melbourne, Australia, 03004
Northside Clinic
North Fitzroy, Australia, 03068
Prahran Market Clinic
Prahran, Australia, 03181
Albion Street Centre
Surry Hills, Australia, 02010
East Sydney Doctors
Sydney, Australia, 02010
Austria
LKH Medical University Graz West, Department of Internal Medicine
Graz, Austria, A-8020
Universitätsklinikum Innsbruck Universitätsklinik für Dermatologie und Venerologie
Innsbruck, Austria, A6020
Department of Dermatology, Allergy, and Infectious Disease University Vienna Medical School
Vienna, Austria, 01090
Belgium
Institute of Tropical Medicine
Antwerp, Belgium, 2000
Cliniques Universitaires Saint-Luc - UCL
Brussels, Belgium, 01200
University Hospitals Leuven
Leuven, Belgium, 03000
Canada, British Columbia
Vancouver ID Research and Care Centre Society
Vancouver, British Columbia, Canada, V6Z2C7
Division of HIV/AIDS, St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario
The Ottawa Hospital, General Campus
Ottawa, Ontario, Canada, K1H 8L6
Maple Leaf Research Maple Leaf Medical Clinic
Toronto, Ontario, Canada, M5G 1K2
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network/Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
McGill University Health Center, Montreal Chest Institute
Montreal, Quebec, Canada, H2X 2P4
Clinique médicale L' Actuel
Montréal, Quebec, Canada, H2L 4P9
France
Hopital Raymond Poincare
Garches, France, 92380
Hôpital de la Croix-Rousse
Lyon, France, 69288
Chu Hotel Dieu
Nantes, France, 44093
CHU Nice - Archet 1
Nice, France, 06200
Hopital Bichat Claude Bernard
Paris, France, 75018
Hopital Saint Antoine- Service Maladies infectieuses
Paris, France, 75571
HOSPITAL SAINT LOUIS - Services des Maladies Infectieuses
Paris, France, 75475
Hopital Tenon Service des Maladies infectieuses et tropicales
Paris, France, 75970
Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses
Paris cedex 13, France, 75651
Centre Hospitalier de Tourcoing
Tourcoing, France, 59208
Germany
EPIMED GmbH
Berlin, Germany, 12157
Medizinische Universitätsklinik I der Friedrich-Wilhelms Universität Bonn
Bonn, Germany, 53105
Department of Dermatology University Hospital Essen
Essen, Germany, 45122
Private Practice Gute & Locher & Lutz, Infektiologikum
Frankfurt am Main, Germany, 60311
Division of Infectious Disease, Department of Medicine, University Hospital Freiburg
Freiburg, Germany, 79106
ICH Study Center
Hamburg, Germany, 20146
Universitätsklinikum Eppendorf Ambulanzzentrum des UKE GmbH, Infekiologie
Hamburg, Germany, 20246
MUC Research GmbH
München, Germany, 80335
Italy
Ospedali Riuniti
Bergamo, Italy, 24128
IRCCS Ospedale San Raffaele Centro San Luigi, Unità Operativa di Malattie Infettive
Milan, Italy, 20127
I Div Infectious Diseases, Luigi Sacco Hospital
Milano, Italy, 20157
San Gerardo Hospital - Uo Malattie Infettive
Monza, Italy, 20092
Foundation "IRCCS Policlinico San Matteo Hospital"
Pavia, Italy, 27100
National Institute for Infectious Diseases "L. Spallanzani" IRCCS
Rome, Italy, 00149
Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 AC
Erasmus MC
Rotterdam, Netherlands, PB 2040
Portugal
Hospital de Santa Maria - CHLN, EPE
Lisbon, Portugal, 1649-035
Hospital de Joaquim urbano
Porto, Portugal, 4369-004
Serviço de Doenças Infecciosas, Hospital S. Joao
Porto, Portugal, 4200-319
Puerto Rico
Clinical Research Puerto Rico
San Juan, Puerto Rico, 00909
Spain
Hospital General Universitario Alicante
Alicante, Spain, 03010
Hospital Universitari de Bellvitge
Cataluña, Spain, 08907
Hospital Universitario de Elche, Unidad de Enfermedades Infecciosas
Elche, Spain, 03202
Hospital Universitario 12 Octubre
Madrid, Spain, 28041
Hospital La Paz
Madrid, Spain, 28046
Unidad HIV. Hospital 12 de Octubre
Madrid, Spain, 28041
Switzerland
Universitätsklinik für Infektiologie
Bern, Switzerland, 03010
CHUV
Lausanne, Switzerland, 01011
University Hospital Zurich
Zurich, Switzerland, 08091
United Kingdom
Royal Sussex County Hospital
Brighton, United Kingdom, BN2 5BE
Ridu, Wgh
Edinburgh, United Kingdom, EH42XU
Guys and St Thomas' NHS trust
London, United Kingdom, SE7 4EH
Royal Free NHS Trust,
London, United Kingdom, NW32QG
Clinical Research, Grahame Hayton Unit Ambrose King Centre, The Royal London Hospital
London, United Kingdom, E11 BB
Chelsea and Westminster Hospital
London, United Kingdom, Sw10 9NH
North Manchester General Hospital
Manchester, United Kingdom, M8 5RB
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Chair: Todd Fralich, M.D. Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01309243     History of Changes
Other Study ID Numbers: GS-US-264-0110
Study First Received: March 3, 2011
Results First Received: September 25, 2013
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Tenofovir disoproxil
Efavirenz
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 28, 2014