Clinical trial NCT01309243: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV
HIV-1
Antiretroviral Treatment-Naïve
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-03-07
Enrollment: 799
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.


Eligibility 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, E138A/G/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

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
timeFrame: Baseline to Week 96
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline to Week 96
measure: Change From Baseline in Fasting Total Cholesterol at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Triglycerides at Week 48
timeFrame: Baseline to Week 48
measure: Development of HIV-1 Drug Resistance Through Week 96, All Participants
timeFrame: Baseline to Week 96
measure: Development of HIV-1 Drug Resistance Through Week 96, Participants With Viral Resistance
timeFrame: Baseline to Week 96
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Beverly Hills
country: United States
facility: AHF Research Center
state: California
city: Hayward
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Long Beach
country: United States
facility: Living Hope Education and Research Consultants
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Los Angeles
country: United States
facility: Jeffrey Goodman Special Care Clinic/Los Angeles Gay and Lesbian Center
state: California
city: Los Angeles
country: United States
facility: Lightsource Medical
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Oasis Clinic
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD Inc
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Group
state: California
city: Oakland
country: United States
facility: East Bay AIDS Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: San Francisco
country: United States
facility: Metropolis Medical/Dr.Fritz
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center, San Francisco
state: California
city: Denver
country: United States
facility: Apex Research LLC
state: Colorado
city: Washington
country: United States
facility: Dupont Circle Physician's Group
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Clinic
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates, PC
state: District of Columbia
city: Washington
country: United States
facility: Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond, M.D., P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Ft. Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato and Associates, LLC
state: Florida
city: Miami
country: United States
facility: The Kinder Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: Valuhealthmd,Llc / Idocf
state: Florida
city: Pensacola
country: United States
facility: Infectious Disease Associates of NW FL
state: Florida
city: Safety Harbor
country: United States
facility: AHF Health Positive - Tampa Bay
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Hospital d/b/a Comprehensive Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of America
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Honolulu
country: United States
facility: Clint Spencer Clinic
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Chicago
country: United States
facility: Northstar Medical Center
state: Illinois
city: Lutherville
country: United States
facility: Johns Hopkins Rockland Physicians Practice and Research Group at Greenspring Station
state: Maryland
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Springfield
country: United States
facility: Claudia T Martorell, MD., LLC dba The Research Institute
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: St. Louis
country: United States
facility: Central West Clinical Research, Inc.
state: Missouri
city: St. Louis
country: United States
facility: Southampton Healthcare
state: Missouri
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Sante Fe
country: United States
facility: Southwest Care Center
state: New Mexico
city: Albany
country: United States
facility: Upstate Infectious Disease Associates
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Flushing
country: United States
facility: New York Hospital Queens
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital--Division of Infectious Diseases
state: New York
city: Mount Vernon
country: United States
facility: Greiger Clinic
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Ricky K. Hsu, Md, Pc
state: New York
city: Chapel Hill
country: United States
facility: Clinical and Translational Research Center - UNC Hospitals
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: The Brody School of Medicine at East Carolina University
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Summa Health System Care Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Trinity Health and Wellness Center
state: Texas
city: Dallas
country: United States
facility: Southwest Infectious Disease Associates, Inc.
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Harlingen
country: United States
facility: Garcia Family Health Group
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, P.A.
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Annandale
country: United States
facility: CARE-ID
state: Virginia
city: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
city: Spokane
country: United States
facility: Rockwood Pulmonary and Critical Care
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital, Sydney
city: Darlinghurst
country: Australia
facility: Taylor Square Private Clinic
city: Melbourne
country: Australia
facility: Clinical Research - Infectious Diseases Unit Alfred Hospital
city: North Fitzroy
country: Australia
facility: Northside Clinic
city: Prahran
country: Australia
facility: Prahran Market Clinic
city: Surry Hills
country: Australia
facility: Albion Street Centre
city: Sydney
country: Australia
facility: East Sydney Doctors
city: Graz
country: Austria
facility: LKH Medical University Graz West, Department of Internal Medicine
city: Innsbruck
country: Austria
facility: Universitätsklinikum Innsbruck Universitätsklinik für Dermatologie und Venerologie
city: Vienna
country: Austria
facility: Department of Dermatology, Allergy, and Infectious Disease University Vienna Medical School
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc - UCL
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Vancouver
country: Canada
facility: Division of HIV/AIDS, St. Paul's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care Centre Society
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Research Maple Leaf Medical Clinic
state: Ontario
city: Toronto
country: Canada
facility: University Health Network/Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center, Montreal Chest Institute
state: Quebec
city: Montréal
country: Canada
facility: Clinique médicale L' Actuel
state: Quebec
city: Garches
country: France
facility: Hopital Raymond Poincare
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Nantes
country: France
facility: Chu Hotel Dieu
city: Nice
country: France
facility: CHU Nice - Archet 1
city: Paris cedex 13
country: France
facility: Hôpital Pitié Salpêtrière - Service des Maladies Infectieuses
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Paris
country: France
facility: HOSPITAL SAINT LOUIS - Services des Maladies Infectieuses
city: Paris
country: France
facility: Hopital Saint Antoine- Service Maladies infectieuses
city: Paris
country: France
facility: Hopital Tenon Service des Maladies infectieuses et tropicales
city: Tourcoing
country: France
facility: Centre Hospitalier de Tourcoing
city: Berlin
country: Germany
facility: EPIMED GmbH
city: Bonn
country: Germany
facility: Medizinische Universitätsklinik I der Friedrich-Wilhelms Universität Bonn
city: Essen
country: Germany
facility: Department of Dermatology University Hospital Essen
city: Frankfurt am Main
country: Germany
facility: Private Practice Gute & Locher & Lutz, Infektiologikum
city: Freiburg
country: Germany
facility: Division of Infectious Disease, Department of Medicine, University Hospital Freiburg
city: Hamburg
country: Germany
facility: ICH Study Center
city: Hamburg
country: Germany
facility: Universitätsklinikum Eppendorf Ambulanzzentrum des UKE GmbH, Infekiologie
city: München
country: Germany
facility: MUC Research GmbH
city: Bergamo
country: Italy
facility: Ospedali Riuniti
city: Milano
country: Italy
facility: I Div Infectious Diseases, Luigi Sacco Hospital
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele Centro San Luigi, Unità Operativa di Malattie Infettive
city: Monza
country: Italy
facility: San Gerardo Hospital - Uo Malattie Infettive
city: Pavia
country: Italy
facility: Foundation "IRCCS Policlinico San Matteo Hospital"
city: Rome
country: Italy
facility: National Institute for Infectious Diseases "L. Spallanzani" IRCCS
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria - CHLN, EPE
city: Porto
country: Portugal
facility: Serviço de Doenças Infecciosas, Hospital S. Joao
city: Porto
country: Portugal
facility: Hospital de Joaquim urbano
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: Alicante
country: Spain
facility: Hospital General Universitario Alicante
city: Cataluña
country: Spain
facility: Hospital Universitari de Bellvitge
city: Elche
country: Spain
facility: Hospital Universitario de Elche, Unidad de Enfermedades Infecciosas
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre
city: Madrid
country: Spain
facility: Unidad HIV. Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Bern
country: Switzerland
facility: Universitätsklinik für Infektiologie
city: Lausanne
country: Switzerland
facility: CHUV
city: Zurich
country: Switzerland
facility: University Hospital Zurich
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Edinburgh
country: United Kingdom
facility: Ridu, Wgh
city: London
country: United Kingdom
facility: Clinical Research, Grahame Hayton Unit Ambrose King Centre, The Royal London Hospital
city: London
country: United Kingdom
facility: Royal Free NHS Trust,
city: London
country: United Kingdom
facility: Guys and St Thomas' NHS trust
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
Study officials:
affiliation: Gilead Sciences
name: Todd Fralich, M.D.
role: STUDY_CHAIR
References: