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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01309243
• Other study ID #: GS-US-264-0110
• Status: Completed
• Phase: Phase 3
• First received: March 3, 2011
• Last updated: February 3, 2015
• Start date: February 2011
• Est. completion date: February 2014

Study information

• Verified date: February 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 799
• Est. completion date: February 2014
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

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
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Portugal,  Puerto Rico,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the US FDA snapshot algorithm.; The snapshot algorithm defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.	Week 48	No
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the US FDA snapshot algorithm.	Baseline to Week 96	No
Secondary	Change From Baseline in CD4 Cell Count at Week 48		Baseline to Week 48	No
Secondary	Change From Baseline in CD4 Cell Count at Week 96		Baseline to Week 96	No
Secondary	Change From Baseline in Fasting Total Cholesterol at Week 48		Baseline to Week 48	No
Secondary	Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48		Baseline to Week 48	No
Secondary	Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48		Baseline to Week 48	No
Secondary	Change From Baseline in Fasting Triglycerides at Week 48		Baseline to Week 48	No
Secondary	Development of HIV-1 Drug Resistance Through Week 96, All Participants	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, 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.	Baseline to Week 96	No
Secondary	Development of HIV-1 Drug Resistance Through Week 96, Participants With Viral Resistance	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.	Baseline to Week 96	No