Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor (PI) and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to a Fixed-dose Tablet Containing Emtricitabine/Rilpivirine/Tenofovir DF
- Registration Number
- NCT01252940
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The purpose of this randomized, open-label, multicenter, active-controlled Phase 3b study is to evaluate the noninferiority of the emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) single-tablet regimen (STR; also referred to as fixed-dose regimen or fixed-dose tablet) relative to regimens consisting of a ritonavir-boosted protease inhibitor (PI+RTV) and two nucleoside reverse transcriptase inhibitors (NRTIs) in virologically suppressed, HIV-1 infected subjects. The FTC/RPV/TDF STR could offer an attractive treatment option to patients who wish to simplify dosing by reducing pill burden or to improve the tolerability of their treatment.
Participants will be randomized into 2 groups, the FTC/RPV/TDF STR group, in which participants will switch treatment regimens at the start of the study, and the Stay on Baseline Regimen (SBR)/Delayed Switch group, in which participants will remain on their baseline regimen during the first 24 weeks of the study (designed to provide an initial active control), and may switch to the FTC/RPV/TDF STR at the Week 24 visit.
After the 48-week study analysis period, participants may continue to receive the FTC/RPV/TDF STR per protocol before switching to a commercially available source.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 482
- Ability to understand and sign a written informed consent form
- Receiving antiretroviral therapy with a ritonavir-boosted PI and two NRTIs continuously for ≥ 6 months preceding the screening visit
- Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels for ≥ 6 months prior to the screening visit and HIV-1 RNA < 50 copies/mL at the screening visit
- On their first or second antiretroviral drug regimen; if on their second regimen, HIV-1 RNA ≤ 50 copies/mL required at the time of the first change in antiretroviral drugs, and no HIV RNA > 50 copies/mL measured at two consecutive time points after first achieving HIV RNA < 50 copies/mL
- No previous use of any approved or experimental nonnucleoside reverse transcriptase inhibitor (NNRTI) drug for any length of time
- Have a genotype prior to starting initial antiretroviral therapy and no known resistance to any of the study agents
- Normal ECG
- Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL)
- Serum amylase ≤ 5 x ULN (subjects with serum amylase > 5 x ULN eligible if serum lipase ≤ 5 x ULN)
- Adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft-Gault formula)
- Males and females of childbearing potential must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must have been an effective barrier method, or been nonheterosexually active, practice sexual abstinence, or have a vasectomized partner) from screening throughout the duration of the study period and for 30 days following the last dose of study drug.
- Age ≥ 18 years
- Life expectancy ≥ 1 year
- A new AIDS-defining condition diagnosed within 30 days prior to screening except cluster of differentiation 4 (CD4) cell count and/or percentage criteria
- Females who are breastfeeding
- Positive serum pregnancy test (female of childbearing potential)
- Proven or suspected acute hepatitis 30 days prior to study entry.
- Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance.
- History of malignancy within 5 years prior to study entry or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
- Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
- Anticipated need to initiate contraindicated drugs during the study, including drugs not to be used with FTC, TDF, RPV; or subjects with known allergies to the excipients of FTC/RPV/TDF STR tablets or Truvada® tablets
- All investigational drugs
- Medications and use of herbal/natural supplements excluded or to be used with caution while participating in the study, including those not to be taken with Viread®, Emtriva®, Truvada, and Rilpivirine.
- Participation in any other clinical trial without prior approval from the sponsor was prohibited while participating in this trial
- Treatment with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study
- History of liver disease, including Gilbert's Disease
- Any other clinical condition or prior therapy making the subject unsuitable for the study or unable to comply with the dosing requirements
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SBR/Delayed Switch NRTIs Participants will stay on baseline regimen (SBR; their existing treatment regimen of PI+RTV plus 2 NRTIs) at the beginning of the study through Week 24, and may switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit. SBR/Delayed Switch FTC/RPV/TDF Participants will stay on baseline regimen (SBR; their existing treatment regimen of PI+RTV plus 2 NRTIs) at the beginning of the study through Week 24, and may switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit. FTC/RPV/TDF FTC/RPV/TDF Participants will switch from their existing treatment regimen to the emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF) single-tablet regimen (STR) at the beginning of the study. SBR/Delayed Switch PI Participants will stay on baseline regimen (SBR; their existing treatment regimen of PI+RTV plus 2 NRTIs) at the beginning of the study through Week 24, and may switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit. SBR/Delayed Switch RTV Participants will stay on baseline regimen (SBR; their existing treatment regimen of PI+RTV plus 2 NRTIs) at the beginning of the study through Week 24, and may switch to the FTC/RPV/TDF STR (Delayed Switch) at the Week 24 visit.
- Primary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis) Week 24 The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Fasting Total Cholesterol Through Week 48 Baseline to Week 48 The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 48 was analyzed.
By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis) Week 48 The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the FDA snapshot analysis.
By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.Change From Baseline in Fasting HDL Cholesterol Through Week 48 Baseline to Week 48 The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 48 was analyzed.
By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48 Baseline to Week 48 The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 48 was analyzed.
By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.Change From Baseline in CD4 Count Through Week 48 Baseline to Week 48 The mean (SD) change in CD4 count was analyzed from baseline through Week 48.
By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24 Baseline to Week 24 The mean (SD) change in CD4 count was analyzed from baseline through Week 24.
Change From Baseline in Fasting Total Cholesterol Through Week 24 Baseline to Week 24 The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 24 was analyzed.
Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24 Baseline to Week 24 The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 24 was analyzed.
Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24 Baseline to Week 24 The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 24 was analyzed.
Change From Baseline in Fasting Triglycerides Through Week 24 Baseline to Week 24 The mean (SD) change from baseline in fasting triglycerides through Week 24 was analyzed.
Change From Baseline in Fasting Triglycerides Through Week 48 Baseline to Week 48 The mean (SD) change from baseline in fasting triglycerides through Week 48 was analyzed.
By Week 48, participants FTC/RPV/TDF had received 48 weeks of treatment with FTC/RPV/TDF, while those in the SBR/Delayed Switch group had received only 24 weeks of treatment with FTC/RPV/TDF.
Trial Locations
- Locations (108)
University of California, Davis
🇺🇸Sacramento, California, United States
Capital Medical Associates PC
🇺🇸Washington, District of Columbia, United States
Univ.-Kklinik fuer Innere Medizin III
🇦🇹Salzberg, Austria
CHU Saint-Pierre University Hospital
🇧🇪Brussels, Belgium
University Hospitals Leuven
🇧🇪Flemish Brabant, Belgium
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Dept. of Dermatology, Div. of Immunology,
🇦🇹Vienna, Austria
Universitaire Ziekenhuis Gent
🇧🇪Ghent, Belgium
Downtown Infectious Disease Clinic - Univ of BC
🇨🇦Vancouver, British Columbia, Canada
Clinique Medicale Du Quartier Latin
🇨🇦Montreal, Quebec, Canada
Peter J. Ruane, MD, Inc.
🇺🇸Los Angeles, California, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of South Carolina
🇺🇸Columbia, South Carolina, United States
Maple Leaf Research
🇨🇦Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Therapeutic Concepts, P.A.
🇺🇸Houston, Texas, United States
Center for Special Immunology
🇺🇸Costa Mesa, California, United States
Southampton Healthcare, Inc.
🇺🇸St. Louis, Missouri, United States
The Living Hope Foundation
🇺🇸Long Beach, California, United States
Health for Life Clinic, PLLC
🇺🇸Little Rock, Arkansas, United States
AIDS Healthcare Foundation-Research Center
🇺🇸Beverly HIlls, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
Oasis Clinic
🇺🇸Los Angeles, California, United States
Orange Coast Medical Group
🇺🇸Newport Beach, California, United States
LKH Graz West
🇦🇹Styria, Austria
Anthony Mills, MD Internal Medicine
🇺🇸Los Angeles, California, United States
Center for HIV and Hepatogastroenterology
🇩🇪Dusseldorf, Germany
Alameda County Medical Center
🇺🇸Oakland, California, United States
The Research Institute
🇺🇸Springfield, Massachusetts, United States
Hôpital Hôtel-Dieu
🇫🇷Lyon, France
Kansas City Free Health Clinic
🇺🇸Kansas City, Missouri, United States
Rosedale Infectious Diseases
🇺🇸Huntersville, North Carolina, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Department of Infectious Diseases, Saint-Louis hospital
🇫🇷Paris, France
Private Office
🇦🇹Vienna, Austria
Midway Immunology & Research Center
🇺🇸Fort Pierce, Florida, United States
ICH Study Center Hamburg
🇩🇪Hamburg, Germany
Chelsea and Westminster Hospital Foundation Trust
🇬🇧London, United Kingdom
Beth Israel Medical Center
🇺🇸New York, New York, United States
Winnipeg Regional Health Authority
🇨🇦Winnipeg, Canada
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Atlanta ID Group
🇺🇸Atlanta, Georgia, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Infectiologie - 7ème Ouest - CHU HOTEL DIEU
🇫🇷Nantes, France
Hôpital Haut Levêque
🇫🇷Pessac, France
Research Access Network
🇺🇸Houston, Texas, United States
South Jersey Infectious Disease
🇺🇸Somer Point, New Jersey, United States
EPIMED GmbH
🇩🇪Berlin, Germany
Barry M. Rodwick, M.D.
🇺🇸Safety Harbor, Florida, United States
Ospedali Riuniti
🇮🇹Bergamo, Italy
Archet 1 CHU de Nice - 6ème Niveau - Infectiology
🇫🇷Nice Cedex 3, France
Northstar Medical Center
🇺🇸Chicago, Illinois, United States
Greiger Clinic
🇺🇸Mt Vernon, New York, United States
Philadelphia FIGHT
🇺🇸Philadelphia, Pennsylvania, United States
ID Consultant, P.A.
🇺🇸Charlotte, North Carolina, United States
Bichat Hospital
🇫🇷Paris, France
Royal Free Hospital
🇬🇧London, United Kingdom
Homerton Unversity Hospital
🇬🇧London, United Kingdom
North Manchester General Hospital
🇬🇧Manchester, United Kingdom
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Nicholaos Bellos, MD, PA
🇺🇸Dallas, Texas, United States
2.Interne Lungenabteilung Otto Wagner Spital
🇦🇹Vienna, Austria
Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hôpital Saint Antoine, Servuce de Maladies Infectieuses
🇫🇷Paris, France
Maladies Infectieuses Dpt
🇫🇷Paris, France
University of Cologne, Department of Internal Medicine
🇩🇪Köln, Germany
Tarrant County Infectious Diseases Associates
🇺🇸Fort Worth, Texas, United States
University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic
🇩🇪Bonn, Germany
Brighton and Sussex University Hospitals NHS Trust
🇬🇧Brighton, East Sussex, United Kingdom
Infectio Research
🇩🇪Frankfurt, Germany
Barts and the London NHS Trust
🇬🇧London, United Kingdom
Clinical Research Puerto Rico, Inc.
🇵🇷San Juan, Puerto Rico
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Kaiser Permanente
🇺🇸San Francisco, California, United States
La Playa Medical Group and Clinical Research
🇺🇸San Diego, California, United States
The Kinder Medical Group
🇺🇸Miami, Florida, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Care Resource
🇺🇸Miami, Florida, United States
Fondazione Centro San Raffaele del Monte Tabor
🇮🇹Milan, Italy
Azienda Ospedaliera San Paolo, Mallattie Infettive e Tropicali
🇮🇹Milan, Italy
Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive
🇮🇹Milan, Italy
National Institute for Infectious Diseases "L. Spallanzani" IRCCS
🇮🇹Rome, Italy
Hopital Tenon
🇫🇷Paris, France
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
University of South Florida - HIV Clinical Research Unit
🇺🇸Tampa, Florida, United States
St. Joseph's Comprehensive Research Institute
🇺🇸Tampa, Florida, United States
ValueHealthMD, LLC/IDOCF
🇺🇸Orlando, Florida, United States
East Bay AIDS Center
🇺🇸Oakland, California, United States
Gary Richmond, MD, PA, Inc.
🇺🇸Fort Lauderdale, Florida, United States
Wohlfeiler, Piperato and Associates, LLC
🇺🇸Miami Beach, Florida, United States
Gordon E. Crofoot, MD, PA
🇺🇸Houston, Texas, United States
Clinical Alliance for Research & Education-Infectious Diseases, LLC (CARE-ID)
🇺🇸Annandale, Virginia, United States
University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
Jeffrey Goodman Special Care Clinic
🇺🇸Los Angeles, California, United States
Metropolis Medical
🇺🇸San Francisco, California, United States
Infectious Disease Specialists of Atlanta (IDSA)
🇺🇸Decatur, Georgia, United States
Wade, Barbara Private Practice
🇺🇸Pensacola, Florida, United States
The Ruth M. Rothstein CORE Center
🇺🇸Chicago, Illinois, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
The Aaron Diamond AIDS Research Center
🇺🇸New York, New York, United States
Garcia Family Medical Clinic
🇺🇸Harlingen, Texas, United States
University Medical Center Hamburg - Eppendorf
🇩🇪Hamburg, Germany
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Johns Hopkins University School of Medicine
🇺🇸Lutherville, Maryland, United States