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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01252940
First received: December 1, 2010
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

The purpose of this randomized, open-label, multicenter, active-controlled Phase 3b study was 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 were randomized into 2 groups, the FTC/RPV/TDF STR group, in which participants switched treatment regimens at the start of the study, and the Stay on Baseline Regimen group, in which participants remained on their baseline regimen during the first 24 weeks of the study (designed to provide an initial active control), and may have switched to the FTC/RPV/TDF STR at the Week 24 visit.

After the 48-week study analysis period, participants may have continued to receive the FTC/RPV/TDF STR per protocol before switching to a commercially available source.


Condition Intervention Phase
HIV-1 Infection
Drug: FTC/RPV/TDF
Drug: Baseline antiretroviral (ARV) Regimen (PI+RTV plus two NRTIs)
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 3 Randomized, Open Label Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor and Two Nucleoside Reverse Transcriptase Inhibitors to Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) Fixed-dose Regimen in Virologically Suppressed, HIV-1 Infected Patients

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 24 (FDA Snapshot Analysis) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.


Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis) [ 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 FDA snapshot analysis.

  • Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The mean (SD) change in CD4 count was analyzed from baseline through Week 24.

  • Change From Baseline in CD4 Count Through Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The mean (SD) change in CD4 count was analyzed from baseline through Week 48.

  • Change From Baseline in Fasting Total Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 24 was analyzed.

  • Change From Baseline in Fasting Total Cholesterol Through Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 48 was analyzed.

  • Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 24 was analyzed.

  • Change From Baseline in Fasting HDL Cholesterol Through Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 48 was analyzed.

  • Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 24 was analyzed.

  • Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 48 was analyzed.

  • Change From Baseline in Fasting Triglycerides Through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting triglycerides through Week 24 was analyzed.

  • Change From Baseline in Fasting Triglycerides Through Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The mean (SD) change from baseline in fasting triglycerides through Week 48 was analyzed.


Enrollment: 482
Study Start Date: November 2010
Estimated Study Completion Date: March 2014
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FTC/RPV/TDF
Participants switched to the FTC/RPV/TDF STR at baseline.
Drug: FTC/RPV/TDF
Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg single-tablet regimen (STR) administered orally with a meal once daily (QD)
Other Names:
  • Complera®
  • Eviplera®
Experimental: Stay on baseline regimen
Participants delayed switch to the FTC/RPV/TDF STR at the Week 24 visit, after staying on their baseline ARV regimen of PI+RTV plus 2 NRTIs for the first 24 weeks after baseline.
Drug: FTC/RPV/TDF
Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg single-tablet regimen (STR) administered orally with a meal once daily (QD)
Other Names:
  • Complera®
  • Eviplera®
Drug: Baseline antiretroviral (ARV) Regimen (PI+RTV plus two NRTIs)

Ritonavir-boosted protease inhibitor (PI+RTV) plus two nucleoside reverse transcriptase inhibitors (NRTIs).

PIs included amprenavir, atazanavir, darunavir, fosamprenavir, Kaletra (lopinavir/ritonavir, coformulated), ritonavir, and saquinavir.

NRTIs included abacavir, emtricitabine, Combivir (lamivudine/zidovudine, coformulated), Epzicom (abacavir/lamivudine, coformulated), lamivudine, stavudine, tenofovir DF, Truvada® (emtricitabine/tenofovir DF, coformulated), and zidovudine.


  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
  • 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
  • Had 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/mm3; platelets ≥ 50,000/mm3; 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 have agreed 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

Exclusion Criteria:

  • 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 were 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01252940

  Hide Study Locations
Locations
United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Spectrum Medical Group
Phoenix, Arizona, United States, 85012
United States, Arkansas
Health for Life Clinic, PLLC
Little Rock, Arkansas, United States, 72207
United States, California
AIDS Healthcare Foundation-Research Center
Beverly HIlls, California, United States, 90211
Center for Special Immunology
Costa Mesa, California, United States, 92626
Kaiser Permanente
Hayward, California, United States, 94545
The Living Hope Foundation
Long Beach, California, United States, 90813
Jeffrey Goodman Special Care Clinic
Los Angeles, California, United States, 90028
Oasis Clinic
Los Angeles, California, United States, 90059
Anthony Mills, MD Internal Medicine
Los Angeles, California, United States, 90069
Peter J. Ruane, MD, Inc.
Los Angeles, California, United States, 90019
Kaiser Permanente
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
Alameda County Medical Center
Oakland, California, United States, 94602
Stanford University
Palo Alto, California, United States, 94303
Kaiser Permanente
Sacramento, California, United States, 95825
University of California, Davis
Sacramento, California, United States, 95187
La Playa Medical Group and Clinical Research
San Diego, California, United States, 92103
Metropolis Medical
San Francisco, California, United States, 94115
Kaiser Permanente
San Francisco, California, United States, 94118
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
United States, Florida
Therafirst Medical Centers
Fort Lauderdale, Florida, United States, 33308
Gary Richmond, MD, PA, Inc.
Fort Lauderdale, Florida, United States, 33316
North Broward Hospital District
Fort Lauderdale, Florida, United States, 33311
Midway Immunology & Research Center
Fort Pierce, Florida, United States, 34982
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
ValueHealthMD, LLC/IDOCF
Orlando, Florida, United States, 32806
Wade, Barbara Private Practice
Pensacola, Florida, United States, 32504
Barry M. Rodwick, M.D.
Safety Harbor, Florida, United States, 34695
University of South Florida - HIV Clinical Research Unit
Tampa, Florida, United States, 33062
St. Joseph's 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
Infectious Disease Specialists of Atlanta (IDSA)
Decatur, Georgia, United States, 30033
Mercer Univ. School of Medicine
Macon, Georgia, United States, 31201
United States, Illinois
Howard Brown Health Center
Chicago, Illinois, United States, 60613
Northstar Medical Center
Chicago, Illinois, United States, 60657
The Ruth M. Rothstein CORE Center
Chicago, Illinois, United States, 60612
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins University School of Medicine
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Community Research Initiative of New England
Boston, Massachusetts, United States, 02215
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
The Research Institute
Springfield, Massachusetts, United States, 01105
United States, Michigan
Be Well Medical Center
Berkley, Michigan, United States, 48072
Henry Ford Hospital Div of Infectious Disease
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, Inc.
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
Somer Point, New Jersey, United States, 08244
United States, New York
New York Hospital Queens
Flushing, New York, United States, 11355
North Shore University Hospital, Division of Infectious Diseases
Manhasset, New York, United States, 11030
Ricky K. Hsu, MD, PC
New York, New York, United States, 10013
Beth Israel Medical Center
New York, New York, United States, 10003
United States, North Carolina
Carolinas Medical Center-Myers Park
Charlotte, North Carolina, United States, 28207
ID Consultant, P.A.
Charlotte, North Carolina, United States, 28209
Duke University Health System, Division of Infectious Disease Clinic 2J
Durham, North Carolina, United States, 27710
East Carolina University, The Brody School of Medicine
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 CARE Center
Akron, Ohio, United States, 44304
United States, Pennsylvania
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
University of South Carolina
Columbia, South Carolina, United States, 29203
United States, Texas
Central Texas Clinical Research
Austin, Texas, United States, 78705
Nicholaos Bellos, MD, PA
Dallas, Texas, United States, 75204
Tarrant County Infectious Diseases Associates
Fort Worth, Texas, United States, 76104
Garcia Family Medical Clinic
Harlingen, Texas, United States, 78550
Gordon E. Crofoot, MD, PA
Houston, Texas, United States, 77098
Therapeutic Concepts, P.A.
Houston, Texas, United States, 77004
Research Access Network
Houston, Texas, United States, 77098
DCOL Center for Clinical Research
Longview, Texas, United States, 75605
United States, Virginia
Clinical Alliance for Research & Education-Infectious Diseases, LLC (CARE-ID)
Annandale, Virginia, United States, 22003
United States, Washington
TribalMed
Seattle, Washington, United States, 98104
Belgium
CHU Saint-Pierre University Hospital
Brussels, Belgium, 1000
Hôpital Universitaire Erasme - ULB
Brussels, Belgium, 1070
Universitaire Ziekenhuis Gent
Ghent, Belgium, 9000
Canada, British Columbia
St. Paul's Hospital AIDS Research Program
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario
Canadian Immunodeficiency Research Collaborative (CIRC)
Toronto, Ontario, Canada, M5B 1l6
Canada, Quebec
Clinique Medicale Du Quartier Latin
Montreal, Quebec, Canada, H2L 5B1
Clinique Medicale L'Actuel Directeur Recherche Clinique
Montreal, Quebec, Canada, H2L 5B1
France
Hôpital Hôtel-Dieu
Lyon, France, 69002
Archet 1 CHU de Nice - 6ème Niveau - Infectiology
Nice Cedex 3, France, 06202
Hôpital Saint Antoine, Servuce de Maladies Infectieuses
Paris, France, 75012
Department of Infectious Diseases, Saint-Louis hospital
Paris, France, 75010
Bichat Hospital
Paris, France, 75018
Germany
EPIMED GmbH
Berlin, Germany, 12157
University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic
Bonn, Germany, 53127
Infectio Research
Frankfurt, Germany, 60596
ICH Study Center Hamburg
Hamburg, Germany, 20146
University of Cologne, Department of Internal Medicine
Köln, Germany, 50937
Italy
Ospedali Riuniti
Bergamo, Italy, 24128
Azienda Ospedaliera San Paolo, Mallattie Infettive e Tropicali
Milan, Italy, 20142
Fondazione Centro San Raffaele del Monte Tabor
Milan, Italy, 20127
Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive
Milan, Italy, 20157
National Institute for Infectious Diseases "L. Spallanzani" IRCCS
Rome, Italy, 20149
Puerto Rico
Clinical Research Puerto Rico, Inc.
San Juan, Puerto Rico, 00909
Spain
Hospital Germans Trias i Pujol
Barcelona, Spain, 28916
Hospital Clinic i Provincial
Barcelona, Spain, 28036
Hospital General Universitario Gregorio Marañon
Madrid, Spain, 28007
Hospital Ramon y Cajal
Madrid, Spain, 28034
Hospital Virgen del Rocio
Sevilla, Spain, 41013
United Kingdom
Brighton and Sussex University Hospitals NHS Trust
Brighton, East Sussex, United Kingdom, BN2 1ES
Chelsea and Westminster Hospital Foundation Trust
London, United Kingdom, SW10 9NH
Royal Free Hospital
London, United Kingdom, NW3 2QG
Barts and the London NHS Trust
London, United Kingdom, E1 1BB
North Manchester General Hospital
Manchester, United Kingdom, M85RB
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Todd Fralich, MD Gilead Sciences
Principal Investigator: Frank Pallela, MD Northwestern University
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01252940     History of Changes
Other Study ID Numbers: GS-US-264-0106, 2010-023178-37
Study First Received: December 1, 2010
Results First Received: March 8, 2013
Last Updated: November 22, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Belgium: Federal Agency for Medicinal Products and Health Products
France: ANSM - Agence national de sécurité du médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:
HIV-1
HIV
Treatment Experienced

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
Protease Inhibitors
Ritonavir
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Emtricitabine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 14, 2014