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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: FTC/RPV/TDF; Drug: PI; Drug: RTV; Drug: NRTIs

• Study Type: Interventional
• Enrollment (Actual): 482
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzberg, Austria
    • Univ.-Kklinik fuer Innere Medizin III
  • Styria, Austria
    • LKH Graz West
  • Vienna, Austria
    • 2.Interne Lungenabteilung Otto Wagner Spital
  • Vienna, Austria
    • Dept. of Dermatology, Div. of Immunology,
  • Vienna, Austria
    • Private office
• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint-Pierre University Hospital
  • Flemish Brabant, Belgium
    • University Hospitals Leuven
  • Ghent, Belgium, 9000
    • Universitaire Ziekenhuis Gent
• Canada
  • Winnipeg, Canada
    • Winnipeg Regional Health Authority
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Downtown Infectious Disease Clinic - Univ of BC
  • Ontario
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada
      • Maple Leaf Research
  • Quebec
    • Montreal, Quebec, Canada, H2L 5B1
      • Clinique Medicale du Quartier Latin
• France
  • Lyon, France, 69002
    • Hôpital Hôtel-Dieu
  • Nantes, France
    • Infectiologie - 7ème Ouest - CHU HOTEL DIEU
  • Nice Cedex 3, France, 06202
    • Archet 1 CHU de Nice - 6ème Niveau - Infectiology
  • Paris, France, 75018
    • Bichat Hospital
  • Paris, France
    • Hopital Tenon
  • Paris, France, 75010
    • Department of Infectious Diseases, Saint-Louis hospital
  • Paris, France, 75012
    • Hôpital Saint Antoine, Servuce de Maladies Infectieuses
  • Paris, France
    • Maladies Infectieuses Dpt
  • Pessac, France
    • Hopital Haut Leveque
• Germany
  • Berlin, Germany, 12157
    • EPIMED GmbH
  • Bonn, Germany, 53127
    • University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic
  • Dusseldorf, Germany
    • Center for HIV and Hepatogastroenterology
  • Frankfurt, Germany, 60596
    • Infectio Research
  • Hamburg, Germany, 20146
    • ICH Study Center Hamburg
  • Hamburg, Germany
    • University Medical Center Hamburg - Eppendorf
  • Köln, Germany, 50937
    • University of Cologne, Department of Internal Medicine
• Italy
  • Bergamo, Italy, 24128
    • Ospedali Riuniti
  • Milan, Italy, 20127
    • Fondazione Centro San Raffaele del Monte Tabor
  • Milan, Italy, 20142
    • Azienda Ospedaliera San Paolo, Mallattie Infettive e Tropicali
  • Milan, Italy, 20157
    • Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive
  • Rome, Italy, 20149
    • National Institute for Infectious Diseases "L. Spallanzani" IRCCS
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico, Inc.
• Spain
  • Barcelona, Spain, 28036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 28916
    • Hospital Germans Trias i Pujol
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, E1 1BB
    • Barts and the London NHS Trust
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital Foundation Trust
  • London, United Kingdom
    • Homerton Unversity Hospital
  • Manchester, United Kingdom, M85RB
    • North Manchester General Hospital
  • East Sussex
    • Brighton, East Sussex, United Kingdom, BN2 1ES
      • Brighton and Sussex University Hospitals NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama - Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health for Life Clinic, PLLC
  • California
    • Beverly HIlls, California, United States, 90211
      • AIDS Healthcare Foundation-Research Center
    • Beverly Hills, California, United States
      • Pacific Oaks Medical Group
    • Costa Mesa, California, United States, 92626
      • Center for Special Immunology
    • Hayward, California, United States, 94545
      • Kaiser Permanente
    • Long Beach, California, United States, 90813
      • The Living Hope Foundation
    • Los Angeles, California, United States, 90028
      • Jeffrey Goodman Special Care Clinic
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90059
      • OASIS Clinic
    • Los Angeles, California, United States, 90069
      • Anthony Mills, MD Internal Medicine
    • Los Angeles, California, United States, 90019
      • Peter J. Ruane, MD, Inc.
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Oakland, California, United States, 94602
      • Alameda County Medical Center
    • Oakland, California, United States, 94609
      • East Bay AIDS Center
    • Palo Alto, California, United States, 94303
      • Stanford University
    • Sacramento, California, United States, 95825
      • Kaiser Permanente
    • Sacramento, California, United States, 95187
      • University of California, Davis
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
    • San Francisco, California, United States, 94118
      • Kaiser Permanente
    • San Francisco, California, United States, 94115
      • Metropolis Medical
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates PC
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary Richmond, MD, PA, Inc.
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology & Research Center
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Miami, Florida, United States
      • Care Resource
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • ValueHealthMD, LLC/IDOCF
    • Pensacola, Florida, United States, 32504
      • Wade, Barbara Private Practice
    • Safety Harbor, Florida, United States, 34695
      • Barry M. Rodwick, M.D.
    • Tampa, Florida, United States, 33614
      • St. Joseph's Comprehensive Research Institute
    • Tampa, Florida, United States, 33062
      • University of South Florida - HIV Clinical Research Unit
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta (IDSA)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
    • Chicago, Illinois, United States, 60612
      • The Ruth M. Rothstein CORE Center
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Springfield, Massachusetts, United States, 01105
      • The Research Institute
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Kansas City, Missouri, United States
      • Kansas City Free Health Clinic
    • St. Louis, Missouri, United States, 63139
      • Southampton Healthcare, Inc.
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
    • Somer Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New York
    • Mt Vernon, New York, United States
      • Greiger Clinic
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10016
      • The Aaron Diamond AIDS Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • ID Consultant, P.A.
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75204
      • Nicholaos Bellos, MD, PA
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Diseases Associates
    • Harlingen, Texas, United States, 78550
      • Garcia Family Medical Clinic
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot, MD, PA
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, P.A.
    • Houston, Texas, United States, 77098
      • Research Access Network
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Clinical Alliance for Research & Education-Infectious Diseases, LLC (CARE-ID)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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
• 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

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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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: SBR/Delayed Switch; 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.	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: PI; Protease inhibitors (PIs) included amprenavir, atazanavir, darunavir, fosamprenavir, Kaletra (lopinavir/ritonavir, coformulated), ritonavir, and saquinavir. PIs were administered according to prescribing information.; Drug: RTV; Ritonavir (RTV) was administered according to prescribing information.; Drug: NRTIs; NRTIs included abacavir, emtricitabine, Combivir (lamivudine/zidovudine, coformulated), Epzicom (abacavir/lamivudine, coformulated), lamivudine, stavudine, tenofovir DF, Truvada® (emtricitabine/tenofovir DF, coformulated), and zidovudine. NRTIs were administered according to prescribing information.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the FDA snapshot analysis.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)	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.	Week 48
Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24	The mean (SD) change in CD4 count was analyzed from baseline through Week 24.	Baseline to Week 24
Change From Baseline in CD4 Count Through 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.	Baseline to Week 48
Change From Baseline in Fasting Total Cholesterol Through Week 24	The mean (SD) change from baseline in fasting total cholesterol (mg/dL) through Week 24 was analyzed.	Baseline to Week 24
Change From Baseline in Fasting Total Cholesterol Through 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.	Baseline to Week 48
Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24	The mean (SD) change from baseline in fasting HDL cholesterol (mg/dL) through Week 24 was analyzed.	Baseline to Week 24
Change From Baseline in Fasting HDL Cholesterol Through 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.	Baseline to Week 48
Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24	The mean (SD) change from baseline in fasting direct LDL cholesterol (mg/dL) through Week 24 was analyzed.	Baseline to Week 24
Change From Baseline in Fasting Direct LDL Cholesterol Through 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.	Baseline to Week 48
Change From Baseline in Fasting Triglycerides Through Week 24	The mean (SD) change from baseline in fasting triglycerides through Week 24 was analyzed.	Baseline to Week 24
Change From Baseline in Fasting Triglycerides Through 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.	Baseline to Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 2, 2010
• First Posted (Estimate): December 3, 2010

Study Record Updates

• Last Update Posted (Estimate): December 4, 2015
• Last Update Submitted That Met QC Criteria: October 27, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment Experienced
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine, Rilpivirine, Tenofovir Drug Combination
• Other Study ID Numbers: GS-US-264-0106; 2010-023178-37 (EudraCT Number)