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

NCT01252940 | Completed Phase 3 Results

• 2 other identifiers: GS-US-264-01062010-023178-37
• Study Type: interventional
• Target: 482
• Locations: 10 countries
• Sites: 111

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.

Conditions

HIV-1 Infection

Keywords

HIV-1; HIV; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)

  Week 48

• Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24

  Baseline to Week 24

• Change From Baseline in CD4 Count Through Week 48

  Baseline to Week 48

• Change From Baseline in Fasting Total Cholesterol Through Week 24

  Baseline to Week 24

• Change From Baseline in Fasting Total Cholesterol Through Week 48

  Baseline to Week 48

Study Arms (2)

FTC/RPV/TDF

EXPERIMENTAL

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

SBR/Delayed Switch

EXPERIMENTAL

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; Drug: PI; Drug: RTV; Drug: NRTIs

Interventions

FTC/RPV/TDF DRUG

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)

Also known as: Complera®, Eviplera®

FTC/RPV/TDF; SBR/Delayed Switch

PI DRUG

Protease inhibitors (PIs) included amprenavir, atazanavir, darunavir, fosamprenavir, Kaletra (lopinavir/ritonavir, coformulated), ritonavir, and saquinavir. PIs were administered according to prescribing information.

SBR/Delayed Switch

RTV DRUG

Ritonavir (RTV) was administered according to prescribing information.

SBR/Delayed Switch

NRTIs DRUG

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.

SBR/Delayed Switch

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (111)

University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

Spectrum Medical Group

Phoenix, Arizona, 85012, United States

Location

Health for Life Clinic, PLLC

Little Rock, Arkansas, 72207, United States

Location

AIDS Healthcare Foundation-Research Center

Beverly Hills, California, 90211, United States

Location

Pacific Oaks Medical Group

Beverly Hills, California, United States

Location

Center for Special Immunology

Costa Mesa, California, 92626, United States

Location

Kaiser Permanente

Hayward, California, 94545, United States

Location

The Living Hope Foundation

Long Beach, California, 90813, United States

Location

Peter J. Ruane, MD, Inc.

Los Angeles, California, 90019, United States

Location

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Jeffrey Goodman Special Care Clinic

Los Angeles, California, 90028, United States

Location

Oasis Clinic

Los Angeles, California, 90059, United States

Location

Anthony Mills, MD Internal Medicine

Los Angeles, California, 90069, United States

Location

Orange Coast Medical Group

Newport Beach, California, 92663, United States

Location

Alameda County Medical Center

Oakland, California, 94602, United States

Location

East Bay AIDS Center

Oakland, California, 94609, United States

Location

Stanford University

Palo Alto, California, 94303, United States

Location

University of California, Davis

Sacramento, California, 95187, United States

Location

Kaiser Permanente

Sacramento, California, 95825, United States

Location

La Playa Medical Group and Clinical Research

San Diego, California, 92103, United States

Location

Metropolis Medical

San Francisco, California, 94115, United States

Location

Kaiser Permanente

San Francisco, California, 94118, United States

Location

Capital Medical Associates PC

Washington D.C., District of Columbia, 20036, United States

Location

Gary Richmond, MD, PA, Inc.

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology & Research Center

Ft. Pierce, Florida, 34982, United States

Location

The Kinder Medical Group

Miami, Florida, 33133, United States

Location

Care Resource

Miami, Florida, United States

Location

Wohlfeiler, Piperato and Associates, LLC

Miami Beach, Florida, 33139, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

ValueHealthMD, LLC/IDOCF

Orlando, Florida, 32806, United States

Location

Wade, Barbara Private Practice

Pensacola, Florida, 32504, United States

Location

Barry M. Rodwick, M.D.

Safety Harbor, Florida, 34695, United States

Location

University of South Florida - HIV Clinical Research Unit

Tampa, Florida, 33062, United States

Location

St. Joseph's Comprehensive Research Institute

Tampa, Florida, 33614, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30308, United States

Location

Atlanta ID Group

Atlanta, Georgia, 30309, United States

Location

Infectious Disease Specialists of Atlanta (IDSA)

Decatur, Georgia, 30033, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

The Ruth M. Rothstein CORE Center

Chicago, Illinois, 60612, United States

Location

Northstar Medical Center

Chicago, Illinois, 60657, United States

Location

Johns Hopkins University School of Medicine

Lutherville, Maryland, 21093, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

The Research Institute

Springfield, Massachusetts, 01105, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Kansas City Free Health Clinic

Kansas City, Missouri, United States

Location

Southampton Healthcare, Inc.

St Louis, Missouri, 63139, United States

Location

Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

South Jersey Infectious Disease

Somer Point, New Jersey, 08244, United States

Location

Greiger Clinic

Mount Vernon, New York, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

The Aaron Diamond AIDS Research Center

New York, New York, 10016, United States

Location

ID Consultant, P.A.

Charlotte, North Carolina, 28209, United States

Location

Rosedale Infectious Diseases

Huntersville, North Carolina, 28078, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

University of South Carolina

Columbia, South Carolina, 29203, United States

Location

Nicholaos Bellos, MD, PA

Dallas, Texas, 75204, United States

Location

Tarrant County Infectious Diseases Associates

Fort Worth, Texas, 76104, United States

Location

Garcia Family Medical Clinic

Harlingen, Texas, 78550, United States

Location

Therapeutic Concepts, P.A.

Houston, Texas, 77004, United States

Location

Gordon E. Crofoot, MD, PA

Houston, Texas, 77098, United States

Location

Research Access Network

Houston, Texas, 77098, United States

Location

DCOL Center for Clinical Research

Longview, Texas, 75605, United States

Location

Clinical Alliance for Research & Education-Infectious Diseases, LLC (CARE-ID)

Annandale, Virginia, 22003, United States

Location

Univ.-Kklinik fuer Innere Medizin III

Salzberg, Austria

Location

LKH Graz West

Styria, Austria

Location

2.Interne Lungenabteilung Otto Wagner Spital

Vienna, Austria

Location

Dept. of Dermatology, Div. of Immunology,

Vienna, Austria

Location

Private Office

Vienna, Austria

Location

CHU Saint-Pierre University Hospital

Brussels, 1000, Belgium

Location

University Hospitals Leuven

Flemish Brabant, Belgium

Location

Universitaire Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Downtown Infectious Disease Clinic - Univ of BC

Vancouver, British Columbia, Canada

Location

Maple Leaf Research

Toronto, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Clinique Medicale Du Quartier Latin

Montreal, Quebec, H2L 5B1, Canada

Location

Winnipeg Regional Health Authority

Winnipeg, Canada

Location

Hôpital Hôtel-Dieu

Lyon, 69002, France

Location

Infectiologie - 7ème Ouest - CHU HOTEL DIEU

Nantes, France

Location

Archet 1 CHU de Nice - 6ème Niveau - Infectiology

Nice, 06202, France

Location

Department of Infectious Diseases, Saint-Louis hospital

Paris, 75010, France

Location

Hôpital Saint Antoine, Servuce de Maladies Infectieuses

Paris, 75012, France

Location

Bichat Hospital

Paris, 75018, France

Location

Hopital Tenon

Paris, France

Location

Maladies Infectieuses Dpt

Paris, France

Location

Hôpital Haut Levêque

Pessac, France

Location

EPIMED GmbH

Berlin, 12157, Germany

Location

University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic

Bonn, 53127, Germany

Location

University of Cologne, Department of Internal Medicine

Cologne, 50937, Germany

Location

Center for HIV and Hepatogastroenterology

Düsseldorf, Germany

Location

Infectio Research

Frankfurt, 60596, Germany

Location

ICH Study Center Hamburg

Hamburg, 20146, Germany

Location

University Medical Center Hamburg - Eppendorf

Hamburg, Germany

Location

Ospedali Riuniti

Bergamo, 24128, Italy

Location

Fondazione Centro San Raffaele del Monte Tabor

Milan, 20127, Italy

Location

Azienda Ospedaliera San Paolo, Mallattie Infettive e Tropicali

Milan, 20142, Italy

Location

Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive

Milan, 20157, Italy

Location

National Institute for Infectious Diseases "L. Spallanzani" IRCCS

Rome, 20149, Italy

Location

Clinical Research Puerto Rico, Inc.

San Juan, 00909, Puerto Rico

Location

Hospital Clinic i Provincial

Barcelona, 28036, Spain

Location

Hospital Germans Trias i Pujol

Barcelona, 28916, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Brighton and Sussex University Hospitals NHS Trust

Brighton, East Sussex, BN2 1ES, United Kingdom

Location

Barts and the London NHS Trust

London, E1 1BB, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Chelsea and Westminster Hospital Foundation Trust

London, SW10 9NH, United Kingdom

Location

Homerton Unversity Hospital

London, United Kingdom

Location

North Manchester General Hospital

Manchester, M85RB, United Kingdom

Location

MeSH Terms

Interventions

Emtricitabine, Rilpivirine, Tenofovir Drug Combination

Intervention Hierarchy (Ancestors)

Rilpivirine; Nitriles; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• John Flaherty, PharmD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 3, 2010
• Study Start: November 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: October 1, 2014
• Last Updated: December 4, 2015
• Results First Posted: April 19, 2013

Record last verified: 2015-10

Locations

CA (5); FR (9); US (66); DE (7); PR (1); IT (5); BE (3); AU (5); ES (4); GB (6)