Clinical trial NCT01252940: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV-1
HIV
Treatment Experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-12-03
Enrollment: 482
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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
* 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

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (FDA Snapshot Analysis)
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (FDA Snapshot Analysis)
timeFrame: Week 48
measure: Change From Baseline in Cluster of Differentiation 4 (CD4) Count Through Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in CD4 Count Through Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Total Cholesterol Through Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Fasting Total Cholesterol Through Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol Through Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Fasting HDL Cholesterol Through Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Direct Low-density Lipoprotein (LDL) Cholesterol Through Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Fasting Direct LDL Cholesterol Through Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Triglycerides Through Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Fasting Triglycerides Through Week 48
timeFrame: Baseline to Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Little Rock
country: United States
facility: Health for Life Clinic, PLLC
state: Arkansas
city: Beverly HIlls
country: United States
facility: AIDS Healthcare Foundation-Research Center
state: California
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Costa Mesa
country: United States
facility: Center for Special Immunology
state: California
city: Hayward
country: United States
facility: Kaiser Permanente
state: California
city: Long Beach
country: United States
facility: The Living Hope Foundation
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, Inc.
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Jeffrey Goodman Special Care Clinic
state: California
city: Los Angeles
country: United States
facility: Oasis Clinic
state: California
city: Los Angeles
country: United States
facility: Anthony Mills, MD Internal Medicine
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Group
state: California
city: Oakland
country: United States
facility: Alameda County Medical Center
state: California
city: Oakland
country: United States
facility: East Bay AIDS Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: Washington
country: United States
facility: Capital Medical Associates PC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA, Inc.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology & Research Center
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato and Associates, LLC
state: Florida
city: Miami
country: United States
facility: The Kinder Medical Group
state: Florida
city: Miami
country: United States
facility: Care Resource
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: ValueHealthMD, LLC/IDOCF
state: Florida
city: Pensacola
country: United States
facility: Wade, Barbara Private Practice
state: Florida
city: Safety Harbor
country: United States
facility: Barry M. Rodwick, M.D.
state: Florida
city: Tampa
country: United States
facility: University of South Florida - HIV Clinical Research Unit
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta (IDSA)
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: The Ruth M. Rothstein CORE Center
state: Illinois
city: Chicago
country: United States
facility: Northstar Medical Center
state: Illinois
city: Lutherville
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Free Health Clinic
state: Missouri
city: St. Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Somer Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Mt Vernon
country: United States
facility: Greiger Clinic
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: The Aaron Diamond AIDS Research Center
state: New York
city: Charlotte
country: United States
facility: ID Consultant, P.A.
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Nicholaos Bellos, MD, PA
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Diseases Associates
state: Texas
city: Harlingen
country: United States
facility: Garcia Family Medical Clinic
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, P.A.
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot, MD, PA
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education-Infectious Diseases, LLC (CARE-ID)
state: Virginia
city: Salzberg
country: Austria
facility: Univ.-Kklinik fuer Innere Medizin III
city: Styria
country: Austria
facility: LKH Graz West
city: Vienna
country: Austria
facility: 2.Interne Lungenabteilung Otto Wagner Spital
city: Vienna
country: Austria
facility: Dept. of Dermatology, Div. of Immunology,
city: Vienna
country: Austria
facility: Private Office
city: Brussels
country: Belgium
facility: CHU Saint-Pierre University Hospital
city: Flemish Brabant
country: Belgium
facility: University Hospitals Leuven
city: Ghent
country: Belgium
facility: Universitaire Ziekenhuis Gent
city: Vancouver
country: Canada
facility: Downtown Infectious Disease Clinic - Univ of BC
state: British Columbia
city: Toronto
country: Canada
facility: Maple Leaf Research
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Clinique Medicale Du Quartier Latin
state: Quebec
city: Winnipeg
country: Canada
facility: Winnipeg Regional Health Authority
city: Lyon
country: France
facility: Hôpital Hôtel-Dieu
city: Nantes
country: France
facility: Infectiologie - 7ème Ouest - CHU HOTEL DIEU
city: Nice Cedex 3
country: France
facility: Archet 1 CHU de Nice - 6ème Niveau - Infectiology
city: Paris
country: France
facility: Department of Infectious Diseases, Saint-Louis hospital
city: Paris
country: France
facility: Hôpital Saint Antoine, Servuce de Maladies Infectieuses
city: Paris
country: France
facility: Bichat Hospital
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Maladies Infectieuses Dpt
city: Pessac
country: France
facility: Hôpital Haut Levêque
city: Berlin
country: Germany
facility: EPIMED GmbH
city: Bonn
country: Germany
facility: University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic
city: Dusseldorf
country: Germany
facility: Center for HIV and Hepatogastroenterology
city: Frankfurt
country: Germany
facility: Infectio Research
city: Hamburg
country: Germany
facility: ICH Study Center Hamburg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Köln
country: Germany
facility: University of Cologne, Department of Internal Medicine
city: Bergamo
country: Italy
facility: Ospedali Riuniti
city: Milan
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Milan
country: Italy
facility: Azienda Ospedaliera San Paolo, Mallattie Infettive e Tropicali
city: Milan
country: Italy
facility: Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive
city: Rome
country: Italy
facility: National Institute for Infectious Diseases "L. Spallanzani" IRCCS
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico, Inc.
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
state: East Sussex
city: London
country: United Kingdom
facility: Barts and the London NHS Trust
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital Foundation Trust
city: London
country: United Kingdom
facility: Homerton Unversity Hospital
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
Study officials:
affiliation: Gilead Sciences
name: John Flaherty, PharmD
role: STUDY_DIRECTOR
References: