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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01252940
• Other study ID #: GS-US-264-0106
• Secondary ID: 2010-023178-37
• Status: Completed
• Phase: Phase 3
• First received: December 1, 2010
• Last updated: October 27, 2015
• Start date: November 2010
• Est. completion date: October 2014

Study information

• Verified date: October 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeSpain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 482
• Est. completion date: October 2014
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No