Safety and Efficacy of COBI-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults

HIV Infections Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9350-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01108510
• Other study ID #: GS-US-216-0114
• Status: Completed
• Phase: Phase 3
• First received: April 20, 2010
• Last updated: May 8, 2015
• Start date: April 2010
• Est. completion date: April 2015

Study information

• Verified date: May 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustria: Austrian Medicines and Medical Devices AgencyBelgium: Federal Agency for Medicines and Health Products, FAMHPBrazil: National Health Surveillance AgencyDenmark: Danish Health and Medicines AuthorityDominican Republic: Dirección General de Drogas y FarmaciasCanada: Health CanadaFrance: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencyMexico: Federal Commission for Sanitary Risks ProtectionNetherlands: Medicines Evaluation Board (MEB)Portugal: INFARMED, National Authority of Medicines and Health Products, IPSpain: Agencia Española de Medicamentos y Productos SanitariosSwitzerland: SwissmedicThailand: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the safety and efficacy of a regimen containing Cobicistat (COBI)-boosted atazanavir (ATV/co) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir (RTV)-boosted atazanavir (ATV/r) plus FTC/TDF in HIV-1-infected, antiretroviral treatment-naive adults. Development of COBI as a "pharmacoenhancer" could provide a beneficial alternative to RTV for use in combination with protease inhibitors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 698
• Est. completion date: April 2015
• Est. primary completion date: November 2011
• 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, which must be obtained prior to initiation of study procedures

• Plasma HIV-1 RNA levels = 5,000 copies/mL at screening

• No prior use of any approved or investigational antiretroviral drug for any length of time

• Screening genotype report must show sensitivity to FTC, TDF and ATV

• Normal ECG

• Adequate renal function (eGFR calculated using the Cockcroft-Gault equation = 70 mL/min)

• 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

• Serum amylase = 5 x ULN

• Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 day s following the last dose of study drug.

• Age = 18 years

• Life expectancy = 1 year

Exclusion Criteria:

• A new AIDS defining condition diagnosed within the 30 days prior to screening

• Receiving drug treatment for Hepatitis C, or anticipated to receive treatment for Hepatitis C

• Subjects experiencing decompensated cirrhosis

• Females who are breastfeeding

• Positive serum pregnancy test (female of childbearing potential)

• Have an implanted defibrillator or pacemaker

• Have an ECG PR interval = 220 msec

• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance.

• A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline.

• Medications contraindicated for use with COBI, emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), atazanavir (ATV), ritonavir (RTV) or subjects with any known allergies to the excipients of COBI tablets, Truvada tablets, atazanavir capsules or ritonavir tablets.

• Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial.

• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make 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: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV
• HIV Infections

Intervention

Drug:
• COBI
Cobicistat (COBI) 150 mg tablet administered orally once daily
• RTV
Ritonavir (RTV) 100 mg tablet administered orally once daily
• ATV
Atazanavir (ATV) 300 mg capsule administered orally once daily
• FTC/TDF
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily
• Placebo to match COBI
Placebo to match COBI administered orally once daily
• Placebo to match RTV
Placebo to match RTV administered orally once daily

Locations

Country	Name	City	State
Australia	Melbourne Sexual Health Centre	Carlton	Victoria
Australia	St Vincent's Hospital, Sydney	Darlinghurst	New South Wales
Australia	Taylor Square Private Clinic	Darlinghurst	New South Wales
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Northside Clinic	Melbourne	Victoria
Australia	Albion Street Centre	Sydney	New South Wales
Australia	Holdsworth House Medical practice	Sydney	New South Wales
Austria	LKH Graz West	Graz
Austria	Allgemeines Krankenhaus	Vienna
Austria	Interne Lungenabteilung, SMZ Baumgartner Hoehe - Otto-Wagner-Spital	Vienna
Belgium	CHU Saint-Pierre University Hospital	Brussels
Belgium	Hôpital Universitaire Erasme - ULB	Brussels
Belgium	University of Ghent	Ghent
Brazil	Universidade Estadual de Campinas	Campinas
Brazil	Instituto De Pesquisa Clinica Evandro Chagas	Rio de Janeiro	RJ
Brazil	URDIP Faculdade de Medicina do ABC	Santo Andre	Sao Paulo
Brazil	Brasilmed Assistencia Medica E Pesquisas	São Paulo
Brazil	Crt-Dst/Aids	São Paulo
Brazil	Instituto De Infectologia Emilo Ribas	São Paulo
Canada	Clinique Medicale du Quartier Latin	Montreal	Quebec
Canada	Clinique medicale l'Actuel	Montreal	Quebec
Canada	Project LORI	Montreal
Canada	Immunodeficiency Service, McGill University Health Centre (MUHC) - Montreal Chest Institute	Montréal	Quebec
Canada	Canadian Immunodeficiency Research Collaborative (CIRC) Inc.	Toronto	Ontario
Canada	University Health Network, Toronto General Hospital	Toronto	Ontario
Canada	Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg	Winnipeg	Manitoba
Denmark	Rigshospitalet, Infektionsklinik 5112	Copenhagen
Dominican Republic	Instituto Dominicano de Estudios Virologicos - IDEV	Santo Domingo
France	Service des Maladies Infectieuses, CHU de Caen	Caen
France	Hôpital de la Croix Rousse - Maladies Infectieuses et Tropicales	Lyon
France	Hopital Sainte Marguerite Service d'Immuno-Hématologie Clinique -CISIH	Marseille
France	CHU de Nantes Hopital de l'Hotel Dieu	Nantes
France	Bichat Hospital	Paris
France	Department of Infectious Diseases, Saint-Louis hospital	Paris
France	Hopital Saint Antoine, Service De Maladies Infectieuses	Paris
France	Maladies Infectieuses Dpt	Paris
France	Tenon Hospital, UPMC	Paris
France	Centre François Magendie, Hôpital du Haut Lévêque	Pessac
France	Centre Hospitalier de Tourcoing	Tourcoing
Germany	EPIMED GmbH	Berlin
Germany	Medizinische Universitätsklinik	Bonn
Germany	Infektio Research GmbH / Infektiologikum Frankfurt	Frankfurt am Main
Germany	ICH Study Center Hamburg	Hamburg
Germany	University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit	Hamburg
Germany	University of Cologne, Department of Internal Medicine	Koln
Italy	Fondazione Centro San Raffaele del Monte Tabor	Milan
Italy	Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive	Milano
Italy	Istituto Nazionale Malattie Infettive Lazzaro Spallanzani	Roma
Italy	Dipartimento di Malattie Infettive	Torino
Mexico	Unidad de VIH, Hospital Civil de Guadalajara, Fray Antonio Alcalde	Guadalajara	Jalisco
Netherlands	Onze lieve vrouw gasthuis	Amsterdam
Portugal	Hospital de Santa Maria - CHLN	Lisbon
Portugal	Serviço de Doenças Infecciosas, Hospital de São João	Porto
Puerto Rico	Instituto de Investigacion Clentifica del Sur	Ponce
Puerto Rico	Clinical Research Puerto Rico	San Juan
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Virgen del Rocio	Sevilla
Switzerland	Universitätsklinik für Infektiologie, Universitätsspital Bern	Bern
Switzerland	CHUV	Lausanne	VD
Switzerland	Division of Infectious Diseases and Hospital Hygiene; University Hospital of Zurich	Zürich
Thailand	HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine Chulalongkorn University	Bangkok
Thailand	Ramathibodi Hospital, Mahidol University	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai University, Faculty of Medicine, Department of Medicine	Chiang Mai
Thailand	Khon Kaen University	Khon Kaen
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton	East Sussex
United Kingdom	Barts and the London NHS Trust	London
United Kingdom	Courtyard Clinic, St. Georges Hospital	London
United Kingdom	Guys and St. Thomas' NHS Trust	London
United Kingdom	Homerton University Hospital	London
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Be Well Medical Center	Berkley	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	Montefiore Medical Center - AIDS Center	Bronx	New York
United States	Carolinas Medical Center-Myers Park	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	University of South Carolina	Columbia	South Carolina
United States	Southwest Infectious Disease Clinical Research, Inc.	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Apex Research, LLC	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Broward Health/Comprehensive Care Center	Fort Lauderdale	Florida
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	East Carolina University, The Brody School of Medicine	Greenville	North Carolina
United States	Garcia's Family Health Group	Harlingen	Texas
United States	Gordon E. Crofoot MD PA	Houston	Texas
United States	Research Access Network	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Health for Life Clinic PLLC	Little Rock	Arkansas
United States	Living Hope Clinical Foundation	Long Beach	California
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Anthony Mills MD Inc	Los Angeles	California
United States	Kaiser Permanente	Los Angeles	California
United States	Los Angeles Gay and Lesbian Center DBA Jeffrey Goodman Special Care Clinic	Los Angeles	California
United States	Oasis Clinic	Los Angeles	California
United States	Peter J Ruane, MD, Inc	Los Angeles	California
United States	Mercer University School of Medicine	Macon	Georgia
United States	North Shore University Hospital	Manhasset	New York
United States	The Kinder Medical Group	Miami	Florida
United States	University of Miami School of Medicine	Miami	Florida
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Chelsea Village Medical, PC	New York	New York
United States	Mt Sinai School of Medicine	New York	New York
United States	Ricky K. Hsu, MD, PC	New York	New York
United States	Saint Michaels Medical Center	Newark	New Jersey
United States	Idocf/ Valuhealthmd, Llc	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Division of Infectious Diseases, Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	University of California, Davis Medical Center	Sacramento	California
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Kaiser Permanente Medical Center, Clinical Trials Unit	San Francisco	California
United States	Metropolis Medical	San Francisco	California
United States	SouthWest CARE Center	Santa Fe	New Mexico
United States	Peter Shalit, M.D.	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	CentralWest Clinical Research	St. Louis	Missouri
United States	Infectious Disease Research Institute Inc.	Tampa	Florida
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department	Tampa	Florida
United States	Dupont Circle Physicians Group	Washington	District of Columbia
United States	George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Whitman-Walker Clinic	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,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Denmark,  Dominican Republic,  France,  Germany,  Italy,  Mexico,  Netherlands,  Portugal,  Puerto Rico,  Spain,  Switzerland,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA snapshot algorithm.	Week 48	No
Secondary	Change From Baseline in CD4 Cell Count at Week 48	The change from baseline in CD4 cell count at Week 48 was analyzed.	Baseline to Week 48	No