Clinical trial NCT01108510: Safety and Efficacy of COBI-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
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-Naive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
HIV Infections
Keywords: Treatment Naive
HIV 1 Infected
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-04-22
Enrollment: 698
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 objective of this study is to evaluate the safety and efficacy of a regimen containing cobicistat-boosted atazanavir (ATV+COBI) plus emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) fixed-dose combination (FDC) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF FDC in HIV-1 infected, antiretroviral treatment-naive adults.

Participants will be randomized in a 1:1 ratio. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or \> 100,000 copies/mL) at screening.


Eligibility criteria: 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 days 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.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192
timeFrame: Week 192
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline to Week 96
measure: Change From Baseline in CD4 Cell Count at Week 144
timeFrame: Baseline to Week 144
measure: Change From Baseline in CD4 Cell Count at Week 192
timeFrame: Baseline to Week 192
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at 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: Long Beach
country: United States
facility: Living Hope Clinical Foundation
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Los Angeles Gay and Lesbian Center DBA Jeffrey Goodman Special Care Clinic
state: California
city: Los Angeles
country: United States
facility: Peter J Ruane, MD, Inc
state: California
city: Los Angeles
country: United States
facility: Oasis Clinic
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD Inc
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group
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 Medical Center, Clinical Trials Unit
state: California
city: Denver
country: United States
facility: Apex Research, LLC
state: Colorado
city: Washington
country: United States
facility: Dupont Circle Physicians Group
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Clinic
state: District of Columbia
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Health/Comprehensive Care Center
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and 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: University of Miami School of Medicine
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: Idocf/ Valuhealthmd, Llc
state: Florida
city: Tampa
country: United States
facility: University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department
state: Florida
city: Tampa
country: United States
facility: Infectious Disease Research Institute Inc.
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: St. Louis
country: United States
facility: CentralWest Clinical Research
state: Missouri
city: Newark
country: United States
facility: Saint Michaels Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Santa Fe
country: United States
facility: SouthWest CARE Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center - AIDS Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Chelsea Village Medical, PC
state: New York
city: New York
country: United States
facility: Mt Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Ricky K. Hsu, MD, PC
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center-Myers Park
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University, The Brody School of Medicine
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: Division of Infectious Diseases, Thomas Jefferson University
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: Southwest Infectious Disease Clinical Research, Inc.
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Harlingen
country: United States
facility: Garcia's Family Health Group
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
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: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital, Sydney
state: New South Wales
city: Darlinghurst
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Albion Street Centre
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical practice
state: New South Wales
city: Carlton
country: Australia
facility: Melbourne Sexual Health Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Northside Clinic
state: Victoria
city: Graz
country: Austria
facility: LKH Graz West
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus
city: Vienna
country: Austria
facility: Interne Lungenabteilung, SMZ Baumgartner Hoehe - Otto-Wagner-Spital
city: Brussels
country: Belgium
facility: CHU Saint-Pierre University Hospital
city: Brussels
country: Belgium
facility: Hôpital Universitaire Erasme - ULB
city: Ghent
country: Belgium
facility: University of Ghent
city: Rio de Janeiro
country: Brazil
facility: Instituto De Pesquisa Clinica Evandro Chagas
state: RJ
city: Santo Andre
country: Brazil
facility: URDIP Faculdade de Medicina do ABC
state: Sao Paulo
city: Campinas
country: Brazil
facility: Universidade Estadual de Campinas
city: São Paulo
country: Brazil
facility: Instituto De Infectologia Emilo Ribas
city: São Paulo
country: Brazil
facility: Brasilmed Assistencia Medica E Pesquisas
city: São Paulo
country: Brazil
facility: Crt-Dst/Aids
city: Winnipeg
country: Canada
facility: Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg
state: Manitoba
city: Toronto
country: Canada
facility: Canadian Immunodeficiency Research Collaborative (CIRC) Inc.
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Clinique medicale l'Actuel
state: Quebec
city: Montreal
country: Canada
facility: Clinique Medicale du Quartier Latin
state: Quebec
city: Montréal
country: Canada
facility: Immunodeficiency Service, McGill University Health Centre (MUHC) - Montreal Chest Institute
state: Quebec
city: Montreal
country: Canada
facility: Project LORI
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Infektionsklinik 5112
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudios Virologicos - IDEV
city: Caen
country: France
facility: Service des Maladies Infectieuses, CHU de Caen
city: Lyon
country: France
facility: Hôpital de la Croix Rousse - Maladies Infectieuses et Tropicales
city: Marseille
country: France
facility: Hopital Sainte Marguerite Service d'Immuno-Hématologie Clinique -CISIH
city: Nantes
country: France
facility: CHU de Nantes Hopital de l'Hotel Dieu
city: Paris
country: France
facility: Department of Infectious Diseases, Saint-Louis hospital
city: Paris
country: France
facility: Hopital Saint Antoine, Service De Maladies Infectieuses
city: Paris
country: France
facility: Bichat Hospital
city: Paris
country: France
facility: Tenon Hospital, UPMC
city: Paris
country: France
facility: Maladies Infectieuses Dpt
city: Pessac
country: France
facility: Centre François Magendie, Hôpital du Haut Lévêque
city: Tourcoing
country: France
facility: Centre Hospitalier de Tourcoing
city: Berlin
country: Germany
facility: EPIMED GmbH
city: Bonn
country: Germany
facility: Medizinische Universitätsklinik
city: Frankfurt am Main
country: Germany
facility: Infektio Research GmbH / Infektiologikum Frankfurt
city: Hamburg
country: Germany
facility: ICH Study Center Hamburg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit
city: Koln
country: Germany
facility: University of Cologne, Department of Internal Medicine
city: Milano
country: Italy
facility: Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive
city: Milan
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Roma
country: Italy
facility: Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
city: Torino
country: Italy
facility: Dipartimento di Malattie Infettive
city: Guadalajara
country: Mexico
facility: Unidad de VIH, Hospital Civil de Guadalajara, Fray Antonio Alcalde
state: Jalisco
city: Amsterdam
country: Netherlands
facility: Onze lieve vrouw gasthuis
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria - CHLN
city: Porto
country: Portugal
facility: Serviço de Doenças Infecciosas, Hospital de São João
city: Ponce
country: Puerto Rico
facility: Instituto de Investigacion Clentifica del Sur
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Lausanne
country: Switzerland
facility: CHUV
state: VD
city: Bern
country: Switzerland
facility: Universitätsklinik für Infektiologie, Universitätsspital Bern
city: Zürich
country: Switzerland
facility: Division of Infectious Diseases and Hospital Hygiene; University Hospital of Zurich
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine Chulalongkorn University
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai University, Faculty of Medicine, Department of Medicine
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
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: Homerton University Hospital
city: London
country: United Kingdom
facility: Guys and St. Thomas' NHS Trust
city: London
country: United Kingdom
facility: Courtyard Clinic, St. Georges Hospital
Study officials:
affiliation: Gilead Sciences
name: Huyen Cao, MD
role: STUDY_DIRECTOR
References:
citation: Gallant JE, Koenig E, Andrade-Villanueva J, Chetchotisakd P, DeJesus E, Antunes F, Arasteh K, Moyle G, Rizzardini G, Fehr J, Liu Y, Zhong L, Callebaut C, Szwarcberg J, Rhee MS, Cheng AK. Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1-infected patients: week 48 results. J Infect Dis. 2013 Jul;208(1):32-9. doi: 10.1093/infdis/jit122. Epub 2013 Mar 26.
citation: Gallant JE, Koenig E, Andrade-Villanueva JF, Chetchotisakd P, DeJesus E, Antunes F, Arasteh K, Rizzardini G, Fehr J, Liu HC, Abram ME, Cao H, Szwarcberg J. Brief Report: Cobicistat Compared With Ritonavir as a Pharmacoenhancer for Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate: Week 144 Results. J Acquir Immune Defic Syndr. 2015 Jul 1;69(3):338-40. doi: 10.1097/QAI.0000000000000598.
citation: Gallant J, Moyle G, Berenguer J, Shalit P, Cao H, Liu YP, Myers J, Rosenblatt L, Yang L, Szwarcberg J. Atazanavir Plus Cobicistat: Week 48 and Week 144 Subgroup Analyses of a Phase 3, Randomized, Double-Blind, Active-Controlled Trial. Curr HIV Res. 2017;15(3):216-224. doi: 10.2174/1570162X14666161021102728.