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

NCT01108510 | Completed Phase 3 Results DMC

• 2 other identifiers: GS-US-216-01142009-016759-22
• Study Type: interventional
• Target: 698
• Locations: 18 countries
• Sites: 131

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.

Conditions

HIV; HIV Infections

Keywords

Treatment Naive; HIV 1 Infected

Outcome Measures

Primary Outcomes (1)

• 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 snapshot algorithm, which defines a participant's virologic response status using only the viral load at the prespecified time point within an allowed window of time, along with study drug discontinuation status.

  Week 48

Secondary Outcomes (7)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96

  Week 96

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144

  Week 144

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192

  Week 192

• Change From Baseline in CD4 Cell Count at Week 48

  Baseline to Week 48

• Change From Baseline in CD4 Cell Count at Week 96

  Baseline to Week 96

Study Arms (2)

ATV+COBI+FTC/TDF

EXPERIMENTAL

COBI + RTV placebo + ATV + FTC/TDF once daily

Drug: COBI; Drug: ATV; Drug: FTC/TDF; Drug: RTV placebo

ATV+RTV+FTC/TDF

ACTIVE COMPARATOR

RTV + COBI placebo + ATV + FTC/TDF once daily

Drug: RTV; Drug: ATV; Drug: FTC/TDF; Drug: COBI placebo

Interventions

COBI DRUG

Cobicistat (COBI) 150 mg tablet administered orally once daily

Also known as: Tybost®, GS-9350

ATV+COBI+FTC/TDF

RTV DRUG

Ritonavir (RTV) 100 mg tablet administered orally once daily

Also known as: Norvir®

ATV+RTV+FTC/TDF

ATV DRUG

Atazanavir (ATV) 300 mg capsule administered orally once daily

Also known as: Reyataz®

ATV+COBI+FTC/TDF; ATV+RTV+FTC/TDF

FTC/TDF DRUG

Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily

Also known as: Truvada®

ATV+COBI+FTC/TDF; ATV+RTV+FTC/TDF

COBI placebo DRUG

Placebo to match COBI administered orally once daily

ATV+RTV+FTC/TDF

RTV placebo DRUG

Placebo to match RTV administered orally once daily

ATV+COBI+FTC/TDF

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, 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (134)

University of Alabama at 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

Living Hope Clinical Foundation

Long Beach, California, 90813, United States

Location

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Los Angeles Gay and Lesbian Center DBA Jeffrey Goodman Special Care Clinic

Los Angeles, California, 90028, United States

Location

Peter J Ruane, MD, Inc

Los Angeles, California, 90036, United States

Location

Oasis Clinic

Los Angeles, California, 90059, United States

Location

Anthony Mills MD Inc

Los Angeles, California, 90069, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Kaiser Permanente Medical Group

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 Medical Center, Clinical Trials Unit

San Francisco, California, 94118, United States

Location

Apex Research, LLC

Denver, Colorado, 80220, United States

Location

Dupont Circle Physicians Group

Washington D.C., District of Columbia, 20009, United States

Location

Whitman-Walker Clinic

Washington D.C., District of Columbia, 20009, United States

Location

George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Therafirst Medical Center

Fort Lauderdale, Florida, 33308, United States

Location

Broward Health/Comprehensive Care Center

Fort Lauderdale, Florida, 33311, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

The Kinder Medical Group

Miami, Florida, 33133, United States

Location

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Wohlfeiler, Piperato and Associates, LLC

Miami Beach, Florida, 33139, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Idocf/ Valuhealthmd, Llc

Orlando, Florida, 32806, United States

Location

University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department

Tampa, Florida, 33602, United States

Location

Infectious Disease Research Institute Inc.

Tampa, Florida, 33614, United States

Location

St. Joseph's Comprehensive Research Institute

Tampa, Florida, 33615, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, 30033, United States

Location

Mercer University School of Medicine

Macon, Georgia, 31210, United States

Location

Howard Brown Health Center

Chicago, Illinois, 60613, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Community Research Initiative of New England

Boston, Massachusetts, 02215, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

CentralWest Clinical Research

St Louis, Missouri, 63108, United States

Location

Saint Michaels Medical Center

Newark, New Jersey, 07102, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

SouthWest CARE Center

Santa Fe, New Mexico, 87505, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Chelsea Village Medical, PC

New York, New York, 10011, United States

Location

Mt Sinai School of Medicine

New York, New York, 10011, United States

Location

Ricky K. Hsu, MD, PC

New York, New York, 10011, United States

Location

Montefiore Medical Center - AIDS Center

The Bronx, New York, 10467, United States

Location

Carolinas Medical Center-Myers Park

Charlotte, North Carolina, 28207, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University, The Brody School of Medicine

Greenville, North Carolina, 27834, 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

Division of Infectious Diseases, Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

University of South Carolina

Columbia, South Carolina, 29203, United States

Location

Southwest Infectious Disease Clinical Research, Inc.

Dallas, Texas, 75204, United States

Location

Tarrant County Infectious Disease Associates

Fort Worth, Texas, 76104, United States

Location

Garcia's Family Health Group

Harlingen, Texas, 78550, United States

Location

Therapeutic Concepts, PA

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

Peter Shalit, M.D.

Seattle, Washington, 98104, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

St Vincent's Hospital, Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Taylor Square Private Clinic

Darlinghurst, New South Wales, 2010, Australia

Location

Albion Street Centre

Sydney, New South Wales, 2010, Australia

Location

Holdsworth House Medical practice

Sydney, New South Wales, 2010, Australia

Location

Melbourne Sexual Health Centre

Carlton, Victoria, 3053, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Northside Clinic

Melbourne, Victoria, 3068, Australia

Location

LKH Graz West

Graz, A-8010, Austria

Location

Allgemeines Krankenhaus

Vienna, 1090, Austria

Location

Interne Lungenabteilung, SMZ Baumgartner Hoehe - Otto-Wagner-Spital

Vienna, 1140, Austria

Location

CHU Saint-Pierre University Hospital

Brussels, 1000, Belgium

Location

Hôpital Universitaire Erasme - ULB

Brussels, 1070, Belgium

Location

University of Ghent

Ghent, 9000, Belgium

Location

Instituto De Pesquisa Clinica Evandro Chagas

Rio de Janeiro, Rio de Janeiro, 21040-900, Brazil

Location

URDIP Faculdade de Medicina do ABC

Santo André, São Paulo, 09060-650, Brazil

Location

Instituto De Infectologia Emilo Ribas

São Paulo, São Paulo, 01246-900, Brazil

Location

Brasilmed Assistencia Medica E Pesquisas

São Paulo, São Paulo, 01416-000, Brazil

Location

Crt-Dst/Aids

São Paulo, São Paulo, 04121-000, Brazil

Location

Universidade Estadual de Campinas

Campinas, 13083-970, Brazil

Location

Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Canadian Immunodeficiency Research Collaborative (CIRC) Inc.

Toronto, Ontario, M5B1L6, Canada

Location

University Health Network, Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Clinique medicale l'Actuel

Montreal, Quebec, H2L 4P9, Canada

Location

Clinique Medicale du Quartier Latin

Montreal, Quebec, H2L 5B1, Canada

Location

Immunodeficiency Service, McGill University Health Centre (MUHC) - Montreal Chest Institute

Montreal, Quebec, H2X 2P4, Canada

Location

Project LORI

Montreal, H3H 1V1, Canada

Location

Rigshospitalet, Infektionsklinik 5112

Copenhagen, 2000, Denmark

Location

Instituto Dominicano de Estudios Virologicos - IDEV

Santo Domingo, Dominican Republic

Location

Service des Maladies Infectieuses, CHU de Caen

Caen, 14033, France

Location

Hôpital de la Croix Rousse - Maladies Infectieuses et Tropicales

Lyon, 69288, France

Location

Hopital Sainte Marguerite Service d'Immuno-Hématologie Clinique -CISIH

Marseille, 13009, France

Location

CHU de Nantes Hopital de l'Hotel Dieu

Nantes, 44093, France

Location

Department of Infectious Diseases, Saint-Louis hospital

Paris, 75010, France

Location

Hopital Saint Antoine, Service De Maladies Infectieuses

Paris, 75012, France

Location

Bichat Hospital

Paris, 75018, France

Location

Tenon Hospital, UPMC

Paris, 75020, France

Location

Maladies Infectieuses Dpt

Paris, 75651, France

Location

Centre François Magendie, Hôpital du Haut Lévêque

Pessac, 33604, France

Location

Centre Hospitalier de Tourcoing

Tourcoing, 59208, France

Location

EPIMED GmbH

Berlin, 12157, Germany

Location

Medizinische Universitätsklinik

Bonn, 53127, Germany

Location

University of Cologne, Department of Internal Medicine

Cologne, 50937, Germany

Location

Infektio Research GmbH / Infektiologikum Frankfurt

Frankfurt am Main, 60311, Germany

Location

ICH Study Center Hamburg

Hamburg, 20146, Germany

Location

University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit

Hamburg, 20246, Germany

Location

Fondazione Centro San Raffaele del Monte Tabor

Milan, 20127, Italy

Location

Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive

Milan, 20157, Italy

Location

Istituto Nazionale Malattie Infettive Lazzaro Spallanzani

Roma, 00149, Italy

Location

Dipartimento di Malattie Infettive

Torino, 10149, Italy

Location

Unidad de VIH, Hospital Civil de Guadalajara, Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Onze lieve vrouw gasthuis

Amsterdam, 1091 AC, Netherlands

Location

Hospital de Santa Maria - CHLN

Lisbon, 1649-035, Portugal

Location

Serviço de Doenças Infecciosas, Hospital de São João

Porto, 4202-451, Portugal

Location

Instituto de Investigacion Clentifica del Sur

Ponce, 00731, Puerto Rico

Location

Clinical Research Puerto Rico

San Juan, 00909, Puerto Rico

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

CHUV

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Universitätsklinik für Infektiologie, Universitätsspital Bern

Bern, 3010, Switzerland

Location

Division of Infectious Diseases and Hospital Hygiene; University Hospital of Zurich

Zurich, 8091, Switzerland

Location

HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine Chulalongkorn University

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai University, Faculty of Medicine, Department of Medicine

Chiang Mai, 50200, Thailand

Location

Khon Kaen University

Khon Kaen, 40002, Thailand

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

Homerton University Hospital

London, E9 6SR, United Kingdom

Location

Guys and St. Thomas' NHS Trust

London, SE1 7EH, United Kingdom

Location

Courtyard Clinic, St. Georges Hospital

London, SW17 0QT, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 23532097 RESULT

• 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.

  PMID: 26181707 RESULT

• 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.

  PMID: 27774892 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Cobicistat; Ritonavir; Atazanavir Sulfate; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

There were no limitations affecting the analysis or results.

Results Point of Contact

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

ClinicalTrialDisclosures@gilead.com

Study Officials

• Huyen Cao, MD

  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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2010
• First Posted: April 22, 2010
• Study Start: April 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: April 1, 2015
• Last Updated: May 23, 2016
• Results First Posted: October 28, 2014

Record last verified: 2016-04

Locations

CH (3); ME (1); PR (2); DO (1); FR (11); NL (1); DE (6); BR (6); AU (7); BE (3); PT (2); IT (4); CA (7); TH (5); DK (1); GB (5); ES (2); US (64)