Safety and Efficacy of Cobicistat-boosted Atazanavir Compared to Ritonavir-boosted Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

NCT00892437 | Completed Phase 2 Results DMC

• 1 other identifier: GS-US-216-0105
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 31

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) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF in HIV-1 infected, antiretroviral treatment-naive adults. Participants will be randomized in a 2:1 ratio. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or \> 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded, at which point all participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive ATV+COBI+FTC/TDF until COBI tablets become commercially available, or until Gilead Sciences elects to terminate the study.

Conditions

HIV-1 Infection

Keywords

HIV; HIV-1; Antiretroviral Treatment-Naive

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24

  The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the missing = failure method, where participants with missing data were considered to have failed to achieve the endpoint.

  Week 24

Secondary Outcomes (5)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48

  Week 48

• Change From Baseline in HIV-1 RNA at Week 24

  Baseline to Week 24

• Change From Baseline in HIV-1 RNA at Week 48

  Baseline to Week 48

• Change From Baseline in CD4 Cell Count at Week 24

  Baseline to Week 24

• Change From Baseline in CD4 Cell Count at Week 48

  Baseline to Week 48

Study Arms (2)

ATV+COBI+FTC/TDF

EXPERIMENTAL

COBI + RTV placebo +ATV+FTC/TDF for 48 weeks

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

ATV+RTV+FTC/TDF

ACTIVE COMPARATOR

RTV + COBI placebo +ATV+FTC/TDF for 48 weeks

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 soft gelatin capsule 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
• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
• No prior use of any approved or experimental anti-HIV drug
• Normal ECG (or if abnormal, determined by the investigator to be not clinically significant)
• Adequate renal function (estimated glomerular filtration rate ≥ 80 mL/min according to the Cockcroft-Gault formula)
• Hepatic transaminases ≤ 2.5 × upper limit of normal
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function (absolute neutrophil count ≥ 1000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
• Cluster of differentiation 4 (CD4) cell count \> 50 cells/µL
• Serum amylase ≤ 1.5 × ULN (subjects with serum amylase \>1.5 × ULN remained eligible if serum lipase is ≤ 1.5 × ULN)
• Normal thyroid-stimulating hormone
• Negative serum pregnancy test (females of childbearing potential only)
• 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 drugs
• Age ≥ 18 years
• Life expectancy ≥ 1 year

You may not qualify if:

• New AIDS-defining condition diagnosed within the 30 days prior to screening
• Documented drug resistance to nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or primary PI resistance mutation(s)
• Hepatitis B surface antigen positive
• Hepatitis C antibody positive
• Participants experiencing cirrhosis
• Participants experiencing ascites
• Participants experiencing encephalopathy
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Vaccinated within 90 days of study dosing
• History or family history of Long QT Syndrome or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30 years
• Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
• Prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) interval at screening (eg, a prolongation of the QTcF interval of greater than 450 msec for males and greater than 470 msec for females)
• PR interval greater than or equal to 200 msec or less than or equal to 120 msec on ECG at screening
• QRS greater than or equal to 120 msec on ECG at screening

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (31)

Southwest Center for HIV/AIDS

Phoenix, Arizona, 85006, United States

Location

Health for Life Clinic, PLLC

Little Rock, Arkansas, 72207, United States

Location

AIDS Healthcare Foundation-Research Center

Beverly Hills, California, 90804, United States

Location

The Living Hope Foundation

Long Beach, California, 90813, United States

Location

Peter J. Ruane, MD, Inc.

Los Angeles, California, 90036, United States

Location

Orange Coast Medical Group

Newport Beach, California, 92663, United States

Location

David J. Shamblaw, MD Inc.

San Diego, California, 92103, United States

Location

Metropolis Medical

San Francisco, California, 94115, United States

Location

Denver Infectious Disease Consultants, PLLC

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

Capital Medical Associates PC

Washington D.C., District of Columbia, 20036, United States

Location

Gary Richmond, MD, PA, Inc.

Fort Lauderdale, Florida, 33316, United States

Location

Wohlfeiler, Piperato and Associates, LLC

Miami Beach, Florida, 33139, United States

Location

ValuehealthMD, LLC

Orlando, Florida, 32806, United States

Location

St. Joseph's Comprehensive Research Institute

Tampa, Florida, 33614, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30308, United States

Location

Infectious Disease Specialists of Atlanta (IDSA)

Decatur, Georgia, 30033, United States

Location

Northstar Medical Center

Chicago, Illinois, 60657, United States

Location

Chase Brexton Health Services, Inc.

Baltimore, Maryland, 21201, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Central West Healthcare

St Louis, Missouri, 63108, United States

Location

Southampton Healthcare, Inc.

St Louis, Missouri, 63139, United States

Location

Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

Southwest C.A.R.E. Center

Santa Fe, New Mexico, 87505, United States

Location

Rosedale Infectious Diseases

Huntersville, North Carolina, 28078, United States

Location

Nicholaos Bellos, MD, PA

Dallas, Texas, 75204, United States

Location

AIDS Arms/ Peabody Health Center

Dallas, Texas, 75215, United States

Location

Gordon E. Crofoot, MD, PA

Houston, Texas, 77098, United States

Location

Therapeutic Concepts, P.A.

Houston, Texas, 77478, United States

Location

TribalMed

Seattle, Washington, 98103, United States

Location

Related Publications (1)

• Elion R, Cohen C, Gathe J, Shalit P, Hawkins T, Liu HC, Mathias AA, Chuck SL, Kearney BP, Warren DR; GS-US-216-0105 Study Team. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. AIDS. 2011 Sep 24;25(15):1881-6. doi: 10.1097/QAD.0b013e32834b4d48.

  PMID: 21811136 RESULT

MeSH Terms

Interventions

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

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

• Marshall Fordyce, MD

  Gilead Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2009
• First Posted: May 4, 2009
• Study Start: May 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2015
• Last Updated: February 15, 2016
• Results First Posted: October 28, 2014

Record last verified: 2016-01

Locations

US (31)