MedPath

Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults

Phase 3
Completed
Conditions
Acquired Immunodeficiency Syndrome
HIV Infections
Interventions
Drug: DRV
Drug: NRTIs
Registration Number
NCT01440569
Lead Sponsor
Gilead Sciences
Brief Summary

This study is to evaluate the safety and tolerability of cobicistat-boosted darunavir plus two fully active nucleoside analogue reverse transcriptase inhibitors in HIV 1 infected, antiretroviral treatment-naive and treatment-experienced adults with no darunavir (DRV) resistance-associated mutations.

After the Week 48 Visit, participants will be given the option to participate in an open-label rollover phase to receive cobicistat and attend visits every 12 weeks until it becomes commercially available, or until Gilead Sciences elects to terminate development of cobicistat.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
314
Inclusion Criteria
  • Adult ≥ 18 years males or non-pregnant females
  • Ability to understand and sign a written informed consent form
  • General medical condition that does not interfere with the assessments and the completion of the trial
  • Treatment Naive: No prior use of any approved or investigational antiretroviral drug for any length of time OR
  • Treatment Experienced: Stable antiretroviral regimen for at least 12 weeks prior to screening
  • Plasma HIV-1 RNA levels ≥ 1000 copies/mL at Screening
  • Screening genotype report shows full sensitivity to two nucleoside analogue reverse transcriptase inhibitors (NRTIs) and no darunavir resistance-associated mutations
  • Normal electrocardiogram (ECG)
  • Hepatic transaminases ≤ 2.5 × upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 mg/dL
  • Adequate hematologic function
  • Serum amylase ≤ 2 × ULN and serum lipase ≤ 3 × ULN
  • Adequate renal function: Estimated glomerular filtration rate ≥ 80 mL/min
  • Females of childbearing potential must agree to utilize protocol-recommended methods of contraception, or be 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.
  • Male subjects must agree to utilize protocol-recommended methods of contraception during heterosexual intercourse from the Screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product or be nonheterosexually active, practice sexual abstinence, or be vasectomized.
Exclusion Criteria
  • Previous or current use of darunavir
  • A new AIDS-defining condition diagnosed within the 30 days prior to Screening
  • Females who are breastfeeding
  • Positive serum pregnancy test (if female of childbearing potential)
  • Proven or suspected acute hepatitis in the 30 days prior to study entry
  • Subjects receiving drug treatment for hepatitis C virus (HCV), or subjects who are anticipated to receive treatment for HCV during the course of the study
  • Have a history of ongoing active liver disease or experiencing decompensated cirrhosis irrespective of liver enzyme levels
  • Have an implanted defibrillator or pacemaker
  • Current alcohol or substance use that may interfere with subject study compliance
  • A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma
  • Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
  • Participation in any other clinical trial
  • Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements.
  • Subjects receiving ongoing therapy with any of the medications, including drugs not to be used with cobicistat, darunavir, or investigator selected NRTIs; or subjects with any known allergies to cobicistat tablets, darunavir tablets or contraindications for the 2 NRTIs as part of the regimen.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
COBI-boosted DRVCOBIParticipants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase.
COBI-boosted DRVDRVParticipants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase.
COBI-boosted DRVNRTIsParticipants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24Up to 24 weeks
Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 24Up to 24 weeks
Change From Baseline in CD4+ Cell Count at Week 48Baseline; Week 48
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 48Up to 48 weeks
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis)Week 24
Change From Baseline in CD4+ Cell Count at Week 24Baseline; Week 24
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis)Week 48

Trial Locations

Locations (49)

Gary J. Richmond,M.D., P.A.

🇺🇸

Fort Lauderdale, Florida, United States

Atlanta ID group

🇺🇸

Atlanta, Georgia, United States

Mercer University

🇺🇸

Macon, Georgia, United States

Howard Brown Health Center

🇺🇸

Chicago, Illinois, United States

Community Research Initiative of New England

🇺🇸

Boston, Massachusetts, United States

Be Well Medical Center

🇺🇸

Berkley, Michigan, United States

North Shore University Hospital / Division of Infectious Diseases

🇺🇸

Manhasset, New York, United States

University of PA

🇺🇸

Philadelphia, Pennsylvania, United States

Trinity Health and Wellness Center/AIDS Arms, Inc.

🇺🇸

Dallas, Texas, United States

Southwest Infectious Disease Clinical Research, Inc.

🇺🇸

Dallas, Texas, United States

Therapeutic Concepts, PA

🇺🇸

Houston, Texas, United States

Gordon Crofoot MD, PA

🇺🇸

Houston, Texas, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

La Playa Medical Group and Clinical Research

🇺🇸

San Diego, California, United States

Philadelphia FIGHT

🇺🇸

Philadelphia, Pennsylvania, United States

Central Texas Clinical Research

🇺🇸

Austin, Texas, United States

Miriam Hospital

🇺🇸

Providence, Rhode Island, United States

Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)

🇺🇸

Annandale, Virginia, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

HIV Program Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Spectrum Medical Group

🇺🇸

Phoenix, Arizona, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Peter J Ruane MD Inc.

🇺🇸

Los Angeles, California, United States

Long Beach Education and Research Consultants, PC

🇺🇸

Long Beach, California, United States

Anthony Mills MD Inc

🇺🇸

Los Angeles, California, United States

Stanford University

🇺🇸

Palo Alto, California, United States

Kaiser Permanente Medical Group

🇺🇸

Sacramento, California, United States

Metropolis Medical

🇺🇸

San Francisco, California, United States

Apex Research LLC

🇺🇸

Denver, Colorado, United States

Dupont Circle Physician's Group

🇺🇸

Washington, District of Columbia, United States

Whitman-Walker Health

🇺🇸

Washington, District of Columbia, United States

Midway Immunology and Research Center

🇺🇸

Fort Pierce, Florida, United States

Wohlfeiler, Piperato and Associates, LLC

🇺🇸

Miami Beach, Florida, United States

Orlando Immunology Center

🇺🇸

Orlando, Florida, United States

St. Joseph's Comprehensive Research Institute

🇺🇸

Tampa, Florida, United States

Infectious Disease Specialists of Atlanta

🇺🇸

Decatur, Georgia, United States

Hawaii Center for AIDS, University of Hawaii

🇺🇸

Honolulu, Hawaii, United States

Northstar Medical Center

🇺🇸

Chicago, Illinois, United States

Johns Hopkins University

🇺🇸

Lutherville, Maryland, United States

Central West Clinical Research Inc

🇺🇸

St. Louis, Michigan, United States

South Jersey Infectious Disease

🇺🇸

Somers Point, New Jersey, United States

Saint Michael's Medical Center

🇺🇸

Newark, New Jersey, United States

Greiger Clinic

🇺🇸

Mt. Vernon, New York, United States

Beth Israel Medical Center

🇺🇸

New York, New York, United States

Carolinas Medical Center-Myer's Park Infectious Disease Clinic

🇺🇸

Charlotte, North Carolina, United States

Wake Forest University Health Services

🇺🇸

Winston-Salem, North Carolina, United States

Tarrant County Infectious Disease

🇺🇸

Fort Worth, Texas, United States

DCOL Center for Clinical Research

🇺🇸

Longview, Texas, United States

Clinical Research Puerto Rico

🇵🇷

San Juan, Puerto Rico

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