Clinical trial NCT01440569: Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
Official title: A Phase 3b, Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Cobicistat-boosted Darunavir Plus Two Fully Active Nucleoside Reverse Transcriptase Inhibitors in HIV-1 Infected, Antiretroviral Treatment-Naïve and -Experienced Adults With No Darunavir Resistance-associated Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Keywords: HIV-1
HIV
Treatment Naïve
Treatment Experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2011-09-26
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis)
timeFrame: Week 24
measure: Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis)
timeFrame: Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48
measure: Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 24
timeFrame: Up to 24 weeks
measure: Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 48
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Long Beach
country: United States
facility: Long Beach Education and Research Consultants, PC
state: California
city: Los Angeles
country: United States
facility: Peter J Ruane MD Inc.
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD Inc
state: California
city: Palo Alto
country: United States
facility: Stanford University
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: Denver
country: United States
facility: Apex Research LLC
state: Colorado
city: Washington
country: United States
facility: Dupont Circle Physician's Group
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Health
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond,M.D., P.A.
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: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID group
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Center for AIDS, University of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Chicago
country: United States
facility: Northstar Medical Center
state: Illinois
city: Lutherville
country: United States
facility: Johns Hopkins University
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 Hospital
state: Michigan
city: St. Louis
country: United States
facility: Central West Clinical Research Inc
state: Michigan
city: Minneapolis
country: United States
facility: HIV Program Hennepin County Medical Center
state: Minnesota
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital / Division of Infectious Diseases
state: New York
city: Mt. Vernon
country: United States
facility: Greiger Clinic
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center-Myer's Park Infectious Disease Clinic
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Services
state: North Carolina
city: Philadelphia
country: United States
facility: University of PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Trinity Health and Wellness Center/AIDS Arms, Inc.
state: Texas
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
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon Crofoot MD, PA
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Marshall Fordyce, MD
role: STUDY_DIRECTOR
References: