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

Phase 3

Completed

Conditions: Acquired Immunodeficiency Syndrome
HIV Infections

Interventions: Drug: COBI
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

Group	Intervention	Description
COBI-boosted DRV	COBI	Participants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase.
COBI-boosted DRV	DRV	Participants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase.
COBI-boosted DRV	NRTIs	Participants 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

Name	Time	Method
Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24	Up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 24	Up to 24 weeks
Change From Baseline in CD4+ Cell Count at Week 48	Baseline; 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 48	Up 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 24	Baseline; Week 24
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis)	Week 48

Trial Locations

Locations (49): Spectrum Medical Group
🇺🇸
Phoenix, Arizona, United States
Long Beach Education and Research Consultants, PC
🇺🇸
Long Beach, California, United States
Peter J Ruane MD Inc.
🇺🇸
Los Angeles, 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
La Playa Medical Group and Clinical Research
🇺🇸
San Diego, 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
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Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States