Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
Condition: Acquired Immunodeficiency Syndrome; HIV Infections
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Intervention: COBI; DRV; NRTIs
Intervention description: 150 mg tablet administered orally with food once daily; 800 mg (2 x 400 mg tablets) administered orally with food once daily; Participants will receive 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) selected by the investigator after resistance testing at screening and administered according to prescribing information. NRTIs may include emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), zidovudine+FTC/TDF, abacavir (ABC)+TDF, ABC+FTC/TDF, ABC+lamivudine (3TC), or didanosine (DDI)+FTC.
Intervention MeSH terms: Darunavir; Cobicistat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 314.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV-1; HIV; Treatment Naïve; Treatment Experienced

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.