SSAT067 PK of Atazanavir/Cobicistat and Darunavir/Cobicistat
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to look at the levels of three HIV medications: atazanavir,
      darunavir and cobicistat in the blood after drug intake has been stopped, in order to
      understand how long these drugs persist in the blood. The study will specifically look at
      blood levels of these three drugs after taking them every day for 10 days. Participants will
      take Evotaz (atazanavir and cobicistat) on a first stage and Rezolsta (darunavir and
      cobicistat) on a second stage.

      If the participants decide to take part, the duration of the study will be up to 33 days plus
      a screening visit which will take place up to 28 days prior to the start of the study, and a
      follow up visit, which takes place 7 to 14 days after the last dose of study medication. This
      study is not randomised which means that all participants will receive all study medications
      in the same order.

      The participant and the study doctor will know which study medications the participant is
      taking at all times during the study.
    

Detailed description: 
      Protocol Number: SSAT067

      EudraCT Number: 2015-002956-28

      Name of Investigational Product: Evotaz®, Rezolsta®

      Name of active ingredients: Atazanavir, darunavir and cobicistat

      Study title: Steady-state Pharmacokinetics of Atazanavir/Cobicistat and Darunavir/Cobicistat
      Once Daily Over 72 Hours in Healthy Volunteers

      Phase of study: Phase I

      Objectives:

      Primary:

      -To assess the steady-state pharmacokinetics of atazanavir/cobicistat and
      darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers.

      Secondary:

        -  To assess the inter subject variability in atazanavir, darunavir and cobicistat plasma
           concentrations over 72 hours

        -  To assess the safety and tolerability of atazanavir/cobicistat and darunavir/cobicistat
           over 10 days of administration to healthy volunteers

        -  To investigate the association between genetic polymorphisms in drug disposition genes
           and drug exposure

      Study design: 33 days (excluding screening and follow up), open label, pharmacokinetic study.

      Indication: Not applicable

      Methodology: Measurements of steady state pharmacokinetic profiles of plasma
      atazanavir/cobicistat and darunavir/cobicistat in male and female healthy volunteers.

      Planned sample size: Up to 30 male and female healthy volunteers will be enrolled at baseline
      in order to achieve 16 completing the study

      Summary of eligibility criteria: Healthy participants as determined by medical history,
      physical examination, 12-lead electrocardiogram, and clinical laboratory evaluations will be
      eligible to participate in the study. Women of childbearing potential must not be nursing or
      pregnant. Women of childbearing potential must have a negative pregnancy test at screening.

      Number of study centres: One

      Duration of treatment: 33 days (excluding screening and follow up visits)

      Dose and route of administration: All participants will be administered Evotaz®) (atazanavir
      300mg + cobicistat 150mg) once daily for 10 days, undergo a ten-day wash out period and then
      take Rezolsta® (darunavir 800mg + cobicistat 150mg) once daily for 10 days.

      Criteria for evaluation:

        -  Pharmacokinetic parameters of atazanavir/cobicistat will be evaluated on blood drawn on
           day 10 at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hours post dose and days 11
           to 13 (up to 72 hours post dose).

        -  Pharmacokinetic parameters of darunavir/cobicistat will be evaluated on blood drawn on
           day 30 at 0 (pre-dose), 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hours post dose and days 31
           to 33 (up to 72 hours post dose).

        -  Safety and tolerability of medications will also be assessed by questions, physical
           examination and laboratory parameters. These will be performed at regular intervals
           during the drug study.

      Primary Endpoint:

      -Steady state plasma concentrations of atazanavir/cobicistat and darunavir/cobicistat up to
      72 hours post-dose.

      Secondary End point:

        -  Safety and tolerability of the studied drugs over 10 days of administration.

        -  Relationship between genetic polymorphisms and exposure to the studied drugs.
    

Intervention name(s): Evotaz; Rezolsta
Intervention type(s): Drug; Drug
Intervention description(s): All participants will be administered Evotaz®) (atazanavir 300mg + cobicistat 150mg) once daily for 10 days; All participants will be administered Rezolsta® (darunavir 800mg + cobicistat 150mg) once daily for 10 days.
Other intervention name(s): atazanavir and cobicistat; darunavir and cobicistat
Intervention MeSH terms: Atazanavir Sulfate; Darunavir; Cobicistat
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment