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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
St Stephen's Centre, Chelsea and Westminster Hospital NHS Foundation Trust
London, London, United Kingdom
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers as measured by Ctrough
Trough concentration (Ctrough) is defined as the concentration at 24 hours after the observed drug dose
Time frame: Days 10 and 30
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by Cmax
Cmax defined as the maximum observed plasma concentration.
Time frame: Days 10 and 30
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by t1/2
t1/2 = Elimination half-life
Time frame: Days 10 and 30
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by Tmax
Tmax = time point at Cmax
Time frame: Days 10 and 30
To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by total drug exposure
Total drug exposure is expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h) and 0-72 hours (AUC0-72h)
Time frame: Days 10 and 30
To assess the inter subject variability in atazanavir, darunavir and cobicistat plasma concentrations over 72 hours
Time frame: Days 10 and 30
To assess the safety and tolerability of the studied drugs over 10 days in HIV negative healthy volunteers, assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events.
Time frame: Screening (day -28) to follow-up visit (day 41-54)
To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by Peak plasma concentration (Cmax)
Time frame: Day 1
To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by trough concentration (Ctrough)
Time frame: Day 1
To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by Area under the plasma concentration versus time curve (AUC)
Time frame: Day 1
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.