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Clinical Trials

MainTitle

SSAT067 PK of Atazanavir/Cobicistat and Darunavir/Cobicistat

This study has been completed
Sponsor
St Stephens Aids Trust

Collaborator
Bristol-Myers Squibb

Information provided by (Responsible Party)
St Stephens Aids Trust
ClinicalTrials.gov Identifier
NCT02589158

First received: October 27, 2015
Last updated: March 21, 2016
Last Verified: March 2016
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV

Drug : Evotaz
Drug : Rezolsta
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Steady-state Pharmacokinetics of Atazanavir/Cobicistat and Darunavir/Cobicistat Once Daily Over 72 Hours in Healthy Volunteers

Further study details as provided by St Stephens Aids Trust:

Primary Outcome Measures

  • To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers as measured by Ctrough [ Time Frame: Days 10 and 30 ]
    Trough concentration (Ctrough) is defined as the concentration at 24 hours after the observed drug dose
  • To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by Cmax [ Time Frame: Days 10 and 30 ]
    Cmax defined as the maximum observed plasma concentration.
  • 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 [ Time Frame: Days 10 and 30 ]
    t1/2 = Elimination half-life
  • To assess the steady-state pharmacokinetics of atazanavir/cobicistat and darunavir/cobicistat over 72 hours, in HIV negative healthy volunteers, as measured by Tmax [ Time Frame: Days 10 and 30 ]
    Tmax = time point at Cmax
  • 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 [ Time Frame: Days 10 and 30 ]
    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)
Secondary Outcome Measures:
  • 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 ]

Enrollment: 16
Study Start Date: November 2015
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Evotaz®, washout, then Rezolsta®
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.
Drug: Evotaz

All participants will be administered Evotaz®) (atazanavir 300mg + cobicistat 150mg) once daily for 10 days

Other Name: atazanavir and cobicistat
Drug: Rezolsta

All participants will be administered Rezolsta® (darunavir 800mg + cobicistat 150mg) once daily for 10 days.

Other Name: darunavir and cobicistat

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.
    onship between genetic polymorphisms and exposure to the studied drugs.

    Eligibility

    Eligibility

    Ages Eligible for Study: 18 Years to 65 Years  
    Sexes Eligible for Study: All  
    Accepts Healthy Volunteers: Yes  

    Criteria

    Inclusion Criteria:

    1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
    2. Male or non-pregnant, non-lactating females
    3. Between 18 to 65 years, inclusive
    4. Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive
    5. ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.
    6. Women of childbearing potential (WOCBP - definition in Appendix 5) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 4 weeks after the study

    A female may be eligible to enter and participate in the study if she:
    1. is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
    2. is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
  • Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications;
  • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
  • Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see protocol appendix 5 for an example listing of approved IUDs);
  • Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject;
  • Approved hormonal contraception (see protocol appendix 5 for a listing of examples of approved hormonal contraception) plus male condom;
  • Any other method with published data showing that the expected failure rate is <1% per year.
  • Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of IP.
  • Men who have partners who are women of childbearing potential (WOCBP - definition in Appendix 5) must be using an adequate method of contraception to avoid pregnancy in their partner throughout the study and for a period of at least 4 weeks after the study (see inclusion criteria 6)
  • Willing to consent to their personal details being entered onto the TOPS database
  • Willing to provide proof of identity by photographic ID at screen and any subsequent visit
  • Registered with a GP in the UK

  • Exclusion Criteria:
  • Any clinically significant acute or chronic medical illness
  • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
  • Positive blood screen for hepatitis B surface antigen or C antibody
  • Positive blood screen for HIV-1 or 2 by antibody/antigen assay
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • History or presence of allergy to darunavir, atazanavir cobicistat or excipients (sodium methyl parahydroxybenzoate, lactulose, Hypromellose Colloidal silicon dioxide, Silicified microcrystalline cellulose Crospovidone, Magnesium stearate, Polyvinyl alcohol- partially hydrolysed, Macrogol 3350,Titanium dioxide, Talc, Iron oxide red, Iron oxide black, Lactose monohydrate, Magnesium stearate, Gelatine Yellow iron oxide, Indigocarmin (E132), White ink, Shellac,Titanium dioxide (E171), Ammonium hydroxide, Propylene glycol , Simethicone, Hypromellose, Polyvinyl alcohol- partially hydrolysed, Macrogol 3350)
  • Current or recent (within 3 months) gastrointestinal disease
  • Known intolerance of lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
  • Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
  • Exposure to any investigational drug (or placebo) or participation in a clinical study involving the donation of blood samples within 3 months of first dose of study drug
  • Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
  • Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 4 weeks after the end of the treatment period

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02589158

    Locations

    United Kingdom
    St Stephen's Centre, Chelsea and Westminster Hospital NHS Foundation Trust
    London, United Kingdom, SW10 9NH

    Sponsors and Collaborators

    St Stephens Aids Trust
    Bristol-Myers Squibb

    Investigators

    Principal Investigator: Marta Boffito St Stephen's AIDS Trust
    More Information

    More Information


    Responsible Party: St Stephens Aids Trust  
    ClinicalTrials.gov Identifier: NCT02589158   History of Changes  
    Other Study ID Numbers: SSAT067  
    Study First Received: October 27, 2015  
    Last Updated: March 21, 2016  

    Additional relevant MeSH terms:
    Darunavir
    Atazanavir Sulfate
    Cobicistat

    ClinicalTrials.gov processed this data on October 20, 2017
    This information is provided by ClinicalTrials.gov.