A Study to Assess the Bioequivalence of Darunavir When Co-Administrated With Cobicistat Under Fed and Fasted Conditions

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01619527
First received: June 12, 2012
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to evaluate the single-dose pharmacokinetics and bioequivalence of darunavir 800 mg when administered as a fixed dose combination relative to 2 x 400 mg tablets of the commercial tablet formulation, in the presence of 150 mg cobicistat, (under fed and fasted conditions) in healthy participants.


Condition Intervention Phase
Healthy Participants
Drug: darunavir
Drug: cobicistat
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Dose, Open-Label, 3-Panel, Randomized, Pivotal Crossover Study to Assess the Bioequivalence of Darunavir When Co-Administrated With Cobicistat as Either a Fixed Dose Combination Tablet (G006) or as Single Agents Under Fed and Fasted Conditions in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • Comparison of maximum plasma analyte concentration (Cmax) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg) [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    The pharmacokinetic parameter (Cmax) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).

  • Comparison of last observed measurable analyte concentration (Clast) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg) [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    The pharmacokinetic parameter (Clast) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).

  • Comparison of actual sampling time to reach the maximum plasma analyte concentration (tmax) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg) [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    The pharmacokinetic parameter (tmax) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg) for assessment of bioequivalance.

  • Area under curve from time of administration up to the last time point with a measurable plasma analyte concentration (AUClast) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg) [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    The pharmacokinetic parameter (AUClast) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).


Secondary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerabilty [ Time Frame: Up to 27 Days ] [ Designated as safety issue: Yes ]
    Safety and tolerability of darunavir/cobicistat co-administration in healthy participants will be assessed by number of participants with adverse events.

  • Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet under fed conditions in healthy participants will be evaluated.

  • Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents under fed conditions in healthy participants will be evaluated.

  • Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet under fasted conditions in healthy participants will be evaluated.

  • Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    Plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents under fasted conditions in healthy participants will be evaluated

  • Evaluation of effect of a high-fat meal on darunavir and cobicistat pharmacokinetics relative to the fasted state [ Time Frame: Up to 27 Days ] [ Designated as safety issue: No ]
    Effects of a high-fat meal on darunavir and cobicistat pharmacokinetics relative to the fasted state will be evaluated.


Enrollment: 133
Study Start Date: April 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fasted condition)
Drug: darunavir
Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat
Drug: cobicistat
Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir
Experimental: Treatment B
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fasted condition).
Drug: darunavir
Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat
Drug: cobicistat
Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir
Experimental: Treatment C
Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fed condition - standardized breakfast).
Drug: darunavir
Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat
Drug: cobicistat
Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir
Experimental: Treatment D
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - standardized breakfast).
Drug: darunavir
Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat
Drug: cobicistat
Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir
Experimental: Treatment E
Single-dose co-administration of the fixed dose combination darunavir/cobicistat 800/150-mg (under fasted condition).
Drug: darunavir
Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat
Drug: cobicistat
Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir
Experimental: Treatment F
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - high-fat breakfast).
Drug: darunavir
Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat
Drug: cobicistat
Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir

Detailed Description:

This is a randomized (the study drug is assigned by chance), open-label (all people know the identity of the intervention), 3-panel, single-center, single-dose, crossover (method used to switch patients from one treatment arm to another in a clinical trial) study in 134 healthy adult participants. The study consists of 3 phases including a screening phase of approximately 3 weeks (Days -21 to -1) followed by an open-label treatment phase consisting of 3 panels with 2 single-dose treatment sessions of 5 days each (Days -1 to 4) separated by a washout period of at least 7 days, and a follow-up period occurring 7 to 10 days after last intake of study drugs. The study consists of 3 panels. In each panel participants will be randomly be assigned to 1 of 2 treatment sequences (AB or BA for Panel 1; CD or DC for Panel 2; and EF or FE for Panel 3). Participants will receive either single-dose darunavir 800 mg as 2 x 400 mg tablets and cobicistat 150 mg tablet or single-dose darunavir/cobicistat 800/150 mg as tablet in each panel (under fed and fasted conditions).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant should be healthy on the basis of physical examination, medical history, vital signs, and electrocardiogram and clinical laboratory tests performed at screening
  • Have a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.5 to 30.0 kg/m2, extremes included
  • Men and women must agree to use a highly effective method of birth control

Exclusion Criteria:

  • Has a positive HIV-1 or HIV-2 test at screening
  • Has a Hepatitis A, B or C infection (confirmed by hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody, respectively) at screening
  • Has any history of renal insufficiency
  • Has a history of significant skin reactions or any history of allergies to drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01619527

Locations
Belgium
Merksem, Belgium
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01619527     History of Changes
Other Study ID Numbers: CR100699, TMC114IFD1003, 2012-000273-23
Study First Received: June 12, 2012
Last Updated: March 1, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
United States: Food and Drug Administration

Keywords provided by Janssen R&D Ireland:
Healthy participants
Darunavir
Cobicistat
Bioequivalence
Fixed dose combination
Pharmacokinetics
Human immunodeficiency virus
Protease inhibitor

Additional relevant MeSH terms:
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014