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

ClinicalTrials.gov processed this record on October 23, 2014