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

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:

MedlinePlus related topics: Malnutrition

Drug Information available for: Darunavir Darunavir ethanolate Cobicistat

U.S. FDA Resources

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 (Adult)
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


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 Cobicistat HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action	Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 29, 2016