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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: darunavir; Drug: cobicistat

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).

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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).	Up to 27 Days
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)	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).	Up to 27 Days
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)	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.	Up to 27 Days
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)	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).	Up to 27 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerabilty	Safety and tolerability of darunavir/cobicistat co-administration in healthy participants will be assessed by number of participants with adverse events.	Up to 27 Days
Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet	Plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet under fed conditions in healthy participants will be evaluated.	Up to 27 Days
Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents	Plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents under fed conditions in healthy participants will be evaluated.	Up to 27 Days
Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet	Plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet under fasted conditions in healthy participants will be evaluated.	Up to 27 Days
Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents	Plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents under fasted conditions in healthy participants will be evaluated	Up to 27 Days
Evaluation of effect of a high-fat meal on darunavir and cobicistat pharmacokinetics relative to the fasted state	Effects of a high-fat meal on darunavir and cobicistat pharmacokinetics relative to the fasted state will be evaluated.	Up to 27 Days

Collaborators and Investigators

• Sponsor: Janssen R&D Ireland

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: June 12, 2012
• First Submitted That Met QC Criteria: June 13, 2012
• First Posted (Estimate): June 14, 2012

Study Record Updates

• Last Update Posted (Estimate): March 4, 2013
• Last Update Submitted That Met QC Criteria: March 1, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Human immunodeficiency virus; Pharmacokinetics; Bioequivalence; Healthy participants; Darunavir; Cobicistat; Fixed dose combination; Protease inhibitor
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Cobicistat; Darunavir
• Other Study ID Numbers: CR100699; TMC114IFD1003 (Other Identifier: Janssen R&D Ireland); 2012-000273-23 (EudraCT Number)