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

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01619527
• Other study ID #: CR100699
• Secondary ID: TMC114IFD1003201
• Status: Completed
• Phase: Phase 1
• First received: June 12, 2012
• Last updated: March 1, 2013
• Start date: April 2012
• Est. completion date: August 2012

Study information

• Verified date: March 2013
• Source: Janssen R&D Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Participants

Intervention

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
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen R&D Ireland

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No