Clinical trial NCT01619527: A Study to Assess the Bioequivalence of Darunavir When Co-Administrated With Cobicistat Under Fed and Fasted Conditions
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Healthy participants
Darunavir
Cobicistat
Bioequivalence
Fixed dose combination
Pharmacokinetics
Human immunodeficiency virus
Protease inhibitor
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2012-06-14
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: 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)
timeFrame: Up to 27 Days
measure: 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)
timeFrame: Up to 27 Days
measure: 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)
timeFrame: Up to 27 Days
measure: 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)
timeFrame: Up to 27 Days
Secondary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerabilty
timeFrame: Up to 27 Days
measure: Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet
timeFrame: Up to 27 Days
measure: Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents
timeFrame: Up to 27 Days
measure: Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet
timeFrame: Up to 27 Days
measure: Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents
timeFrame: Up to 27 Days
measure: Evaluation of effect of a high-fat meal on darunavir and cobicistat pharmacokinetics relative to the fasted state
timeFrame: Up to 27 Days
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References: