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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: darunavir
* Drug: cobicistat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fasted condition) | Drug: darunavir<br>* Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat<br>Drug: cobicistat<br>* Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir<br>|
| Experimental: Treatment B<br>Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fasted condition). | Drug: darunavir<br>* Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat<br>Drug: cobicistat<br>* Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir<br>|
| Experimental: Treatment C<br>Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fed condition - standardized breakfast). | Drug: darunavir<br>* Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat<br>Drug: cobicistat<br>* Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir<br>|
| Experimental: Treatment D<br>Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - standardized breakfast). | Drug: darunavir<br>* Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat<br>Drug: cobicistat<br>* Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir<br>|
| Experimental: Treatment E<br>Single-dose co-administration of the fixed dose combination darunavir/cobicistat 800/150-mg (under fasted condition). | Drug: darunavir<br>* Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat<br>Drug: cobicistat<br>* Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir<br>|
| Experimental: Treatment F<br>Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - high-fat breakfast). | Drug: darunavir<br>* Type=exact number, unit=mg, number=400, form=tablet, route=oral. Two tablets as a single dose or a tablet in combination with cobicistat<br>Drug: cobicistat<br>* Type=exact number, unit=mg, number=150, form=tablet, route=oral. One tablet as a single dose or a tablet in combination with darunavir<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cobicistat, Bioequivalence, Fixed dose combination, Pharmacokinetics, Human immunodeficiency virus, Protease inhibitor, Healthy participants, Darunavir