The purpose of this study is to evaluate the pharmacokinetics and relative bioavailability of Emtricitabine (FTC) and Tenofovir alafenamide (TAF) when administered as a fixed-dose combination (FDC) with darunavir (DRV) and cobicistat (COBI) (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) relative to administration as an FDC with Elvitegravir (EVG) and COBI (Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide), under fed conditions in healthy subjects (Panel 1); evaluate the single-dose pharmacokinetics and relative bioavailability of DRV, COBI, FTC and TAF when administered as an FDC (D/C/F/TAF) or as separate agents (D+C+FTC/TAF), under fed conditions in healthy subjects (Panel 2) and to evaluate the impact of food (fasting or high-fat breakfast) on the single-dose pharmacokinetics of DRV, COBI, FTC, and TAF when administered as an FDC (D/C/F/TAF) in healthy subjects (Panel 3).
This is a Phase 1, 3-panel, open-label, randomized, 2-way crossover study in healthy subjects. Healthy subjects will be divided over 3 panels (Panel 1, 2 and 3). Subjects will be randomized within each panel. In each panel, during 2 subsequent sessions, each subject will receive 2 treatments (Treatments A and B in Panel 1, Treatments C and D in Panel 2, and Treatments E and F in Panel 3). Each treatment is defined as follows: Treatment A: single oral dose of D/C/F/TAF 800/150/200/10 milligram (mg) as FDC tablet under fed conditions (standardized regular breakfast); Treatment B: single oral dose of E/C/F/TAF 150/150/200/10 mg as FDC tablet under fed conditions; Treatment C: single oral dose of D/C/F/TAF 800/150/200/10 mg as FDC tablet under fed conditions; Treatment D: single oral dose of DRV as 800-mg tablet, FTC/TAF as 200/10 mg tablet and COBI 150 mg tablet under fed conditions. Treatment E: single oral dose of D/C/F/TAF 800/150/200/10 mg as FDC tablet, under fasted condition and Treatment F: single oral dose of D/C/F/TAF 800/150/200/10 mg tablet, with a standardized high-fat breakfast. Each treatment will be separated by a washout period of at least 7 days. Primarily pharmacokinetic parameters will be assessed. Subjects' safety will be assessed throughout.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
72
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
A tablet containing EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
A tablet containing Darunavir (DRV) 800 mg will be administered.
A tablet containing Emtricitabine (FTC) 200 mg and Tenofovir alafenamide (TAF) 10 mg will be administered.
A tablet containing cobicistat (COBI) 150 mg will be administered.
High-fat breakfast will be administered.
Standardized regular breakfast will administered.
Unnamed facility
Antwerp, Belgium
Maximum Observed Plasma Concentration (Cmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The Cmax is the maximum observed plasma concentration.
Time frame: Up to 72 Hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Time frame: Up to 72 Hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Time frame: Up to 72 Hours after study drug administration
Number of Subjects with Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration
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