The purpose of this study is to evaluate the single-dose pharmacokinetics and pivotal bioequivalence of Darunavir (DRV) 800 milligram (mg), Emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg when administered as a fixed-dose combination (FDC) (D/C/F/TAF) relative to the separate agents (DRV 800 mg tablet formulation and FTC/TAF 200/10 mg FDC) in the presence of 150 mg Cobicistat (COBI), under fed conditions, in healthy participants.
This is a Phase 1, open-label, randomized, 2-way crossover study in 96 healthy adult participants. The study consists of 2 treatment sessions. Participants will receive in one session a single dose of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 milligram (mg) tablets as fixed-dose combination (FDC) and in another session Darunavir (DRV) as 1x 800 mg tablet, Emtricitabine/ tenofovir alafenamide (FTC/TAF) as 1x 200/10 mg FDC tablet, and Cobicistat (COBI) 150 mg as 1x 150 mg tablet all under fed conditions. Treatment sessions will be separated by a washout period of at least 7 days. The duration of the study for an individual participant will be at least 12 days, Screening and Follow-up not included. Participants safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
126
A single tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg will be administered.
A single tablet containing FTC 200 mg and TAF 10 mg will be administered.
A single tablet containing darunavir 800 mg will be administered.
Unnamed facility
Groningen, Netherlands
Maximum Observed Plasma Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
The Cmax is the maximum observed plasma concentration.
Time frame: Up to 72 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
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 post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
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 post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Time frame: Up to 72 hours post-dose
Plasma Concentration at the Last Quantifiable Time Point (Clast) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The Clast is the last observed quantifiable plasma concentration above the quantification limit.
Time frame: Up to 72 hours post-dose
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A single table containing cobistat 150 mg will be administered.
Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Lambda(z) is firstorder elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log linear phase of the drug concentrationtime curve.
Time frame: Up to 72 hours post-dose
Elimination HalfLife (t1/2) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The elimination halflife (t1/2) is the time needed for the plasma concentration to decrease to 1 half of its original value. It is associated with the terminal slope of the semi logarithmic drug concentrationtime curve, and is calculated as 0.693/lambda(z).
Time frame: Up to 72 hours post-dose
Time to Last Quantifiable Plasma Concentration (Tlast) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The Tlast is the time to last observed quantifiable plasma concentration.
Time frame: Up to 72 hours post-dose
Ratio of AUClast of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Ratio of individual AUClast values between Treatment A and B.
Time frame: Up to 72 hours post-dose
Ratio of AUC[0infinity] of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Ratio of individual AUC\[0infinity\] values between Treatment A and B.
Time frame: Up to 72 hours post-dose
Ratio of Cmax of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Ratio of individual Cmax values between Treatment A and B.
Time frame: Up to 72 hours post-dose
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