A Single-Dose, Open-Label, Randomized, Crossover Study to Assess the Bioequivalence of Darunavir 800 mg, Emtricitabine 200 mg, and Tenofovir Alafenamide 10 mg, in the Presence of Cobicistat 150 mg, Administered as Either a Fixed-Dose Combination Tablet or as Separate Agents in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Janssen Sciences Ireland UC
- Enrollment
- 126
- Primary Endpoint
- Maximum Observed Plasma Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Study Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Participant must be non-smoker for at least 3 months prior to selection
- •Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening. If the results are outside the normal reference ranges, the participant may be included only if they are not listed under the exclusion criteria and if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed/signed by the Investigator
- •Participant must have a body mass index (BMI), between 18.5 and 30 kilogram per square meter (kg/m^2) (inclusive)
- •Participant must be healthy on the basis of clinical laboratory tests performed at Screening. If the results of the biochemistry panel, blood coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the abnormalities or deviations from normal are not listed in the exclusion criteria, and the Investigator judges they are not clinically significant. This determination must be recorded in the participant's source documents and initialed/signed by the Investigator
- •All female participants, except when postmenopausal, must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at Screening and must not breastfeed from Screening onwards
Exclusion Criteria
- •Participant has a positive human immunodeficiency virus - type (HIV-1) or human immunodeficiency virus - type 2 (HIV-2) test at Screening
- •Participant has hepatitis A, B, or C infection (confirmed by a positive hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen, and/or hepatitis C virus antibody, respectively) at Screening
- •Participant has currently significant and active gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, endocrinologic, genitourinary, renal, hepatic, respiratory, inflammatory, neoplastic, or infectious disease. Currently active dermatological disease that would interfere with a correct assessment of possible skin reactions to the study drugs
- •Participant has currently significant and active diarrhea, nausea, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability
- •Participant has any history of renal insufficiency
Arms & Interventions
Treatment Sequence (AB)
Participant will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) (Treatment A) in period 1, then 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 2
Intervention: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC) (Drug)
Treatment Sequence (AB)
Participant will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) (Treatment A) in period 1, then 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 2
Intervention: Emtricitabine/tenofovir alafenamide FDC (Drug)
Treatment Sequence (AB)
Participant will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) (Treatment A) in period 1, then 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 2
Intervention: Darunavir (Drug)
Treatment Sequence (AB)
Participant will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) (Treatment A) in period 1, then 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 2
Intervention: Cobicistat (Drug)
Treatment Sequence (BA)
Participant will receive 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 1, then a single oral tablet of D/C/F/TAF (800/150/200/10 mg) FDC (Treatment A) in period 2
Intervention: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC) (Drug)
Treatment Sequence (BA)
Participant will receive 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 1, then a single oral tablet of D/C/F/TAF (800/150/200/10 mg) FDC (Treatment A) in period 2
Intervention: Emtricitabine/tenofovir alafenamide FDC (Drug)
Treatment Sequence (BA)
Participant will receive 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 1, then a single oral tablet of D/C/F/TAF (800/150/200/10 mg) FDC (Treatment A) in period 2
Intervention: Darunavir (Drug)
Treatment Sequence (BA)
Participant will receive 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 1, then a single oral tablet of D/C/F/TAF (800/150/200/10 mg) FDC (Treatment A) in period 2
Intervention: Cobicistat (Drug)
Outcomes
Primary Outcomes
Maximum Observed Plasma Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Time Frame: Up to 72 hours post-dose
The Cmax is the maximum observed plasma concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Time Frame: Up to 72 hours post-dose
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.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Time Frame: Up to 72 hours post-dose
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Secondary Outcomes
- Ratio of AUClast of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)(Up to 72 hours post-dose)
- Ratio of AUC[0infinity] of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)(Up to 72 hours post-dose)
- Number of Subjects with Adverse Events(From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)(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)(Up to 72 hours post-dose)
- Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)(Up to 72 hours post-dose)
- Time to Last Quantifiable Plasma Concentration (Tlast) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)(Up to 72 hours post-dose)
- Ratio of Cmax of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)(Up to 72 hours post-dose)
- Elimination HalfLife (t1/2) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)(Up to 72 hours post-dose)