A Bioequivalence Study of Darunavir, Emtricitabine, and Tenofovir Alafenamide, in the Presence of Cobicistat in Healthy Participants

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC); Drug: Cobicistat; Drug: Emtricitabine/tenofovir alafenamide FDC; Drug: Darunavir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02578550

TMC114FD2HTX1001 (Other Identifier)

CR107887

2015-001264-18 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 126 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

126 participants in 2 patient groups

Treatment Sequence (AB)

Experimental group

Description:

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

Treatment:

Drug: Darunavir

Drug: Emtricitabine/tenofovir alafenamide FDC

Drug: Cobicistat

Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC)

Treatment Sequence (BA)

Experimental group

Description:

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

Treatment:

Drug: Darunavir

Drug: Emtricitabine/tenofovir alafenamide FDC

Drug: Cobicistat

Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC)