Clinical trial NCT02578550: A Bioequivalence Study of Darunavir, Emtricitabine, and Tenofovir Alafenamide, in the Presence of Cobicistat in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Immunodeficiency Virus Type 1, Human
Darunavir
Cobicistat
Emtricitabine
Tenofovir alafenamide
Healthy participants
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2015-10-19
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
timeFrame: Up to 72 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
timeFrame: Up to 72 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
timeFrame: Up to 72 hours post-dose
Secondary outcomes:
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Plasma Concentration at the Last Quantifiable Time Point (Clast) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Elimination HalfLife (t1/2) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Time to Last Quantifiable Plasma Concentration (Tlast) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Ratio of AUClast of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Ratio of AUC[0infinity] of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Ratio of Cmax of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: Up to 72 hours post-dose
measure: Number of Subjects with Adverse Events
timeFrame: From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration
Other outcomes:
Locations:
city: Groningen
country: Netherlands
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Crauwels HM, Baugh B, Van Landuyt E, Vanveggel S, Hijzen A, Opsomer M. Bioequivalence of the Once-Daily Single-Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability. Clin Pharmacol Drug Dev. 2019 May;8(4):480-491. doi: 10.1002/cpdd.628. Epub 2018 Nov 9.