Clinical trial NCT02984852: Study to Evaluate the Relative Bioavailability of Fixed-dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) as a Whole Tablet, as a Split Tablet, and as Crushed Tablet in Healthy Adult Participants
Official title: A Single-dose, Open-label, Randomized, Crossover Study to Assess the Relative Bioavailability of the Fixed-dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Administered Orally as a Whole Tablet, as a Split Tablet, and as Crushed Tablet in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
First posted: 2016-12-07
Enrollment: 30
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 relative bioavailability of Darunavir (DRV) 800 milligram (mg), Cobicistat (COBI) 150 mg, Emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg when administered as a fixed-dose combination (FDC) (D/C/F/TAF) tablet in healthy adult participants when given as Treatment A (reference): a single dose of D/C/F/TAF (800/150/200/10 mg) FDC tablet swallowed as a whole, intact tablet with 240milliliter (mL) of noncarbonated water.Treatment B (test): a single dose of D/C/F/TAF (800/150/200/10 mg) FDC tablet as a split tablet swallowed with 240 mL of noncarbonated water. Treatment C (test): a single dose of D/C/F/TAF (800/150/200/10 mg) FDC tablet as a crushed tablet mixed in 4 ounces (oz) of applesauce.


Eligibility criteria: Inclusion Criteria:

* Non-smoker for at least 3 months prior to selection
* Body mass index (BMI) of 18.0 to 32 kilogram per square meter (kg/m\^2), inclusive
* Woman must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) pregnancy test at screening and a negative sensitive urine pregnancy test on Day -1 before the first dose of study drug
* Woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of study drug
* During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, a non-vasectomized man who is sexually active with a woman of childbearing potential must agree to use a highly effective barrier method of contraception

Exclusion Criteria:

* Positive human immunodeficiency virus -1 (HIV-1) or HIV-2 test at screening
* Hepatitis A, B, or C infection, confirmed by a positive hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV) test, respectively, at screening
* History of renal insufficiency
* History of significant drug-induced skin reactions (such as, but not limited, to Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and/or erythema multiforme) or history of allergies to drugs (such as, but not limited to, sulfonamides and penicillins)
* Previously participated in a multiple-dose study with Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC), Tenofovir Alafenamide (TAF), or Tenofovir Disoproxil Fumarate (TDF)

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Up to Day 4
measure: Area Under the Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last])
timeFrame: Up to Day 4
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
timeFrame: Up to Day 4
Secondary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
measure: Number of Participants With Clinical Laboratory Results as a Measure of Safety and Tolerability
timeFrame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
measure: Number of Participants With Vital Signs as a Measure of Safety and Tolerability
timeFrame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
measure: Number of Participants With Physical Examination Findings as a Measure of Safety and Tolerability
timeFrame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
Other outcomes:
Locations:
city: Tempe
country: United States
state: Arizona
Study officials:
affiliation: Janssen Scientific Affairs, LLC
name: Janssen Scientific Affairs, LLC Clinical Trial
role: STUDY_DIRECTOR
References: