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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Emtricitabine (FTC); Drug: Cobicistat (COBI); Drug: Darunavir (DRV); Drug: Tenofovir Alafenamide (TAF)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02984852

TMC114FD2HTX1004 (Other Identifier)

CR108258

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 6 patient groups

Treatment sequence ABC

Experimental group

Description:

Participants 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 (whole tablet) as reference in session 1 then Treatment B(split tablet) as test in session 2 followed by Treatment C (crushed tablet mixed in applesauce) as test in session 3 under fed conditions (standardized breakfast) on Day 1 of each treatment session. There will be a washout period of at least 7 days between consecutive drug intakes.

Treatment:

Drug: Tenofovir Alafenamide (TAF)

Drug: Cobicistat (COBI)

Drug: Darunavir (DRV)

Drug: Emtricitabine (FTC)

Treatment sequence ACB

Experimental group

Description:

Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment A in treatment session 1, then Treatment C in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.

Treatment:

Drug: Tenofovir Alafenamide (TAF)

Drug: Cobicistat (COBI)

Drug: Darunavir (DRV)

Drug: Emtricitabine (FTC)

Treatment sequence BCA

Experimental group

Description:

Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment B in session 1 then Treatment C in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.

Treatment:

Drug: Tenofovir Alafenamide (TAF)

Drug: Cobicistat (COBI)

Drug: Darunavir (DRV)

Drug: Emtricitabine (FTC)

Treatment sequence BAC

Experimental group

Description:

Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment B in session 1 then Treatment A in session 2 followed by Treatment C in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.

Treatment:

Drug: Tenofovir Alafenamide (TAF)

Drug: Cobicistat (COBI)

Drug: Darunavir (DRV)

Drug: Emtricitabine (FTC)

Treatment sequence CAB

Experimental group

Description:

Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment C in session 1 then Treatment A in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.

Treatment:

Drug: Tenofovir Alafenamide (TAF)

Drug: Cobicistat (COBI)

Drug: Darunavir (DRV)

Drug: Emtricitabine (FTC)

Treatment sequence CBA

Experimental group

Description:

Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment C in session 1 then Treatment B in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.

Treatment:

Drug: Tenofovir Alafenamide (TAF)

Drug: Cobicistat (COBI)

Drug: Darunavir (DRV)

Drug: Emtricitabine (FTC)