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
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02984852
- Lead Sponsor
- Janssen Scientific Affairs, LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment sequence ABC Cobicistat (COBI) 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 sequence ABC Emtricitabine (FTC) 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 sequence ABC Tenofovir Alafenamide (TAF) 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 sequence BAC Emtricitabine (FTC) 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 sequence BAC Tenofovir Alafenamide (TAF) 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 sequence ACB Cobicistat (COBI) 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 sequence ACB Emtricitabine (FTC) 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 sequence ACB Tenofovir Alafenamide (TAF) 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 sequence BAC Cobicistat (COBI) 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 sequence CAB Cobicistat (COBI) 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 sequence CAB Emtricitabine (FTC) 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 sequence ABC Darunavir (DRV) 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 sequence ACB Darunavir (DRV) 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 sequence BCA Darunavir (DRV) 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 sequence BCA Cobicistat (COBI) 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 sequence BCA Emtricitabine (FTC) 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 sequence BCA Tenofovir Alafenamide (TAF) 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 sequence BAC Darunavir (DRV) 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 sequence CAB Darunavir (DRV) 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 sequence CAB Tenofovir Alafenamide (TAF) 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 sequence CBA Darunavir (DRV) 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 sequence CBA Cobicistat (COBI) 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 sequence CBA Emtricitabine (FTC) 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 sequence CBA Tenofovir Alafenamide (TAF) 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.
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) Up to Day 4 Cmax is defined as the maximum observed plasma concentration.
Area Under the Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last]) Up to Day 4 AUC (0-last) is the area under the Plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) Up to Day 4 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 (0-last) and C (0-last)/lambda(z)Íž wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events as a Measure of Safety and Tolerability Screening (21 days ) to End of the study (7 to 10 days after the last dose) Number of Participants With Clinical Laboratory Results as a Measure of Safety and Tolerability Screening (21 days ) to End of the study (7 to 10 days after the last dose) Number of Participants With Vital Signs as a Measure of Safety and Tolerability Screening (21 days ) to End of the study (7 to 10 days after the last dose) Number of Participants With Physical Examination Findings as a Measure of Safety and Tolerability Screening (21 days ) to End of the study (7 to 10 days after the last dose)