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

NCT02984852 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR108258TMC114FD2HTX1004
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax)

  Cmax is defined as the maximum observed plasma concentration.

  Up to Day 4

• Area Under the Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last])

  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.

  Up to Day 4

• Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity])

  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); 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.

  Up to Day 4

Secondary Outcomes (4)

• 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)

Study Arms (6)

Treatment sequence ABC

EXPERIMENTAL

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.

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

Treatment sequence ACB

EXPERIMENTAL

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.

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

Treatment sequence BCA

EXPERIMENTAL

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.

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

Treatment sequence BAC

EXPERIMENTAL

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.

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

Treatment sequence CAB

EXPERIMENTAL

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.

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

Treatment sequence CBA

EXPERIMENTAL

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.

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

Interventions

Darunavir (DRV) DRUG

Darunavir 800 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/TAF(10mg).

Treatment sequence ABC; Treatment sequence ACB; Treatment sequence BAC; Treatment sequence BCA; Treatment sequence CAB; Treatment sequence CBA

Cobicistat (COBI) DRUG

Cobicistat 150 milligram (mg) will be taken orally in FDC together with DRV(800mg)/FTC(200mg)/TAF(10mg).

Treatment sequence ABC; Treatment sequence ACB; Treatment sequence BAC; Treatment sequence BCA; Treatment sequence CAB; Treatment sequence CBA

Emtricitabine (FTC) DRUG

Emtricitabine 200 milligram (mg) will be taken orally in FDC together with COBI(150mg)/DRV(800mg)/TAF(10mg).

Treatment sequence ABC; Treatment sequence ACB; Treatment sequence BAC; Treatment sequence BCA; Treatment sequence CAB; Treatment sequence CBA

Tenofovir Alafenamide (TAF) DRUG

Tenofovir Alafenamide 10 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/DRV(800mg).

Treatment sequence ABC; Treatment sequence ACB; Treatment sequence BAC; Treatment sequence BCA; Treatment sequence CAB; Treatment sequence CBA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead

Study Sites (1)

Unknown Facility

Tempe, Arizona, United States

Location

MeSH Terms

Interventions

Darunavir; Cobicistat; Emtricitabine; Racivir; tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 7, 2016
• Study Start: December 1, 2016
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

US (1)