Back to resultsStudy 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
Primary Purpose
Healthy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Darunavir (DRV)
Cobicistat (COBI)
Emtricitabine (FTC)
Tenofovir Alafenamide (TAF)
Sponsored by
About this trial
This is an interventional treatment trial for Healthy
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Treatment sequence ABC
Treatment sequence ACB
Treatment sequence BCA
Treatment sequence BAC
Treatment sequence CAB
Treatment sequence CBA
Arm 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.
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax)
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])
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])
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.
Secondary Outcome Measures
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Number of Participants With Clinical Laboratory Results as a Measure of Safety and Tolerability
Number of Participants With Vital Signs as a Measure of Safety and Tolerability
Number of Participants With Physical Examination Findings as a Measure of Safety and Tolerability
Full Information
NCT ID
NCT02984852
First Posted
December 5, 2016
Last Updated
March 31, 2017
Sponsor
Janssen Scientific Affairs, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02984852
Brief Title
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
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
December 2016 (Actual)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
February 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Scientific Affairs, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment sequence ABC
Arm Type
Experimental
Arm 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.
Arm Title
Treatment sequence ACB
Arm Type
Experimental
Arm 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.
Arm Title
Treatment sequence BCA
Arm Type
Experimental
Arm 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.
Arm Title
Treatment sequence BAC
Arm Type
Experimental
Arm 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.
Arm Title
Treatment sequence CAB
Arm Type
Experimental
Arm 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.
Arm Title
Treatment sequence CBA
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Darunavir (DRV)
Intervention Description
Darunavir 800 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/TAF(10mg).
Intervention Type
Drug
Intervention Name(s)
Cobicistat (COBI)
Intervention Description
Cobicistat 150 milligram (mg) will be taken orally in FDC together with DRV(800mg)/FTC(200mg)/TAF(10mg).
Intervention Type
Drug
Intervention Name(s)
Emtricitabine (FTC)
Intervention Description
Emtricitabine 200 milligram (mg) will be taken orally in FDC together with COBI(150mg)/DRV(800mg)/TAF(10mg).
Intervention Type
Drug
Intervention Name(s)
Tenofovir Alafenamide (TAF)
Intervention Description
Tenofovir Alafenamide 10 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/DRV(800mg).
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax)
Description
Cmax is defined as the maximum observed plasma concentration.
Time Frame
Up to Day 4
Title
Area Under the Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last])
Description
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.
Time Frame
Up to Day 4
Title
Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
Description
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.
Time Frame
Up to Day 4
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame
Screening (21 days ) to End of the study (7 to 10 days after the last dose)
Title
Number of Participants With Clinical Laboratory Results as a Measure of Safety and Tolerability
Time Frame
Screening (21 days ) to End of the study (7 to 10 days after the last dose)
Title
Number of Participants With Vital Signs as a Measure of Safety and Tolerability
Time Frame
Screening (21 days ) to End of the study (7 to 10 days after the last dose)
Title
Number of Participants With Physical Examination Findings as a Measure of Safety and Tolerability
Time Frame
Screening (21 days ) to End of the study (7 to 10 days after the last dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Scientific Affairs, LLC Clinical Trial
Organizational Affiliation
Janssen Scientific Affairs, LLC
Official's Role
Study Director
Facility Information:
City
Tempe
State/Province
Arizona
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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