Relative Bioavailability and Food Effect for Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination
A Single-dose, Open-label, Randomized, Crossover Study to Assess the Impact of Food on the Pharmacokinetics of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Administered as a Fixed-dose Combination Tablet, and the Relative Bioavailability
3 other identifiers
interventional
72
1 country
1
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics and relative bioavailability of Emtricitabine (FTC) and Tenofovir alafenamide (TAF) when administered as a fixed-dose combination (FDC) with darunavir (DRV) and cobicistat (COBI) (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) relative to administration as an FDC with Elvitegravir (EVG) and COBI (Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide), under fed conditions in healthy subjects (Panel 1); evaluate the single-dose pharmacokinetics and relative bioavailability of DRV, COBI, FTC and TAF when administered as an FDC (D/C/F/TAF) or as separate agents (D+C+FTC/TAF), under fed conditions in healthy subjects (Panel 2) and to evaluate the impact of food (fasting or high-fat breakfast) on the single-dose pharmacokinetics of DRV, COBI, FTC, and TAF when administered as an FDC (D/C/F/TAF) in healthy subjects (Panel 3).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 healthy
Started Jun 2015
Shorter than P25 for phase_1 healthy
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2015
CompletedFirst Submitted
Initial submission to the registry
June 15, 2015
CompletedFirst Posted
Study publicly available on registry
June 18, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 14, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
August 14, 2015
CompletedOctober 17, 2017
October 1, 2017
2 months
June 15, 2015
October 16, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Maximum Observed Plasma Concentration (Cmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The Cmax is the maximum observed plasma concentration.
Up to 72 Hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Up to 72 Hours after study drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
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(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Up to 72 Hours after study drug administration
Secondary Outcomes (1)
Number of Subjects with Adverse Events
From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration
Other Outcomes (7)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Up to 72 Hours after study drug administration
Plasma Concentration at the Last Quantifiable Time Point (Clast) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Up to 72 Hours after study drug administration
Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Up to 72 Hours after study drug administration
- +4 more other outcomes
Study Arms (6)
Panel 1: Group 1
EXPERIMENTALSubject will receive a single oral tablet of fixed dose combination (FDC) containing darunavir (DRV)/ cobicistat (COBI)/emtricitabine (FTC) /tenofovir alafenamide (TAF) (D/C/F/TAF) under fed conditions (standardized regular breakfast, test Panel 1) on Day 1 of treatment period 1 and by FDC of elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/ tenofovir alafenamide (TAF) (E/C/F/TAF) under fed conditions (standardized regular breakfast, reference Panel 1) on Day 1 of treatment period 2.
Panel 1: Group 2
EXPERIMENTALSubject will receive a single oral tablet of FDC containing E/C/F/TAF under fed conditions (standardized regular breakfast, reference Panel 1) on Day 1 of treatment period 1 and a single oral tablet of FDC containing D/C/F/TAF under fed conditions (standardized regular breakfast, test Panel 1) on Day 1 of treatment period 2.
Panel 2: Group 1
EXPERIMENTALSubject will receive a single oral tablet of D/C/F/TAF under fed conditions (standardized regular breakfast, test Panel 2) on Day 1 of treatment period 1 and a single oral tablet of DRV, a tablet of emtricitabine/ tenofovir alafenamide (FTC/TAF) and a tablet of COBI under fed conditions (standardized regular breakfast, reference Panel 2) on Day 1 of treatment period 2.
Panel 2: Group 2
EXPERIMENTALSubject will receive a single oral tablet of DRV, a tablet of FTC/TAF and a tablet of COBI under fed conditions (standardized regular breakfast, reference Panel 2) on Day 1 of treatment period 2 and a single oral tablet of D/C/F/TAF under fed conditions (standardized regular breakfast, test Panel 2) on Day 1 of treatment period 2.
Panel 3: Group 1
EXPERIMENTALSubject will receive a single oral tablet of D/C/F/TAF under fasted conditions (test Panel 3) on Day 1 of treatment period 1 and a single oral tablet of D/C/F/TAF with a standardized high-fat breakfast (reference Panel 3) on Day 1 of treatment period 2.
Panel 3: Group 2
EXPERIMENTALSubject will receive a single oral tablet of D/C/F/TAF with a standardized high-fat breakfast (reference Panel 3) on Day 1 of treatment period 1 followed by a single oral tablet of D/C/F/TAF under fasted conditions (test Panel 3) on Day 1 of treatment period 2.
Interventions
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
A tablet containing EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
A tablet containing Darunavir (DRV) 800 mg will be administered.
A tablet containing Emtricitabine (FTC) 200 mg and Tenofovir alafenamide (TAF) 10 mg will be administered.
A tablet containing cobicistat (COBI) 150 mg will be administered.
Standardized regular breakfast will administered.
Eligibility Criteria
You may qualify if:
- Subject must be a non-smoker for at least 3 months prior to selection
- Subject must have a body mass index (BMI, weight in kg divided by the square of height in meters) of 18.5 to 30.0 kg/m\^2, extremes included
You may not qualify if:
- Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
- Subject has a positive human immunodeficiency virus-1 (HIV-1) or HIV-2 test at screening
- Subject has hepatitis A, B, or C infection (confirmed by a positive hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen, and/or hepatitis C virus antibody, respectively) at screening
- Subject has currently significant and active diarrhea, nausea, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability
- Subject has any history of renal insufficiency
- Subject has known allergies, hypersensitivity, or intolerance to DRV, COBI (GS-9350), EVG (Panel 1 only), FTC, TAF or their excipients
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Unknown Facility
Antwerp, Belgium
Related Publications (1)
Crauwels HM, Baugh B, Van Landuyt E, Vanveggel S, Hijzen A, Opsomer M. Bioequivalence of the Once-Daily Single-Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability. Clin Pharmacol Drug Dev. 2019 May;8(4):480-491. doi: 10.1002/cpdd.628. Epub 2018 Nov 9.
PMID: 30412360DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Janssen Sciences Ireland UC Clinical Trials
Janssen Sciences Ireland UC
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
June 15, 2015
First Posted
June 18, 2015
Study Start
June 1, 2015
Primary Completion
August 14, 2015
Study Completion
August 14, 2015
Last Updated
October 17, 2017
Record last verified: 2017-10