- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02475135
Relative Bioavailability and Food Effect for Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination
October 16, 2017 updated by: Janssen Sciences Ireland UC
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
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).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is a Phase 1, 3-panel, open-label, randomized, 2-way crossover study in healthy subjects.
Healthy subjects will be divided over 3 panels (Panel 1, 2 and 3).
Subjects will be randomized within each panel.
In each panel, during 2 subsequent sessions, each subject will receive 2 treatments (Treatments A and B in Panel 1, Treatments C and D in Panel 2, and Treatments E and F in Panel 3).
Each treatment is defined as follows: Treatment A: single oral dose of D/C/F/TAF 800/150/200/10 milligram (mg) as FDC tablet under fed conditions (standardized regular breakfast); Treatment B: single oral dose of E/C/F/TAF 150/150/200/10 mg as FDC tablet under fed conditions; Treatment C: single oral dose of D/C/F/TAF 800/150/200/10 mg as FDC tablet under fed conditions; Treatment D: single oral dose of DRV as 800-mg tablet, FTC/TAF as 200/10 mg tablet and COBI 150 mg tablet under fed conditions.
Treatment E: single oral dose of D/C/F/TAF 800/150/200/10 mg as FDC tablet, under fasted condition and Treatment F: single oral dose of D/C/F/TAF 800/150/200/10 mg tablet, with a standardized high-fat breakfast.
Each treatment will be separated by a washout period of at least 7 days.
Primarily pharmacokinetic parameters will be assessed.
Subjects' safety will be assessed throughout.
Study Type
Interventional
Enrollment (Actual)
72
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Antwerp, Belgium
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
- Subject must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening. If the results are outside the normal reference ranges, the subject may be included only if they are not listed under the exclusion criteria and if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the Investigator
- Subject must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the biochemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the abnormalities or deviations from normal are not listed in the exclusion criteria, and the Investigator judges they are not clinically significant. This determination must be recorded in the subject's source documents and initialed by the Investigator
- Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Panel 1: Group 1
Subject 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.
|
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.
Standardized regular breakfast will administered.
|
Experimental: Panel 1: Group 2
Subject 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.
|
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.
Standardized regular breakfast will administered.
|
Experimental: Panel 2: Group 1
Subject 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.
|
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Standardized regular breakfast will 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.
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Experimental: Panel 2: Group 2
Subject 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.
|
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Standardized regular breakfast will 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.
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Experimental: Panel 3: Group 1
Subject 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.
|
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
|
Experimental: Panel 3: Group 2
Subject 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.
|
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
High-fat breakfast will be administered.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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The Cmax is the maximum observed plasma concentration.
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Up to 72 Hours after study drug administration
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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)
Time Frame: Up to 72 Hours after study drug administration
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The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
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Up to 72 Hours after study drug administration
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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)
Time Frame: Up to 72 Hours after study drug administration
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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.
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Up to 72 Hours after study drug administration
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Subjects with Adverse Events
Time Frame: From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration
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An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
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From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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Up to 72 Hours after study drug administration
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Plasma Concentration at the Last Quantifiable Time Point (Clast) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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The Clast is the last observed quantifiable plasma concentration above the quantification limit.
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Up to 72 Hours after study drug administration
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Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log linear phase of the drug concentration-time curve.
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Up to 72 Hours after study drug administration
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Elimination Half-Life (t1/2) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.
It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
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Up to 72 Hours after study drug administration
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Time to Last Quantifiable Plasma Concentration (Tlast) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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The Tlast is the time to last observed quantifiable plasma concentration.
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Up to 72 Hours after study drug administration
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Ratio of AUClast of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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Ratio of individual AUClast values between test and reference treatment will be observed.
For Panel 1, test will be treatment A and reference will be treatment B, for Panel 2, test will be treatment C and reference will be treatment D and for Panel 3, test will be treatment D and reference will be treatment F.
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Up to 72 Hours after study drug administration
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Ratio of AUC[0-infinity] of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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Ratio of individual AUC[0-infinity] values between test and reference treatment will be observed.
For Panel 1, test will be treatment A and reference will be treatment B, for Panel 2, test will be treatment C and reference will be treatment D and for Panel 3, test will be treatment D and reference will be treatment F.
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Up to 72 Hours after study drug administration
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2015
Primary Completion (Actual)
August 14, 2015
Study Completion (Actual)
August 14, 2015
Study Registration Dates
First Submitted
June 15, 2015
First Submitted That Met QC Criteria
June 15, 2015
First Posted (Estimate)
June 18, 2015
Study Record Updates
Last Update Posted (Actual)
October 17, 2017
Last Update Submitted That Met QC Criteria
October 16, 2017
Last Verified
October 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Integrase Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Tenofovir
- Emtricitabine
- Emtricitabine tenofovir alafenamide
- Cobicistat
- Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
- Darunavir
- Elvitegravir
- Cobicistat mixture with darunavir
Other Study ID Numbers
- CR107430
- 2015-001213-27 (EudraCT Number)
- TMC114FD2HTX1002 (Other Identifier: Janssen Sciences Ireland UC)
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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