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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Drug: Elvitegravir /Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
A tablet containing EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Other: Standardized Regular Breakfast
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.
Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Drug: Elvitegravir /Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
A tablet containing EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Other: Standardized Regular Breakfast
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.
Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Other: Standardized Regular Breakfast
Standardized regular breakfast will administered.
Drug: Darunavir
A tablet containing Darunavir (DRV) 800 mg will be administered.
Drug: Emtricitabine/Tenofovir alafenamide (FTC/TAF)
A tablet containing Emtricitabine (FTC) 200 mg and Tenofovir alafenamide (TAF) 10 mg will be administered.
Drug: Cobicistat
A tablet containing cobicistat (COBI) 150 mg will be administered.
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.
Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Other: Standardized Regular Breakfast
Standardized regular breakfast will administered.
Drug: Darunavir
A tablet containing Darunavir (DRV) 800 mg will be administered.
Drug: Emtricitabine/Tenofovir alafenamide (FTC/TAF)
A tablet containing Emtricitabine (FTC) 200 mg and Tenofovir alafenamide (TAF) 10 mg will be administered.
Drug: Cobicistat
A tablet containing cobicistat (COBI) 150 mg will be administered.
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.
Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
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.
Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide FDC
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered.
Other: High-fat Breakfast
High-fat breakfast will be administered.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
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)
Time Frame: Up to 72 Hours after study drug administration
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)
Time Frame: Up to 72 Hours after study drug administration
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
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.
From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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)
Time Frame: Up to 72 Hours after study drug administration
The Clast is the last observed quantifiable plasma concentration above the quantification limit.
Up to 72 Hours after study drug administration
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
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.
Up to 72 Hours after study drug administration
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
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).
Up to 72 Hours after study drug administration
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
The Tlast is the time to last observed quantifiable plasma concentration.
Up to 72 Hours after study drug administration
Ratio of AUClast of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
Time Frame: Up to 72 Hours after study drug administration
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.
Up to 72 Hours after study drug administration
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
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.
Up to 72 Hours after study drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Sciences Ireland UC

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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 14, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 14, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 17, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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Conditions

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