TMC435-TiDP16-C107: This Study Measures the (Possible) Influence of TMC435 on the Activity of a Selected Set of Drug-degrading Proteins by Measuring the Blood Levels of Drugs That Have Been Taken Together With TMC435 and That Are Known to be Specifically Degraded by These Drug-degrading Proteins.

April 26, 2010 updated by: Tibotec Pharmaceuticals, Ireland

A Phase I, Open Label, 2-period, Randomized, Crossover Trial in 16 Healthy Subjects to Assess the Drug Interaction Potential of TMC435 With Oral Midazolam and With a Drug Cocktail Representative of CYP1A2, CYP2C9, CYP2D6, CYP3A4, and CYP2C19 Substrates.

The purpose of this study is to determine whether TMC435 influences the activity of certain drug-degrading proteins in the human body. The drug-degrading proteins investigated in this study belong to the Cytochrome P (CYP) family and are called CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP2C19. The activity of these drug-degrading enzymes are determined by measuring the blood levels of a selected set of drugs, which are taken together with TMC435, and, which are known to be specifically degraded by a certain member of the CYP family. This selected set of drugs (which are taken together and therefore called a "drug cocktail") are considered as "probes" of these respective drug-degrading enzymes. By measuring the levels of these probes in human blood, the activity of these degrading enzymes are being revealed. In this way, we can determine if TMC435 influences in one way or another the activity of one or several of these selected drug-degrading proteins.

Study Overview

Status

Status

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

Conditions

Conditions

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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 an open-label 2-period randomized cross-over trial in 16 healthy volunteers. Eligible volunteers will be randomized to 2 groups. Volunteers in Group A will receive in Period 1 a single dose of oral midazolam and a drug cocktail alone on Day 1 and 2, respectively (Treatment A). In Period 2, they will receive 150 mg TMC435 once daily on Days 1-11 with a single dose of oral midazolam and a drug cocktail on Day 10 and 11, respectively (Treatment B). Volunteers in Group B will receive in Period 1 Treatment B and in Period 2 Treatment A. There is a period of at least 14 days between the two periods to ensure that all drugs administered in the previous period have been degraded and will not interfere with the measurements of the following period. The cocktail consists of midazolam (administered intravenously (abbreviated as "i.v.", which means directly injected into a blood vein. Injection occurs over a period of 1 minute via a a small tube (canula) that is brought into the blood vein to ease slow injection of the drug), omeprazole, dextromethorphan, caffeine and warfarin. Each of these drugs is being degraded by a specific drug-degrading protein of the CYP family, and are therefore ideal tools to reveal the activity of this specific protein. The amount of TMC435, midazolam, cocktail drugs (and some of their metabolites, i.e. degradation products) in blood will be assessed on selected time points. Safety and tolerability of the coadministration of TMC435 and oral midazolam and of TMC435 and the drug cocktail will be assessed throughout the trial. Safety and tolerability follow up includes the assessment of several blood parameters (blood cells, biochemical activity of certain proteins, minerals, coagulation factors, …), of several parameters in urine (blood cells, proteins, glucose, …) and of the cardiac activity (via electrocardiogram, blood pressure, pulse rate). Healthy volunteers will receive treatments in either A-B sequence or B-A sequence. Treatment A consists of oral midazolam (0.075 mg/kg) on Day1 and cocktail (*) on Day2. Treatment B consists of TMC435 (150 mg q.d.) on Day1-11, oral midazolam (0.075 mg/kg) on Day10 and cocktail (*) on Day11. (*) Cocktail: 0.025 mg/kg midazolam (i.v.), dextromethorphan (30 mg, orally), caffeine (150 mg, orally), omeprazole (40 mg, orally) and warfarin (10 mg, orally) supplemented with vitamin K (10 mg, orally)

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.
16

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

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:

  • Volunteer is a non-smoker for at least 3 months prior to screening
  • Healthy on the basis of a physical examination, medical history, electrocardiogram, vital signs and the results of blood biochemistry, blood coagulation, and hematology tests and a urinalysis carried out at screening
  • Normal weight as defined by a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2, extremes included

Exclusion Criteria:

  • No volunteers who carry certain forms of the CYP2D6, CYP2C9 and CYP2C19 genes, which cause a weak activity of these drug-degrading proteins. These forms are: genotype *3, *4, *5, *6 for CYP2D6, *2, *3 for CYP2C9 or *2, *3, *4, *8 for CYP2C19
  • No Hepatitis A, B, or C infection at screening
  • No history and/or clinical signs and symptoms of hereditary or acquired coagulation disorders
  • No positive Human Immunodeficiency Virus (HIV) 1 or 2 test
  • No positive pregnancy test or breast-feeding at screening
  • No subjects not using adequate birth control methods.

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

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
Time Frame
Plasma levels of TMC435, midazolam and the compounds of the cocktail (+ metabolites) will be assessed.
Time Frame: On defined time points on Day1-6 (Treatment A) and Day1-15 (Treatment B).
On defined time points on Day1-6 (Treatment A) and Day1-15 (Treatment B).

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
Time Frame
To determine the short-term safety and tolerability of the concomitant use of TMC435 and oral midazolam or a cocktail of representative probes of drug-degrading enzymes of the CYP family
Time Frame: On days 1, 2, 3 and 5 of Treatment A and on days 1, 2, 10, 11, 12 and 15 of Tretament B
On days 1, 2, 3 and 5 of Treatment A and on days 1, 2, 10, 11, 12 and 15 of Tretament B
To determine the steady-state pharmacokinetics of TMC435 given 150 mg once daily
Time Frame: On days 9, 10, 11, 12, 13, 14 and 15 of Treatment B
On days 9, 10, 11, 12, 13, 14 and 15 of Treatment B

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.
Tibotec Pharmaceuticals, Ireland

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

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.
March 1, 2009

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.
July 1, 2009

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.
July 1, 2009

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).
March 19, 2009

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.
March 19, 2009

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.
March 23, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

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.
April 28, 2010

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.
April 26, 2010

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.
April 1, 2010

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.
  • CR015949

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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