PK Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects (TMC207-CL002)

September 4, 2019 updated by: Global Alliance for TB Drug Development

A Phase I Open-label Trial to Investigate the Pharmacokinetic Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects

This is a open-label study, 2-treatment, 2-period, single sequence design. Period 1 will examine the pharmacokinetics of TMC207 in the absence of rifapentine or rifampicin. Subjects will receive a single 400-mg dose of TMC207 administered alone on Study Day 1. Period 2 will examine the effects of repeated doses of either rifapentine or rifampicin on TMC207 pharmacokinetics and will begin on Study Day 20. During Period 2, subjects will receive 22 daily doses of either 600 mg rifapentine or rifampicin from Study Day 20 through Study Day 41. A single 400-mg dose of TMC207 will be administered on Study Day 29. Subjects will be confined to the clinic from Study Day-1 to Study Day 2 in the morning of Period 1, and Study Day 19 to Study Day 30 in the morning of Period 2. The study hypothesis is to determine whether Rifapentine affects the pharmacokinetics of TMC207 as measured by effects on Cmax and AUC(0-t) to a lesser degree than rifampicin.

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.

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.
32

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

  • United States
    • Nebraska
      • Lincoln, Nebraska, United States, 68502
        • Celerion (MDS Pharma Services)

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

15 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged between 19 and 55 years, extremes included.
  • Non tobacco/nicotine using (at least 3 months prior to screening).
  • Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, inclusive.
  • Informed Consent Form (ICF) signed voluntarily before the first trial-related activity.
  • Able to comply with protocol requirements.
  • Healthy on the basis of a medical evaluation or history that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, electrocardiogram (ECG), vital signs, and the results of blood biochemistry, and hematology tests and a urinalysis carried out at screening (See Section 6.1).

Exclusion Criteria:

  • Female, except if postmenopausal since more than 2 years, or post-hysterectomy, or post surgical sterilization, i.e., tubal ligation (without reversal operation) or total hysterectomy.
  • History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise subject's safety and/or compliance with the trial procedures.
  • Any clinically significant (as deemed by the Principle Investigator) history acute illness (resolved within 4 weeks of screening), or presence of cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (including eating disorders), endocrine, metabolic, immunologic, dermatologic, neurologic, psychological, or psychiatric disease.
  • Currently significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability.
  • Any history of significant skin disease such as, but not limited to, rash or eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis, or urticaria. Subjects with a history of skin disease may be enrolled into the study after consultation with the Sponsor Medical Monitor.
  • Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication administered in this trial (i.e. rifapentine, rifampicin, and TMC207).
  • Subjects with QTcF [Fredericia correction] interval > 450 msec (based on the average of the triplicate ECGs) at screening (and confirmed by repeat ECG).
  • Subjects with any other clinically significant ECG abnormality at screening, such as arrhythmia, ischemia, or evidence of heart failure or with a family history of Long QT Syndrome.
  • Use of concomitant medication, including over-the-counter products and dietary supplements, except for ibuprofen and paracetamol up to 7 days before the first dose of trial medication and all prescribed medication must have been discontinued at least 14 days before first intake of trial medication.
  • Participation in an investigational drug trial within 60 days prior to the first intake of trial medication.
  • Donation of blood or significant loss of blood within 56 days or plasma donation within 7 days preceding the first intake of trial medication.
  • Having received TMC207 in a previous trial.
  • Positive HIV-1 or HIV-2 test at screening
  • Hepatitis A, B, or C infection (confirmed by hepatitis A antibody IgM, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) at screening.
  • A positive urine drug test at screening. Urine will be tested to check the current use of alcohol, amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids.
  • Subjects with the following laboratory abnormalities at screening as defined by the NIH, NIAID, Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table and in accordance with the normal ranges of the clinical laboratory: Serum creatinine grade 1 or greater (> 1.0 x ULN); Pancreatic lipase grade 1 or greater (> 1.0 x ULN); Hemoglobin grade 1 or greater (≤ 10.5 g/dL); Platelet count grade 1 or greater (≤ 99000/mm3); Absolute neutrophil count grade 1 or greater (≤ 1500/mm3); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (> 1.0 x ULN); Total bilirubin grade 1 or greater (> 1.0 x ULN); Any other toxicity grade 2 or above, including: proteinuria (spot urine) > 1+ and gross hematuria.

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: Parallel Assignment
  • Masking: None (Open Label)

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: Group 1 TMC207 alone
A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1.
Drug: TMC207
This is a two group, 2 period study design with both groups in the first period receiving TMC207 alone, followed by one group in the second period receiving TMC207 in the presence of dosing with rifapentine and the other group receiving TMC207 in the presence of dosing with rifampicin. All treatments details specified under "Arms" description.
Other Names:
  • bedaquiline
Experimental: Group 1 TMC207 and rifapentine
A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 29 and 600 mg of rifapentine administered as 4 tablets of 150 mg per tablet on each of Study Days 20-41.
Drug: rifapentine
Drug: TMC207
This is a two group, 2 period study design with both groups in the first period receiving TMC207 alone, followed by one group in the second period receiving TMC207 in the presence of dosing with rifapentine and the other group receiving TMC207 in the presence of dosing with rifampicin. All treatments details specified under "Arms" description.
Other Names:
  • bedaquiline
Experimental: Group 2 TMC207 alone
A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1.
Drug: TMC207
This is a two group, 2 period study design with both groups in the first period receiving TMC207 alone, followed by one group in the second period receiving TMC207 in the presence of dosing with rifapentine and the other group receiving TMC207 in the presence of dosing with rifampicin. All treatments details specified under "Arms" description.
Other Names:
  • bedaquiline
Experimental: Group 2 TMC207 and rifampicin
A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 29 and 600 mg of rifampicin administered as 4 capsules of 150 mg per capsule on each of Study Days 20-41.
Drug: TMC207
This is a two group, 2 period study design with both groups in the first period receiving TMC207 alone, followed by one group in the second period receiving TMC207 in the presence of dosing with rifapentine and the other group receiving TMC207 in the presence of dosing with rifampicin. All treatments details specified under "Arms" description.
Other Names:
  • bedaquiline
Drug: rifampicin

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 TMC207 concentration in ng/mL [Cmax] between Groups 1 and 2
Time Frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on Cmax of TMC207, the Cmax of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration-time curve in ng*hr/mL [AUC0-t] between Groups 1 and 2
Time Frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-t of TMC207, the AUC0-t of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration cuve from time zero to infinity in ng*hr/mL [AUC0-inf] between Groups 1 and 2
Time Frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-inf of TMC207, the AUC0-inf of TMC207 was compared between Group 1 (rifapentine) and Group 2 (rifampicin) using analysis of variance model (ANOVA).
through 336 hours post dosing in Period 1 and Period 2

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
Maximum observed TMC207 concentration in ng/mL [Cmax] within treatment groups between Periods 1 and 2
Time Frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on Cmax of TMC207, the Cmax of TMC207 was compared between the TMC207 + rifapentine treatment (Group 1) or rifampicin (Group 2) and TMC207 alone using analysis of variance model (ANOVA).
through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration-time curve in ng*hr/mL [AUC0-t] within treatment groups between Periods 1 and 2
Time Frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-t of TMC207, the AUC0-t of TMC207 was compared between the TMC207 + rifapentine treatment (Group 1) or rifampicin (Group 2) and TMC207 alone using analysis of variance model (ANOVA).
through 336 hours post dosing in Period 1 and Period 2
Area under the TMC207 concentration cuve from time zero to infinity in ng*hr/mL [AUC0-inf] within treatment groups between Periods 1 and 2
Time Frame: through 336 hours post dosing in Period 1 and Period 2
To evaluate the relative effect of rifapentine and rifampicin on AUC0-inf of TMC207, the AUC0-inf of TMC207 was compared between the TMC207 + rifapentine treatment (Group 1) or rifampicin (Group 2) and TMC207 alone using analysis of variance model (ANOVA).
through 336 hours post dosing in Period 1 and Period 2

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
Number of participants with adverse events
Time Frame: through study day 57
To compare the safety and tolerability as measured by the number of participants with adverse events.
through study day 57

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.
Global Alliance for TB Drug Development

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Scott Rasmussen, MD, Celerion (MDS Pharma Services)

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

Helpful Links

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, 2010

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.
May 1, 2010

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.
May 1, 2010

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).
August 12, 2014

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.
August 12, 2014

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.
August 13, 2014

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.
September 6, 2019

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.
September 4, 2019

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.
September 1, 2019

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.
  • TMC207-CL002

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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