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

NCT02216331 | Completed Phase 1

• 1 other identifier: TMC207-CL002
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis

Keywords

tuberculosis; PK; TMC207; bedaquiline; rifapentine; rifampicin; drug drug interaction

Outcome Measures

Primary Outcomes (3)

• Maximum observed TMC207 concentration in ng/mL [Cmax] between Groups 1 and 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

  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

  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 Outcomes (3)

• Maximum observed TMC207 concentration in ng/mL [Cmax] within treatment groups between Periods 1 and 2

  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

  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

  through 336 hours post dosing in Period 1 and Period 2

Other Outcomes (1)

• Number of participants with adverse events

  through study day 57

Study Arms (4)

Group 1 TMC207 alone

EXPERIMENTAL

A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1.

Drug: TMC207

Group 1 TMC207 and rifapentine

EXPERIMENTAL

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: TMC207; Drug: rifapentine

Group 2 TMC207 alone

EXPERIMENTAL

A single 400 mg dose of TMC207 will be administered as 4 tablets of 100 mg per tablet on Study Day 1.

Drug: TMC207

Group 2 TMC207 and rifampicin

EXPERIMENTAL

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; Drug: rifampicin

Interventions

TMC207 DRUG

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.

Also known as: bedaquiline

Group 1 TMC207 alone; Group 1 TMC207 and rifapentine; Group 2 TMC207 alone; Group 2 TMC207 and rifampicin

rifapentine DRUG

Group 1 TMC207 and rifapentine

rifampicin DRUG

Group 2 TMC207 and rifampicin

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (1)

Celerion (MDS Pharma Services)

Lincoln, Nebraska, 68502, United States

Location

Related Publications (1)

• Winter H, Egizi E, Murray S, Erondu N, Ginsberg A, Rouse DJ, Severynse-Stevens D, Pauli E. Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects. Antimicrob Agents Chemother. 2015 Feb;59(2):1219-24. doi: 10.1128/AAC.04171-14. Epub 2014 Dec 15.

  PMID: 25512422 DERIVED

Related Links

• Global Alliance for TB Drug Development website

MeSH Terms

Conditions

Tuberculosis

Interventions

bedaquiline; rifapentine; Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Scott Rasmussen, MD

  Celerion (MDS Pharma Services)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2014
• First Posted: August 13, 2014
• Study Start: March 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 6, 2019

Record last verified: 2019-09

Locations

US (1)