A Study of TMC207 in Patients With Moderately Impaired Hepatic Function

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics (what the body does to the medication), safety and tolerability of TMC207 and its N-monodesmethyl metabolite (M2) in healthy participants and in patients with moderate hepatic impairment after administration of a single 400 mg dose of TMC207.

Detailed Description
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This is a Phase I, open label (all people know the identity of the intervention) study of TMC207. The study consists of a screening period and a 4-weeks treatment period. Sixteen participants will be enrolled in two panels. Panel A will include 8 patients of moderate hepatic impairment and Panel B will include 8 healthy participants. Safety evaluations including adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination will be monitored throughout the study. The entire study duration for each participant will be approximately 7 weeks.

Official Title
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Pharmacokinetics, Safety, and Tolerability of TMC207 in Subjects With Moderately Impaired Hepatic Function

Conditions
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Moderate Hepatic Impairment

Intervention / Treatment
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* Drug: TMC207


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For healthy participant Panel A: Healthy on the basis of physical examination, medical history, vital signs, electrocardiogram and clinical laboratory tests performed at screening Should match to a patient with hepatic impairment with regards to sex, age (more or less to 5 years), and body mass index For patients in Panel B with moderate hepatic impairment: history of hepatic disease, documented liver cirrhosis and moderate liver function impairment defined by the Child-Pugh classification Exclusion Criteria: A positive tuberculin skin test indicating latent tuberculosis A positive human immunodeficiency virus (HIV)-1 or HIV-2 test at screening Moderate hepatic impairment patients with acute hepatitis, Hepatic carcinoma, Grade 3 or 4 encephalopathy, or active candidate for liver transplantation Matched healthy participants with current active hepatic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A<br>8 patients with moderate hepatic impairment classified as moderate as per the Child Pugh Classification. | Drug: TMC207<br>* 400 mg (4 tablets of 100 mg) of TMC207 will be administered as a single dose on Day 1 of the treatment period to participants of both the Panels (Panel A and Panel B)<br>* Other names: R207910;|
| Experimental: Panel B<br>8 healthy participants who will match to patients with hepatic impairment in Panel A with regards to sex, age (more or less to 5 years), and body mass index. | Drug: TMC207<br>* 400 mg (4 tablets of 100 mg) of TMC207 will be administered as a single dose on Day 1 of the treatment period to participants of both the Panels (Panel A and Panel B)<br>* Other names: R207910;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration of TMC207 |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Time to reach the maximum plasma concentration of TMC207 |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Area under curve from time of administration up to 72 hours post dosing of TMC207 |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Area under curve from time of administration up to the last time point with a measurable concentration post dosing of TMC207 |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Area under curve extrapolated to infinity of TMC207 |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Maximum plasma concentration of N-monodesmethyl metabolite |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Time to reach the maximum plasma concentration of N-monodesmethyl metabolite |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Area under curve from time of administration up to 72 hours post dosing of N-monodesmethyl metabolite |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Area under curve from time of administration up to the last time point with a measurable concentration post dosing of N-monodesmethyl metabolite |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 
| Area under curve extrapolated to infinity of N-monodesmethyl metabolite |  | 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events as a measure of safety and tolerability |  | up to Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate Hepatic Impairment, Tuberculosis, TMC207, Mycobacterial adenosine triphosphate (ATP)-synthase