A Study of TMC207 in Patients With Moderately Impaired Hepatic Function

Phase 1

Completed

• Conditions: Moderate Hepatic Impairment
• Interventions: Drug: TMC207

• Registration Number: NCT01012284
• Lead Sponsor: Tibotec BVBA

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2009-11-12
• Study First Submitted QC: 2009-11-12
• Study First Posted: 2009-11-13
• Study Start: 2010-01
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Status Verified: 2012-12
• Last Update Submitted: 2012-12-19
• Last Update Posted: 2012-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Panel A	TMC207	8 patients with moderate hepatic impairment classified as moderate as per the Child Pugh Classification.
Panel B	TMC207	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.

Primary Outcome Measures

Name	Time	Method
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 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
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
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 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
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

Name	Time	Method
Number of patients with adverse events as a measure of safety and tolerability	up to Day 29