A Study of TMC207 in Patients With Moderately Impaired Hepatic Function

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

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.

Study Overview

• Status: Completed
• Conditions: Moderate Hepatic Impairment
• Intervention / Treatment: Drug: 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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A; 8 patients with moderate hepatic impairment classified as moderate as per the Child Pugh Classification.	Drug: TMC207; 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); Other Names: R207910
Experimental: Panel B; 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; 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); Other Names: R207910

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tibotec BVBA

Publications and helpful links

Helpful Links

• An Open-Label, Prospective, Non-Comparative Study to Evaluate the Efficacy and Safety of Paliperidone Palmitate in Subjects With Acute Schizophrenia.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: November 12, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (Estimate): November 13, 2009

Study Record Updates

• Last Update Posted (Estimate): December 20, 2012
• Last Update Submitted That Met QC Criteria: December 19, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Tuberculosis; TMC207; Moderate Hepatic Impairment; Mycobacterial adenosine triphosphate (ATP)-synthase
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Antitubercular Agents; Bedaquiline
• Other Study ID Numbers: CR007501; TMC207-TiDP13-C112 (Other Identifier: Tibotec-Virco Virology BVBA); 2009-016437-99 (EudraCT Number)