A Study of TMC207 in Patients With Moderately Impaired Hepatic Function

Sponsor

Tibotec BVBA (Industry)

Overall Status

Completed

CT.gov ID

NCT01012284

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Moderate Hepatic Impairment	Drug: TMC207	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Jan 1, 2011

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Number of patients with adverse events as a measure of safety and tolerability [up to Day 29]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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