Clinical trial NCT01012284: A Study of TMC207 in Patients With Moderately Impaired Hepatic Function
Official title: Pharmacokinetics, Safety, and Tolerability of TMC207 in Subjects With Moderately Impaired Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Moderate Hepatic Impairment
Keywords: Moderate Hepatic Impairment
Tuberculosis
TMC207
Mycobacterial adenosine triphosphate (ATP)-synthase
Lead sponsor: Tibotec BVBA
Sponsor class: INDUSTRY
First posted: 2009-11-13
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum plasma concentration of TMC207
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Time to reach the maximum plasma concentration of TMC207
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Area under curve from time of administration up to 72 hours post dosing of TMC207
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Area under curve from time of administration up to the last time point with a measurable concentration post dosing of TMC207
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Area under curve extrapolated to infinity of TMC207
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Maximum plasma concentration of N-monodesmethyl metabolite
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Time to reach the maximum plasma concentration of N-monodesmethyl metabolite
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Area under curve from time of administration up to 72 hours post dosing of N-monodesmethyl metabolite
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Area under curve from time of administration up to the last time point with a measurable concentration post dosing of N-monodesmethyl metabolite
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
measure: Area under curve extrapolated to infinity of N-monodesmethyl metabolite
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours
Secondary outcomes:
measure: Number of patients with adverse events as a measure of safety and tolerability
timeFrame: up to Day 29
Other outcomes:
Locations:
Study officials:
affiliation: Tibotec BVBA
name: Tibotec-Virco Virology BVBA Clinical Trial
role: STUDY_DIRECTOR
References: