A Study of TMC207 in Patients With Moderately Impaired Hepatic Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec BVBA
ClinicalTrials.gov Identifier:
NCT01012284
First received: November 12, 2009
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Moderate Hepatic Impairment
Drug: TMC207
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics, Safety, and Tolerability of TMC207 in Subjects With Moderately Impaired Hepatic Function

Resource links provided by NLM:


Further study details as provided by Tibotec BVBA:

Primary Outcome Measures:
  • Maximum plasma concentration of TMC207 [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Time to reach the maximum plasma concentration of TMC207 [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Area under curve from time of administration up to 72 hours post dosing of TMC207 [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Area under curve from time of administration up to the last time point with a measurable concentration post dosing of TMC207 [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Area under curve extrapolated to infinity of TMC207 [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Maximum plasma concentration of N-monodesmethyl metabolite [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Time to reach the maximum plasma concentration of N-monodesmethyl metabolite [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Area under curve from time of administration up to 72 hours post dosing of N-monodesmethyl metabolite [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Area under curve from time of administration up to the last time point with a measurable concentration post dosing of N-monodesmethyl metabolite [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]
  • Area under curve extrapolated to infinity of N-monodesmethyl metabolite [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 216, 264, 336, 504, 672 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: up to Day 29 ] [ Designated as safety issue: Yes ]

Enrollment: 16
Study Start Date: January 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: R207910

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01012284

Sponsors and Collaborators
Tibotec BVBA
Investigators
Study Director: Tibotec-Virco Virology BVBA Clinical Trial Tibotec BVBA
  More Information

Additional Information:
No publications provided

Responsible Party: Tibotec BVBA
ClinicalTrials.gov Identifier: NCT01012284     History of Changes
Other Study ID Numbers: CR007501, TMC207-TiDP13-C112, 2009-016437-99
Study First Received: November 12, 2009
Last Updated: December 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Tibotec BVBA:
Moderate Hepatic Impairment
Tuberculosis
TMC207
Mycobacterial adenosine triphosphate (ATP)-synthase

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Bedaquiline
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014