An Exploratory Study of TMC207 in Japanese Participants With Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Tuberculosis, Multidrug-Resistant

Treatments: Drug: Background Regimen (BR); Drug: TMC207 (bedaquiline)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02365623

TMC207TBC2001 (Other Identifier)

CR105158

Details and patient eligibility

About

The purpose of this study is to explore safety and efficacy of TMC207 administered as part of a multi-drug regimen for 24 to 48-week treatment in Japanese participants with pulmonary multi-drug resistant tuberculosis (MDR-TB), and to evaluate pharmacokinetics (PK) of TMC207 and its primary metabolite M2.

Full description

This is an open-label (everyone know the study intervention), single-arm, multicenter trial to explore safety, efficacy and PK of TMC207 in Japanese participants with pulmonary MDR-TB. The participants will receive TMC207 for 24 weeks in combination with individualized BR drugs selected by the Investigator on Day -1. Participants will primarily be assessed for sputum culture conversion at Week 24. Safety will be monitored throughout the study.

Enrollment: 6 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must have confirmed pulmonary multi-drug resistant tuberculosis (MDR-TB) infection, which is defined as infection by a strain of M. tuberculosis resistant to both rifampicin and isoniazid (RFP and INH) by previous screening from a TB treatment
• Must have confirmed positive results for acid-fast bacilli (AFB) on direct smear examination of expectorated sputum specimen (more than [>] 1+ smear-positive) during the Screening Phase or sputum culture positive for M. tuberculosis within the preceding 3 months
• A women must not be of childbearing potential: postmenopausal or permanently sterilized or otherwise be incapable of pregnancy, or if childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods and a man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control
• Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
• Must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study

Exclusion criteria

• Has any concomitant severe illness or rapidly deteriorating health condition, including immune deficiency that would make implementation of the protocol or interpretation of the study results difficult or otherwise make the subject a poor candidate for a clinical study
• Has complicated or severe extra-pulmonary manifestations of TB, including central nervous system infection
• Participants with significant cardiac arrhythmia requiring medication
• Participants with the abnormal electrocardiogram (ECG) parameters as defined in protocol
• Has human immuno deficiency virus (HIV) antibody positive during the Screening Phase

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

TMC207 (bedaquiline) + Background Regimen (BR)

Experimental group

Description:

Participants will receive TMC207 (bedaquiline) 400 milligram (mg) as 4\*100 mg tablets once daily 2 weeks (14 days). From Week 3, participants will receive 200 mg (2 tablets) TMC207 (bedaquiline) 3 times a week up to Week 24 along with background regimen (BR). Based on the discussion with the Pharmaceuticals and Medical Devices Agency (PMDA), the extension of 24-week TMC207 treatment with BR drugs may occur up to Week 48, under certain circumstances, such that many BR drugs which are susceptible at the beginning of the Treatment Phase show resistance during the Treatment Phase. After TMC207 is stopped, the BR will be continued up to 78 weeks after conversion or 102 weeks after day 1 (what happens first).

Treatment:

Drug: TMC207 (bedaquiline)

Drug: Background Regimen (BR)