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

NCT02365623 | Completed Phase 2

• 2 other identifiers: CR105158TMC207TBC2001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Tuberculosis, Multidrug-Resistant

Keywords

Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB); TMC207; Bedaquiline

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sputum Culture Conversion

  Sputum culture conversion is defined as 2 consecutive negative cultures from sputa collected at least 25 days apart.

  Week 24

Secondary Outcomes (1)

• Number of Participants With Multidrug resistant (MDRTB) Outcome

  Week 102

Study Arms (1)

TMC207 (bedaquiline) + Background Regimen (BR)

EXPERIMENTAL

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).

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

Interventions

TMC207 (bedaquiline) DRUG

TMC207 (bedaquiline): Participants will receive TMC207 (bedaquiline) 400 milligram (mg) as 4\*100 mg tablets once daily 2 weeks (14 days) followed by 200 mg (2 tablets) 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.

Also known as: Bedaquiline

TMC207 (bedaquiline) + Background Regimen (BR)

Background Regimen (BR) DRUG

Participants will receive anti-bacterial tuberculosis drugs (pyrazinamide \[PZA\], ethambutol \[EB, EMB\], streptomycin \[SM\], kanamycin \[KM, KAN\], enviomycin \[EVM\], ethionamide \[TH\], cycloserine \[CS\], para-aminosalicylic acid \[PAS\], amikacin \[AMK\], levofloxacin \[LVFX\] and other fluoroquinolone. Other drugs are used less commonly, such as amoxicillin-clavulanate, linezolid and clofazimine based on Investigator's decision twice a week from Day 1 up to 78 weeks after conversion or 102 weeks after day 1 (what happens first).

TMC207 (bedaquiline) + Background Regimen (BR)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (2)

Unknown Facility

Kiyose, Japan

Location

Unknown Facility

Sakai, Japan

Location

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

bedaquiline

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Janssen Pharmaceutical K.K. Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 19, 2015
• Study Start: February 18, 2015
• Primary Completion: November 8, 2018
• Study Completion: November 8, 2018
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

JP (2)