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

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ClinicalTrials.gov Identifier: NCT02365623
Recruitment Status : Active, not recruiting
First Posted : February 19, 2015
Last Update Posted : May 24, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

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.

Condition or disease Intervention/treatment Phase
Tuberculosis, Multidrug-Resistant Drug: TMC207 (bedaquiline) Drug: Background Regimen (BR) Phase 2

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study to Explore the Safety, Efficacy and Pharmacokinetics of TMC207 in Japanese Patients With Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB)
Actual Study Start Date : February 18, 2015
Estimated Primary Completion Date : July 31, 2018
Estimated Study Completion Date : September 12, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: TMC207 (bedaquiline) + Background Regimen (BR)
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)
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.
Other Name: Bedaquiline

Drug: Background Regimen (BR)
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).




Primary Outcome Measures :
  1. Percentage of Participants With Sputum Culture Conversion [ Time Frame: Week 24 ]
    Sputum culture conversion is defined as 2 consecutive negative cultures from sputa collected at least 25 days apart.


Secondary Outcome Measures :
  1. Number of Participants With Multidrug resistant (MDRTB) Outcome [ Time Frame: Week 102 ]
    Outcome is defined as, Cured: Participants who completed the study and has been consistently culture-negative (at least 5 consecutive negative cultures) for at least 48 weeks. If only 1 positive culture is reported in that time, participant may still be considered cured, provided that this positive culture is followed by a minimum of 3 consecutive negative cultures. Treatment failure: Participants who completed the study and was not cured. Death: Participants who died during study. Participants reported as dead during survival follow-up before or within Week 126 window were included in this category. Participants reported as dead during after Week 126 window are not included in this category as event occurred after planned duration (126 weeks) of study. Transfer out/Default: Participants who discontinued from study for any reason. Treatment completed: Participants who completed the study but did not meet definition for cure or treatment failure due to lack of bacteriologic results.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02365623


Locations
Japan
Kiyose, Japan
Sakai, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K. Clinical Trial Janssen Pharmaceutical K.K.

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT02365623     History of Changes
Other Study ID Numbers: CR105158
TMC207TBC2001 ( Other Identifier: Janssen Pharmaceutical K.K. )
First Posted: February 19, 2015    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Pharmaceutical K.K.:
Pulmonary Multi-Drug Resistant Tuberculosis (MDR-TB)
TMC207
Bedaquiline

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bedaquiline
Diarylquinolines
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents