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To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB.

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ClinicalTrials.gov Identifier: NCT00910871
Recruitment Status : Completed
First Posted : June 1, 2009
Results First Posted : May 16, 2013
Last Update Posted : April 24, 2015
Sponsor:
Information provided by (Responsible Party):
Janssen Infectious Diseases BVBA

Tracking Information
First Submitted Date  ICMJE May 28, 2009
First Posted Date  ICMJE June 1, 2009
Results First Submitted Date  ICMJE January 30, 2013
Results First Posted Date  ICMJE May 16, 2013
Last Update Posted Date April 24, 2015
Study Start Date  ICMJE September 2009
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2015)
The Median Time to Sputum Culture Conversion [ Time Frame: Up to Week 24 ]
The table below shows the median time in days to culture conversion for the modified intent-to-treat (mITT) population up to Week 24. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued during the 24-week period were considered non-responders (based on Mycobacteria Growth Indicator Tube [MGIT]).
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2009)
Time to sputum culture conversion in MGIT during and beyond treatment with TMC207. Sputum culture conversion will be defined as 2 consecutive negative cultures from sputa collected at least 28 days apart. [ Time Frame: During 17 visits over 100 weeks ]
Change History Complete list of historical versions of study NCT00910871 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2015)
The Percentage of Participants With Sputum Culture Conversion [ Time Frame: Week 120 ]
The table below shows the percentage of participants who were responders to treatment. Sputum culture conversion is defined as 2 consecutive sputum cultures negative for multi-drug resistant tuberculosis (MDR-TB) taken at least 25 days apart. Participants who discontinued or died during the trial were considered non-responders.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2009)
To evaluate the pharmacokinetics of TMC207 and its primary metabolite M2, and pharmacokinetic/pharmacodynamic relationships for safety and efficacy. [ Time Frame: 7 visits during treatment period of 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB.
Official Title  ICMJE A Phase II, Open-label Trial With TMC207 as Part of a Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Subjects With Sputum Smear-positive Pulmonary Infection With MDR-TB.
Brief Summary The purpose of this study is to evaluate the safety, tolerability and effectiveness of TMC207 in combination with an individualized background regimen (BR) of antibacterial drugs as treatment for MDR-TB
Detailed Description

This is a Phase II, open-label (all people involved know the identity of the intervention) trial to evaluate the safety, tolerability, and efficacy of TMC207 as part of an individualized Multi-drug Resistant Tuberculosis (MDR-TB) treatment regimen in participants with sputum smear-positive pulmonary MDR-TB. Approximately 225 participants will receive TMC207 for 24 weeks in combination with an individualized background regimen (BR) of antibacterial drugs used in the treatment of TB according to national and international guidelines and selected at the baseline visit. TMC207 dosage will be 400 mg once daily (q.d.) for the first 2 weeks and 200 mg 3 times/week (t.i.w.) for the following 22 weeks. Upon completion of the 24-week treatment with TMC207, all participants will continue to receive their BR under the care of their physician and in accordance with national TB program (NTP) treatment guidelines.

Additionally, the pharmacokinetics (how the body absorbs, distributes, metabolizes and eliminates a drug) of TMC207 and its N-monodesmethyl metabolite (M2), and pharmacokinetic/pharmacodynamic (the study of the action or effects a drug has on the body) relationships for safety and efficacy will be assessed. Safety evaluations that will be performed are lab tests, vital signs, ECG, reporting of adverse events, physical examinations and X-rays.

All participants will be followed up for 19 months after their last intake of TMC207. Also participants who prematurely withdraw (unless they withdraw consent) will be followed for this period or until the last follow-up visit for the last patient in the trial. Investigators will be asked to provide information about the survival/clinical outcome of these participants throughout the follow-up period, approximately every 6 months.

Primary outcome is time to sputum culture conversion in Mycobacteria Growth Indicator Tube (MGIT) during and beyond treatment with TMC207. Sputum culture conversion will be defined as 2 consecutive negative cultures from sputa collected at least 28 days apart.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tuberculosis
Intervention  ICMJE
  • Drug: TMC207
    TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks.
  • Drug: Background Regimen (BR) for MDR-TB
    Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as specified in the protocol for up to 96 weeks.
Study Arms  ICMJE Experimental: TMC207
TMC207 400mg once daily for 2 weeks then 200mg three times a week for 22 weeks in addition to Background Regimen (BR) for the treatment of multi-drug resistant tuberculosis (MDR-TB).
Interventions:
  • Drug: TMC207
  • Drug: Background Regimen (BR) for MDR-TB
Publications * Pym AS, Diacon AH, Tang SJ, Conradie F, Danilovits M, Chuchottaworn C, Vasilyeva I, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, Van Baelen B, van Heeswijk RP, Dannemann B; TMC207-C209 Study Group. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis. Eur Respir J. 2016 Feb;47(2):564-74. doi: 10.1183/13993003.00724-2015. Epub 2015 Dec 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2013)
241
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2009)
225
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Females of child-bearing potential must be using and are willing to continue using effective birth control methods, or be willing to practice sexual abstinence throughout treatment or be nonheterosexual active
  • Confirmed pulmonary MDR-TB infection including those infected with XDR (extensively drug resistant)-TB
  • Positive for acid-fast bacilli (AFB) on direct smear examination of expectorated sputum specimen (= 1+ smear-positive)
  • HIV-positive patients are eligible, provided they meet the requirements as described in the protocol
  • Must voluntarily sign the Informed Consent Form (ICF) prior to starting any study activities
  • Willing to comply with protocol requirements
  • Willing to comply with NTP treatment guidelines

Exclusion Criteria:

  • Patients having a known or suspected hypersensitivity or serious adverse reaction to TMC207
  • Patients with significant cardiac arrhythmia requiring medication
  • Patients with complicated or severe extrapulmonary manifestations of TB, including central nervous system infection
  • Patients with certain QT/QTc interval characteristics as described in the protocol
  • Patients having participated in other clinical studies with investigational agents, within 8 weeks prior to trial start
  • Women who are pregnant or breastfeeding
  • Patients who have previously received treatment with TMC207 as part of a clinical trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China,   Estonia,   Kenya,   Korea, Republic of,   Latvia,   Peru,   Philippines,   Russian Federation,   South Africa,   Thailand,   Turkey,   Ukraine
Removed Location Countries Brazil,   Hong Kong,   Mexico
 
Administrative Information
NCT Number  ICMJE NCT00910871
Other Study ID Numbers  ICMJE CR012352
TMC207-TiDP13-C209 ( Other Identifier: Janssen Infectious Diseases BVBA )
2008-008444-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Infectious Diseases BVBA
Study Sponsor  ICMJE Janssen Infectious Diseases BVBA
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Infectious Diseases BVBA Clinical Trial Janssen Infectious Diseases BVBA
PRS Account Janssen Infectious Diseases BVBA
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP