TMC207-TiDP13-C209 Trial to Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Patients With Sputum Smear-positive Pulmonary MDR-TB


Tracking Information

Start Date  ICMJEJuly 2009
Estimated Primary Completion DateJune 2012   (final data collection date for primary outcome measure)
Current 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 ] [ Designated as safety issue: No ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00910871 on ClinicalTrials.gov Archive Site
Current 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 ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJETMC207-TiDP13-C209 Trial to Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Patients With Sputum Smear-positive Pulmonary MDR-TB.
Official Title  ICMJEA 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 patients with sputum smear-positive pulmonary MDR-TB. Approximately 225 patients 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 patients 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 patients will be followed up for 19 months after their last intake of TMC207. Also patients 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 patients 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.

TMC207 will be dosed as 400 mg once daily for the first 2 weeks and 200 mg 3 times/ week for the following 22 weeks, on top of a background regimen.

Study PhasePhase II
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Condition  ICMJETuberculosis
Intervention  ICMJEDrug: TMC207
400mg qd X 2wks then 200mg tiw X 22wks+individualized BR of antibacterial drugs
Study Arms / Comparison Groups001: Experimental
TMC207 400mg qd X 2wks then 200mg tiw X 22wks+individualized BR of antibacterial drugs
Intervention: Drug: TMC207

Recruitment Information

Estimated Enrollment  ICMJE225
Estimated Completion DateJune 2012
Estimated Primary Completion DateJune 2012   (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.
GenderBoth
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:info1@veritasmedicine.com
Location Countries  ICMJEBrazil,   China,   Estonia,   Kenya,   Korea, Republic of,   Latvia,   Peru,   Philippines,   Russian Federation,   South Africa,   Thailand,   Turkey,   Ukraine

Administrative Information

NCT ID  ICMJENCT00910871
Responsible PartyCompound Development Team Leader, Tibotec Pharmaceuticals, Ireland
Study ID Numbers  ICMJECR012352, TMC207-TiDP13-C209
Study Sponsor  ICMJETibotec-Virco Virology BVBA
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:Tibotec-Virco Virology BVBA Clinical TrialTibotec-Virco Virology BVBA
Information Provided ByTibotec-Virco Virology BVBA