TMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Patients With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB)


Tracking Information

Start Date  ICMJEMay 2007
Estimated Primary Completion DateFebruary 2010   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: December 20, 2007)
The primary outcome parameter will be the time to sputum culture conversion during treatment with TMC207 or placebo [ Time Frame: Stage 1 consists of 8 week treatment period (11 visits). Stage II consists of 24 week treatment period (19 visits). All subjects will be followed for 96 weeks after last dose of TMC207 or placebo. ] [ Designated as safety issue: Yes ]
Original Primary Outcome Measures  ICMJE 
 (submitted: March 16, 2007)
  • The primary outcome parameter will be the time to sputum culture conversion during treatment with TMC207 or placebo
  • Primary and secondary outcomes will be measured when all patients have completed stages 1 and 2, respectively, with a final analysis of a
Change HistoryComplete list of historical versions of study NCT00449644 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: February 14, 2008)
Pharmacokinetics of TMC207 and its N-monodesmethyl metabolite (M2) in plasma and sputum, pharmacokinetic/pharmacodynamic relationships for activity and tolerability/safety, and drug-drug interactions between TMC207 and drugs in the BR will be assessed. [ Time Frame: Stage 1 consists of 8 week treatment period (11 visits). Stage II consists of 24 week treatment period (19 visits). All subjects will be followed for 96 weeks after last dose of TMC207 or placebo. ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJETMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Patients With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).
Official Title  ICMJEA Phase II, Placebo-controlled, Double-blind, Randomized Trial to Evaluate the Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Subjects With Newly Diagnosed Sputum Smear-positive Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).
Brief Summary

The objective of this study is to demonstrate that the antibacterial activity of TMC207 is better than placebo when added to a standardized Background Regimen (BR) for treatment of multi-drug resistant TB. Also safety and tolerability will be evaluated.

Detailed Description

The trial will be conducted in 2 consecutive stages, an exploratory (investigative) stage (Stage 1) and a proof of effectiveness stage (Stage 2). During Stage 1, a panel of 50 patients will be randomized (patients are assigned different treatments based on chance) to receive either TMC207 or placebo for 8 weeks on top of a BR. In Stage 2, another panel of 150 patients will be randomized to receive either TMC207 or placebo for 24 weeks on top of a BR. TMC207 will be dosed as 400 mg every day for the first 2 weeks, and as 200 mg 3 times/week for the following 6 or 22 weeks during Stages 1 and 2, respectively.When the patients in Stage 1 have completed 8 weeks double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage) treatment with TMC207 or placebo (or have discontinued earlier), the primary Stage 1 analysis will be performed on all data of the first 8 weeks of treatment.Following this Stage 1 analysis, Stage 2 will be initiated and a panel of 150 new patients will be enrolled.The primary efficacy analysis will be performed on all Stage 2 patients when they have completed the 24-week double blind treatment with TMC207 or placebo (or have discontinued earlier). After the double-blind treatment phase in both Stage 1 and Stage 2, patients will continue to receive MDR-TB treatment as per national treatment guidelines. They will be followed for safety, tolerability, pharmacokinetics, and microbiological efficacy for 96 weeks after receiving their last dose of TMC207 or placebo. The Data Safety Monitoring Board Committee will review these data on a regular basis. The DSMB/DSMC is a group of experts in tuberculosis and clinical trial conduct who have no commercial interests in the development of TMC207 and the company (Tibotec, BVBA) that is developing the new TB drug. During Stage 1, a panel of 50 patients will be randomized to receive either TMC207 or placebo for 8 weeks on top of a BR. In Stage 2, another panel of 150 patients will be randomized to receive either TMC207 or placebo for 24 weeks on top of a BR. TMC207 will be dosed as 400 mg per day for the first 2 weeks, and as 200 mg 3 times/week

Study PhasePhase II
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Safety/Efficacy Study
Condition  ICMJETuberculosis
Intervention  ICMJE
  • Drug: TMC207
    400mg (4 tabs) QD for 14 days, 200mg (2 tabs) tiw for 6 or 22 weeks
  • Drug: Placebo
    4 tabs QD for 14 days, 2 tabs tiw for 6 or 22 weeks
Study Arms / Comparison Groups
  • 001: Experimental
    TMC207 400mg (4 tabs) QD for 14 days, 200mg (2 tabs) tiw for 6 or 22 weeks
    Intervention: Drug: TMC207
  • 002: Placebo Comparator
    Placebo 4 tabs QD for 14 days, 2 tabs tiw for 6 or 22 weeks
    Intervention: Drug: Placebo
Publications *Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, Pistorius C, Krause R, Bogoshi M, Churchyard G, Venter A, Allen J, Palomino JC, De Marez T, van Heeswijk RP, Lounis N, Meyvisch P, Verbeeck J, Parys W, de Beule K, Andries K, Mc Neeley DF. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009 Jun 4;360(23):2397-405.

Recruitment Information

Estimated Enrollment  ICMJE200
Estimated Completion DateFebruary 2012
Estimated Primary Completion DateFebruary 2010   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Females of non-childbearing potential
  • Patients with newly diagnosed sputum smear-positive pulmonary MDR-TB infection
  • Patients must consent to HIV-testing
  • Patients must be willing to discontinue all TB drugs to allow 7 days washout
  • Patients having normal weight
  • Patients are willing to be hospitalized per standard of care.

Exclusion Criteria:

  • Previously having been treated for MDR-TB
  • Having a significant cardiac arrhythmia that requires medication
  • For HIV infected patients, having a CD4+ count < 300 cells/µL
  • Patients with complicated or severe extrapulmonary manifestations of TB or neurological manifestations of TB
  • Patients who will require surgical procedure for management of their TB
  • Evidence of chorioretinitis, optic neuritis, or uveitis at screening
  • Having had a drug susceptibility test performed prior to screening and being not susceptible to at least 3 of the 5 classes of TB drugs used to treat MDR-TB
  • Women who are pregnant and/or breastfeeding.
GenderBoth
Ages18 Years to 65 Years
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,   India,   Latvia,   Peru,   Philippines,   Russian Federation,   South Africa,   Thailand

Administrative Information

NCT ID  ICMJENCT00449644
Responsible PartyCompound Development Team Leader TMC207, Tibotec BVBA
Study ID Numbers  ICMJECR011929, TMC207-TIDP13-C208
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