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

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ClinicalTrials.gov Identifier: NCT00449644
Recruitment Status : Completed
First Posted : March 20, 2007
Results First Posted : June 25, 2013
Last Update Posted : April 29, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen Infectious Diseases BVBA

Tracking Information
First Submitted Date  ICMJE March 16, 2007
First Posted Date  ICMJE March 20, 2007
Results First Submitted Date  ICMJE January 29, 2013
Results First Posted Date  ICMJE June 25, 2013
Last Update Posted Date April 29, 2014
Study Start Date  ICMJE June 2007
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2013)
  • The Time to Sputum Culture Conversion at Week 8 (Stage 1) [ Time Frame: Week 8, Stage 1 ]
    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.
  • The Time to Sputum Culture Conversion at Week 24 (Stage 2) [ Time Frame: Week 24, Stage 2 ]
    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.
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 History Complete list of historical versions of study NCT00449644 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2013)
  • The Time to Sputum Culture Conversion at Week 24 (Stage 1) [ Time Frame: Week 24, Stage 1 ]
    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.
  • The Time to Sputum Culture Conversion at Week 72 (Stage 2) [ Time Frame: Week 72, Stage 2 ]
    The table below shows the time to sputum culture conversion. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders and censored at their last assessment.
  • The Percentage of Participants With Sputum Culture Conversion (Stage 1) [ Time Frame: Week 8, 24, and 104 (Stage 1) ]
    The table below shows the percentage of participants in Stage 1 who were responders to treatment. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders.
  • The Percentage of Participants With Sputum Culture Conversion (Stage 2) [ Time Frame: Week 24, Week 72, and Week 120 (Stage 2) ]
    The table below shows the percentage of participants in Stage 2 who were responders to treatment. Sputum culture conversion is defined as as having 2 consecutive negative cultures at least 25 days apart, not followed by a confirmed positive during the considered time period. Participants who discontinue or die during the considered time period are considered as non-responders.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Participants With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).
Official Title  ICMJE A 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 participants will be randomized (participants 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 participants 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 participants in Stage 1 have completed 8 weeks double-blind (neither theparticipant 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 participants will be enrolled. After the double-blind treatment phase in both Stage 1 and Stage 2, participants 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Tuberculosis
Intervention  ICMJE
  • Drug: TMC207
    TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 or 22 weeks.
  • Drug: Placebo
    Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 or 22 weeks.
  • Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
    Background Regimen (BR) of antibacterial drugs used in the treatment of TB according to national TB program and selected at the baseline visit as speciified in the protocol for up to 96 weeks.
Study Arms  ICMJE
  • Experimental: TMC207 Stage 1
    TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 6 weeks in addition to Background Regimen (BR) for multi-drug resistant tuberculosis (MDR-TB).
    Interventions:
    • Drug: TMC207
    • Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
  • Placebo Comparator: Placebo Stage 1
    Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 6 weeks in addition to BR for MDR-TB.
    Interventions:
    • Drug: Placebo
    • Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
  • Experimental: TMC207 Stage 2
    TMC207 400mg (4 tablets) once daily for 14 days, 200mg (2 tablets) three times a week for 22 weeks in addition to BR for MDR-TB.
    Interventions:
    • Drug: TMC207
    • Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
  • Placebo Comparator: Placebo Stage 2
    Placebo 4 tablets once daily for 14 days, 2 tablets three times a week for 22 weeks in addition to BR for MDR-TB.
    Interventions:
    • Drug: Placebo
    • Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
Publications *

*   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: March 8, 2012)
208
Original Enrollment  ICMJE
 (submitted: March 16, 2007)
200
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date March 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (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 Brazil,   India,   Latvia,   Peru,   Philippines,   Russian Federation,   South Africa,   Thailand
Removed Location Countries China,   Kenya,   Lithuania,   Uganda
 
Administrative Information
NCT Number  ICMJE NCT00449644
Other Study ID Numbers  ICMJE CR011929
TMC207-TIDP13-C208 ( Other Identifier: Janssen Infectious Diseases BVBA )
2007-004462-40 ( 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 2014

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