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Trial record 1 of 1 for:    00449644
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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).

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier:
NCT00449644
First received: March 16, 2007
Last updated: April 10, 2014
Last verified: April 2014
  Purpose
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.

Condition Intervention Phase
Tuberculosis Drug: TMC207 Drug: Placebo Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Janssen Infectious Diseases BVBA:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 208
Study Start Date: June 2007
Study Completion Date: October 2012
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Drug: TMC207
TMC207 400mg (4 tablets) once daily for 14 days, 200mg (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.
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.
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.
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.
Drug: TMC207
TMC207 400mg (4 tablets) once daily for 14 days, 200mg (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.
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.
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00449644

Locations
Brazil
Rio De Janeiro, Brazil
India
Chennai, India
New Delhi, India
Latvia
Stopinu Region, Latvia
Peru
Lima, Peru
Philippines
Quezon City, Philippines
Russian Federation
Moscow, Russian Federation
South Africa
Bethelsdorp, South Africa
Cape Town, South Africa
Durban, South Africa
George, South Africa
Klerksdorp, South Africa
Sandringham, South Africa
Thailand
Chiang Mai, Thailand
Nakhon, Thailand
Nonthaburi, Thailand
Sponsors and Collaborators
Janssen Infectious Diseases BVBA
Investigators
Study Director: Janssen Infectious Diseases BVBA Clinical Trial Janssen Infectious Diseases BVBA
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier: NCT00449644     History of Changes
Obsolete Identifiers: NCT00614627, NCT00980265
Other Study ID Numbers: CR011929
TMC207-TIDP13-C208 ( Other Identifier: Janssen Infectious Diseases BVBA )
2007-004462-40 ( EudraCT Number )
Study First Received: March 16, 2007
Results First Received: January 29, 2013
Last Updated: April 10, 2014

Keywords provided by Janssen Infectious Diseases BVBA:
Tuberculosis
MDR TB

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

ClinicalTrials.gov processed this record on August 23, 2017