Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT00910871
Previous Study | Return to List | Next Study

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.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Tuberculosis
Interventions Drug: TMC207
Drug: Background Regimen (BR) for MDR-TB
Enrollment 241
Recruitment Details A Phase II open label trial with TMC207 as part of multi-drug resistant mycobacterium tuberculosis (MDR-TB) treatment regimen in participants with sputum smear-positive pulmonary infection with MDR-TB.
Pre-assignment Details A total of 241 participants were enrolled in the study; 8 participants were withdrawn from the study before study drug administration and 233 started treatment with study drug.
Arm/Group Title TMC207
Hide Arm/Group Description Participants will receive 400 milligram (mg) TMC207 tablets orally 2 times a day along with background regimen from Day 1 to Week 2 followed by 200 mg TMC207 tablets orally 3 times a day from Week 3 to Week 24 along with background regimen, then background therapy from Week 25 to end of study (Week 120).
Period Title: Overall Study
Started 233
Completed 179
Not Completed 54
Reason Not Completed
Adverse Event             5
Death             12
Lost to Follow-up             8
Protocol Violation             11
Withdrawal by Subject             12
Subject didn’t meet eligibility criteria             5
Undefined             1
Arm/Group Title TMC207
Hide Arm/Group Description Participants will receive 400 milligram (mg) TMC207 tablets orally 2 times a day along with background regimen from Day 1 to Week 2 followed by 200 mg TMC207 tablets orally 3 times a day from Week 3 to Week 24 along with background regimen, then background therapy from Week 25 to end of study (Week 120).
Overall Number of Baseline Participants 233
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all participants who had at least 1 dose of TMC207, regardless of their compliance with the protocol.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 233 participants
34.6  (12.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 233 participants
Female
83
  35.6%
Male
150
  64.4%
1.Primary Outcome
Title The Median Time to Sputum Culture Conversion
Hide Description 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]).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) population used for all efficacy analyses included all randomized participants who received at least 1 dose of TMC207 excluding participants with drug-susceptible tuberculosis (DS-TB) or participants that were not evaluable for efficacy.
Arm/Group Title TMC207
Hide Arm/Group Description:
Participants will receive 400 milligram (mg) TMC207 tablets orally 2 times a day along with background regimen from Day 1 to Week 2 followed by 200 mg TMC207 tablets orally 3 times a day from Week 3 to Week 24 along with background regimen, then background therapy from Week 25 to end of study (Week 120).
Overall Number of Participants Analyzed 205
Median (95% Confidence Interval)
Unit of Measure: Days
57
(56.00 to 83.00)
2.Secondary Outcome
Title The Percentage of Participants With Sputum Culture Conversion
Hide Description 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.
Time Frame Week 120
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) population used for all efficacy analyses included all randomized participants who received at least 1 dose of TMC207 excluding participants with drug-susceptible tuberculosis (DS-TB) or participants that were not evaluable for efficacy.
Arm/Group Title TMC207
Hide Arm/Group Description:
Participants will receive 400 milligram (mg) TMC207 tablets orally 2 times a day along with background regimen from Day 1 to Week 2 followed by 200 mg TMC207 tablets orally 3 times a day from Week 3 to Week 24 along with background regimen, then background therapy from Week 25 to end of study (Week 120).
Overall Number of Participants Analyzed 205
Measure Type: Number
Unit of Measure: Percentage of Participants
72.2
Time Frame Baseline up to Week 120
Adverse Event Reporting Description Only participants who had at least one of the treatment emergent adverse events (TEAEs) listed in the other (non-serious) adverse events table are included in the total number of participants with non-serious adverse events.
 
Arm/Group Title TMC207
Hide Arm/Group Description Participants will receive 400 milligram (mg) TMC207 tablets orally 2 times a day along with background regimen from Day 1 to Week 2 followed by 200 mg TMC207 tablets orally 3 times a day from Week 3 to Week 24 along with background regimen, then background therapy from Week 25 to end of study (Week 120).
All-Cause Mortality
TMC207
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
TMC207
Affected / at Risk (%)
Total   47/233 (20.17%) 
Blood and lymphatic system disorders   
Anaemia * 1  2/233 (0.86%) 
Cardiac disorders   
Cardiac failure * 1  1/233 (0.43%) 
Cardiac failure congestive * 1  2/233 (0.86%) 
Cor pulmonale * 1  1/233 (0.43%) 
Ear and labyrinth disorders   
Deafness * 1  1/233 (0.43%) 
Gastrointestinal disorders   
Ileus paralytic * 1  1/233 (0.43%) 
Vomiting * 1  1/233 (0.43%) 
Alcoholic pancreatitis * 1  1/233 (0.43%) 
Gastritis * 1  1/233 (0.43%) 
Inguinal hernia * 1  1/233 (0.43%) 
General disorders   
Treatment failure * 1  2/233 (0.86%) 
Hepatobiliary disorders   
Cholelithiasis * 1  1/233 (0.43%) 
Liver disorder * 1  1/233 (0.43%) 
Hepatitis * 1  1/233 (0.43%) 
Infections and infestations   
Gastroenteritis * 1  1/233 (0.43%) 
Lung infection * 1  2/233 (0.86%) 
Pneumonia * 1  3/233 (1.29%) 
Tuberculosis * 1  6/233 (2.58%) 
Hepatitis a * 1  1/233 (0.43%) 
Lung abscess * 1  1/233 (0.43%) 
Lymph node tuberculosis * 1  1/233 (0.43%) 
Pyopneumothorax * 1  1/233 (0.43%) 
Injury, poisoning and procedural complications   
Concussion * 1  1/233 (0.43%) 
Contusion * 1  1/233 (0.43%) 
Investigations   
Blood glucose fluctuation * 1  1/233 (0.43%) 
Electrocardiogram qt prolonged * 1  1/233 (0.43%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  1/233 (0.43%) 
Dehydration * 1  1/233 (0.43%) 
Diabetes mellitus inadequate control * 1  1/233 (0.43%) 
Hyponatraemia * 1  1/233 (0.43%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  1/233 (0.43%) 
Fistula * 1  1/233 (0.43%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Basal cell carcinoma * 1  1/233 (0.43%) 
Nervous system disorders   
Cerebral haemorrhage * 1  1/233 (0.43%) 
Ischaemic cerebral infarction * 1  1/233 (0.43%) 
Neurotoxicity * 1  1/233 (0.43%) 
Psychiatric disorders   
Emotional disorder * 1  1/233 (0.43%) 
Hallucination * 1  1/233 (0.43%) 
Psychiatric symptom * 1  1/233 (0.43%) 
Renal and urinary disorders   
Renal impairment * 1  1/233 (0.43%) 
Ureteric stenosis * 1  1/233 (0.43%) 
Respiratory, thoracic and mediastinal disorders   
Chronic obstructive pulmonary disease * 1  1/233 (0.43%) 
Dyspnoea * 1  2/233 (0.86%) 
Hydropneumothorax * 1  2/233 (0.86%) 
Pneumothorax * 1  5/233 (2.15%) 
Cough * 1  1/233 (0.43%) 
Haemoptysis * 1  4/233 (1.72%) 
Pulmonary bulla * 1  1/233 (0.43%) 
Pulmonary haemorrhage * 1  1/233 (0.43%) 
Respiratory failure * 1  1/233 (0.43%) 
Surgical and medical procedures   
Surgery * 1  1/233 (0.43%) 
Lung operation * 1  1/233 (0.43%) 
Vascular disorders   
Hypertension * 1  1/233 (0.43%) 
Hypovolaemic shock * 1  1/233 (0.43%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TMC207
Affected / at Risk (%)
Total   179/233 (76.82%) 
Blood and lymphatic system disorders   
Anaemia * 1  13/233 (5.58%) 
Ear and labyrinth disorders   
Tinnitus * 1  18/233 (7.73%) 
Gastrointestinal disorders   
Diarrhoea * 1  27/233 (11.59%) 
Nausea * 1  35/233 (15.02%) 
Vomiting * 1  26/233 (11.16%) 
Abdominal pain * 1  14/233 (6.01%) 
Dyspepsia * 1  14/233 (6.01%) 
General disorders   
Injection site pain * 1  15/233 (6.44%) 
Chest pain * 1  17/233 (7.30%) 
Infections and infestations   
Nasopharyngitis * 1  17/233 (7.30%) 
Upper respiratory tract infection * 1  13/233 (5.58%) 
Investigations   
Blood uric acid increased * 1  20/233 (8.58%) 
Alanine aminotransferase increased * 1  12/233 (5.15%) 
Aspartate aminotransferase increased * 1  14/233 (6.01%) 
Hepatic enzyme increased * 1  12/233 (5.15%) 
Metabolism and nutrition disorders   
Hyperuricaemia * 1  36/233 (15.45%) 
Hypokalaemia * 1  19/233 (8.15%) 
Decreased appetite * 1  12/233 (5.15%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  35/233 (15.02%) 
Pain in extremity * 1  16/233 (6.87%) 
Nervous system disorders   
Dizziness * 1  13/233 (5.58%) 
Headache * 1  31/233 (13.30%) 
Psychiatric disorders   
Insomnia * 1  18/233 (7.73%) 
Respiratory, thoracic and mediastinal disorders   
Haemoptysis * 1  17/233 (7.30%) 
Skin and subcutaneous tissue disorders   
Pruritus * 1  18/233 (7.73%) 
Rash * 1  13/233 (5.58%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.1
In Participant Flow, the 12 deaths shown are restricted to those that occurred during the trial and do not include 4 deaths reported after discontinuation in long-term survival follow-up.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
It is the policy of the sponsor not to allow the investigators to publish their results or findings prior to the sponsor’s publication of the overall trial results.The investigator agrees that before he/she publishes any results of this trial, he/she shall provide the sponsor with at least 45 days for full review of the prepublication manuscript prior to submission of the manuscript to the publisher.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Leader
Organization: Janssen Infectious Diseases – Diagnostics BVBA
Phone: 1 609 730-7768
Layout table for additonal information
Responsible Party: Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier: NCT00910871     History of Changes
Obsolete Identifiers: NCT00980811
Other Study ID Numbers: CR012352
TMC207-TiDP13-C209 ( Other Identifier: Janssen Infectious Diseases BVBA )
2008-008444-25 ( EudraCT Number )
First Submitted: May 28, 2009
First Posted: June 1, 2009
Results First Submitted: January 30, 2013
Results First Posted: May 16, 2013
Last Update Posted: April 24, 2015