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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Tuberculosis
Interventions Drug: TMC207
Drug: Placebo
Drug: Background regimen (BR) for MDR-TB (multi-drug resistant tuberculosis)
Enrollment 208
Recruitment Details This trial consisted of an exploratory stage (Stage 1) and a proof-of-efficacy stage (Stage 2). Different participants were enrolled in each stage. Participants in Stage 2 who met protocol-specified criteria were offered open-label treatment with TMC207 after Week 24 (ie, rollover arm).
Pre-assignment Details A total of 208 participants were randomized and 207 (47 participants in Stage 1 and 160 participants in Stage 2) started treatment with placebo or TMC207 (1 participant did not receive study drug). One placebo participant in Stage 2 rolled-over to treatment with TMC207 after Week 24.
Arm/Group Title TMC207 / BR (Stage 1) Placebo / BR (Stage 1) TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Hide Arm/Group Description Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 8. Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 8. Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 24. Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 24.
Period Title: Overall Study
Started 23 24 79 81
Rollover 0 0 0 1
Completed 13 11 50 49 [1]
Not Completed 10 13 29 32
Reason Not Completed
Adverse Event             0             0             3             5
Death             1             0             6             1
Lost to Follow-up             1             1             5             3
Pregnancy             0             0             3             2
Protocol Violation             4             4             3             7
Withdrawal by Subject             3             4             6             7
Inclusion/exclusion criteria not met             0             0             2             6
Not specified             1             4             1             0
Rolled-over to treatment with TMC207             0             0             0             1
[1]
After Week 24, 1 patient rolled over to treatment with TMC207 and was not completed or discontinued.
Arm/Group Title TMC207 / BR (Stage 1) Placebo / BR (Stage 1) TMC207 / BR (Stage 2) Placebo / BR (Stage 2) Total
Hide Arm/Group Description Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 8. Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 8. Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 24. Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 24. Total of all reporting groups
Overall Number of Baseline Participants 23 24 79 81 207
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 24 participants 79 participants 81 participants 207 participants
35.6  (11.66) 33.6  (11.04) 36.2  (13.13) 35.8  (11.01) 35.7  (11.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 24 participants 79 participants 81 participants 207 participants
Female
5
  21.7%
7
  29.2%
27
  34.2%
32
  39.5%
71
  34.3%
Male
18
  78.3%
17
  70.8%
52
  65.8%
49
  60.5%
136
  65.7%
1.Primary Outcome
Title The Time to Sputum Culture Conversion at Week 8 (Stage 1)
Hide Description 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.
Time Frame Week 8, Stage 1
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 study drug and did not have extensively drug resistant tuberculosis (XDR-TB) or non-multi-drug resistant tuberculosis (non-MDR-TB) at the start of the trial and were evaluable for efficacy.
Arm/Group Title TMC207 / BR (Stage 1) Placebo / BR (Stage 1)
Hide Arm/Group Description:
Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: 200 mg TMC207 three times a week administered as 2 tablets, and BR. Only BR after Week 8.
Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 8.
Overall Number of Participants Analyzed 21 23
Median (95% Confidence Interval)
Unit of Measure: Days
51 [1] 
(30 to NA)
NA [2] 
(NA to NA)
[1]
The curve of the upper limit around the time to response curve does not cross 50%.
[2]
The Kaplan-Meier curve of time to response does not cross the 50% line for Placebo.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 1), Placebo / BR (Stage 1)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Cox proportional hazards model
Comments Treatment, lung cavitation and pooled center were used as covaritates.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 11.77
Confidence Interval (2-Sided) 95%
2.26 to 61.23
Estimation Comments [Not Specified]
2.Primary Outcome
Title The Time to Sputum Culture Conversion at Week 24 (Stage 2)
Hide Description 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.
Time Frame Week 24, Stage 2
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 study drug and did not have extensively drug resistant tuberculosis (XDR-TB) or non-multi-drug resistant tuberculosis (non-MDR-TB) at the start of the trial and were evaluable for efficacy.
Arm/Group Title TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Hide Arm/Group Description:
Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 24.
Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 24.
Overall Number of Participants Analyzed 66 66
Median (95% Confidence Interval)
Unit of Measure: Days
83
(56 to 97)
125
(98 to 168)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 2), Placebo / BR (Stage 2)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox proportional hazards model
Comments Treatment, lung cavitation and pooled center were used as covaritates.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.44
Confidence Interval (2-Sided) 95%
1.57 to 3.80
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The Time to Sputum Culture Conversion at Week 24 (Stage 1)
Hide Description 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.
Time Frame Week 24, Stage 1
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 study drug and did not have extensively drug resistant tuberculosis (XDR-TB) or non-multi-drug resistant tuberculosis (non-MDR-TB) at the start of the trial and were evaluable for efficacy.
Arm/Group Title TMC207 / BR (Stage 1) Placebo / BR (Stage 1)
Hide Arm/Group Description:
Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: 200 mg TMC207 three times a week administered as 2 tablets, and BR. Only BR after Week 8.
Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 8.
Overall Number of Participants Analyzed 21 23
Median (95% Confidence Interval)
Unit of Measure: Days
70
(49 to 100)
126
(98 to 134)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 1), Placebo / BR (Stage 1)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments [Not Specified]
Method Cox-proportional hazards model
Comments Treatment, lung cavitation and pooled center were used as covaritates.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.14
Confidence Interval (2-Sided) 95%
1.51 to 6.53
Estimation Comments [Not Specified]
4.Secondary Outcome
Title The Time to Sputum Culture Conversion at Week 72 (Stage 2)
Hide Description 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.
Time Frame Week 72, Stage 2
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 study drug and did not have extensively drug resistant tuberculosis (XDR-TB) or non-multi-drug resistant tuberculosis (non-MDR-TB) at the start of the trial and were evaluable for efficacy.
Arm/Group Title TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Hide Arm/Group Description:
Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 24.
Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 24.
Overall Number of Participants Analyzed 66 66
Median (95% Confidence Interval)
Unit of Measure: Days
86
(70 to 99)
168
(112 to 345)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 2), Placebo / BR (Stage 2)
Comments MGIT negative (Responders)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0290
Comments [Not Specified]
Method Cox proportional hazards model
Comments Treatment, lung cavitation and pooled center were used as covaritates.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
1.05 to 2.59
Estimation Comments [Not Specified]
5.Secondary Outcome
Title The Percentage of Participants With Sputum Culture Conversion (Stage 1)
Hide Description 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.
Time Frame Week 8, 24, and 104 (Stage 1)
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 study drug and did not have extensively drug resistant tuberculosis (XDR-TB) or non-multi-drug resistant tuberculosis (non-MDR-TB) at the start of the trial and were evaluable for efficacy.
Arm/Group Title TMC207 / BR (Stage 1) Placebo / BR (Stage 1)
Hide Arm/Group Description:
Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: 200 mg TMC207 three times a week administered as 2 tablets, and BR. Only BR after Week 8.
Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week.
Overall Number of Participants Analyzed 21 23
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 8 47.6 8.7
Week 24 81.0 65.2
Week 104 (Stage 1 Trial End) 52.4 43.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 1), Placebo / BR (Stage 1)
Comments Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Regression, Logistic
Comments Treatment as covariate
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 38.9
Confidence Interval (2-Sided) 95%
13.97 to 63.88
Parameter Dispersion
Type: Standard Error of the mean
Value: 12.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 1), Placebo / BR (Stage 1)
Comments Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.237
Comments [Not Specified]
Method Regression, Logistic
Comments Treatment as covariate
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 15.7
Confidence Interval (2-Sided) 95%
-10.70 to 42.17
Parameter Dispersion
Type: Standard Error of the mean
Value: 13.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 1), Placebo / BR (Stage 1)
Comments Week 104 (Stage 1 Trial End)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5564
Comments [Not Specified]
Method Regression, Logistic
Comments Treatment as covariate
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 8.9
Confidence Interval (2-Sided) 95%
-21.37 to 39.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 15.02
Estimation Comments [Not Specified]
6.Secondary Outcome
Title The Percentage of Participants With Sputum Culture Conversion (Stage 2)
Hide Description 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.
Time Frame Week 24, Week 72, and Week 120 (Stage 2)
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 study drug and did not have extensively drug resistant tuberculosis (XDR-TB) or non-multi-drug resistant tuberculosis (non-MDR-TB) at the start of the trial and were evaluable for efficacy.
Arm/Group Title TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Hide Arm/Group Description:
Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: 200 mg TMC207 three times a week administered as 2 tablets, and BR. Only BR after Week 8.
Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 8.
Overall Number of Participants Analyzed 66 66
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 24 78.8 57.6
Week 72 71.2 56.1
Week 120 62.1 43.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 2), Placebo / BR (Stage 2)
Comments Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Regression, Logistic
Comments Treatment as covariate
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 21.2
Confidence Interval (2-Sided) 95%
5.59 to 36.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 7.90
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 2), Placebo / BR (Stage 2)
Comments Week 72
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments [Not Specified]
Method Regression, Logistic
Comments Treatment as covariate
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 15.2
Confidence Interval (2-Sided) 95%
-1.21 to 31.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 8.27
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TMC207 / BR (Stage 2), Placebo / BR (Stage 2)
Comments Week 120
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Regression, Logistic
Comments Treatment as covariate
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 18.2
Confidence Interval (2-Sided) 95%
1.28 to 35.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 8.54
Estimation Comments [Not Specified]
Time Frame Stage 1: Adverse Events were collected from 05-Jun-2007 to 04-Dec-2009. Stage 2: Adverse events were collected from 23-Apr-2008 to 31-Jan-2012.
Adverse Event Reporting Description Treatment-Emergent Adverse Events (TEAE) from overall treatment phase are reported. Only patients who had at least one of the TEAEs are listed in the Other (non Serious) Adverse Event table are included in the total number of patients with Non-Serious Adverse Events.
 
Arm/Group Title TMC207 / BR (Stage 1) Placebo / BR (Stage 1) TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Hide Arm/Group Description Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 8. Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 8: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 8. Weeks 1 and 2: 400 mg TMC207 once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: 200 mg TMC207 three times per week administered as 2 tablets, and BR. Only BR after Week 24. Weeks 1 and 2: Placebo once daily administered as 4 tablets, and Background Regimen (BR) for Multi-drug resistant tuberculosis (MDR-TB). Week 3 to 24: Placebo three times per week administered as 2 tablets, and BR. Only BR after Week 24.
All-Cause Mortality
TMC207 / BR (Stage 1) Placebo / BR (Stage 1) TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
TMC207 / BR (Stage 1) Placebo / BR (Stage 1) TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/23 (4.35%)   1/24 (4.17%)   18/79 (22.78%)   15/81 (18.52%) 
Blood and lymphatic system disorders         
Anaemia * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Lymphadenopathy mediastinal * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Ear and labyrinth disorders         
Conductive deafness * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Gastrointestinal disorders         
Abdominal pain * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Pancreatitis acute * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Immune system disorders         
Hypersensitivity * 1  0/23 (0.00%)  0/24 (0.00%)  0/79 (0.00%)  1/81 (1.23%) 
Infections and infestations         
Bronchiectasis * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Pneumonia * 1  0/23 (0.00%)  0/24 (0.00%)  2/79 (2.53%)  0/81 (0.00%) 
Pulmonary tuberculosis * 1  0/23 (0.00%)  0/24 (0.00%)  2/79 (2.53%)  1/81 (1.23%) 
Pyothorax * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Tuberculosis * 1  0/23 (0.00%)  0/24 (0.00%)  2/79 (2.53%)  3/81 (3.70%) 
Injury, poisoning and procedural complications         
Alcohol poisoning * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Drug toxicity * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Humerus fracture * 1  0/23 (0.00%)  0/24 (0.00%)  0/79 (0.00%)  1/81 (1.23%) 
Pelvic fracture * 1  0/23 (0.00%)  0/24 (0.00%)  0/79 (0.00%)  1/81 (1.23%) 
Soft tissue injury * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Metabolism and nutrition disorders         
Diabetic ketoacidosis * 1  1/23 (4.35%)  0/24 (0.00%)  0/79 (0.00%)  0/81 (0.00%) 
Nervous system disorders         
Cerebrovascular accident * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Hemiparesis * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Pregnancy, puerperium and perinatal conditions         
Abortion spontaneous * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  1/81 (1.23%) 
Psychiatric disorders         
Suicidal ideation * 1  0/23 (0.00%)  0/24 (0.00%)  1/79 (1.27%)  0/81 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Haemoptysis * 1  0/23 (0.00%)  0/24 (0.00%)  2/79 (2.53%)  1/81 (1.23%) 
Pneumothorax * 1  0/23 (0.00%)  1/24 (4.17%)  0/79 (0.00%)  1/81 (1.23%) 
Pulmonary cavitation * 1  0/23 (0.00%)  0/24 (0.00%)  0/79 (0.00%)  1/81 (1.23%) 
Surgical and medical procedures         
Surgery * 1  0/23 (0.00%)  0/24 (0.00%)  0/79 (0.00%)  4/81 (4.94%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TMC207 / BR (Stage 1) Placebo / BR (Stage 1) TMC207 / BR (Stage 2) Placebo / BR (Stage 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/23 (91.30%)   23/24 (95.83%)   75/79 (94.94%)   75/81 (92.59%) 
Blood and lymphatic system disorders         
Anaemia * 1  0/23 (0.00%)  0/24 (0.00%)  6/79 (7.59%)  3/81 (3.70%) 
Ear and labyrinth disorders         
Deafness * 1  1/23 (4.35%)  1/24 (4.17%)  5/79 (6.33%)  4/81 (4.94%) 
Deafness bilateral * 1  3/23 (13.04%)  3/24 (12.50%)  5/79 (6.33%)  7/81 (8.64%) 
Deafness unilateral * 1  3/23 (13.04%)  5/24 (20.83%)  10/79 (12.66%)  7/81 (8.64%) 
Ear pain * 1  0/23 (0.00%)  0/24 (0.00%)  4/79 (5.06%)  3/81 (3.70%) 
Tinnitus * 1  0/23 (0.00%)  0/24 (0.00%)  3/79 (3.80%)  11/81 (13.58%) 
Eye disorders         
Visual acuity reduced * 1  0/23 (0.00%)  0/24 (0.00%)  5/79 (6.33%)  2/81 (2.47%) 
Gastrointestinal disorders         
Abdominal pain * 1  0/23 (0.00%)  2/24 (8.33%)  6/79 (7.59%)  6/81 (7.41%) 
Abdominal pain upper * 1  1/23 (4.35%)  1/24 (4.17%)  10/79 (12.66%)  8/81 (9.88%) 
Constipation * 1  1/23 (4.35%)  1/24 (4.17%)  4/79 (5.06%)  0/81 (0.00%) 
Diarrhoea * 1  3/23 (13.04%)  1/24 (4.17%)  5/79 (6.33%)  15/81 (18.52%) 
Dyspepsia * 1  1/23 (4.35%)  1/24 (4.17%)  4/79 (5.06%)  12/81 (14.81%) 
Gastritis * 1  0/23 (0.00%)  0/24 (0.00%)  9/79 (11.39%)  16/81 (19.75%) 
Nausea * 1  6/23 (26.09%)  1/24 (4.17%)  32/79 (40.51%)  30/81 (37.04%) 
Vomiting * 1  1/23 (4.35%)  3/24 (12.50%)  23/79 (29.11%)  22/81 (27.16%) 
General disorders         
Chest pain * 1  0/23 (0.00%)  2/24 (8.33%)  10/79 (12.66%)  8/81 (9.88%) 
Fatigue * 1  0/23 (0.00%)  0/24 (0.00%)  6/79 (7.59%)  1/81 (1.23%) 
Injection site pain * 1  0/23 (0.00%)  0/24 (0.00%)  9/79 (11.39%)  10/81 (12.35%) 
Non-cardiac chest pain * 1  2/23 (8.70%)  2/24 (8.33%)  2/79 (2.53%)  0/81 (0.00%) 
Pain * 1  0/23 (0.00%)  0/24 (0.00%)  2/79 (2.53%)  6/81 (7.41%) 
Pyrexia * 1  0/23 (0.00%)  1/24 (4.17%)  8/79 (10.13%)  7/81 (8.64%) 
Infections and infestations         
Influenza * 1  1/23 (4.35%)  0/24 (0.00%)  6/79 (7.59%)  9/81 (11.11%) 
Nasopharyngitis * 1  0/23 (0.00%)  1/24 (4.17%)  11/79 (13.92%)  4/81 (4.94%) 
Pharyngitis * 1  0/23 (0.00%)  1/24 (4.17%)  6/79 (7.59%)  5/81 (6.17%) 
Urinary tract infection * 1  0/23 (0.00%)  0/24 (0.00%)  5/79 (6.33%)  2/81 (2.47%) 
Investigations         
Alanine aminotransferase increased * 1  0/23 (0.00%)  0/24 (0.00%)  4/79 (5.06%)  1/81 (1.23%) 
Aspartate aminotransferase increased * 1  0/23 (0.00%)  0/24 (0.00%)  5/79 (6.33%)  2/81 (2.47%) 
Blood uric acid increased * 1  1/23 (4.35%)  2/24 (8.33%)  5/79 (6.33%)  3/81 (3.70%) 
Transaminases increased * 1  0/23 (0.00%)  0/24 (0.00%)  5/79 (6.33%)  0/81 (0.00%) 
Weight decreased * 1  0/23 (0.00%)  0/24 (0.00%)  3/79 (3.80%)  5/81 (6.17%) 
Metabolism and nutrition disorders         
Anorexia * 1  0/23 (0.00%)  1/24 (4.17%)  9/79 (11.39%)  6/81 (7.41%) 
Hyperuricaemia * 1  4/23 (17.39%)  3/24 (12.50%)  20/79 (25.32%)  27/81 (33.33%) 
Hypokalaemia * 1  0/23 (0.00%)  0/24 (0.00%)  4/79 (5.06%)  3/81 (3.70%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  4/23 (17.39%)  3/24 (12.50%)  29/79 (36.71%)  22/81 (27.16%) 
Back pain * 1  0/23 (0.00%)  3/24 (12.50%)  9/79 (11.39%)  8/81 (9.88%) 
Musculoskeletal pain * 1  1/23 (4.35%)  0/24 (0.00%)  4/79 (5.06%)  4/81 (4.94%) 
Myalgia * 1  0/23 (0.00%)  1/24 (4.17%)  6/79 (7.59%)  7/81 (8.64%) 
Pain in extremity * 1  2/23 (8.70%)  4/24 (16.67%)  2/79 (2.53%)  3/81 (3.70%) 
Nervous system disorders         
Dizziness * 1  3/23 (13.04%)  2/24 (8.33%)  11/79 (13.92%)  11/81 (13.58%) 
Headache * 1  2/23 (8.70%)  2/24 (8.33%)  23/79 (29.11%)  18/81 (22.22%) 
Neuropathy peripheral * 1  0/23 (0.00%)  0/24 (0.00%)  4/79 (5.06%)  2/81 (2.47%) 
Paraesthesia * 1  0/23 (0.00%)  0/24 (0.00%)  4/79 (5.06%)  4/81 (4.94%) 
Psychiatric disorders         
Depression * 1  0/23 (0.00%)  0/24 (0.00%)  3/79 (3.80%)  7/81 (8.64%) 
Insomnia * 1  0/23 (0.00%)  1/24 (4.17%)  13/79 (16.46%)  10/81 (12.35%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  0/23 (0.00%)  0/24 (0.00%)  7/79 (8.86%)  8/81 (9.88%) 
Dyspnoea * 1  0/23 (0.00%)  1/24 (4.17%)  3/79 (3.80%)  6/81 (7.41%) 
Dyspnoea exertional * 1  0/23 (0.00%)  0/24 (0.00%)  4/79 (5.06%)  0/81 (0.00%) 
Haemoptysis * 1  3/23 (13.04%)  4/24 (16.67%)  15/79 (18.99%)  13/81 (16.05%) 
Pharyngolaryngeal pain * 1  1/23 (4.35%)  2/24 (8.33%)  1/79 (1.27%)  4/81 (4.94%) 
Pleuritic pain * 1  2/23 (8.70%)  0/24 (0.00%)  2/79 (2.53%)  5/81 (6.17%) 
Rhinorrhoea * 1  0/23 (0.00%)  0/24 (0.00%)  4/79 (5.06%)  0/81 (0.00%) 
Skin and subcutaneous tissue disorders         
Acne * 1  1/23 (4.35%)  2/24 (8.33%)  0/79 (0.00%)  2/81 (2.47%) 
Pruritus * 1  2/23 (8.70%)  2/24 (8.33%)  11/79 (13.92%)  15/81 (18.52%) 
Rash * 1  2/23 (8.70%)  4/24 (16.67%)  6/79 (7.59%)  4/81 (4.94%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.0
In Participant Flow, deaths occurring during the trial are reported. In addition, 1 TMC207 and 2 placebo subjects in stage 1 and 4 TMC207 and 1 placebo subject in stage 2 died after discontinuation during 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
Name/Title: Medical Leader
Organization: Janssen Infectious Diseases – Diagnostics BVBA
Phone: 1 609 730-7768
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 )
First Submitted: March 16, 2007
First Posted: March 20, 2007
Results First Submitted: January 29, 2013
Results First Posted: June 25, 2013
Last Update Posted: April 29, 2014