CClinicalTrials.gg
Sign In
CompletedNCT01215110Updated Apr 26, 2017Results posted

Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (TMC207-CL001)

A Phase 2 interventional study of TMC207 and Rifafour e-275 mg in Pulmonary Tuberculosis, sponsored by Global Alliance for TB Drug Development. Completed at 1 site in South Africa. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-04-26.

Sponsored by Global Alliance for TB Drug Development · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
68
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of TMC207 at multiple doses as determined by the rate of change of log10 colony forming units (CFU) per ml sputum over the time period Day 7-14 in participants with smear positive pulmonary tuberculosis (TB). A control group will receive standard treatment.

02

Conditions studied

  • Pulmonary Tuberculosis

Keywords

  • Bedaquiline
  • Sirturo
  • Early Bactericidal Activity
  • EBA
  • Pulmonary Tuberculosis
  • TMC207
03

In context

Tuberculosis

1,417 studies on the registry are indexed under Tuberculosis; 208 are open to participants now.

This study's enrollment of 68 is below the median of 150 across 952 interventional studies indexed under Tuberculosis.

Browse Tuberculosis studies →

Lead sponsor

Global Alliance for TB Drug Development is the lead sponsor of 30 studies on the registry; 1 is open to participants now.

Of its 10 completed or terminated interventional studies of FDA-regulated products, 6 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Provide written, informed consent prior to all trial-related procedures including HIV testing.
  • Male or female, aged between 18 and 65 years inclusive.
  • Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
  • Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary TB.
  • A chest X-ray picture which in the opinion of the Investigator is compatible with TB.
  • Sputum positive on direct microscopy for acid-fast bacilli ...(at least 1+ on the International Union Against Tuberculosis and Lung Disease (IUATLD)/World Health Organization (WHO) scale).
  • Ability to produce an adequate volume of sputum as estimated from a spot assessment (estimated 10 ml or more overnight production).
  • Females may participate if they are of non-childbearing potential, if they are using effective birth control methods and are willing to continue practicing birth control methods throughout treatment or if they are non-heterosexually active or willing to practice sexual abstinence throughout the treatment period or have a vasectomized partner (confirmed sterile). Therefore to be eligible for this study women of childbearing potential should either:1) use a double barrier method to prevent pregnancy (i.e. use a condom with either diaphragm or cervical cap) or 2) use hormonal based contraceptives in combination with a barrier contraceptive, or 3) use an intrauterine device in combination with a barrier contraceptive. They must also be willing to continue these contraception until 6 months after last study drug or 6 months after discontinuation from study medication in case of premature discontinuation. (Note: Hormone-based contraception may not be reliable when taking TMC207; therefore, hormone-based contraceptives cannot be used by female patients to prevent pregnancy).
  • Male patients must be willing to use a condom with spermicide when having heterosexual intercourse throughout treatment and until 1 month after last study drug administration or 1 month after discontinuation from study medication in case of premature discontinuation.

Exclusion criteria

Exclusion Criteria:

  1. Evidence of clinically significant metabolic, gastrointestinal neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
  2. Known or suspected hypersensitivity to study medications (including any rifamycin antibiotics)
  3. Rifampicin-resistant and/or isoniazid-resistant bacteria detected with a sputum specimen collected within the pre-treatment period and tested at the study laboratory.
  4. Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the investigator.
  5. Current or past history of alcohol and/or drug use that, in the investigator's opinion, would compromise the participant's safety or compliance to the study protocol procedures.

  6. HIV infected patients:

    1. having a cluster of differentiation 4 (CD4)+ count \<300 cells/µL;
    2. or having received antiretroviral therapy medication within the last 90 days:
    3. or having received oral or intravenous antifungal medication within the last 90 days;
    4. or with an AIDS-defining opportunistic infection or malignancies (except pulmonary TB).
  7. Significant cardiac arrhythmia requiring medication
  8. Having participated in other clinical studies with investigational agents within 8 weeks prior to trial start.

  9. Patients with the following QT/corrected QT(QTc) interval characteristics at screening:

    1. Marked prolongation of QT/QTc interval, e.g., confirmed demonstration of QT corrected for heart rate using Fridericia's method (QTcF) interval >450 ms at screening;
    2. History of additional risk factors for Torsade de Pointes, e.g., heart failure, hypokalemia, family history of Long QT Syndrome;
    3. Use of concomitant medications that prolong the QT/QTc interval listed as disallowed medication in Section 2.10.2;
    4. Pathological Q waves (defined as >40ms or depth >0.4-0.5mV);
    5. Evidence of ventricular pre-excitation;
    6. ECG evidence of complete or incomplete left bundle branch block or right bundle branch block;
    7. Evidence of second or third degree heart block;
    8. Intraventricular conduction delay with QRS duration >120ms;
    9. Bradycardia as defined by sinus rate \<50bpm
  10. Women who are pregnant or breastfeeding
  11. History and/or presence (or evidence) of neuropathy or epilepsy.
  12. Diabetics using insulin
  13. Poor general condition where any delay in treatment cannot be tolerated per discretion of Investigator.
  14. Previously received treatment with TMC207 as part of a clinical trial.
  15. Treatment received with any drug active against Mycobacterium tuberculosis within 3 months prior to Visit 1.
  16. Any disease or conditions in which any of the medicinal products listed in the section pertaining to prohibited medications is used.

  17. Patients with the following toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007):

    1. creatinine grade 2 or greater (>1.5 times upper limit of normal [ULN]);
    2. lipase grade 3 or greater (>2.0 x ULN);
    3. hemoglobin grade 4 (\<6.5 g/dL) except after discussion with the Medical Monitor;
    4. aspartate aminotransferase (AST) grade 4 (>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with Medical Monitor;
    5. alanine aminotransferase (ALT) grade 4 (>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with Medical Monitor;
    6. alkaline phosphatase (ALP) grade 4 (>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with Medical Monitor;
    7. total bilirubin grade 3 or greater (>2.00 x ULN, or >1.50 x ULN when accompanied by any increase in other liver function test) to be excluded, grade 2 (>1.50 x ULN, or >1.25 x ULN when accompanied by any increase in other liver function test) must be discussed with the Medical Monitor
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
68 participants (actual)

Study arms

  • Experimental
    TMC207 700/500/400

    TMC207- 700 mg Day 1; 500 mg Day 2; 400 mg Days 3-14

    Drug: TMC207

  • Experimental
    TMC207 500/400/300

    TMC207- 500 mg Day 1; 400 mg Day 2 and 300 mg Days 3-14.

    Drug: TMC207

  • Experimental
    TMC207 400/300/200

    TMC207- 400 mg Day 1; 300 mg Day 2 and 200 mg Days 3-14

    Drug: TMC207

  • Experimental
    TMC207 200/100

    TMC207- 200 mg Day 1 and 100 mg Days 2-14

    Drug: TMC207

  • Active comparator
    Rifafour e-275 mg

    Rifafour e-275 mg

    Drug: Rifafour e-275 mg

Interventions

  • DrugTMC207
  • DrugRifafour e-275 mg
06

What researchers measure

Primary outcomes

  1. Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).

    The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

    Time frame: Fourteen consecutive days of treatment

Secondary outcomes

  1. Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).

    The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Since Day 7 is later than the node day, the rate of change for this outcome is equal to the slope at Day 14. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

    Time frame: Days 7-14 of fourteen consecutive days of treatment

  2. Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).

    The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

    Time frame: Days 2-14 of fourteen consecutive days of treatment

  3. Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).

    The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Since this range (Days0-2) is before the node day, the rate of change for this outcome is equal to the slope at Day 0. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

    Time frame: Two consecutive days of treatment

  4. Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)

    The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

    Time frame: Fourteen consecutive days of treatment

  5. Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2)

    The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

    Time frame: Two consecutive days of treatment

  6. Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14)

    The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

    Time frame: Days 2-14 of fourteen consecutive days of treatment

  7. Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 7-14)

    The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

    Time frame: Days 7-14 of fourteen consecutive days of treatment

  8. Summary of Statistical Analysis of TMC207 Maximum Plasma Concentration Following Dosing (C(Max)) on Days 1 and 14

    Time frame: Day 1 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose) or Day 14 (0, 1, 3, 5, 6, 8, 12, 24, and 30 hour post-dose)

  9. Summary of Statistical Analysis of TMC207 Time of Maximum Plasma Concentration (T(Max)) on Days 1 and 14

    Time frame: Day 1 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose) or Day 14 (0, 1, 3, 5, 6, 8, 12, 24, and 30 hour post-dose)

  10. Summary of Statistical Analysis of TMC207 Area Under the Concentration-time Curve Over the Dose Interval of 0 to 24 h (AUC(0-24)) on Day 1 and Day 14

    Time frame: Day 1 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose) or Day 14 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose)

07

Results

Posted Apr 26, 2017

Participant flow

Participant flow — Overall Study
MilestoneTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Started151515158
Completed151513148
Not completed00210

Outcome measures

PrimaryEarly Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).

The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

Time frame:
Fourteen consecutive days of treatment
Reported as:
Mean · log10CFU/ml/day
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).
log10CFU/ml/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).0.040 ± 0.0680.056 ± 0.0510.077 ± 0.0640.104 ± 0.0770.112 ± 0.077
SecondaryEarly Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).

The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Since Day 7 is later than the node day, the rate of change for this outcome is equal to the slope at Day 14. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

Time frame:
Days 7-14 of fourteen consecutive days of treatment
Reported as:
Mean · log10CFU/ml/day
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).
log10CFU/ml/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).0.053 ± 0.0880.086 ± 0.0480.098 ± 0.0840.107 ± 0.0820.046 ± 0.101
SecondaryEarly Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).

The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

Time frame:
Days 2-14 of fourteen consecutive days of treatment
Reported as:
Mean · log10CFU/ml/day
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).
log10CFU/ml/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).0.047 ± 0.0740.071 ± 0.0470.088 ± 0.0710.106 ± 0.0780.046 ± 0.101
SecondaryEarly Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).

The rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group. The nodes (point of inflection, i.e. where slope changes) used in these bi-linear regressions, as determined by visual inspection, were Day 3.5. node. Throughout the analyses, the established node at Day 2.5 was used in the Rifafour e-275 arm. Since this range (Days0-2) is before the node day, the rate of change for this outcome is equal to the slope at Day 0. Note that to facilitate interpretation the sign of these slopes were reversed for log10CFU/ml.

Time frame:
Two consecutive days of treatment
Reported as:
Mean · log10CFU/ml/day
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).
log10CFU/ml/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).0.004 ± 0.168-0.033 ± 0.1280.015 ± 0.1490.093 ± 0.1360.413 ± 0.291
SecondaryRate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)

The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

Time frame:
Fourteen consecutive days of treatment
Reported as:
Mean · hours/day
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)
hours/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)4.0 ± 5.14.2 ± 3.14.9 ± 5.15.4 ± 3.414.3 ± 11.4
SecondaryRate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2)

The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

Time frame:
Two consecutive days of treatment
Reported as:
Mean · hours/day
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2)
hours/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2)1.5 ± 2.33.7 ± 4.34.1 ± 4.76.2 ± 3.327.3 ± 13.8
SecondaryRate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14)

The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

Time frame:
Days 2-14 of fourteen consecutive days of treatment
Reported as:
Mean · hours/day
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14)
hours/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14)4.4 ± 5.94.3 ± 3.15.1 ± 5.35.3 ± 3.511.5 ± 13.9
SecondaryRate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 7-14)

The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated from the two slopes of the bi-linear (piece-wise) regression, for each treatment group.

Time frame:
Days 7-14 of fourteen consecutive days of treatment
Reported as:
Mean · hours/day
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 7-14)
hours/dayTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 7-14)6.9 ± 11.24.8 ± 4.45.9 ± 7.24.4 ± 5.011.5 ± 13.9
SecondarySummary of Statistical Analysis of TMC207 Maximum Plasma Concentration Following Dosing (C(Max)) on Days 1 and 14
Time frame:
Day 1 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose) or Day 14 (0, 1, 3, 5, 6, 8, 12, 24, and 30 hour post-dose)
Reported as:
Mean · ng/mL
Summary of Statistical Analysis of TMC207 Maximum Plasma Concentration Following Dosing (C(Max)) on Days 1 and 14
ng/mLTMC207 100TMC207 200TMC207 300TMC207 400
C(max) Day 11846.13 ± 613.552700.73 ± 858.543128.00 ± 1239.265386.67 ± 3069.95
C(max) Day 141553.27 ± 691.362884.67 ± 789.443902.31 ± 771.775178.57 ± 2663.75
SecondarySummary of Statistical Analysis of TMC207 Time of Maximum Plasma Concentration (T(Max)) on Days 1 and 14
Time frame:
Day 1 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose) or Day 14 (0, 1, 3, 5, 6, 8, 12, 24, and 30 hour post-dose)
Reported as:
Mean · hour
Summary of Statistical Analysis of TMC207 Time of Maximum Plasma Concentration (T(Max)) on Days 1 and 14
hourTMC207 100TMC207 200TMC207 300TMC207 400
T(max) Day 15.33 ± 1.805.20 ± 1.905.53 ± 0.835.67 ± 1.05
T(max) Day 145.13 ± 1.194.60 ± 1.065.15 ± 1.465.29 ± 1.59
SecondarySummary of Statistical Analysis of TMC207 Area Under the Concentration-time Curve Over the Dose Interval of 0 to 24 h (AUC(0-24)) on Day 1 and Day 14
Time frame:
Day 1 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose) or Day 14 (0, 1, 3, 5, 6, 8, 12, and 24 hour post-dose)
Reported as:
Mean · ng*h/mL
Summary of Statistical Analysis of TMC207 Area Under the Concentration-time Curve Over the Dose Interval of 0 to 24 h (AUC(0-24)) on Day 1 and Day 14
ng*h/mLTMC207 100TMC207 200TMC207 300TMC207 400
AUC(0-24) Day 118995.57 ± 6947.9226619.51 ± 8453.0931357.35 ± 10596.7453179.27 ± 20699.64
AUC(0-24) Day 1418689.03 ± 4450.5633314.07 ± 5780.0250547.15 ± 11914.1669069.64 ± 27062.36

Adverse events

Collected over 49 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TMC207 100—0/15 (0%)4/15 (26.7%)
TMC207 200—0/15 (0%)4/15 (26.7%)
TMC207 300—0/15 (0%)5/15 (33.3%)
TMC207 400—1/15 (6.7%)5/15 (33.3%)
Rifafour e-275 mg—0/8 (0%)2/8 (25%)
Most frequent serious events
Most frequent serious events
EventTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
HepatitisHepatobiliary disorders0/150/150/151/150/8
Most frequent other events
Showing 10 of 19
Most frequent other events
EventTMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mg
VomitingGastrointestinal disorders0/150/150/151/152/8
HeadacheNervous system disorders2/150/151/151/150/8
PruritusSkin and subcutaneous tissue disorders0/150/152/151/150/8
Weight decreasedInvestigations0/150/150/150/151/8
Non-cardiac chest painGeneral disorders0/150/150/150/151/8
DizzinessNervous system disorders0/150/150/150/151/8
Aspartate aminotransferase increasedInvestigations1/150/150/150/150/8
Hepatic enzyme increasedInvestigations0/151/150/150/150/8
Chest discomfortGeneral disorders0/150/151/150/150/8
Body tineaInfections and infestations0/151/150/150/150/8

Baseline characteristics

Age, Continuous
Age, Continuous(years)TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Mean29.5 ± 9.434.7 ± 18.131.4 ± 7.431.8 ± 10.926.1 ± 4.927 ± 11.45
Sex: Female, Male
Sex: Female, Male(Participants)TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Female6475224
Male911810644
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Black6597633
Mixed Ethnic91068235
Height
Height(meters (m))TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Mean1.638 ± 0.0821.677 ± 0.0941.674 ± 0.0821.660 ± 0.0571.660 ± 0.0871.662 ± 0.080
Weight at Day 1
Weight at Day 1(kilograms (kg))TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Mean53.0 ± 7.7452.5 ± 7.5552.7 ± 8.2050.6 ± 5.9649.1 ± 6.6951.8 ± 7.23
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Mean19.80 ± 2.98818.63 ± 1.95518.80 ± 2.75418.36 ± 2.17417.83 ± 2.01818.77 ± 2.459
HIV Status
HIV Status(participants)TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Positive111216
Negative14141413762
Baseline log10 colony forming units (CFU) of M. Tuberculosis per ml sputum
Baseline log10 colony forming units (CFU) of M. Tuberculosis per ml sputum(log(10) CFU/ml)TMC207 100TMC207 200TMC207 300TMC207 400Rifafour e-275 mgTotal
Mean6.302 ± 0.6976.001 ± 0.9036.071 ± 1.0876.625 ± 0.7565.995 ± 1.0186.199 ± 0.892

1 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Karl Bremer Hospital
    Belville, Cape Town 7531, South Africa
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 26, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01215110
Lead sponsor
Global Alliance for TB Drug Development
Responsible party
Sponsor
First posted
Oct 6, 2010
Start date
Apr 2010
Primary completion
Aug 2010
Completion
Sep 2010
Results posted
Apr 26, 2017
Last update
Apr 26, 2017

Study contacts

Andreas Diacon
principal investigator · TASK APPLIED SCIENCE, Karl Bremer Hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Tuberculosis→

Other studies from this sponsor

Global Alliance for TB Drug Development

Start the discussion