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    The EU Clinical Trials Register currently displays   43889   clinical trials with a EudraCT protocol, of which   7298   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    EudraCT Number:2007-004462-40
    Sponsor's Protocol Code Number:TMC207-TiDP13-C208
    National Competent Authority:Latvia - SAM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-11-05
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedLatvia - SAM
    A.2EudraCT number2007-004462-40
    A.3Full title of the trial
    A Phase II, placebo-controlled, double-blind, randomized trial to evaluate the anti-bacterial activity, safety, and tolerability of TMC207 in subjects with sputum smear-positive pulmonary infection with multi-drug resistant Mycobacterium tuberculosis (MDR-TB).
    A.4.1Sponsor's protocol code numberTMC207-TiDP13-C208
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorTibotec BVBA
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/314
    D.3 Description of the IMP
    D.3.1Product nameTMC207 (as fumarate salt), R403323
    D.3.2Product code F001
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 845533-86-0
    D.3.9.2Current sponsor codeTMC207
    D.3.9.3Other descriptive nameR403323
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product Information not present in EudraCT
    D. ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D. on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10044755
    E.1.2Term Tuberculosis
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Stage 1: The objective of Stage 1 is to evaluate the pharmacokinetics, anti-bacterial activity, safety, and tolerability of TMC207 compared to placebo when added for 8 weeks to a BR, in subjects with newly diagnosed sputum smear-positive pulmonary MDR-TB infection.
    Stage 2: The primary objective of Stage 2 is to demonstrate superiority in the anti-bacterial activity of TMC207 compared to placebo when added for 24 weeks to a BR in subjects with newly diagnosed sputum smear-positive pulmonary MDR-TB infection.
    The primary outcome parameter will be the time to sputum culture conversion during treatment with TMC207 or placebo.
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    - To investigate the pharmacokinetics of TMC207 and M2 in plasma and sputum of subjects receiving multiple doses of TMC207 in combination with a BR, during treatment and after discontinuation;
    - To explore drug-drug interactions between TMC207 and drugs in the BR;
    - To explore pharmacokinetic/pharmacodynamic relationships for activity and tolerability/safety. To evaluate and compare the safety and tolerability of 24 week treatment with TMC207 or placebo on top of the BR.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects who meet all of the following criteria are eligible for this trial:
    1. Male or female subjects. Females may participate if they are of non-childbearing potential, if they are using effective non-hormone based birth control methods and are willing to continue practicing birth control methods throughout MDR-TB treatment, or if they are non-heterosexually active or willing to practice sexual abstinence throughout MDR-TB treatment.
    2. Aged between 18 and 65 years, extremes included.
    3. Subjects with newly diagnosed sputum smear-positive pulmonary MDR-TB infection, with confirmed resistance to at least both RMP and INH by previous
    screening from a TB treatment facility, who are willing to start TB-therapy according to national TB guidelines.
    Resistance to RMP and INH may be shown by susceptibility culture and/or the rapid screen tests, i.e., fast plaque and Genotype MTBDR line probe (both rapid screen tests need to be repeated at the screening visit and must be positive).
    Subjects with newly diagnosed MDR-TB are defined as a) subjects with MDR-TB who
    have never been treated for TB before, or b) subjects with MDR-TB who have previously been treated with only first-line TB drugs (INH, RMP, EMB, PZA, or SM).
    4. Positive for AFB on direct smear examination of expectorated sputum specimen [≥1+ smear positive].
    5. Subjects with a sputum production of a magnitude that makes ability to produce 10 mL per night likely.
    6. Subjects must consent to HIV-testing unless an HIV-test was performed within 1 month prior to trial start and documentation can be provided (ELISA and/or Western Blot).
    7. Subjects must be willing to discontinue all TB drugs to allow 7 days washout before baseline assessments and starting treatment with TMC207 or placebo.
    8. Subjects having a Quetelet Index (Body Mass Index [BMI]) between 15.0 and 28.0 kg/m2, extremes included. If the subject’s BMI is below 15 kg/m2 or above 28 kg/m2, inclusion can be discussed with the sponsor.
    9. Subjects having signed ICF voluntarily before first trial-related activity.
    10. Subjects agree to hospitalization if needed per local standard of care.
    E.4Principal exclusion criteria
    Subjects meeting one or more of the following criteria cannot be selected for this trial:
    1. Previously having been treated for MDR-TB.
    Subjects previously treated for MDR-TB are defined as those having received any secondline TB drug, including any of the following anti-mycobacterials: any aminoglycoside except streptomycin, any fluoroquinolone, the thioamides prothionamide or ethionamide, and cycloserine.
    2. Having a known or suspected hypersensitivity or serious adverse reaction to the study medication.
    3. Having a current or past history of alcohol and/or drug use that, in the investigator's opinion, would compromise the subject's safety or compliance to the study protocol procedures.
    4. Having a clinically significant active medical condition, which in the opinion of the
    investigator would prevent appropriate participation in the trial.
    5. Having a significant cardiac arrhythmia that requires medication.
    6. For HIV infected subjects, having a CD4+ count < 300 cells/µL or having received
    antiretroviral therapy and/or oral or intravenous antifungal medication within the last
    90 days. Also subjects, who, in the opinion of the investigator, might need to start
    antiretroviral therapy during the 8-week treatment period of Stage 1 or the 24-week
    treatment period of Stage 2, are not eligible for the trial.
    7. Subjects with complicated or severe extrapulmonary manifestations of TB or neurological manifestations of TB.
    8. Presence of any concomitant severe illness or rapidly deteriorating health condition, including immune deficiency that would make implementation of the protocol or interpretation of the study results difficult, or gastrointestinal disease that might, in the judgment of the investigator, interfere with the absorption of TMC207.
    9. Subjects who, upon the evaluation of their pulmonary disease, will require surgical
    procedure for management of their TB within the 8-week treatment period of Stage 1 or the 24-week treatment period of Stage 2.
    10. Subjects with the following QT/QTc interval characteristics at screening:
    a. A marked prolongation of QT/QTc interval, e.g., repeated demonstration of QTcF
    (Fredericia correction) interval > 450 ms;
    b. A history of additional risk factors for Torsade de Pointe, e.g., heart failure,
    hypokalemia, family history of Long QT Syndrome;
    c. The use of concomitant medications that prolong the QT/QTc interval listed as
    disallowed medication in the study protocol.
    11. Subjects with certain toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Diseases (DMID) adult toxicity table (May 2001).
    12. Having evidence of chorioretinitis, optic neuritis, or uveitis at screening.
    13. Having previously participated in an investigational drug trial with TMC207.
    14. Having participated in other clinical studies with investigational agents, within 8 weeks prior to trial start.
    15. 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.
    16. Having any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the trial.
    17. Being unlikely to comply with the protocol, e.g., uncooperative attitude or unlikelihood of completing the trial.
    18. Women who are pregnant and/or breastfeeding.
    E.5 End points
    E.5.1Primary end point(s)
    Time to sputum culture conversion during treatment with TMC207 or Placebo.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    tolerability, anti-bacterial activity
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA1
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last visit of the last subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months10
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 15
    F.4.2.2In the whole clinical trial 150
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2007-12-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-11-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-10-09
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