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).
- Conditions
- TuberculosisMedDRA version: 9.1Level: LLTClassification code 10044755Term: Tuberculosis
- Registration Number
- EUCTR2007-004462-40-LV
- Lead Sponsor
- Tibotec BVBA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method