TMC207-C202: Study to Evaluate Bactericidal Activity of Multiple Oral Doses of TMC207 in Subjects With Sputum-Smear Positive Tuberculosis

Tibotec Pharmaceutical

Status and phase

Completed

Phase 2

Conditions

Tuberculosis

Treatments

Drug: TMC207

Study type

Interventional

Funder types

Industry

Identifiers

NCT00523926

CR002725

Details and patient eligibility

About

The purpose of this study is to assess the effects of 3 different oral doses of TMC207 administered over a 7 day period on the organism that causes tuberculosis

Full description

This is a Phase IIa, open-label, randomized trial in treatment-naïve, sputum smear-positive, subjects with pulmonary TB to assess the extended early bactericidal activity (eEBA) of TMC207. The study population will consist of 60 treatment-naive subjects with M. tuberculosis infection.

Subjects will receive orally 25 mg TMC207 po q.d. (Treatment A), 100 mg TMC207 po q.d. (Treatment B) or 400 mg TMC207 po q.d. (Treatment C) daily for 7 days. Subjects in treatment group D will receive 600 mg rifampin po q.d. daily for 7 days and subjects in treatment group E will receive 300 mg isoniazid po q.d. daily for 7 days. After 7 days, subjects in all treatment groups will receive appropriate anti-TB therapy according to national standards of country TB guidelines and culture and sensitivity results of the sputum specimens until clinical and microbiological cures have been achieved. Three once-daily dose regimens of TMC207, for 7 days, will be studied versus 2 comparator treatments, rifampin and isoniazid in the present trial.TMC207 treatment groups: 25 mg TMC207 po q.d; 100 mg. TMC207 po q.d; 400 mg TMC207 po q.d.; TMC207 will be administered as a 10 or 40 mg/mL oral solution. Comparator groups: 600 mg rifampin po q.d. administered as capsules containing 300 mg rifampin; 300 mg isoniazid po q.d. administered as tablets containing 300 mg isoniazid.

Enrollment

75 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Treatment-naive subjects with pulmonary M. tuberculosis infection, willing to start anti-TB therapy
Positive for acid-fast bacilli on direct smear exam of sputum specimen
Must consent to HIV testing
Must agree to hospital admission

Exclusion criteria

History or presence of hepatic or GI disease that may interfere with the absorption of TMC207, isoniazid or rifampin
Subjects who received previous anti-mycobacterial drugs for the treatment of a mycobacteria infection and subjects who have received more than 2 weeks of treatment with a fluoroquinolone
Subjects who have received antiretroviral therapy and/or oral or I.V. anti-fungal medication w/in the last 90 days
Subjects with sputum cultures of M. tuberculosis resistant to rifampin
Impaired hepatic function