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

Tuberculosis Clinical Trial

Official title:

An Open-label Study to Evaluate the Extended Early Bactericidal Activity, Safety, Tolerability and Pharmacokinetics of Multiple Oral Doses of TMC207 in Treatment-na�ve Subjects With Sputum Smear Positive Pulmonary Tuberculosis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00523926
• Other study ID #: CR002725
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2007
• Last updated: August 14, 2012
• Start date: May 2005
• Est. completion date: October 2005

Study information

• Verified date: August 2012
• Source: Tibotec BVBA
• Contact: n/a
• Is FDA regulated: No
• Health authority: USA: FOOD AND DRUG ADMINISTRATION - CENTER FOR DRUG EVALUATION AND RESEARCH
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• TMC207

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tibotec BVBA

References & Publications (1)

Rustomjee R, Diacon AH, Allen J, Venter A, Reddy C, Patientia RF, Mthiyane TC, De Marez T, van Heeswijk R, Kerstens R, Koul A, De Beule K, Donald PR, McNeeley DF. Early bactericidal activity and pharmacokinetics of the diarylquinoline TMC207 in treatment — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the effects of 3 doses of TMC207 administered over a 7 day period on M. tuberculosis in sputum compared to effects of treatment with standard doses of isoniazid and rifampin
Secondary	Assess the short term safety, tolerability and PK of multiple oral doses of TMC207 in treatment-naïve subjects with pulmonary M.tuberculosis infection