Evaluation of a Rifapentine-Containing Regimen for Intensive Phase Treatment of Pulmonary Tuberculosis (Study 29); Pharmacokinetic and Pharmacodynamic Studies of Efficacy, Tolerability and Safety of Higher Dosage Rifapentine for Treatment of Tuberculosis (Study 29PK)
Sponsor - U.S. Centers for Disease Control & Prevention - Tuberculosis Trials Consortium (TBTC - 200-2009-32598)
Principal Investigator - John L. Johnson, MD, CWRU
|Type of Study||Phase 2 clinical trial of TB treatment with pharmacokinetic and surrogate biomarker substudies; current trials being conducted \x96 TBTC Study 29; TBTC Study 29 PK|
|Design||Phase 2 multi-center, randomized, open label clinical trial comparing bacteriologic activity and tolerability of rifampin and rifapentine-containing regimens during the intensive phase of TB treatment in HIV-infected and \x96uninfected adults with newly diagnosed, smear positive pulmonary TB with PK sub-studies|
|Sample Size||Study 29 & 29X: 960 subjects; Uganda Enrollment: 300
Study 29PK & 29XPK: 60 subjects; Uganda Enrollment: 50
|Population||HIV-infected and HIV-uninfected adults with initial episodes of newly diagnosed smear-positive, pulmonary TB|
|Study Period||December 2008-March 2013|
|Interactions||Collaborating investigators/staff, utilizing shared infrastructure|
TBTC Study 29 & 29X:
This phase 2b randomized, open label clinical trial compares the antimicrobial activity and safety of a standard daily intensive phase TB treatment regimen comprised of rifampin (10 mg/kg/dose) + isoniazid + pyrazinamide + ethambutol (RHZE) to that of an experimental regimen comprised of rifapentine (10 mg/kg/dose) + isoniazid + pyrazinamide + ethambutol (PHZE). An extension phase (Study 29X) was subsequently activated to increase enrollment and site participation to further evaluate Rifapentine in this study.
Current 6-month duration TB treatment regimens are associated with unacceptably high rates of treatment default under program conditions, contributing to individual morbidity and mortality, disease transmission, and drug resistance. Highly potent regimens of shorter duration may facilitate treatment completion and direct observation of treatment, thereby improving individual and public health. Animal studies indicate that rifapentine-based regimens are highly potent and can reduce overall TB treatment duration to approximately 3 months. This phase 2b trial will evaluate the safety, tolerability, and antimicrobial activity of a regimen in which rifampin is replaced by rifapentine during intensive phase (first 8 weeks) of pulmonary TB treatment.
TBTC Study 29PK & 29XPK:
The primary objective of this study is to characterize rifapentine pharmacokinetic parameters (AUC0-24 and peak concentration) in patients with TB during combination chemotherapy. This is a one-period, non-blinded, multi-center pharmacokinetic substudy of rifapentine and rifampin in patients with tuberculosis enrolled in TBTC Study 29.