(provided by the applicant): There is a need for highly potent TB treatments that can cure disease in substantially fewer than the six months currently required. Rifapentine is a long-acting rifamycin that has potent anti-TB activity and is currently FDA-approved for TB treatment at a dose of 600 mg twice weekly. Evidence using a mouse model of TB treatment indicates that a multi-drug regimen containing daily rifapentine can cure TB within three to four months. However, there are critical knowledge gaps;the efficacy of daily rifapentine has not been assessed in clinical trials and the optimal dose of once daily rifapentine for clinical use is not known. Preclinical and Phase 1 studies suggest that the optimal daily dose is likely to lie between 450 and 600 mg. The overall goal of this proposal is to determine the optimal daily dose of rifapentine in the context of multidrug intensive phase treatment for pulmonary TB, in order to guide dose selection for future Phase 3 clinical trials. The proposed Phase 2 clinical trial is intended to determine the antimicrobial activity and safety of rifapentine doses of 450 mg and 600 mg administered once daily with isoniazid, pyrazinamide, and ethambutol during intensive phase (first eight weeks) treatment of smear-positive pulmonary TB in Cape Town, South Africa.

Public Health Relevance

and Relevance Tuberculosis (TB) is a leading cause of infectious disease death worldwide, and new drugs are needed to shorten treatment from the current six months to four months or less. Rifapentine is highly active against TB and preclinical studies show that daily rifapentine may enable reduction of treatment duration. However, the optimal rifapentine daily dose for use in multidrug treatment for pulmonary TB is not known. The goal of this project is to determine the optimal daily dose of rifapentine when used with other standard TB medicines during the first two months of pulmonary TB treatment. The antimicrobial activity and safety of 450- and 600- mg of once daily rifapentine will be determined. This project is relevant to public health because project results will provide new information about how rifapentine may best be used in TB treatment, and whether rifapentine holds promise for being able to shorten TB treatment.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
5R01FD003524-04
Application #
8320752
Study Section
Special Emphasis Panel (ZFD1-OPD-N (S1))
Project Start
2009-01-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218