Phase II Study of Daily Rifapentine for Pulmonary Tuberculosis (IND 62,611; 1/2/0

描述(由申请人提供)： 需要高度有效的结核病治疗方法，能够在比目前要求的6个月短得多的时间内治愈疾病。利福喷丁是一种长效利福霉素，具有强大的抗结核病活性，目前已被FDA批准用于结核病治疗，每周两次，剂量为600毫克。使用小鼠结核病治疗模型的证据表明，含有每日利福喷丁的多种药物方案可以在三到四个月内治愈结核病。 然而，存在关键的知识差距；每日利福喷丁的疗效尚未在临床试验中评估，临床使用的每日一次利福喷丁的最佳剂量尚不清楚。临床前和第一阶段研究表明，最佳日剂量可能在450至600毫克之间。这项建议的总体目标是在肺结核多药强化阶段治疗的背景下确定利福喷丁的最佳日剂量，以指导未来第三阶段临床试验的剂量选择。拟议的第二阶段临床试验旨在确定在南非开普敦的涂阳肺结核的强化治疗阶段(前8周)，利福喷丁剂量为450毫克和600毫克，每天与异烟肼、吡津酰胺和乙胺丁醇一起服用一次的抗菌活性和安全性。

DESCRIPTION (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.