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

描述（由申请人提供）： 需要一种高效的结核病治疗方法，可以在比目前所需的六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，具有有效的抗结核活性，目前FDA批准用于结核病治疗，剂量为600 mg，每周两次。使用结核病治疗的小鼠模型的证据表明，每天含有利福喷丁的多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，每日一次利福喷丁用于临床的最佳剂量尚不清楚。临床前和1期研究表明，最佳日剂量可能在450至600 mg之间。本提案的总体目标是确定利福喷丁在肺结核多药强化治疗阶段的最佳日剂量，以指导未来III期临床试验的剂量选择。拟定的II期临床试验旨在确定在南非开普敦进行的涂阳肺结核强化治疗期（前8周），利福喷丁剂量为450 mg和600 mg，每日一次，与异烟肼、吡嗪酰胺和乙胺丁醇联合给药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.