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

每日利福喷丁治疗肺结核的 II 期研究（IND 62,611；1/2/0

• 批准号: 8141454
• 负责人: Susan E Dorman
• 金额: $ 40万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8141454
• 关键词: Phase; II; Study; Daily; Rifapentine

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.

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，剂量为每周两次 600 毫克。使用结核病治疗小鼠模型的证据表明，每日服用利福喷丁的多药治疗方案可以在三到四个月内治愈结核病。 然而，存在严重的知识差距；每日一次利福喷汀的疗效尚未在临床试验中进行评估，并且每日一次利福喷汀临床使用的最佳剂量尚不清楚。临床前和一期研究表明，最佳每日剂量可能在 450 至 600 毫克之间。该提案的总体目标是确定肺结核多药强化阶段治疗背景下利福喷汀的最佳每日剂量，以指导未来3期临床试验的剂量选择。拟议的 2 期临床试验旨在确定南非开普敦涂阳肺结核强化治疗阶段（前八周）期间每日一次服用利福喷汀 450 毫克和 600 毫克剂量与异烟肼、吡嗪酰胺和乙胺丁醇的抗菌活性和安全性。