对抗结核病药物的第一个住院疗效研究2a阶段的翻译预测
Jacqueline P Ernest1,2, Janice Jia Ni Goh1,2, Natasha Strydom1,2
1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
The European respiratory journal
|June 15, 2023
概括
使用临床前数据预测结核病药物疗效可以加速开发. 一个新的模型从小鼠的药理动力学-药理动力学数据准确预测临床早期杀菌活性 (EBA),可能取代昂贵的2a期试验.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物开发 药物开发
- 传染性疾病 传染性疾病
背景情况:
- 2a期结核病试验使用早期杀菌活性 (EBA) 来测试药物的疗效.
- 这些试验是昂贵的 (7-1960万美元),超过30%的药物在第三阶段之前失败.
- 在临床前预测药物成功可以降低成本并加速开发.
研究的目的:
- 使用临床前体内药理动力学 (PK) - 药理动力学 (PD) 数据预测临床EBA.
- 用基于模型的翻译药理学方法来预测药物的疗效.
- 加快结核病药物开发,降低与2a期试验相关的成本.
主要方法:
- 编译的小鼠和临床PK和PD模型.
- 开发了小鼠PK-PD模型以建立暴露-反应关系.
- 使用小鼠PK-PD数据,临床PK模型和特定物种的蛋白质结合,进行了临床EBA的翻译预测.
主要成果:
- 从小鼠模型准确预测临床疗效的存在或缺乏.
- 在治疗的前2天预测的每日CFU下降与临床观察一致.
- 在第2天和第14天之间预测的CFU下降与临床发现一致.
结论:
- 开发的平台可以为EBA的2a期试验提供信息或取代它.
- 它弥合了临床前疗效研究和后期临床试验 (2b/3期) 之间的差距.
- 这种方法大大加速了结核病药物的开发.
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