超越边界:利用边界结果得分的纵向暴露-反应模型,在加速药物开发范式中为决策提供信息
Yeamin Huh1, Jessica Wojciechowski2, Vivek S Purohit2
1Worldwide Development, Research and Medical, Pfizer Inc, 280 Shennecossett Rd, Groton, CT, 06340, USA. yeamin.huh@pfizer.com.
Clinical pharmacokinetics
|February 15, 2024
概括
基于模型的药物开发 (MIDD) 使用连续边界结果 (CBO) 建模支持阿洛佩西亚带状脱发症里特利西丁的加速开发. 模拟表明,暂时的治疗中断长达6周不会显著影响疗效.
科学领域:
- 药学指标 (Pharmacometrics) 是一个指标.
- 量化药理学 量化药理学
- 药物开发科学 药物开发科学
背景情况:
- 基于模型的药物开发 (MIDD) 通过对数据进行上下文化和帮助决策来加速治疗的可用性.
- 这项研究以Ritlecitinib的联合2b期和单一关键试验中的MIDD为例,这是一种JAK3 / TEC家族激酶抑制剂.
研究的目的:
- 描述一个MIDD应用在药物开发中的例子.
- 使用纵向暴露-反应 (ER) 建模来评估利西提尼布在白发症患者的疗效.
主要方法:
- 使用纵向暴露-反应 (ER) 建模来描述利西提尼的疗效.
- 脱发症严重程度工具 (SALT) 评分,连续边界结果 (CBO),作为主要疗效终点.
- 在SALT得分间隔内的平均药物度是暴露度量.
主要成果:
- 该CBO模型准确地描绘了纵向SALT得分和边界数据频率.
- 测试的剂量位于上升的ER区域,加载剂量会影响发病,但不会影响长期益处.
- 疾病严重程度是唯一影响疗效的共同变量.
- 基于模型的模拟表明,暂时的治疗中断 (≤6周) 对疗效的影响最小.
结论:
- CBO建模方法和模拟支持单一的关键试验策略,以加速Ritelecitinib的开发.
- 这种方法适用于使用边界有效度表的其他适应症.
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