人口剂量-反应-时间分析减少和患者报告的耐受性支持Linerixibat的III期剂量选择
Fernando Carreño1,2, Eleni Karatza1,3, Rashmi Mehta3
1UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Clinical pharmacology and therapeutics
|November 13, 2023
概括
通过抑制胆酸再吸收,Linerixibat有效地减少了初级胆道胆炎患者的. 然而,增加腹风险需要仔细选择剂量,每日两次剂量显示适度益处.
科学领域:
- 药理学 药理学是指药理学的学科.
- 胃肠病学 胃肠病学
- 临床试验 临床试验
背景情况:
- 血清胆汁酸 (BAs) 的升高与初级胆道胆炎 (PBC) 中的胆固醇性有关.
- 林尼里克西巴特 (Linerixibat) 是一种以利亚胆酸转运抑制剂,可减少全身胆酸转运抑制剂,但可引起腹等胃肠道副作用.
研究的目的:
- 开发一种动力学-药学动力学 (k-PD) 模型,以优化linerixibat的剂量,以最大限度地减少PBC患者的和最小的腹.
- 量化评估剂量反应关系,以有效性 (减少) 和耐受性 (腹) 进行量化评估.
主要方法:
- 一个k-PD模型是使用IIb期GLIMMER试验 (NCT02966834) 的数据开发的.
- 该模型分析了最严重的每日 (患者报告的结果) 和腹 (GI-5) 发生情况,以应对不同的linerixibat剂量 (每天一次或两次).
主要成果:
- 该k-PD模型准确地描述了linerixibat对减少和腹发病率的影响.
- 观察到反应者和腹频率的剂量依赖增加.
- 每天两次 (每天两次) 与每天一次 (q.d.) 相比,剂量显示反应者的适度增加. 剂量. 剂量. 这是.
结论:
- 开发的k-PD模型为平衡linerixibat的疗效和耐受性提供了一个定量框架.
- 这些发现支持选择40毫克两次一天的选择. 对于GLISTEN第三阶段试验 (NCT04950127) 的linerixibat.
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