尼拉帕里布片在患有高级固体瘤的患者中的相对生物可用性,生物等价性和食物效应研究
Gerald Falchook1, Amita Patnaik2, Debra L Richardson3
1Sarah Cannon Research Institute at HealthONE, Denver, Colorado.
Clinical therapeutics
|February 29, 2024
概括
尼拉帕里布 (Niraparib) 片与卵巢癌维持治疗的囊具有生物同等性. 高脂饮食对药理动力学产生了适度的影响,不被认为具有临床意义.
科学领域:
- 在瘤学瘤学.
- 药理动力学 药理动力学
- 药物开发 药物开发
背景情况:
- 尼拉帕里布是一种多 (ADP-ribose) 聚合酶抑制剂,用于晚期卵巢癌的维持治疗.
- 它以100毫克囊的形式提供,具有既定的剂量方案.
- 其他固体瘤的研究使用正在进行中.
研究的目的:
- 为了评估与3 × 100mg囊相比,300mg尼拉帕里布片的相对生物可用性 (BA) 和生物等价性 (BE).
- 为了研究高脂肪餐对尼拉巴里布片的药理动力学 (PK) 特性的食物影响 (FE).
主要方法:
- 一个美国的,三阶段的,开放标签,多中心,单个交叉,随机序列研究.
- 患有晚期固体瘤的患者在BA/BE阶段接受尼拉巴里布片或囊,或在FE阶段接受禁食/食状态的片.
- 药物动力学参数在剂量后的7天内进行评估;监测耐受性.
主要成果:
- 尼拉帕里布片与囊表现出生物等价性,Cmax,AUC0-t和AUC0-∞的90%CI在BE限 (0.80-1.25) 范围内.
- 一个高脂肪的食物增加了Cmax,AUC0-t和AUC0-∞分别为11%,32%和28%,在食和禁食状态.
- 在安全人群中没有发现新的安全信号 (n=168在BE阶段).
结论:
- 尼拉帕里布片与目前可用的囊配方具有生物等价性.
- 在高脂肪餐饮中观察到适度的食物效应,但由于固有的PK变异性,它不被认为具有临床意义.
- 这支持了临床实践中尼拉帕里布 (niraparib) 的药片配方的潜力.
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