一项1期、多中心、开放标签研究,与健康受试者相比,评估Iberdomide在轻度、中度或重度肝功能损害患者中的药代动力学。

IF 3.1 Q2 PHARMACOLOGY & PHARMACY
Yiming Cheng, Ying Ye, Allison Gaudy, Atalanta Ghosh, Yongjun Xue, Alice Wang, Simon Zhou, Yan Li
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引用次数: 1

摘要

简介:Iberdomide是一种新型小脑调节剂(CELMoD®),目前正处于血液学适应症的临床研究中。为了评估肝功能损害对伊伯度胺及其主要活性代谢物M12的药代动力学(PK)的影响,我们在健康受试者和轻度、中度和重度肝功能损害受试者中进行了一项多中心、开放标签的1期研究。方法:40例受试者按肝功能分为5组。给药1 mg伊伯多胺,收集血浆样品,评价伊伯多胺和M12的药代动力学。结果:单剂量伊伯多胺(1mg)后,平均伊伯多胺Cmax(最大观察浓度)和AUC(浓度-时间曲线下面积)暴露在肝功能损害(HI)受试者(重度、中度和轻度)和各自匹配的正常对照之间大致相当。代谢产物M12的平均Cmax和AUC暴露在轻度HI和匹配的正常受试者之间大致相当。然而,与相应的正常对照相比,中度和重度HI受试者的M12平均Cmax降低了30%和65%,AUC降低了57%和63%。然而,与母体药物相比,M12暴露量相对较低,观察到的差异被认为没有临床意义。结论:总的来说,1 mg单次口服伊伯度胺的耐受性良好。HI(轻度、中度或重度)对伊伯多胺PK无临床相关影响,因此无需调整剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects.

A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects.

A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects.

Introduction: Iberdomide, a novel cereblon modulator (CELMoD®), is currently under clinical investigation for hematology indications. To evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of iberdomide and its major active metabolite M12, a phase 1, multicenter, open-label study was conducted in healthy subjects and subjects with mild, moderate, and severe hepatic impairment.

Methods: Forty subjects were enrolled in the study and divided into five groups based on hepatic function. 1 mg iberdomide was administered and plasma samples were collected to evaluate the pharmacokinetics of iberdomide and M12.

Results: After a single dose of iberdomide (1 mg), mean iberdomide Cmax (maximum observed concentration) and AUC (area under the concentration-time curve) exposure were generally comparable between hepatic impairment (HI) subjects (severe, moderate and mild) and their respective matched normal controls. Mean Cmax and AUC exposure of the metabolite M12 were generally comparable between mild HI and matched normal subjects. However, mean Cmax of the M12 was 30% and 65% lower and AUC was 57% and 63% lower in moderate and severe HI subjects as compared to their respective matched normal controls. However, given the relatively low M12 exposure as compared to its parent drug, the observed differences were not considered clinically meaningful.

Conclusion: In summary, 1 mg single oral dose of iberdomide was generally well-tolerated. HI (mild, moderate or severe) had no clinically relevant impact on iberdomide PK and therefore, no dose adjustment is warranted.

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来源期刊
CiteScore
4.60
自引率
0.00%
发文量
14
审稿时长
16 weeks
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