一项在健康成年受试者中开展的关于ubrogepant的两部分、开放标签、1期生物等效性和食物影响研究。

A 2-Part, Open-Label, Phase 1 Bioequivalence and Food-Effect Study of Ubrogepant in Healthy Adult Participants.

作者信息

Boinpally Ramesh, Trugman Joel M

机构信息

Clinical Pharmacology, AbbVie Inc., North Chicago, IL, USA.

Neuroscience Clinical Development, AbbVie Inc., North Chicago, IL, USA.

出版信息

Clin Pharmacol Drug Dev. 2025 Jul;14(7):511-519. doi: 10.1002/cpdd.1546. Epub 2025 May 10.

Abstract

This Phase 1 study of ubrogepant was conducted to establish the bioequivalence (BE) of the 50- and 100-mg to-be-marketed (TBM) tablet formulations with the clinical trial (CT) 100-mg tablet formulation and evaluate the food effect on the bioavailability of the 100-mg TBM tablet. This 2-part study enrolled healthy participants aged 18-45 years. Part A assessed BE following a single dose of TBM versus CT tablets. Part B evaluated the impact of a high-fat meal on ubrogepant pharmacokinetics. Safety and tolerability were assessed along with standard pharmacokinetic parameters. In Part A (n  =   47), the geometric mean ratio and 90% confidence intervals for maximum plasma drug concentration, area under the plasma concentration-time curve (AUC) from time zero to time t, and AUC from time zero to infinity for the TBM and CT formulations demonstrated BE. The time to peak exposure was the same for both formulations. In Part B (n  =  18), a high-fat meal delayed time to peak exposure and reduced maximum plasma drug concentration by 22%, with no effect on AUC. The occurrence of treatment-emergent adverse events was low, and the majority were mild. Ubrogepant TBM and CT tablets (1 × 100 mg or 2 × 50 mg) were bioequivalent under fasted conditions, and a high-fat meal had no clinically relevant effect on the bioavailability of the TBM tablet formulation.

摘要

本项ubrogepant的1期研究旨在确定50毫克和100毫克待上市(TBM)片剂配方与临床试验(CT)100毫克片剂配方的生物等效性(BE),并评估高脂餐对100毫克TBM片剂生物利用度的影响。这项分为两部分的研究纳入了18至45岁的健康参与者。A部分评估了单次服用TBM片剂与CT片剂后的生物等效性。B部分评估了高脂餐对ubrogepant药代动力学的影响。在评估标准药代动力学参数的同时,对安全性和耐受性也进行了评估。在A部分(n = 47)中,TBM和CT配方的最大血浆药物浓度、从零时间到t时间的血浆浓度-时间曲线下面积(AUC)以及从零时间到无穷大的AUC的几何平均比值和90%置信区间显示具有生物等效性。两种配方达到峰值暴露的时间相同。在B部分(n = 18)中,高脂餐使达到峰值暴露的时间延迟,最大血浆药物浓度降低了22%,但对AUC没有影响。治疗中出现的不良事件发生率较低,且大多数为轻度。在禁食条件下,ubrogepant TBM片剂和CT片剂(1×100毫克或2×50毫克)具有生物等效性,高脂餐对TBM片剂配方的生物利用度没有临床相关影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c3e/12209997/84668138936a/CPDD-14-511-g001.jpg

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