Bristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA.
Janssen Research & Development, LLC, Titusville, NJ, USA.
Clin Pharmacokinet. 2022 Oct;61(10):1405-1416. doi: 10.1007/s40262-022-01150-1. Epub 2022 Jul 30.
The aim of this study was to assess the effect of moderate or severe renal impairment on the pharmacokinetic (PK) properties of milvexian.
This open-label, parallel-group study assessed the PK, safety, and tolerability of a single oral 60 mg dose of milvexian in participants with normal renal function (n = 8; estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m) and participants with moderate (n = 8; eGFR ≥ 30 to ≤ 59 mL/min/1.73 m) or severe (n = 8; eGFR < 30 mL/min/1.73 m) renal impairment. Regression analysis was performed using linear regression of log-transformed PK parameters versus eGFR.
Milvexian was well tolerated, with no deaths, serious adverse events, or serious bleeding reported. The maximum milvexian concentration (C) was similar for all groups. Based on a regression analysis of milvexian concentration versus eGFR, participants with eGFR values of 30 and 15 mL/min/1.73 m, respectively, had area under the curve (AUC) values that were 41% and 54% greater than in participants with normal renal function. Median time to maximum concentration (T) was similar for the three groups (4.5-5.0 h). The half-life increased for participants with moderate (18.0 h) or severe (17.7 h) renal impairment compared with those with normal renal function (13.8 h).
A single dose of milvexian 60 mg was safe and well tolerated in participants with normal renal function and moderate or severe renal impairment. There was a similar increase in milvexian exposure between the moderate and severe renal groups.
This study was registered with ClinicalTrials.gov (NCT03196206, first posted 22 June 2017).
本研究旨在评估中重度肾功能损害对米伐醌药代动力学（PK）特性的影响。
本开放标签、平行组研究评估了健康受试者（n=8；估计肾小球滤过率[eGFR]≥90 mL/min/1.73 m）和中重度肾功能损害受试者（n=8；eGFR≥30 至≤59 mL/min/1.73 m）单次口服 60 mg 米伐醌的 PK、安全性和耐受性。使用线性回归对 log 转换后的 PK 参数与 eGFR 进行回归分析。
米伐醌耐受性良好，无死亡、严重不良事件或严重出血报告。所有组的米伐醌最大浓度（C）相似。基于米伐醌浓度与 eGFR 的回归分析，eGFR 值分别为 30 和 15 mL/min/1.73 m 的受试者的 AUC 值分别比健康受试者高 41%和 54%。三组的达峰时间（T）相似（4.5-5.0 h）。与健康受试者相比，中重度肾功能损害受试者（18.0 h）和重度肾功能损害受试者（17.7 h）的半衰期延长。
60 mg 单剂量米伐醌在健康受试者和中重度肾功能损害受试者中安全且耐受良好。中重度肾功能损害组之间米伐醌暴露量呈相似增加。
本研究在 ClinicalTrials.gov 注册（NCT03196206，首次发布于 2017 年 6 月 22 日）。
