Single-Dose Pharmacokinetics of Milvexian in Participants with Normal Renal Function and Participants with Moderate or Severe Renal Impairment

Abstract

Objective: The aim of this study was to assess the effect of moderate or severe renal impairment on the pharmacokinetic (PK) properties of milvexian.

Methods: 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 m²) and participants with moderate (n = 8; eGFR ≥ 30 to ≤ 59 mL/min/1.73 m²) or severe (n = 8; eGFR < 30 mL/min/1.73 m²) renal impairment. Regression analysis was performed using linear regression of log-transformed PK parameters versus eGFR.

Results: Milvexian was well tolerated, with no deaths, serious adverse events, or serious bleeding reported. The maximum milvexian concentration (C_max) 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 m², 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_max) 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).

Conclusion: 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.

Clinical trials registration: This study was registered with ClinicalTrials.gov (NCT03196206, first posted 22 June 2017).