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

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 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.

RESULTS

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).

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).