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Open Access 09-03-2022 | Pharmacokinetics | Original Research Article

Single-Dose Pharmacokinetics of Milvexian in Participants with Mild or Moderate Hepatic Impairment Compared with Healthy Participants

Authors: Vidya Perera, Grigor Abelian, Danshi Li, Zhaoqing Wang, Liping Zhang, Susan Lubin, Wei Chen, Akintunde Bello, Bindu Murthy

Published in: Clinical Pharmacokinetics | Issue 6/2022

Abstract

Background

Patients with hepatic impairment receiving antithrombotic agents metabolized primarily through the liver can be at risk for bleeding. Milvexian (BMS-986177/JNJ-70033093) is a small-molecule, active-site inhibitor of activated Factor XI (FXIa). Modulation of FXI may provide systemic anticoagulation without increased risk of clinically significant bleeding.

Objective

This open-label study evaluated the effects of mild or moderate hepatic impairment on the pharmacokinetics of milvexian to assess their impact on safety and dosing.

Methods

Single doses of milvexian 60 mg were administered to participants with mild hepatic impairment (n = 9), moderate hepatic impairment (n = 8), and normal hepatic function (n = 9). Healthy participants were matched to participants with hepatic impairment by body weight, age, and sex. Analysis of variance was performed on natural log-transformed milvexian exposure parameters, with hepatic function group as a fixed effect.

Results

Single doses of milvexian 60 mg were generally well tolerated, with no serious adverse events (AEs), bleeding AEs, or discontinuations due to AEs. Geometric mean ratios (90% confidence interval) for total milvexian maximum observed plasma concentration and area under the plasma concentration–time curve from time zero extrapolated to infinite time were 1.180 (0.735–1.895) and 1.168 (0.725–1.882), respectively, for mild hepatic impairment versus normal hepatic function and 1.140 (0.699–1.857) and 0.996 (0.609–1.628), respectively, for moderate hepatic impairment versus normal hepatic function. Across groups, milvexian exposure–related increases were observed for activated partial thromboplastin time.

Conclusion

Milvexian was well tolerated in participants with normal, mildly impaired, and moderately impaired hepatic function. Observed pharmacokinetic changes suggest it is unlikely that dose adjustments will be necessary in patients with mild or moderate hepatic impairment. Clinical Trial RegistrationClinicaltrials.gov identifier: NCT02982707.

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Title: Single-Dose Pharmacokinetics of Milvexian in Participants with Mild or Moderate Hepatic Impairment Compared with Healthy Participants
Authors: Vidya Perera
Grigor Abelian
Danshi Li
Zhaoqing Wang
Liping Zhang
Susan Lubin
Wei Chen
Akintunde Bello
Bindu Murthy
Publication date: 09-03-2022
Publisher: Springer International Publishing
Keyword: Pharmacokinetics
Published in: Clinical Pharmacokinetics / Issue 6/2022
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-022-01110-9

At a glance: The STEP trials

Springer Medicine

Single-Dose Pharmacokinetics of Milvexian in Participants with Mild or Moderate Hepatic Impairment Compared with Healthy Participants

Abstract

Background

Objective

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Objective

Methods

Results

Conclusion

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