Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults
Zhu Luo,1 Jie Wang,2 Zhuolu Niu,3 Cuili Hu,4 Madhu Chintala,5 Xinchao Luo,3 Tsung-I Lee,3 Alexei N Plotnikov,5 Peter Zannikos5 1Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Hematology, West China Hospital, Sichuan University, Che...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-03-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/pharmacokinetics-pharmacodynamics-safety-and-tolerability-of-milvexian-peer-reviewed-fulltext-article-DDDT |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850179884519784448 |
|---|---|
| author | Luo Z Wang J Niu Z Hu C Chintala M Luo X Lee TI Plotnikov AN Zannikos P |
| author_facet | Luo Z Wang J Niu Z Hu C Chintala M Luo X Lee TI Plotnikov AN Zannikos P |
| author_sort | Luo Z |
| collection | DOAJ |
| description | Zhu Luo,1 Jie Wang,2 Zhuolu Niu,3 Cuili Hu,4 Madhu Chintala,5 Xinchao Luo,3 Tsung-I Lee,3 Alexei N Plotnikov,5 Peter Zannikos5 1Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Hematology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Johnson & Johnson, Shanghai, People’s Republic of China; 4Johnson & Johnson, Beijing, People’s Republic of China; 5Johnson & Johnson, Raritan, NJ, USACorrespondence: Zhuolu Niu, Janssen Research & Development, 65 Gui Qing Road, Shanghai, 200233, People’s Republic of China, Email Zniu4@its.jnj.comBackground: Milvexian is a small molecule, selective factor XIa (FXIa) inhibitor being developed as an oral anticoagulant. This study assessed the pharmacokinetics, pharmacodynamics (activated partial thromboplastin time [aPTT]), and safety of milvexian in healthy Chinese subjects.Methods: Part 1: Thirty subjects were randomly assigned 1:1:1 to receive milvexian 25 mg on Day 1 followed by 25 mg once daily (QD) on Days 5– 12; milvexian 25 mg twice daily at 12-hour intervals (BID) on Days 1– 8; or milvexian 100 mg BID on Days 1– 8. Part 2: Ten subjects received milvexian 200 mg on Day 1 followed by 200 mg BID on Days 5– 12. Plasma samples were collected for pharmacokinetics and aPTT assessments. Safety and tolerability were assessed.Results: Milvexian was rapidly absorbed (median tmax of 3– 4 hours after a single dose and repeated administration). Mean maximum concentrations or area under the concentration-time curve values of milvexian in plasma after single doses or BID administration of 25 mg, 100 mg, or 200 mg increased in a dose-dependent manner. Steady state conditions were achieved within 6 days of repeated administration based on milvexian trough concentration values. Mean terminal half-life values (9– 10 hours) were independent of the dose. Milvexian reversibly prolonged aPTT in a manner that was directly related to milvexian dose and exposure. All milvexian regimens were safe and well tolerated, with only mild treatment-emergent adverse events and no clinically significant bleeding events. No new safety signals were identified.Conclusion: The pharmacokinetic, pharmacodynamic, and safety profiles of milvexian demonstrate suitability for further clinical development in Chinese participants.Keywords: anticoagulant, aPTT, FXIa inhibitor, milvexian, pharmacokinetics |
| format | Article |
| id | doaj-art-a9c392d22db644579e250263d6fe5f06 |
| institution | OA Journals |
| issn | 1177-8881 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj-art-a9c392d22db644579e250263d6fe5f062025-08-20T02:18:23ZengDove Medical PressDrug Design, Development and Therapy1177-88812025-03-01Volume 1915031514100715Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese AdultsLuo ZWang JNiu ZHu CChintala MLuo XLee TIPlotnikov ANZannikos PZhu Luo,1 Jie Wang,2 Zhuolu Niu,3 Cuili Hu,4 Madhu Chintala,5 Xinchao Luo,3 Tsung-I Lee,3 Alexei N Plotnikov,5 Peter Zannikos5 1Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Hematology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Johnson & Johnson, Shanghai, People’s Republic of China; 4Johnson & Johnson, Beijing, People’s Republic of China; 5Johnson & Johnson, Raritan, NJ, USACorrespondence: Zhuolu Niu, Janssen Research & Development, 65 Gui Qing Road, Shanghai, 200233, People’s Republic of China, Email Zniu4@its.jnj.comBackground: Milvexian is a small molecule, selective factor XIa (FXIa) inhibitor being developed as an oral anticoagulant. This study assessed the pharmacokinetics, pharmacodynamics (activated partial thromboplastin time [aPTT]), and safety of milvexian in healthy Chinese subjects.Methods: Part 1: Thirty subjects were randomly assigned 1:1:1 to receive milvexian 25 mg on Day 1 followed by 25 mg once daily (QD) on Days 5– 12; milvexian 25 mg twice daily at 12-hour intervals (BID) on Days 1– 8; or milvexian 100 mg BID on Days 1– 8. Part 2: Ten subjects received milvexian 200 mg on Day 1 followed by 200 mg BID on Days 5– 12. Plasma samples were collected for pharmacokinetics and aPTT assessments. Safety and tolerability were assessed.Results: Milvexian was rapidly absorbed (median tmax of 3– 4 hours after a single dose and repeated administration). Mean maximum concentrations or area under the concentration-time curve values of milvexian in plasma after single doses or BID administration of 25 mg, 100 mg, or 200 mg increased in a dose-dependent manner. Steady state conditions were achieved within 6 days of repeated administration based on milvexian trough concentration values. Mean terminal half-life values (9– 10 hours) were independent of the dose. Milvexian reversibly prolonged aPTT in a manner that was directly related to milvexian dose and exposure. All milvexian regimens were safe and well tolerated, with only mild treatment-emergent adverse events and no clinically significant bleeding events. No new safety signals were identified.Conclusion: The pharmacokinetic, pharmacodynamic, and safety profiles of milvexian demonstrate suitability for further clinical development in Chinese participants.Keywords: anticoagulant, aPTT, FXIa inhibitor, milvexian, pharmacokineticshttps://www.dovepress.com/pharmacokinetics-pharmacodynamics-safety-and-tolerability-of-milvexian-peer-reviewed-fulltext-article-DDDTanticoagulantapttfxia inhibitormilvexianpharmacokinetics |
| spellingShingle | Luo Z Wang J Niu Z Hu C Chintala M Luo X Lee TI Plotnikov AN Zannikos P Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults Drug Design, Development and Therapy anticoagulant aptt fxia inhibitor milvexian pharmacokinetics |
| title | Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults |
| title_full | Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults |
| title_fullStr | Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults |
| title_full_unstemmed | Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults |
| title_short | Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Milvexian in Healthy Chinese Adults |
| title_sort | pharmacokinetics pharmacodynamics safety and tolerability of milvexian in healthy chinese adults |
| topic | anticoagulant aptt fxia inhibitor milvexian pharmacokinetics |
| url | https://www.dovepress.com/pharmacokinetics-pharmacodynamics-safety-and-tolerability-of-milvexian-peer-reviewed-fulltext-article-DDDT |
| work_keys_str_mv | AT luoz pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT wangj pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT niuz pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT huc pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT chintalam pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT luox pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT leeti pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT plotnikovan pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults AT zannikosp pharmacokineticspharmacodynamicssafetyandtolerabilityofmilvexianinhealthychineseadults |