{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:18:12Z","timestamp":1791235092936,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Coagulation factor XI (FXI) plays a crucial role in the intrinsic coagulation pathway, and inhibitors targeting it may mitigate the risk of haemorrhage compared to anticoagulants currently on the market. SKB336, a novel selective inhibitor of FXI\/FXIa, has been shown to prolong the activated partial thromboplastin time (APTT) in both in vitro and in vivo studies. This study aimed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of SKB336 in healthy subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this randomized, single\u2010blinded, placebo\u2010controlled and dose\u2010escalation first\u2010in\u2010human phase I study, 60 healthy subjects were allocated to 6 cohorts (0.1, 0.3, 0.6, 1.25, 2.5 and 4\u00a0mg\/kg) and received a single subcutaneous injection of SKB336 or placebo in a 4:1 ratio. The safety, tolerability, pharmacokinetics and immunogenicity were measured up to 85\u2009days postdose. Exploratory analysis consisted of FXI activity and APTT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SKB336 was well tolerated in all 6 cohorts, without any haemorrhagic events, reported deaths or serious adverse events. No significant dose\u2010dependent correlation was observed with the incidence of adverse events. Dose\u2010dependent increases in the maximum observed drug concentration and area under the plasma concentration\u2013time curve were observed. The mean elimination half\u2010life was 21.3\u201333.5\u00a0days, indicating a potential monthly dosing frequency. The maximum inhibition rate of FXI activity for all 6 cohorts reached 0, 17, 28, 48, 54 and 59%, respectively. The maximum APTT ratio to baseline reached 1.09\u2010, 1.26\u2010, 1.47\u2010, 1.77, 1.91\u2010 and 2.00\u2010fold, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SKB336 was generally tolerated, without any bleeding events in healthy volunteers. Besides, SKB336 presented a persistent dose\u2010dependent prolongation of APTT and duration of FXI inhibition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70043","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T20:15:16Z","timestamp":1744229716000},"page":"2817-2826","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics, pharmacodynamics and safety profile of SKB336, a selective inhibitor of coagulation factor XI\/XIa in healthy subjects"],"prefix":"10.1002","volume":"91","author":[{"given":"Qian","family":"Xiang","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiufen","family":"Xie","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Institution Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Institution Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyu","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-3934","authenticated-orcid":false,"given":"Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Institution Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Sichuan Kelun\u2010Biotech Biopharmaceutical Co., Ltd.  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