{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T02:18:23Z","timestamp":1781921903953,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin\u2010A (ET<jats:sub>A<\/jats:sub>) receptor antagonist, in healthy subjects. The primary objectives of this first\u2010in\u2010human phase I study, comprised of single\u2010ascending\u2010dose, multiple\u2010ascending\u2010dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin\u20101 (ET\u20101) and total bile acids (TBA). Single doses of 10 to 100\u2009mg and multiple daily doses of 20 and 50\u2009mg for 6\u2009days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half\u2010life (<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET\u20101 concentrations were dose\u2010proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50\u2009mg dose of SC0062 after a high\u2010fat meal, <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> values for SC0062 and M18 increased by 41% and 32%, respectively, and median <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> values for SC0062 were 3\u2009h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.<\/jats:p>","DOI":"10.1111\/cts.13750","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T13:54:06Z","timestamp":1709819646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin\u2010A receptor antagonist"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9214-413X","authenticated-orcid":false,"given":"Yun","family":"Liu","sequence":"first","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai Engineering Research Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1411-5638","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai Engineering Research Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5209-805X","authenticated-orcid":false,"given":"Hongjie","family":"Qian","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai Engineering Research Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1555-233X","authenticated-orcid":false,"given":"Yuzhou","family":"Gui","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai Engineering Research Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7582-030X","authenticated-orcid":false,"given":"Yating","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai Engineering Research Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2220-7371","authenticated-orcid":false,"given":"Rong","family":"Song","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai Engineering Research Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9834-6912","authenticated-orcid":false,"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Xuhui Central Hospital\/Zhongshan\u2010Xuhui Hospital Fudan University  Shanghai China"},{"name":"Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai Engineering Research Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0848-4826","authenticated-orcid":false,"given":"Eric","family":"Rowinsky","sequence":"additional","affiliation":[{"name":"Biocity Biopharmaceutics Co., Ltd.  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