{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:01:52Z","timestamp":1780732912760,"version":"3.54.1"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>SC1011 (sufenidone) is a novel pyridone derivative with therapeutic potential for idiopathic pulmonary fibrosis (IPF). Two Phase 1 studies evaluated the safety and pharmacokinetics of single (SAD) and multiple ascending doses (MAD) of SC1011 immediate\u2010release (IR) and modified\u2010release (MR) oral formulations in healthy adult subjects. In Phase 1a, subjects were randomized to receive oral SC1011 IR or placebo in SAD (50\u2009mg\u2010300\u2009mg) or MAD (100\u2009mg and 200\u2009mg) twice daily for 7\u2009days. The Phase 1b study consisted of three treatment groups that received 100, 150, or 200\u2009mg SC1011 MR twice daily for 7\u2009days. SC1011 IR was absorbed rapidly (mean time to maximum concentration, T<jats:sub>max<\/jats:sub> \u2264\u20091\u2009h) and eliminated rapidly (mean terminal half\u2010life, t<jats:sub>1\/2<\/jats:sub>: 1.23\u20132.64\u2009h) following 50\u2013300\u2009mg single\u2010dose administrations. Reduced maximum plasma concentration (C<jats:sub>max<\/jats:sub>), delayed T<jats:sub>max<\/jats:sub>, and comparable total exposure were observed with the MR formulation compared with the IR formulation. Both formulations demonstrated dose\u2010proportional pharmacokinetics at the applied dose ranges, and no obvious accumulation of systemic exposure was observed upon repeated administration. All treatment\u2010emergent adverse events (TEAEs) with both formulations were mild or moderate in severity, and gastrointestinal reactions were the most frequently reported TEAEs. The tolerability of SC1011 was markedly improved with the MR formulation. Exposure\u2013adverse event (AE) analysis with the most frequent AEs identified C<jats:sub>max<\/jats:sub> rather than total exposure as a good predictor of AEs. Compared to the IR formulation, SC1011 MR demonstrated improved exposure and tolerability, supporting its further development in patients with IPF.<\/jats:p>","DOI":"10.1111\/cts.70179","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:47:55Z","timestamp":1741754875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety, Tolerability, and Pharmacokinetics of <scp>SC1011<\/scp> (Sufenidone), a Novel Antifibrotic Small Molecule, in Phase 1 Studies in Healthy Subjects"],"prefix":"10.1111","volume":"18","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"}]},{"given":"Xiaoning","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou Joyo Pharmatech Co., Ltd., Building C, Yunsheng Science Park  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8103-7465","authenticated-orcid":false,"given":"Huimin","family":"Tang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"},{"name":"Guangdong Clinical Research Academy of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Jiang","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\/0009-0006-0682-5080","authenticated-orcid":false,"given":"Yaqin","family":"Tang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"},{"name":"Guangdong Clinical Research Academy of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2575-6306","authenticated-orcid":false,"given":"Huijuan","family":"Zhu","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\/0009-0008-6822-0612","authenticated-orcid":false,"given":"Yanping","family":"Du","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"},{"name":"Guangdong Clinical Research Academy of Chinese Medicine  Guangzhou Guangdong 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\/0000-0002-0930-0910","authenticated-orcid":false,"given":"Shuyun","family":"Liu","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"}]},{"given":"Xiaoshu","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangzhou Joyo Pharmatech Co., Ltd., Building C, Yunsheng Science Park  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zan","sequence":"additional","affiliation":[{"name":"Guangzhou Joyo Pharmatech Co., Ltd., Building C, Yunsheng Science Park  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexia","family":"Zeng","sequence":"additional","affiliation":[{"name":"Guangzhou Joyo Pharmatech Co., Ltd., Building C, Yunsheng Science Park  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Joyo Pharmatech Co., Ltd., Building C, Yunsheng Science Park  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Ge","sequence":"additional","affiliation":[{"name":"Guangzhou Joyo Pharmatech Co., Ltd., Building C, Yunsheng Science Park  Guangzhou Guangdong China"},{"name":"Hangzhou Chengbang Pharmaceutical Technology Co., Ltd.  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongguo","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Joyo Pharmatech Co., Ltd., Building C, Yunsheng Science Park  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3582-2672","authenticated-orcid":false,"given":"Zhongqi","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"},{"name":"Guangdong Clinical Research Academy of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1705751"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30866-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.5355"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.170"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.8693"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202112-2824OC"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202401-0116OC"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0350-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00174914"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.23955"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2023-001687"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11010143"},{"key":"e_1_2_9_14_1","first-page":"2376","article-title":"Modified Release Formulations to Achieve the Quality Target Product Profile (Qtpp)","volume":"3","author":"Kumar J. M.","year":"2012","journal-title":"International Journal of Pharmaceutical Sciences and Research"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsab200"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e05279"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60405-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200528110-00003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2009.03.003"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T06:54:22Z","timestamp":1743317662000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/cts.70179"],"URL":"https:\/\/doi.org\/10.1111\/cts.70179","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70179"}}