{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:53:18Z","timestamp":1772988798616,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The oral, small molecule inhibitor of activin receptor\u2010like kinase\u20102, zilurgisertib (INCB000928), is under evaluation in fibrodysplasia ossificans progressiva. Cardiac safety was assessed using electrocardiogram (ECG) parameters and a plasma concentration\u2010heart rate\u2010corrected QT (C\u2010QTc) interval analysis of pooled data from single ascending dose (SAD) and multiple ascending dose (MAD) studies of zilurgisertib in healthy adult participants (SAD: 10\u2010500\u00a0mg; INCB00928\u2010102: 50\u2010400\u00a0mg QD, 300\u00a0mg BID). Overall, 91 (SAD) and 79 (MAD) participants provided at least one pair of PK\/ECG data. As both studies indicated a dose\u2010dependent effect of zilurgisertib on heart rate, individualized QT correction (QTcI) was used as the primary endpoint for QTc analysis. Estimated population slope of the individualized C\u2010\u0394QTc (C\u2010\u0394QTcI) relationship was shallow (0.02\u00a0ms per \u00b5\n                    <jats:sc>m<\/jats:sc>\n                    [90% CI, \u22120.60, 0.65]) and not statistically significantly different from 0; treatment effect\u2013specific intercept was small and not significant (\u22120.83\u00a0ms [90% CI, \u22122.26, 0.61]). No significant relationship between zilurgisertib plasma concentration and change in QTcI was identified; zilurgisertib did not have a clinically relevant effect on QTc prolongation. QT effect\n                    <jats:italic>&gt;<\/jats:italic>\n                    10 ms could therefore be excluded within the dose range studied (up to 300\u00a0mg BID). No clinically meaningful effects on cardiac conduction (PR and QRS intervals) or any categorical PR or QRS outliers were observed. These data support further clinical development of zilurgisertib.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1618","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:15:01Z","timestamp":1761218101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of clinical cardiac safety of zilurgisertib, an activin receptor\u2010like kinase\u20102 (ALK2) inhibitor, in healthy participants"],"prefix":"10.1002","volume":"15","author":[{"given":"Yan\u2010ou","family":"Yang","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohua","family":"Gong","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay","family":"Getsy","sequence":"additional","affiliation":[{"name":"Early Clinical Development Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Rockich","sequence":"additional","affiliation":[{"name":"Early Clinical Development Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-136138"},{"key":"e_1_2_10_3_1","unstructured":"National Center for Biotechnology Information.PubChem Compound Summary for CID 138628908 Zilurgisertib. Accessed June 20 2025.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Zilurgisertib."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16010154"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070736"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14010101"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-181055"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-024-00926-z"},{"issue":"4","key":"e_1_2_10_10_1","first-page":"401","article-title":"Improving the precision of QT measurements","volume":"18","author":"Darpo B","year":"2011","journal-title":"Cardiol J"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533558"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011419851"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/75.4.800"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.779"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1021379866"},{"key":"e_1_2_10_16_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER).Guidance for industry. E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs. Accessed November 19 2024.https:\/\/www.fda.gov\/media\/71372\/download"},{"key":"e_1_2_10_17_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER).Guidance for industry. E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs \u2014 questions and answers (R3). Accessed November 19 2024.https:\/\/www.fda.gov\/media\/71379\/download"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15047"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009341184"},{"key":"e_1_2_10_20_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER).Guidance for industry. E14 and S7B clinical and nonclinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential \u2014 questions and answers. Accessed July 7 2025.https:\/\/www.fda.gov\/media\/161198\/download."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.528"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.808"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1553"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1618","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1618","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1618","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:40:05Z","timestamp":1772970005000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1618"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/cpdd.1618"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1618","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"assertion":[{"value":"2025-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1618"}}