{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:32:29Z","timestamp":1777948349431,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Small\u2010molecule activin receptor\u2010like kinase\u20102 inhibitor zilurgisertib (INCB000928) is under investigation in a pivotal trial for the treatment of fibrodysplasia ossificans progressiva (FOP), an ultrarare genetic condition. This analysis assessed effects of renal and hepatic impairment on zilurgisertib pharmacokinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two open\u2010label, parallel\u2010group studies were conducted. Participants with renal or hepatic impairment were matched with healthy controls and received a single 200\u2010mg dose of zilurgisertib; those with end\u2010stage renal disease (ESRD) received doses before and after haemodialysis. Plasma concentrations were quantified via validated assay; pharmacokinetic parameters were derived from non\u2010compartmental analysis. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for C\n                      <jats:sub>max<\/jats:sub>\n                      , AUC\n                      <jats:sub>0\u2010t<\/jats:sub>\n                      and AUC\n                      <jats:sub>0\u2010\u221e<\/jats:sub>\n                      were compared by ANOVA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with matched controls, GMRs (90% CIs) for C\n                      <jats:sub>max<\/jats:sub>\n                      and AUC\n                      <jats:sub>0\u2010\u221e<\/jats:sub>\n                      were as follows: mild renal impairment, 0.92 (0.64\u20131.34) and 0.98 (0.77\u20131.24); moderate, 1.22 (0.92\u20131.63) and 1.64 (1.28\u20132.10); severe, 1.00 (0.74\u20131.35) and 1.70 (1.33\u20132.16), respectively. Among participants with ESRD, values were the following: before haemodialysis, 1.17 (0.91\u20131.49) and 1.47 (1.15\u20131.88); after, 1.32 (1.00\u20131.75) and 1.68 (1.29\u20132.19), respectively. Among participants with hepatic impairment, values were as follows: moderate, 1.06 (0.80\u20131.42) and 1.13 (0.93\u20131.38); severe: 1.36 (1.05\u20131.76) and 1.25 (1.06\u20131.48), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Zilurgisertib exposure was unchanged with mild renal or moderate hepatic impairment, but increased by 30%\u201370% with moderate or more severe renal impairment and by 25% with severe hepatic impairment. These findings, alongside the therapeutic index, to be defined by the ongoing pivotal FOP trial (NCT05090891), will guide dosing in these populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70372","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T01:44:08Z","timestamp":1765244648000},"page":"1339-1351","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Renal and Hepatic Impairment on the Pharmacokinetics of Zilurgisertib"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4869-9492","authenticated-orcid":false,"given":"Yan\u2010ou","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0400-514X","authenticated-orcid":false,"given":"Phillip","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioanalysis Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay","family":"Getsy","sequence":"additional","affiliation":[{"name":"Department of Early Development Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Rockich","sequence":"additional","affiliation":[{"name":"Department of Early Development Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102020\u2010136138"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010181055"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c02983"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.12.007"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070736"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.10556"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010021\u201001983\u20102"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.29245\/2572\u20109411\/2020\/2.1196"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/ORR.S337491"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318\u2010024\u201000926\u2010z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1553"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.8.1065"},{"key":"e_1_2_10_15_1","unstructured":"US Department of Health and Human Services Food and Drug Administration. 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