{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:43:19Z","timestamp":1770824599804,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peroxisome proliferator\u2010activated receptor \u03b4 (PPAR\u03b4) plays a central role in modulating mitochondrial function in ischemia\u2010reperfusion injury. ASP1128, a potent and selective modulator of PPAR\u03b4, is currently under investigation for treating acute kidney injury. This randomized, first\u2010in\u2010human study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of ASP1128 administered intravenously in healthy participants. Forty\u2010nine participants received a single dose of ASP1128 0.3\u201310\u00a0mg (n\u00a0=\u00a037) or placebo (n\u00a0=\u00a012) and 53 received daily (7\u00a0days) doses of ASP1128 3\u2013100\u00a0mg (n\u00a0=\u00a039) or placebo (n\u00a0=\u00a014), including a cohort aged \u226565\u00a0years (ASP1128 100\u00a0mg, n\u00a0=\u00a03; placebo, n\u00a0=\u00a02). Treatment\u2010emergent adverse events occurred in 37.8%, 59.0%, and 33.3%\u201335.7% of participants in the single ASP1128, multiple ASP1128, and placebo groups, respectively. All were mild in severity, and the frequency of adverse events did not appear to be dose\u2010related. One participant (multiple ASP1128 3\u00a0mg group) withdrew with an infusion site erythema, possibly related to study drug. Exposure was roughly dose\u2010proportional, and elimination was generally consistent across doses (mean t<jats:sub>\u00bd<\/jats:sub> 14.6\u201317.4\u00a0hours in the 10, 30, and 100\u00a0mg groups on day 7). There was little accumulation in plasma following multiple dosing; steady state was reached after \u223c4\u00a0days. ASP1128 treatment led to rapid and dose\u2010related upregulation of six fatty acid oxidation\u2010related PPAR\u03b4 target genes at \u226510\u00a0mg, which lasted &gt;24\u00a0hours postdose. In conclusion, single and multiple intravenous doses of ASP1128 were generally well tolerated, with dose\u2010dependent pharmacokinetics and target gene engagement in healthy participants.<\/jats:p>","DOI":"10.1002\/cpdd.1236","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T08:17:48Z","timestamp":1679386668000},"page":"810-818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single\u2010 and Multiple\u2010dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP1128, a Novel Peroxisome Proliferator\u2010activated Receptor \u03b4 Modulator, in Healthy Participants"],"prefix":"10.1002","volume":"12","author":[{"given":"Yuta","family":"Taniuchi","sequence":"first","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. W. Olivier","family":"van Till","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Wojtkowski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Toyoshima","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Koibuchi","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Briana","family":"Sargent","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Han","sequence":"additional","affiliation":[{"name":"Parexel Early Phase\/California Clinical Trials Medical Group  Glendale California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.03.015"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32563-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaa231"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000228"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/13813455.2016.1164186"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/13813455.2013.829105"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2014.876992"},{"key":"e_1_2_9_10_1","first-page":"188","article-title":"PPAR\u03b4 modulator MTB\u20102 enhances FAO in vitro and attenuates ischemia\u2010reperfusion\u2010induced gene expression changes in vivo 48 hours and 14 days post AKI [Abstract TH\u2010PO339]","volume":"28","author":"Bracken C","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_9_11_1","first-page":"165","article-title":"Modulation of PPAR\u03b4 with MTB\u20102 post\u2010reperfusion attenuates IR\u2010induced AKI injury biomarkers and histopathology in rats [Abstract TH\u2010PO243]","volume":"28","author":"Bracken C","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0262"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12452"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087327"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-11-10"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11040521"},{"key":"e_1_2_9_18_1","first-page":"452","article-title":"Design of the 1128\u2010CL\u20100201 study: a phase 2 proof of concept, double\u2010blind, randomized, placebo\u2010controlled study of ASP1128 in patients at risk for AKI after cardiac surgery [FR\u2010PO077]","volume":"30","author":"Till O","year":"2019","journal-title":"J Am Soc Nephrol"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1236","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1236","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T23:44:24Z","timestamp":1692229464000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/cpdd.1236"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1236","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,21]]},"assertion":[{"value":"2022-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}