{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:40:03Z","timestamp":1792723203987,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Bocidelpar is a peroxisome proliferator\u2010activated receptor \u03b4 modulator designed to address mitochondrial impairment. Two open\u2010label, single\u2010dose phase 1 studies (NCT05117294\/NCT04942964) investigated the effect of severe renal or mild\/moderate hepatic impairment on bocidelpar pharmacokinetics and safety. Adult participants received 75\u2009mg bocidelpar and underwent serial blood and urine sampling over 4\u2009days to evaluate the pharmacokinetics of bocidelpar. Thirteen participants were included in the renal cohort (severe impairment, <jats:italic>n<\/jats:italic>\u2009=\u20097; healthy participants, <jats:italic>n<\/jats:italic>\u2009=\u20096). A minimal increase was observed in the maximum concentration (C<jats:sub>max<\/jats:sub>) of the severe impairment group versus healthy participants (geometric least squares mean [GeoLSM] ratio [90% CI], 139.66% [86.33, 225.92]). No clear changes were observed in the area under the curve (AUC). Twenty\u2010five participants were included in the hepatic cohort (mild impairment, <jats:italic>n<\/jats:italic>\u2009=\u20098; moderate impairment, <jats:italic>n<\/jats:italic>\u2009=\u20098; healthy participants, <jats:italic>n<\/jats:italic>\u2009=\u20099). Compared with matched controls, increased C<jats:sub>max<\/jats:sub> was observed in the mild (GeoLSM ratio [90% CI], 181.37% [95.47, 344.56]) and moderate (GeoLSM ratio [90% CI], 298.78% [145.00, 615.65]) impairment groups. Mild impairment did not substantially affect the AUC<jats:sub>inf<\/jats:sub> versus matched controls (GeoLSM ratio [90% CI], 110.73% [82.16, 149.24]); however, it was higher in the moderate impairment group versus matched controls (GeoLSM ratio [90% CI], 195.58% [115.26, 331.88]). Across both studies, five treatment\u2010emergent adverse events were observed in five participants; all were considered mild in severity. Overall, bocidelpar was well tolerated and had an acceptable safety profile. Severe renal impairment had a minimal effect on bocidelpar pharmacokinetics, while moderate hepatic impairment resulted in increased bocidelpar concentration and exposure compared with matched controls.<\/jats:p>","DOI":"10.1111\/cts.70310","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T16:39:54Z","timestamp":1754066394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics of Bocidelpar, <scp>ASP0367<\/scp>, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4323-8266","authenticated-orcid":false,"given":"Megumi","family":"Iwai","sequence":"first","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakyo","family":"Heo","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayuri","family":"Guro","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Moy","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Spence","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Wojtkowski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4718-8023","authenticated-orcid":false,"given":"Lauren","family":"Benner","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2551-0164","authenticated-orcid":false,"given":"Melanie","family":"Helmick","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9305-458X","authenticated-orcid":false,"given":"Tong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1885-9205","authenticated-orcid":false,"given":"Brian C.","family":"Ferslew","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.26402\/jpp.2021.2.01"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2023.11.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010018\u201000674\u20104"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/neurolint16040055"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)60025\u20103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.19082\/3896"},{"key":"e_1_2_10_8_1","unstructured":"Santhera \u201cSanthera to Discontinue Phase 3 SIDEROS Study and Development of Puldysa in Duchenne Muscular Dystrophy (DMD) and Focus on Vamorolone \u201daccessed October 25 2024 https:\/\/www.santhera.com\/assets\/files\/press\u2010releases\/2020\u201010\u201006_SiderosPuldysa_e_final.pdf."},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475\u20102891\u201013\u201017"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020294"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113339"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2014.11.002"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001839\u20108"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27436"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/2049936113519089"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.8.1065"},{"key":"e_1_2_10_17_1","unstructured":"European Medicines Agency \u201cGuideline on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients With Impaired Hepatic Function \u201daccessed November 5 2024 https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/guideline\u2010evaluation\u2010pharmacokinetics\u2010medicinal\u2010products\u2010patients\u2010impaired\u2010hepatic\u2010function_en.pdf."},{"key":"e_1_2_10_18_1","unstructured":"U.S. Food & Drug Administration \u201cPharmacokinetics in Patients With Impaired Hepatic Function: Study Design Data Analysis and Impact on Dosing and Labeling \u201daccessed November 5 2024 https:\/\/www.fda.gov\/media\/71311\/download."},{"key":"e_1_2_10_19_1","unstructured":"U.S. Food & Drug Administration \u201cPharmacokinetics in Patients With Impaired Renal Function\u2014Study Design Data Analysis and Impact on Dosing \u201daccessed November 5 2024 https:\/\/www.fda.gov\/media\/78573\/download."},{"key":"e_1_2_10_20_1","unstructured":"European Medicines Agency \u201cNote for Guidance on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients With Impaired Renal Function \u201daccessed November 5 2024 https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/note\u2010guidance\u2010evaluation\u2010pharmacokinetics\u2010medical\u2010products\u2010patients\u2010impaired\u2010renal\u2010function_en.pdf."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijnrd.S291348"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.00340118"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T17:20:45Z","timestamp":1755969645000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":21,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/cts.70310"],"URL":"https:\/\/doi.org\/10.1111\/cts.70310","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70310"}}