{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:03:25Z","timestamp":1790334205435,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>ASP0367, or bocidelpar sulfate, is an orally administered small molecule that potently and selectively modulates peroxisome proliferator\u2013activated receptor \u03b4 (PPAR\u03b4) to address mitochondrial dysfunction occurring in diseases including primary mitochondrial myopathy and Duchenne muscular dystrophy. The objectives of this first\u2010in\u2010human trial were to evaluate the safety\/tolerability, pharmacokinetics, and pharmacodynamics of ASP0367 in healthy participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this double\u2010blind phase 1 study, adult participants were randomized to single or multiple ascending oral doses of ASP0367 or placebo. The study duration was 1 and 14\u2009days, respectively. Pharmacokinetic parameters under fed conditions were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 64 (single\u2010dose cohort) and 37 (multiple\u2010dose cohort) participants were included in the study. After single doses of 1 to 120\u2009mg, ASP0367 was rapidly absorbed, with median time to maximum plasma concentration (t<jats:sub>max<\/jats:sub>) of 1.50 to 2.24\u2009hours under fasting conditions; ASP0367 concentrations declined in a multiphasic manner after reaching maximum plasma concentration. Under fed conditions, t<jats:sub>max<\/jats:sub> was delayed 1.7\u00a0hours. After multiple once\u2010daily doses, mean half\u2010life of ASP0367 10 to 75\u2009mg ranged from 14.1 to 17.5\u00a0hours; steady state was reached after 4\u2009days. Negligible accumulation was observed after repeated dosing. No participants receiving ASP0367 discontinued treatment, and all treatment\u2010emergent adverse events were mild to moderate in severity; none were considered drug\u2010related. No clinically significant changes were observed on laboratory or electrocardiographic evaluation. Treatment\u2010 and dose\u2010dependent upregulation of six PPAR\u03b4 target genes was observed with single and multiple doses of ASP0367.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>ASP0367, or bocidelpar sulfate, was well tolerated; rapid absorption, roughly dose\u2010proportional bioavailability, and effects on PPAR\u03b4 target genes were demonstrated in healthy adult participants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27436","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T05:49:37Z","timestamp":1634104177000},"page":"110-120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Single\u2010 and multiple\u2010dose safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of <scp>ASP0367<\/scp>, or bocidelpar sulfate, a novel modulator of peroxisome proliferator\u2010activated receptor delta in healthy adults: Results from a phase 1 study"],"prefix":"10.1002","volume":"65","author":[{"given":"Mototsugu","family":"Ito","sequence":"first","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitra","family":"Tauscher\u2010Wisniewski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald A.","family":"Smulders","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Wojtkowski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yamada","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Koibuchi","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolga","family":"Uz","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard J.","family":"Marek","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"Goldwater","sequence":"additional","affiliation":[{"name":"Parexel International  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0188-3"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12413"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60025-3"},{"key":"e_1_2_11_5_1","unstructured":"Santhera to discontinue phase 3 SIDEROS study and development of Puldysa\u00ae in Duchenne muscular dystrophy (DMD) and focus on vamorolone.https:\/\/www.santhera.com\/assets\/files\/press-releases\/2020-10-06_siderospuldysa_e_final.pdf. Updated October 6 2020. Accessed July 15 2021."},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27108"},{"key":"e_1_2_11_7_1","unstructured":"Amondys 45 (casimersen) injection prescribing information.https:\/\/www.amondys45.com\/amondys45_(casimersen)_prescribing_information.pdf. Updated February 2021. Accessed July 15 2021."},{"key":"e_1_2_11_8_1","unstructured":"Exondys 51 (eteplirsen) injection prescribing information.https:\/\/www.exondys51.com\/modules\/exondys\/files\/exondys51pi.pdf. Updated July 2020. Accessed July 15 2021."},{"key":"e_1_2_11_9_1","unstructured":"Vyondys 53 (golodirsen) injection prescribing information.https:\/\/www.vyondys53.com\/static\/patient\/assets\/vyondys53_(golodirsen)_prescribing_Information.pdf. Updated February 2021. Accessed July 15 2021."},{"key":"e_1_2_11_10_1","unstructured":"Emflaza\u00ae (deflazacort) tablets prescribing information.https:\/\/emflaza.com\/wp-content\/uploads\/2020\/10\/prescribing-information.pdf. Updated June 2021. Accessed July 15 2021."},{"key":"e_1_2_11_11_1","unstructured":"Viltepso (viltolarsen) injection prescribing information.https:\/\/www.viltepso.com\/prescribing-information. Updated March 2021. Accessed July 15 2021."},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-00674-4"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.127"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001416"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30024-3"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11080837"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2015.08.015"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilu011"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026952"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.6.1321"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000743"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218056"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.354415"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27955"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/13813455.2013.829105"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2018.02.006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.051"},{"key":"e_1_2_11_28_1","first-page":"CD004426","article-title":"Treatment for mitochondrial disorders","volume":"4","author":"Pfeffer G","year":"2012","journal-title":"Cochrane Database Syst Rev."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005255"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22317"},{"key":"e_1_2_11_31_1","first-page":"783","article-title":"Immunosuppressive effects of deflazacort\u2013a new glucocorticoid with bone\u2010sparing and carbohydrate\u2010sparing properties: comparison with prednisone","volume":"8","author":"Hahn BH","year":"1981","journal-title":"J Rheumatol."},{"key":"e_1_2_11_32_1","unstructured":"U.S. FDA grants fast track designation for ASP0367\/MA\u20100211 a selective PPAR\u03b4 modulator being developed for the treatment of primary mitochondrial myopathies.https:\/\/www.astellas.com\/en\/news\/16136. 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Accessed July 15 2021."}],"updated-by":[{"DOI":"10.1002\/mus.70352","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000}}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27436","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.27436","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T16:59:18Z","timestamp":1692982758000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.27436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,28]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/mus.27436"],"URL":"https:\/\/doi.org\/10.1002\/mus.27436","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,28]]},"assertion":[{"value":"2021-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}