{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:20:04Z","timestamp":1787664004942,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014421","name":"EA Pharma Co., Ltd.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This first\u2010in\u2010human study evaluated the safety, pharmacokinetics (PK), food effect, and pharmacodynamics (PD) of AJM347, a novel orally active, selective \u03b14\u03b27 integrin antagonist, in healthy Caucasian and Japanese adult males. The study consisted of three parts. In the single\u2010ascending dose (SAD) study (Part 1), AJM347 was administered in doses ranging from 6 to 2420\u00a0mg. The effect of food was evaluated in Part 2. In the multiple\u2010ascending dose (MAD) study (Part 3), AJM347 was administered twice daily (200\u2013800 mg) for 7 days. Single and multiple oral doses of AJM347 were safe and well tolerated. No changes in lymphocyte counts in whole blood and cerebrospinal fluid were observed. AJM347 was rapidly absorbed and the active metabolite, CAN2281, was rapidly formed. Administration of AJM347 after meals achieved higher trough concentrations of CAN2281 compared with administration under fasted conditions. AJM347 rapidly and dose\u2010dependently inhibited mucosal addressin cell adhesion molecule\u20101 binding to CD4+ T cells. Doses \u2265200 mg twice daily maintained &gt;90% inhibition (\u03b14\u03b27 receptor occupancy) for up to 24 h. PD effects correlated well with plasma concentrations of the active metabolite CAN2281. AJM347 demonstrated a favorable safety profile, effective target engagement, and promising PK properties for oral administration. The timing of dosing relative to meals did not affect the safety or overall PK profiles, but postprandial administration led to higher trough concentrations, suggesting that dosing after meals may represent the optimal regimen for the continued clinical development of AJM347. Blood samples were collected to assess PK and PD (\u03b14\u03b27 receptor occupancy). Samples were also collected to measure lymphocyte counts in peripheral blood and cerebrospinal fluid (CSF).<\/jats:p>","DOI":"10.1002\/jcph.70260","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:30:45Z","timestamp":1786710645000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, Pharmacokinetics, Food effect, and Pharmacodynamics of AJM347, a Selective \u03b14\u03b27 Integrin Antagonist: A First\u2010in\u2010Human Single\u2010 and Multiple\u2010Ascending Dose Study in Healthy Male Volunteers"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8202-1530","authenticated-orcid":false,"given":"Tetsuya","family":"Koyama","sequence":"first","affiliation":[{"name":"Pharmaceutical Development Department EA Pharma Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsunori","family":"Seki","sequence":"additional","affiliation":[{"name":"Pharmaceutical Development Department EA Pharma Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603283341307"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2013.06.001"},{"issue":"45","key":"e_1_2_13_4_1","first-page":"768","article-title":"Treatment strategies in inflammatory bowel diseases","volume":"120","author":"Stallmach A","year":"2023","journal-title":"Dtsch Arztebl Int."},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32126-2"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1102942"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1439-1"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v31.i29.107745"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-01035-7"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00953-0"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2025.101981"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107829"},{"issue":"2","key":"e_1_2_13_13_1","first-page":"117","article-title":"Stratification and monitoring of natalizumab\u2010associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group","volume":"87","author":"McGuigan C","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-022-02347-1"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2021.11.014"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16060"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21236"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjw092"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjy011"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0242342"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.10.1383"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2023.2221027"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215734"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2013.08.011"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-018-0669-8"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70260","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70260","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:33:24Z","timestamp":1787661204000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jcph.70260"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70260","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70260"}}