{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T03:22:52Z","timestamp":1768879372208,"version":"3.49.0"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A novel, oral phosphodiesterase 4 (PDE4) inhibitor, ME3183, is under development for the treatment of psoriasis, atopic dermatitis, and other inflammatory diseases. To evaluate its safety, tolerability, and pharmacokinetics, double\u2010blind, placebo\u2010controlled, single ascending dose (SAD), and multiple ascending dose (MAD) phase 1 studies were conducted in 126 healthy adults. The food effect was evaluated in a randomized, open\u2010label, crossover manner (n = 5). ME3183 was safe and tolerable up to 25\u00a0mg in the SAD part and up to 10\u00a0mg twice daily in the MAD part. Frequently observed treatment\u2010emergent adverse events included diarrhea and headache, as commonly reported for approved PDE4 inhibitors, providing no novel safety concerns. Pharmacokinetic analysis showed dose\u2010dependent increases in C<jats:sub>max<\/jats:sub> and AUC, with later t<jats:sub>max<\/jats:sub> and longer t<jats:sub>1\/2<\/jats:sub> than apremilast, an approved PDE4 inhibitor. The food effect study showed slightly decreased systemic exposure. In the MAD part, plasma exposure levels of ME3183 were higher even at the minimal dose (2.5\u00a0mg twice daily) than the estimated therapeutically effective level. These results show the safe profile of ME3183 and support further studies to confirm the safety and efficacy of the drug in patients with psoriasis and other inflammatory diseases.<\/jats:p>","DOI":"10.1002\/cpdd.1351","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T14:57:10Z","timestamp":1702911430000},"page":"341-348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety, Tolerability, and Pharmacokinetics of a Novel Oral Phosphodiesterase 4 Inhibitor, ME3183: First\u2010in\u2010Human Phase 1 Study"],"prefix":"10.1002","volume":"13","author":[{"given":"Seiji","family":"Kato","sequence":"first","affiliation":[{"name":"R&amp;D Division Meiji Seika Pharma Co., Ltd.  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