{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:52:55Z","timestamp":1791665575105,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic pain represents a significant unmet medical need, affecting one\u2010fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non\u2010opioid, non\u2010NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated the safety and pharmacokinetic profile of EC5026 in two phase I trials, a single\u2010ascending dose (SAD) study and a fed\u2010fasted study. The SAD study evaluated EC5026 doses ranging from 0.5 to 24\u2009mg in healthy volunteers. EC5026 was well tolerated. No treatment\u2010emergent adverse events were considered related to EC5026. No apparent treatment\u2010 or dose\u2010related trends in laboratory results, vital signs, physical examinations, or electrocardiograms were observed. A linear, near\u2010dose\u2010proportional increase in exposure was observed with progressive doses in the SAD study; plasma exposure was below or near the lower limit of quantification after 0.5\u20132\u2009mg doses. Mean half\u2010lives ranged from 41.8 to 59.1\u2009h. for doses of 8\u201324\u2009mg, supporting a once\u2010daily dosing regimen. In the fed\u2010fasted study using 8\u2009mg EC5026 tablets, higher peak concentrations (66%) and total exposures (53%) were observed under the fed condition. Plasma concentrations declined in a monoexponential manner with mean half\u2010lives of 59.5\u2009h. in the fed state and 66.9\u2009h. in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity.<\/jats:p>","DOI":"10.1111\/cts.70033","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T01:09:57Z","timestamp":1726794597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Randomized, double\u2010blind, phase 1a single\u2010ascending dose and food effect studies assessing safety and pharmacokinetics of EC5026 in healthy volunteers"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-4810","authenticated-orcid":false,"given":"William K.","family":"Schmidt","sequence":"first","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Cort\u00e9s\u2010Puch","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy B.","family":"McReynolds","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn E.","family":"Croston","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hee","family":"Hwang","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa L.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Wagner","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa T.","family":"Pham","sequence":"additional","affiliation":[{"name":"PPD Development, LP  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hunt","sequence":"additional","affiliation":[{"name":"PPD Development, LP  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Hammock","sequence":"additional","affiliation":[{"name":"EicOsis Human Health Inc., a Subsidiary of EicOsis LLC  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"1","article-title":"Chronic pain and high\u2010impact chronic pain among U.S. adults, 2019","volume":"390","author":"Zelaya CE","year":"2020","journal-title":"NCHS Data Brief"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S105892"},{"key":"e_1_2_11_4_1","unstructured":"Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA).The Voice of the Patient. 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