{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T10:27:01Z","timestamp":1772015221053,"version":"3.50.1"},"reference-count":9,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":20,"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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>PF614, a trypsin\u2010activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two\u2010part design including a multi\u2010ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200\u2009mg, <jats:italic>n<\/jats:italic>\u2009=\u20096\/cohort) or OxyContin (20, 40, or 80\u2009mg; <jats:italic>n<\/jats:italic>\u2009=\u20092\/cohort) in ascending cohorts, delivered every 12\u2009h for a total of nine doses. In part B, 60 subjects randomized in a four\u2010way crossover to evaluate BE, received PF614 100\u2009mg and OxyContin 40\u2009mg in fasted and fed (high\u2010fat diet) states. All subjects were naltrexone blocked prior to first study drug administration to protect against opioid\u2010related adverse effects; repeat doses were provided on days 1\u20135. In part A, PF614 was well\u2010tolerated following twice daily doses of up to 200\u2009mg for 5\u2009days. Plasma oxycodone maximal plasma concentration and area under the concentration time curve increased linearly with increasing doses. Part B showed that plasma oxycodone BE was achieved following 100\u2009mg PF614 or 40\u2009mg OxyContin under both fasted and fed conditions. Additionally, PF614 provided similar oxycodone exposures following both fasted and fed states. This study confirms findings from our single\u2010ascending dose study, showing that PF614 100\u2009mg releases oxycodone with a PK profile comparable to 40\u2009mg OxyContin under both fasted and fed conditions and with a similar safety profile under naltrexone\u2010blocked conditions.<\/jats:p>","DOI":"10.1111\/cts.13765","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T10:10:00Z","timestamp":1711015800000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi\u2010ascending dose study with a bioequivalence arm in healthy volunteers"],"prefix":"10.1111","volume":"17","author":[{"given":"D. Lynn","family":"Kirkpatrick","sequence":"first","affiliation":[{"name":"Ensysce Biosciences Inc.  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cari","family":"Evans","sequence":"additional","affiliation":[{"name":"Ensysce Biosciences Inc.  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda A.","family":"Pestano","sequence":"additional","affiliation":[{"name":"Ensysce Biosciences Inc.  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6568-5667","authenticated-orcid":false,"given":"Jeffrey","family":"Millard","sequence":"additional","affiliation":[{"name":"Ensysce Biosciences Inc.  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9514-0753","authenticated-orcid":false,"given":"Matthew","family":"Johnston","sequence":"additional","affiliation":[{"name":"ICON  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Mick","sequence":"additional","affiliation":[{"name":"ICON  Lenexa Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-4810","authenticated-orcid":false,"given":"William K.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Ensysce Biosciences Inc.  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.36076\/ppj.2008\/11\/S63"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr6501e1"},{"key":"e_1_2_10_4_1","volume-title":"Relieving pain in America: a blueprint for transforming prevention, care, education, and research","author":"IOM (Institute of Medicine)","year":"2011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.5055\/jom.2011.0069"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.1991.tb01754.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780203911259.ch35"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2012.01.315"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.5055\/jom.2017.0366"},{"issue":"5","key":"e_1_2_10_10_1","first-page":"752","article-title":"First\u2010in\u2010human pharmacokinetics & safety study of PF614: orally activated oxycodone prodrug","volume":"124","author":"Schmidt WK","year":"2017","journal-title":"Anesth Analg"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13765","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T06:33:10Z","timestamp":1744871590000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13765"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":9,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/cts.13765"],"URL":"https:\/\/doi.org\/10.1111\/cts.13765","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13765"}}