{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:14:33Z","timestamp":1791317673542,"version":"4.3.1"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This single\u2010center, open\u2010label, randomized, multiple\u2010dose, pharmacokinetic bridging study was conducted to compare systemic exposure (AUC and C\n                    <jats:sub>max<\/jats:sub>\n                    ) of a sublingual tablet formulation of cyclobenzaprine hydrochloride (TNX\u2010102 SL, approved as TONMYA) at steady\u2010state with that of an approved reference product, an oral, extended\u2010release (ER) capsule formulation, supporting development under the 505(b)(2) regulatory pathway. Healthy adults (N = 60) were randomly assigned 1:1 to receive two sublingual 2.8\u2010mg tablets or one oral ER 30\u2010mg capsule once daily for 20 days. At steady state, 2 sublingual 2.8 mg tablets provided lower exposure to cyclobenzaprine and norcyclobenzaprine compared with one oral 30\u2010mg ER capsule. However, when exposures were normalized by dose, cyclobenzaprine AUC\n                    <jats:sub>0\u201024<\/jats:sub>\n                    and C\n                    <jats:sub>max<\/jats:sub>\n                    were higher on both Day 1 and Day 20 with two sublingual tablets versus one oral ER capsule, supporting higher bioavailability of the sublingual tablet formulation. For Day 20, the dose\u2010normalized ratios (two sublingual tablets: one oral ER capsule) for AUC\n                    <jats:sub>0\u2010\u03c4 ss<\/jats:sub>\n                    and C\n                    <jats:sub>max ss<\/jats:sub>\n                    were 140% and 152%, respectively. Sublingual tablets and oral ER capsules had comparable metabolic profiles of Phase I and II metabolites in plasma over 20 days, with no unique metabolites by the sublingual route. Sublingual cyclobenzaprine HCl tablets were generally safe and well\u2010tolerated.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70060","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T08:48:59Z","timestamp":1775638139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Steady\u2010State Pharmacokinetic Properties of TNX\u2010102 SL, a Sublingual Tablet Formulation of Cyclobenzaprine Hydrochloride (HCl), With Daily Dosing in Healthy Volunteers: A Randomized, Open\u2010Label Trial"],"prefix":"10.1002","volume":"15","author":[{"given":"Gregory M.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Tonix Pharmaceuticals, Inc.  Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Meibohm","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center  Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errol","family":"Gould","sequence":"additional","affiliation":[{"name":"Tonix Medicines, Inc.  Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Tonix Pharmaceuticals, Inc.  Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Lederman","sequence":"additional","affiliation":[{"name":"Tonix Pharmaceuticals, Inc.  Berkeley Heights NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2016.08.012"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-197507000-00008"},{"issue":"6","key":"e_1_2_11_4_1","first-page":"1193","article-title":"Cyclic alternating pattern: a new marker of sleep alteration in patients with fibromyalgia?","volume":"31","author":"Rizzi M","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(96)03226-5"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.564412"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2011.05.031"},{"key":"e_1_2_11_8_1","unstructured":"McNeil Consumer & Specialty Pharmaceuticals.Flexeril. Cyclobenzaprine HCL.McNeil Consumer & Specialty Pharmaceuticals;2005."},{"key":"e_1_2_11_9_1","volume-title":"Cyclobenzaprine hydrochloride extended\u2010release capsules","author":"Teva Pharmaceuticals USA, Inc","year":"2019"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2021.113974"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.25142"},{"key":"e_1_2_11_12_1","volume-title":"Steady\u2010state pharmacokinetic properties of a sublingual formulation of cyclobenzaprine (CBP) HCl (TNX\u2010102 SL*): comparison to simulations of oral immediate release CBP","author":"Sullivan G","year":"2019"},{"key":"e_1_2_11_13_1","unstructured":"Tonix Pharmaceuticals Holding Corp.Tonmya\u2122. Cyclobenzaprine hydrochloride sublingual tablets. Tonix Pharmaceuticals;2025."},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2165\/0002512-200926020-00001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnaf089"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1991.tb05514.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.07.001"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/NSS.S134864"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70060","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70060","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T03:08:50Z","timestamp":1777086530000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/cpdd.70060"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70060","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2026-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70060"}}