{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:05:53Z","timestamp":1791885953177,"version":"4.3.4"},"reference-count":65,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,9]],"date-time":"2020-08-09T00:00:00Z","timestamp":1596931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Tetrodotoxin (TTX) is a highly specific voltage-gated sodium channel (VGSC) blocker in clinical evaluation as a peripheral-acting analgesic for chronic pain. This study presents the first published results of the safety including cardiac liability of TTX at therapeutic-relevant concentrations in twenty-five healthy adults. Randomized, double-blind, placebo-, and positive- (moxifloxacin) controlled study evaluated single ascending doses of 15 \u00b5g, 30 \u00b5g, and 45 \u00b5g TTX over 3 periods with a 7-day washout between each period. Subcutaneous injections of TTX were readily absorbed, reaching maximum plasma concentration (Cmax) within 1.5 h. Both extent of exposure (AUC) and Cmax increased in proportion to dose. No QT prolongation was identified by concentration-QTc analysis and the upper bounds of the two-sided 90% confidence interval of predicted maximum baseline and placebo corrected QTcF (\u0394\u0394QTcF) value did not exceed 10 ms for all tetrodotoxin doses, thereby meeting the criteria of a negative QT study. Safety assessments showed no clinically relevant changes with values similar between all groups and no subject withdrawing due to adverse events. Paresthesia, oral-paresthesia, headache, dizziness, nausea, and myalgia were the most common TEAEs (overall occurrence \u22655%) in the TTX treatment groups. TTX doses investigated in this study are safe, well-tolerated, and lack proarrhythmic proclivity.<\/jats:p>","DOI":"10.3390\/toxins12080511","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T07:25:03Z","timestamp":1597044303000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Safety, Tolerability, Pharmacokinetics, and Concentration-QTc Analysis of Tetrodotoxin: A Randomized, Dose Escalation Study in Healthy Adults"],"prefix":"10.3390","volume":"12","author":[{"given":"Mojgan","family":"Kavoosi","sequence":"first","affiliation":[{"name":"WEX Pharmaceuticals Inc., Vancouver, BC V6E-4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry E.","family":"O\u2019Reilly","sequence":"additional","affiliation":[{"name":"Celerion Inc., Tempe, AZ 85283, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran","family":"Kavoosi","sequence":"additional","affiliation":[{"name":"WEX Pharmaceuticals Inc., Vancouver, BC V6E-4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chai","sequence":"additional","affiliation":[{"name":"Celerion Inc., Lincoln, NE 68502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Engel","sequence":"additional","affiliation":[{"name":"Celerion Inc., Montreal, QC H4M-2P1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Korz","sequence":"additional","affiliation":[{"name":"WEX Pharmaceuticals Inc., Vancouver, BC V6E-4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Gallen","sequence":"additional","affiliation":[{"name":"WEX Pharmaceuticals Inc., Vancouver, BC V6E-4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Lester","sequence":"additional","affiliation":[{"name":"Celerion Inc., Tempe, AZ 85283, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2458-11-770","article-title":"Pain as a global public health priority","volume":"11","author":"Goldberg","year":"2011","journal-title":"BMC Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jpain.2006.01.444","article-title":"The role of sodium channels in chronic inflammatory and neuropathic pain","volume":"7","author":"Amir","year":"2006","journal-title":"J. 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