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dc.contributor.authorLobo, Kimberly
dc.contributor.authorDonado, Carolina
dc.contributor.authorCornelissen, Laura Louise
dc.contributor.authorKim, Joseph
dc.contributor.authorOrtiz, Rebeca
dc.contributor.authorPeake, Roy
dc.contributor.authorKellogg, Mark David
dc.contributor.authorAlexander, Mark Edward
dc.contributor.authorZurakowski, David
dc.contributor.authorKurgansky, Katherine E.
dc.contributor.authorPeyton, James Matthew
dc.contributor.authorBilge, Aykut
dc.contributor.authorBoretsky, Karen Rach
dc.contributor.authorMcCann, Mary Ellen
dc.contributor.authorBerde, Charles Benjamin
dc.contributor.authorCravero, Joseph Peter
dc.date.accessioned2018-03-06T20:41:06Z
dc.date.issued2015
dc.identifierQuick submit: 2017-03-03T10:12:32-0500
dc.identifier.citationLobo, Kimberly, Carolina Donado, Laura Cornelissen, Joseph Kim, Rebeca Ortiz, Roy W. A. Peake, Mark Kellogg, et al. 2015. “A Phase 1, Dose-Escalation, Double-Blind, Block-Randomized, Controlled Trial of Safety and Efficacy of Neosaxitoxin Alone and in Combination with 0.2% Bupivacaine, with and Without Epinephrine, for Cutaneous Anesthesia.” Anesthesiology 123 (4) (October): 873–885. doi:10.1097/aln.0000000000000831.en_US
dc.identifier.issn0003-3022en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34900485
dc.description.abstractBACKGROUND: Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker that produces prolonged local anesthesia in animals and humans. Under a Food and Drug Administration-approved phase 1 Investigational New Drug trial, the authors evaluated safety and efficacy of NeoSTX alone and combined with 0.2% bupivacaine (Bup) with and without epinephrine. METHODS: The authors conducted a double-blind, randomized, controlled trial involving healthy male volunteers aged 18 to 35 yr receiving two 10-ml subcutaneous injections. Control sites received Bup. In part 1, active sites received (1) 5 to 40 μg NeoSTX+Saline (NeoSTX-Saline), (2) 5 to 40 μg NeoSTX+Bup (NeoSTX-Bup), or (3) placebo (Saline). In part 2, active sites received 10 or 30 μg NeoSTX+Bup+Epinephrine (NeoSTX-Bup-Epi) or placebo. Primary outcome measures were safety and adverse events associated with NeoSTX. Secondary outcomes included clinical biochemistry, NeoSTX pharmacokinetics, and cutaneous hypoesthesia. RESULTS: A total of 84 subjects were randomized and completed the two-part trial with no serious adverse events or clinically significant physiologic impairments. Perioral numbness and tingling increased with NeoSTX dose for NeoSTX-Saline and NeoSTX-Bup. All symptoms resolved without intervention. NeoSTX-Bup-Epi dramatically reduced symptoms compared with other NeoSTX combinations (tingling: 0 vs. 70%, P = 0.004; numbness: 0 vs. 60%, P = 0.013) at the same dose. Mean peak plasma NeoSTX concentration for NeoSTX-Bup-Epi was reduced at least two-fold compared with NeoSTX-Saline and NeoSTX-Bup (67 ± 14, 134 ± 63, and 164 ± 81 pg/ml, respectively; P = 0.016). NeoSTX-Bup showed prolonged cutaneous block duration compared with Bup, NeoSTX-Saline, or placebo, at all doses. Median time to near-complete recovery for 10 μg NeoSTX-Bup-Epi was almost five-fold longer compared with Bup (50 vs. 10 h, P = 0.007). CONCLUSION: NeoSTX combinations have a tolerable side effect profile and appear promising for prolonged local anesthesia.en_US
dc.language.isoen_USen_US
dc.publisherOvid Technologies (Wolters Kluwer Health)en_US
dc.relation.isversionofdoi:10.1097/ALN.0000000000000831en_US
dash.licenseMETA_ONLY
dc.titleA Phase 1, Dose-escalation, Double-blind, Block-randomized, Controlled Trial of Safety and Efficacy of Neosaxitoxin Alone and in Combination with 0.2% Bupivacaine, with and without Epinephrine, for Cutaneous Anesthesiaen_US
dc.typeJournal Articleen_US
dc.date.updated2017-03-03T15:12:32Z
dc.description.versionVersion of Recorden_US
dc.relation.journalAnesthesiologyen_US
dash.depositing.authorCornelissen, Laura Louise
dash.embargo.until10000-01-01
dc.date.available2015
dc.identifier.doi10.1097/ALN.0000000000000831*
dash.authorsorderedfalse
dash.contributor.affiliatedAlexander, Mark
dash.contributor.affiliatedKellogg, Mark
dash.contributor.affiliatedPeake, Roy
dash.contributor.affiliatedCornelissen, Laura
dash.contributor.affiliatedCravero, Joseph
dash.contributor.affiliatedMcCann, Mary Ellen
dash.contributor.affiliatedBoretsky, Karen
dash.contributor.affiliatedPeyton, James
dash.contributor.affiliatedBilge, Aykut
dash.contributor.affiliatedBerde, Charles
dash.contributor.affiliatedZurakowski, David


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