López Cedrún, JoséVidela, SebastiàBurgueño, MiguelJuárez, InmaAboul-Hosn, SamirMartín Granizo, RafaelGrau, JoanPuche, MiguelGil Diez, José LuisHueto, José AntonioVaqué, AnnaSust, MarianoPlata Salamán, CarlosMonner, AntoniCo-Crystal of Tramadol-Celecoxib Team2020-12-012020-12-0120181174-5886https://hdl.handle.net/2445/172495Background Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceu- tical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. Methods A dose-finding, double-blind, randomised, pla- cebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778- 21) was performed in male and female patients aged C 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Results Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treat- ment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizzi- ness, and vomiting the most frequent events. Conclusion Significant improvement in the benefit-risk ratio was observed for CTC (doses C 100 mg) over tra- madol and placebo in the treatment of acute pain following oral surgery.12 p.application/pdfengcc-by-nc (c) López Cedrún, José et al., 2018http://creativecommons.org/licenses/by-nc/3.0/esTractament del dolorDolor postoperatoriDolor orofacialPain treatmentPostoperative painOrofacial paininfo:eu-repo/semantics/article6979772020-12-01info:eu-repo/semantics/openAccess29799099