Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

ABSTRACT: BACKGROUND:Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical 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, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged???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 treatment: 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, dizziness, and vomiting the most frequent events. CONCLUSION:Significant improvement in the benefit-risk ratio was observed for CTC (doses???100 mg) over tramadol and placebo in the treatment of acute pain following oral surgery. FUNDING:Laboratorios del Dr. Esteve, S.A.U.

SUBMITTER: Lopez-Cedrun J 

PROVIDER: S-EPMC5995791 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature