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

被引:33
|
作者
Lopez-Cedrun, Jose [1 ]
Videla, Sebastian [2 ,11 ]
Burgueno, Miguel [3 ]
Juarez, Inma [4 ]
Aboul-Hosn, Samir [5 ]
Martin-Granizo, Rafael [6 ]
Grau, Joan [7 ]
Puche, Miguel [8 ]
Gil-Diez, Jose-Luis [9 ]
Hueto, Jose-Antonio [10 ]
Vaque, Anna [2 ]
Sust, Mariano [2 ]
Plata-Salaman, Carlos [2 ]
Monner, Antoni [4 ]
机构
[1] Complexo Hosp Univ A Coruna, Dept Maxillofacial Surg, La Coruna, Spain
[2] SAU, Clin Invest Dept, Labs Dr Esteve, Ave Mare de Deu de Montserrat 221, Barcelona 08041, Spain
[3] Hosp Univ La Paz, Maxillofacial Surg Unit, Madrid, Spain
[4] Hosp Univ Bellvitge, Dept Oral & Maxillofacial Surg, Barcelona, Spain
[5] Hosp Plato, Dept Maxillofacial Surg, Barcelona, Spain
[6] Hosp Clin San Carlos, Dept Maxillofacial Surg, Madrid, Spain
[7] Hosp Gen Granollers, Dept Maxillofacial Surg, Granollers, Spain
[8] Hosp Clin Valencia, Dept Maxillofacial Surg, Valencia, Spain
[9] Hosp Univ La Princesa, Dept Maxillofacial Surg, Madrid, Spain
[10] Hosp Univ Vall dHebron, Maxillofacial Surg Unit, Barcelona, Spain
[11] Bellvitge Univ Hosp, IDIBELL, Dept Clin Pharmacol, Clin Res Support Unit, Barcelona, Spain
关键词
BASE-LINE PAIN; POSTOPERATIVE PAIN; PHARMACOKINETICS;
D O I
10.1007/s40268-018-0235-y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:137 / 148
页数:12
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