TY - JOUR
T1 - Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain
T2 - A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial
AU - López-Cedrún, José
AU - Videla, Sebastián
AU - Burgueño, Miguel
AU - Juárez, Inma
AU - Aboul-Hosn, Samir
AU - Martín-Granizo, Rafael
AU - Grau, Joan
AU - Puche, Miguel
AU - Gil-Diez, José-Luis
AU - Hueto, José-Antonio
AU - Vaqué, Anna
AU - Sust, Mariano
AU - Plata-Salamán, Carlos
AU - Monner, Antoni
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Adult
KW - Analgesics, Opioid/therapeutic use
KW - Celecoxib/therapeutic use
KW - Cyclooxygenase 2 Inhibitors/therapeutic use
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Drug Combinations
KW - Female
KW - Humans
KW - Male
KW - Pain, Postoperative/drug therapy
KW - Tramadol/therapeutic use
KW - Young Adult
U2 - 10.1007/s40268-018-0235-y
DO - 10.1007/s40268-018-0235-y
M3 - Artículo
C2 - 29799099
SN - 1174-5886
VL - 18
SP - 137
EP - 148
JO - Drugs in R and D
JF - Drugs in R and D
IS - 2
ER -