Etoricoxib in acute pain associated with dental surgery: A randomized, double-blind, placebo- and active comparator-controlled dose-ranging study

• Published in: Clinical therapeutics 2004-05, Vol.26 (5), p.667-679
• Main Authors: Malmstrom, Kerstin, Sapre, Aditi, Couglin, Heather, Agrawal, Nancy G.B, Mazenko, Ralph S, Fricke, James R
• Format: Article
• Language: English
• Subjects: acute dental pain; Adolescent; Adult; analgesia; Analgesics; Biological and medical sciences; Clinical trials; Cyclooxygenase 2; cyclooxygenase-2-selective inhibitor; Dental surgery; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; etoricoxib; Female; Humans; ibuprofen; Isoenzymes - antagonists & inhibitors; Laboratories; Male; Medical sciences; Membrane Proteins; Nonsteroidal anti-inflammatory drugs; Osteoarthritis; Pain; Pain, Postoperative - drug therapy; Pain, Postoperative - etiology; Pharmacology. Drug treatments; postsurgery; Prostaglandin-Endoperoxide Synthases; Pyridines - administration & dosage; Pyridines - pharmacokinetics; Pyridines - therapeutic use; R&D; Research & development; Rheumatoid arthritis; Rheumatology; Sulfones - administration & dosage; Sulfones - pharmacokinetics; Sulfones - therapeutic use; Tooth Extraction - adverse effects
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(04)90067-7

Background: Patients experiencing acute pain after surgery, including dental surgery, often require analgesia. Ideally, the chosen analgesic should have a rapid onset and sustained effect. Etoricoxib is a new cyclooxygenase-2-selective inhibitor that has demonstrated analgesic efficacy in the treatment of acute pain with a rapid onset and long-lasting pain relief. Objective: The goal of this study was to determine the analgesic effect of single oral doses of etoricoxib 60, 120, 180, and 240 mg compared with placebo in the treatment of pain after dental surgery. Ibuprofen was used as an active control. Methods: This was a randomized, double-blind, parallel-group, single-dose, placebo- and active comparator-controlled study performed at a single center. It consisted of 3 visits (prestudy, treatment, and poststudy). Eligible patients were aged ≥16 years with moderate or severe pain after surgical extraction of ≥2 third molars, of which ≥1 was an impacted mandibular molar. Patients were assessed over 24 hours and reported pain intensity and pain relied at 14 predefined time points. Plasma samples for a pharmacokinetic/pharmacodynamic analysis were collected from a subset of patients at baseline and the 14 predefined time points. The end points included total pain relief over 8 hours (TOPAR8, the primary end point), sum of pain intensity difference over 8 hours, patient's global evaluation of treatment, median time to onset of pain relief (2-stopwatch method), peak pain relief, and duration of analgesic effect (median time to use of rescue medication). Adverse events were collected up to 14 days postdose. Results: Three hundred ninety-eight (63.1% women, 36.9% men; mean age, 21.1 years; 72.1% white, 27.9% other; mean number of third molars removed, 3.5; 65.2% experiencing moderate pain) were randomly allocated to receive etoricoxib 60 mg (n = 75), etoricoxib 120 mg (n = 76), etoricoxib 180 mg (n = 74), etoricoxib 240 mg (n = 76), ibuprofen 400 mg (n = 48), and placebo (n = 49). All active treatments had significantly greater overall analgesic effect (TOPAR8) compared with placebo ( P ≤ 0.001). Patients who received etoricoxib 120 and 180 mg had significantly higher TOPAR8 scores than those who received etoricoxib 60 mg ( P ≤ 0.001) and ibuprofen ( P < 0.05 etoricoxib 120 mg; P ≤ 0.001 etoricoxib 180 mg). Least-squares mean TOPAR8 scores for etoricoxib 60, 120, 180, and 240 mg, ibuprofen, and placebo were 16.0, 22.0, 23.5, 20.7, 18.6, and 5.2, respectively. The