A Randomized, Controlled, Dose-ranging Study Investigating Single Doses of GW406381, Naproxen Sodium, or Placebo in Patients With Acute Pain After Third Molar Tooth Extraction

Objectives: To evaluate the efficacy and tolerability of 4 doses of GW406381. a cyclooxygenase-2 inhibitor, compared with placebo in a standard model of acute inflammatory pain. Methods: This randomized, double-blind, placebo-controlled, single-center study compared single doses of GW406381 (10 to 70 mg) or naproxen sodium 550 mg with placebo in patients after extraction of 2 or more partially bony impacted third molar teeth. A total of 300 patients were randomized (50 per group). The primary efficacy variable was the pain relief intensity difference score at each time point, which was calculated as the sum of the pain intensity difference and pain relief categorical scores at each time point. Each treatment was compared with placebo at each time point using an ordered hierarchical approach with closed testing procedures and last observation carried forward imputation methods. Results: Pain relief intensity differences from placebo were statistically significant beginning at 1.5 hours postdosing for GW406381 70 and 50 mg and at 2-hour postdosing for GW406381 25 and 10 mg. The median time to onset of analgesia was 71 minutes, for GW406381 50 mg, 72 minutes for GW406381 70 mg, and 36 minutes for naproxen. The median duration of analgesia was 5.9 hours for GW406381 50 mg. 7.9 hours for GW406391 70 mg, and 11.3 hours for naproxen. All treatments were well tolerated. Discussion: GW406381 50 and 70 mg demonstrated clinically meaningful analgesia in the acute pain setting, although the onset of analgesia was greater than I hour.