Purpose: Two studies evaluated the efficacy and safety of a single dose of naproxen sodium 440 mg (NS) compared to the combination of acetaminophen 600 mg and codeine phosphate 60 mg (AC) in subjects with postoperative dental pain. Methods: The two studies were single center, randomized, double-blind and double-dummy trials. In both studies, subjects were randomized into one of the following three treatments in a 2:2:1 ratio, respectively: NS, AC, or placebo (PBO). Subjects were administered study medication when they had at least moderate pain following the surgical removal of three or four impacted molars, at least one of which was a mandibular partial or complete bony impaction. Efficacy assessments were completed over an 8-hour evaluation period. The co-primary efficacy assessments in both studies were time-weighted sum of categorical pain intensity differences over 4 hours (SPID4) and time-weighted sum of pain relief scores over 4 hours (TOTPAR4). Other efficacy assessments such as summed scores over 8 hours, time to onset of relief, time to rescue medication and global rating of medication were also assessed. Results: In Study 1, there were 225 subjects evaluated for efficacy, and 228 evaluated for safety. In Study 2, there were 230 subjects evaluated for efficacy and safety. In both studies, NS and AC were significantly better than placebo for almost all efficacy measures. In Study 1, NS was significantly superior to AC for all summed efficacy scores over 4 and 8 hours except for SPID4. NS was also superior to AC for most individual time point scores from 3 through 8 hours, as well as for the time to taking rescue medication. Both actives had a similar onset of effect. The incidence of adverse events (AEs) was significantly higher in the AC group compared to NS and PBO. The most frequently reported AEs with AC were gastrointestinal (GI) and nervous system events. In Study 2, there were no statistically significant differences between the two active treatments for any summed efficacy score, except for TOTPAR8, where NS was significantly better than AC. NS was significantly better than AC for individual pain relief time point scores from 3 through 8 hours and significantly better for individual pain intensity difference scores from 5 through 8 hours. AC had a significantly faster onset of effect compared to NS, but NS had a significantly longer time to rescue compared to AC. Nervous system AEs (dizziness and somnolence) were reported significantly more frequently with AC compared to NS. In conclusion, Both NS and AC are effective in the relief of postoperative dental pain. NS provided comparable to superior relief vs. AC and its analgesic effects lasted significantly longer. NS was well tolerated and resulted in a lower rate of AEs than AC.
