Two randomized, double-blind, placebo-controlled, single-dose studies were conducted in patients undergoing extraction of > or =2 third molars, with > or =1 mandibular impaction, who experienced moderate or severe
pain after extraction. In study 1, patients were randomized in a 4:4:1 ratio to receive
rofecoxib 50 mg,
valdecoxib 20 mg, or placebo. In study 2, which was an exploratory study, patients were randomized in a 2:2:1 ratio to receive reofecoxib 50 mg,
valdecoxib 40 mg, or palcebo. The primary efficacy end point was total
pain relief at 12 hours (TOPAR12) for
rofecoxib compared with
valdecoxib 20 mg (study 1) or
valdecoxib 40 mg (study 2). Tolerability was assessed based on clinical adverse experiences (AEs) and vital signs. These studies were performed before both agents were withdrawn from the market.
RESULTS: In study 1, 200 patients were randomized to receive
rofecoxib 50 mg, 201 to
valdecoxib 20 mg, and 49 to placebo. In study 2, 51 patients were randomized to receive
rofecoxib 50 mg, 50 to
valdecoxib 40 mg, and 24 to placebo. The majority of patients in both studies were female (approximately 54%) and white ( approximately 66%), with a mean age of approximately 22 years and a mean weight of approximately 75 kg. Most (approximately 58%) patients reported experiencing moderate
postoperative pain. In study 1, mean TOPAR12 scores were 30.7 for
rofecoxib 50 mg, 28.9 for
valdecoxib 20 mg, and 5.5 for placebo; in study 2, TOPAR12 scores were 27.0 for
rofecoxib 50 mg, 28.6 for
valdecoxib 40 mg, and 6.9 for placebo. In both studies, the active treatments were comparable in terms of the primary end point and were statistically superior to placebo (P<0.001). In study 1,
rofecoxib was associated with a longer median time to use of rescue medication compared with
valdecoxib 20 mg (>24 hours vs 23 hours 58 minutes; P=0.010) and a significantly smaller proportion of patients using rescue medication over 24 hours (35.0% vs 50.2%; P<0.001). In study 2, there were no significant differences in the median time to use of rescue medication or the proportion of patients using rescue medication between active treatments. There were no significant differences in total
pain relief at 4 or 8 hours, patients' global assessment, onset of
analgesia, or AEs between active treatments in either study. The incidence of clinical AEs in study 1 was similar for
rofecoxib 50 mg,
valdecoxib 20 mg, and placebo (39.5%, 36.8%, and 49.0%, respectively). In study 2, AEs occurred significantly less frequently with
rofecoxib 50 mg compared with placebo (35.3% vs 70.8%, respectively; P<0.01); there was no significant difference between the rate of AEs with
valdecoxib 40 mg (50.0%) and placebo.
CONCLUSIONS: