¹Scios Inc., Scirex Corporation, Fremont, CA.

Abstract

This double-blind, randomized study compared the analgesic efficacy, safety and tolerability of pre- and post-operatively administered oral SCIO-469 vs. placebo, and compared oral ibuprofen 400 mg vs. placebo, in post-surgical dental pain. Subjects (n=263) undergoing extraction of at least one impacted third molar were enrolled to receive pre-operative treatment with 150 mg, 300 mg, or 210 mg oral SCIO-469, ibuprofen, or placebo 60 min before surgery. One hour after first incision, subjects received 90 mg SCIO-469 (210 mg group only) or placebo. Median time to first rescue medication was estimated for each group using the Kaplan-Meier product limit estimator. All SCIO-469 groups had a significantly longer time to rescue medication compared to placebo; pre-and post-operative treatment of 210+90 mg SCIO-469 had the greatest difference: 8.1 vs 4.1 hours for placebo (p = 0.003). Ibuprofen showed significant increase in time to rescue (p=0.04) and validated the study. For the 150 mg and 210+90 mg groups, pain intensity at hours 2|[ndash]|24 was significantly reduced (p<0.05) compared to placebo. A significantly greater percentage of these subjects rated SCIO-469 treatment as |[ldquo]|good|[rdquo]| to |[ldquo]|excellent|[rdquo]| vs placebo (p<0.04). A subset of 81 subjects underwent PK profiling; SCIO-469 levels were dose proportional. Overall, SCIO-469 was safe and well tolerated. These results are the first clinical demonstration of significant anti-nociceptive effects in acute pain for this novel mechanism of action.