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SCIO‐469, a novel P38A MAPK Inhibitor, provides efficacy in acute post‐surgical dental pain
Author(s) -
Tong S. E.,
Daniels S. E.,
Montano T.,
Chang S.,
Desjardins P.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.011
Subject(s) - placebo , ibuprofen , medicine , tolerability , anesthesia , analgesic , adverse effect , pharmacology , alternative medicine , pathology
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 2–24 was significantly reduced (p<0.05) compared to placebo. A significantly greater percentage of these subjects rated SCIO‐469 treatment as “good” to “excellent” 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. Clinical Pharmacology & Therapeutics (2004) 75 , P3–P3; doi: 10.1016/j.clpt.2003.11.011