PRELIMINARY-STUDY OF THE SAFETY AND EFFICACY OF SC-58635, A NOVEL CYCLOOXYGENASE-2 INHIBITOR - EFFICACY AND SAFETY IN 2 PLACEBO-CONTROLLED TRIALS IN OSTEOARTHRITIS AND RHEUMATOID-ARTHRITIS, AND STUDIES OF GASTROINTESTINAL AND PLATELET EFFECTS

Objective. To investigate the efficacy and safety of SC-58635 (celecox ib), an antiinflammatory and analgesic agent that acts by selective cy clooxygenase 2 (COX-2) inhibition and is not expected to cause the typ ical gastrointestinal (GI), renal, and platelet-related side effects a ssociated with inhibition of the COX-1 enzyme. Methods, Four phase II trials were performed: a 2-week osteoarthritis efficacy trial, a 4-wee k rheumatoid arthritis efficacy trial, a 1-week endoscopic study of GI mucosal effects, and a 1-week study of effects on platelet function. Results. The 2 arthritis trials identified SC-58635 dosage levels that were consistently effective in treating the signs and symptoms of art hritis and were distinguished from placebo on standard arthritis scale s. In the upper GI endoscopy study, 19% of subjects receiving naproxen (6 of 32) developed gastric ulcers, whereas no ulcers occurred in sub jects receiving SC-58635 or placebo. The study of platelet effects rev ealed no meaningful effect of SC-58635 on platelet aggregation or thro mboxane B-2 levels, whereas aspirin caused significant decreases in 2 of 3 platelet aggregation measures and thromboxane B-2 levels. In all 4 trials, SC-58635 was well tolerated, with a safety profile similar t o that of placebo. Conclusion. SC-58635 achieves analgesic and antiinf lammatory efficacy in arthritis through selective COX-2 inhibition, wi thout showing any evidence of 2 of the toxic effects of COX-1 inhibiti on associated with nonsteroidal antiinflammatory drugs.