A double-blind, placebo-controlled dose ranging study to evaluate the efficacy of valdecoxib, a novel cox-2 specific inhibitor, in treating the signs and symptoms of osteoarthritis of the knee

JJ Fiechtner, D Sikes, D ReckerRheumatology Clinic, East Lansing Clinical Research Division, Florida Medical Clinic, Zephyr Hills Research and Development, Pharmacia Corporation, Skokie, USABackground Valdecoxib is a novel oral COX-2 specific inhibitor being developed for the treatment of pain and inflammation, which does not cause the side effects commonly associated with the COX-1 inhibition of conventional NSAIDs. Objectives The objective of this study was to evaluate the efficacy of multiple doses of valdecoxib in treating the signs and symptoms of osteoarthritis (OA) of the knee. Methods In this multicenter, double-blind, placebo-controlled, parallel-group, dose-ranging study, 642 OA patients were randomised to receive valdecoxib 0.5, 1.25, 2.5, 5 or 10 mg BID, valdecoxib 10 mg QD, naproxen 500 mg BID, or placebo BID for 6 weeks. Patient’s Assessment of Arthritis Pain (visual analogue scale, VAS), Patient’s Global Assessment of Arthritis (VAS) and Western Ontario and McMasters Universities (WOMAC) OA Index were assessed at Baseline and after 1, 2, and 6 weeks of treatment. Vital signs and adverse events were monitored throughout the study. Results Valdecoxib demonstrated efficacy that was significantly greater than placebo (p < = 0.05) in all primary efficacy measures listed above, at every dose except 0.5 mg BID. Improvements in OA signs and symptoms in response to valdecoxib were dose-dependent, with the greatest improvements in primary efficacy measures observed at 5 mg BID, 10 mg QD, and 10 mg BID, compared with placebo (p < = 0.004). Valdecoxib doses of 5 mg BID, 10 mg QD, and 10 mg BID were also as effective as naproxen 500 mg in the treating signs and symptoms of OA. There were no statistically significant differences between any of the treatment groups in the number of adverse events or in vital signs or clinical laboratory measurements. Abstract OP0048 Table 1 Least Square Mean Change from Baseline at Week 2 Least Square Mean Change from Baseline at Week 6 Placebo -11.46 -10.44 Valdecoxib 0.5 mg BID -13.84 -15.74 Valdecoxib 1.25 mg BID -19.09 -24.32 Valdecoxib 2.5 mg BID -24.30 -28.08 Valdecoxib 5 mg BID -28.12 -29.42 Valdecoxib 10 mg QD -27.77 -29.50 Valdecoxib 10 mg BID -30.28 -29.24 Naproxen 500 mg BID -27.76 -30.05 Patient’s Global Assessment of Arthritis at Weeks 2 and 6 (*p < = 0.05 vs naproxen **p < = 0.05 vs placebo). Conclusion Valdecoxib is an effective therapy among patients with symptomatic OA of the knee. Valdecoxib doses of 5 mg BID, 10 mg QD, and 10 mg BID are maximally efficacious, as they are superior to placebo and comparable to naproxen 500 mg BID in all primary efficacy measures. Valdecoxib is well tolerated at all doses. Sponsored by Pharmacia Corporation and Pfizer, Inc. Citation: Ann Rheum Dis, volume 60, supplement 1, year 2001, page A162Session: Osteoarthritis – Clinical aspects and treatment