Efficacy and safety of flavocoxid compared with naproxen in subjects with osteoarthritis of the knee- a subset analysis.

OBJECTIVE: twice-daily flavocoxid, a cyclooxygenase and 5-lipoxygenase inhibitor with potent antioxidant activity of botanical origin, was evaluated for 12 weeks in a randomized, double-blind, active-comparator study against naproxen in 220 subjects with moderate-severe osteoarthritis (OA) of the knee. As previously reported, both groups noted a significant reduction in the signs and symptoms of OA with no detectable differences in efficacy between the groups when the entire intent-to-treat population was considered. This post-hoc analysis compares the efficacy of flavocoxid to naproxen in different subsets of patients, specifically those related to age, gender, and disease severity as reported at baseline for individual response parameters. METHODS: in the original randomized, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. In this subgroup analysis, primary outcome measures including the Western Ontario and McMaster Universities OA index and subscales, timed walk, and secondary efficacy variables, including investigator global assessment for disease and global response to treatment, subject visual analog scale for discomfort, overall disease activity, global response to treatment, index joint tenderness and mobility, were evaluated for differing trends between the study groups. RESULTS: subset analyses revealed some statistically significant differences and some notable trends in favor of the flavocoxid group. These trends became stronger the longer the subjects continued on therapy. These observations were specifically noted in older subjects (>60 years), males and in subjects with milder disease, particularly those with lower subject global assessment of disease activity and investigator global assessment for disease and faster walking times at baseline. CONCLUSIONS: initial analysis of the entire intent-to-treat population revealed that flavocoxid was as effective as naproxen in managing the signs and symptoms of OA of the knee. Detailed analyses of subject subsets demonstrated distinct trends in favor of flavocoxid for specific groups of subjects.

Efficacy and safety of flavocoxid, a novel therapeutic, compared with naproxen: a randomized multicenter controlled trial in subjects with osteoarthritis of the knee.

INTRODUCTION: Flavocoxid is a novel flavonoid-based "dual inhibitor" of the 5-lipoxygenase (5-LOX) enzyme and the cyclooxygenase (COX) enzymes. This study was designed to compare the effectiveness and safety of flavocoxid to naproxen in subjects with moderate to severe osteoarthritis (OA) of the knee. METHODS: In this randomized, multicenter, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. The trial was structured to show noninferiority of flavocoxid to naproxen. Primary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subscales and a timed walk. RESULTS: More than 90% of the subjects in both groups noted significant reduction in the signs and symptoms of knee OA. There were no statistically significant differences in efficacy between the flavocoxid and naproxen groups when the entire intent-to-treat population was analyzed. The flavocoxid group had significantly fewer upper gastrointestinal (UGI) and renal (edema) adverse events (AEs) as well as a strong trend toward fewer respiratory AEs. CONCLUSION: Flavocoxid, a first-in-class flavonoid-based therapeutic that inhibits COX-1 and COX-2 as well as 5-LOX, was as effective as naproxen in managing the signs and symptoms of OA of the knee. Flavocoxid demonstrated better UGI, renal (edema), and respiratory safety profiles than naproxen.