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


CONCLUSIONS
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.
Levy
Robert M
RM
Primus Pharmaceuticals, Inc., Scottsdale, AZ 85251, USA. rlevy@primusrx.com
Khokhlov
Alexander
A
Kopenkin
Sergey
S
Bart
Boris
B
Ermolova
Tatiana
T
Kantemirova
Raiasa
R
Mazurov
Vadim
V
Bell
Marjorie
M
Caldron
Paul
P
Pillai
Lakshmi
L
Burnett
Bruce P
BP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002392:Catechin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D012140:Respiratory Tract Diseases / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D016859:Lipoxygenase Inhibitors; C544478:flavocoxid; D009288:Naproxen; D002392:Catechin