title: Efficacy and safety of flavocoxid, a novel therapeutic, compared with naproxen: a randomized multicenter controlled trial in subjects with osteoarthritis of the knee.
abstract: 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.
authors.affiliation: Primus Pharmaceuticals, Inc., Scottsdale, AZ 85251, USA. rlevy@primusrx.com
authors.forename: Robert M
authors.initials: RM
authors.lastname: Levy
authors.forename: Alexander
authors.initials: A
authors.lastname: Khokhlov
authors.forename: Sergey
authors.initials: S
authors.lastname: Kopenkin
authors.forename: Boris
authors.initials: B
authors.lastname: Bart
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ermolova
authors.forename: Raiasa
authors.initials: R
authors.lastname: Kantemirova
authors.forename: Vadim
authors.initials: V
authors.lastname: Mazurov
authors.forename: Marjorie
authors.initials: M
authors.lastname: Bell
authors.forename: Paul
authors.initials: P
authors.lastname: Caldron
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Pillai
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Burnett
mesh_terms: 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
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D016859:Lipoxygenase Inhibitors; C544478:flavocoxid; D009288:Naproxen; D002392:Catechin