Efficacy and safety of naproxcinod in patients with osteoarthritis of the knee: a 53-week prospective randomized multicenter study.
OBJECTIVE
Comparison of naproxcinod (375 and 750 mg), placebo (up to 13 weeks), and naproxen 500 mg (all bid) for treatment of osteoarthritis (OA) signs and symptoms.


METHODS
A 53-week, randomized, double-blind, parallel-group study. One thousand twenty patients with primary knee OA were randomized to naproxcinod 750 mg, naproxcinod 375 mg, naproxen 500 mg, or placebo (all bid). Coprimary efficacy endpoints were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) pain and function subscales and patient overall rating of disease status. An analysis of covariance model tested superiority for both naproxcinod doses over placebo at week 13, and noninferiority of naproxcinod 750 mg bid versus naproxen at weeks 13 and 26.


RESULTS
Least-square mean changes from baseline were greater for both naproxcinod doses compared with placebo at week 13 for WOMAC pain (-31.3 [standard error 1.67], -28.1 [1.64], and -20.4 [1.62] mm with naproxcinod 750 mg bid [P < 0.0001], 375 mg bid [P = 0.0008], and placebo, respectively), WOMAC function (-27.8 [1.60], -23.8 [1.58], and -14.9 [1.56] mm, respectively, P < 0.0001), and patient overall rating of disease status (1.00 [0.061], 0.81 [0.060], and 0.49 [0.059], respectively, P < 0.0001). Naproxcinod 750 mg bid was noninferior to naproxen at weeks 13 and 26. Naproxcinod was well tolerated, with no notable differences in orthostatic blood pressure response between treatments.


CONCLUSIONS
Naproxcinod 750 mg bid and 375 mg bid demonstrated superior efficacy over placebo for treatment of OA and were well tolerated over 1 year. Naproxcinod 750 mg bid was noninferior to naproxen 500 mg bid.
Schnitzer
Thomas J
TJ
Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Hochberg
Marc C
MC
Marrero
Christopher E
CE
Duquesroix
Brigitte
B
Frayssinet
Hayet
H
Beekman
Maarten
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D011446:Prospective Studies; D016896:Treatment Outcome
D020030:Nitric Oxide Donors; C111751:naproxen-n-butyl nitrate; D009288:Naproxen