Comparison of the COX-inhibiting nitric oxide donator AZD3582 and rofecoxib in treating the signs and symptoms of Osteoarthritis of the knee.
OBJECTIVE
To compare the efficacy, safety, and tolerability of AZD3582 with that of rofecoxib, naproxen, and placebo in patients with osteoarthritis (OA) of the knee, and to define the dosage of AZD3582 (125 mg, 375 mg, and 750 mg twice a day) that is noninferior in efficacy to rofecoxib.


METHODS
A double-blind study of 672 patients with OA of the knee was conducted. Patients who experienced increased pain on withdrawal of analgesia were randomized to receive AZD3582 125 mg, 375 mg, or 750 mg twice a day; rofecoxib 25 mg once a day; naproxen 500 mg twice a day; or placebo for 6 weeks. Efficacy, tolerability, and safety were monitored throughout the study. The primary variable was the change in Western Ontario and McMaster Universities Osteoarthritis Index pain subscale from baseline to the mean of weeks 4 and 6, comparing AZD3582 with placebo for superiority and with rofecoxib for noninferiority using a predefined margin of 10 mm.


RESULTS
For the primary variable, AZD3582 375 mg and 750 mg were superior to placebo (least squares mean difference [95% confidence interval] -12 mm [-18, -6], P < 0.001 and -13 mm [-19, -7], P < 0.001, respectively) and were noninferior to rofecoxib (-2 mm [-8, 4], P < 0.001 and -3 mm [-9, 3], P < 0.001, respectively). AZD3582 125 mg was not significantly different from placebo for the primary variable.


CONCLUSIONS
AZD3582 375 mg and 750 mg twice a day were superior to placebo and as effective as rofecoxib 25 mg/day in treating the signs and symptoms of OA of the knee. AZD3582 125 mg twice a day was not statistically different from placebo.
Schnitzer
Thomas J
TJ
Northwestern Center for Clinical Research, Chicago, Illinois 60611, USA. tjs@nwu.edu
Kivitz
Alan J
AJ
Lipetz
Robert S
RS
Sanders
Nick
N
Hee
Angela
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D009288:Naproxen / Q000627:therapeutic use* / Q000031:analogs & derivatives; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D012720:Severity of Illness Index; D013450:Sulfones / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D009281:Naphthalenes; D013450:Sulfones; C111751:naproxen-n-butyl nitrate; C116926:rofecoxib; D009288:Naproxen