Efficacy, safety, and tolerability of the cyclooxygenase-inhibiting nitric oxide donator naproxcinod in treating osteoarthritis of the hip or knee.
OBJECTIVE
Naproxcinod, a cyclooxygenase-inhibiting nitric oxide donator antiinflammatory drug, was evaluated in this phase 2, double-blind, randomized, parallel group study to determine its optimal dose in patients with osteoarthritis (OA).


METHODS
In total 543 patients with OA of the hip or knee were randomized to receive naproxcinod 750 mg once daily (qd), 750 mg twice daily (bid), 1125 mg bid, rofecoxib 25 mg qd, or placebo for 6 weeks. The primary efficacy variable was the within-patient change from baseline to the average of Weeks 4 and 6 in WOMAC pain subscale score. Treatment-group differences were compared using ANCOVA with factors for treatment and country, and baseline pain subscale score as a covariate. Safety endpoints included vital signs and adverse events. Treatment-group differences in mean change from baseline to Week 6 in systolic blood pressure (SBP) were compared using an ANCOVA with treatment and country as fixed factors and baseline SBP as covariate.


RESULTS
All active treatments showed statistically significant reductions in WOMAC pain score compared to placebo (p<or=0.02). Naproxcinod was well tolerated. The 750 mg bid dose appeared to have the best balance of benefit versus safety. All 3 naproxcinod doses showed a reduction in SBP, while an increase was shown for rofecoxib. The changes for the naproxcinod groups were statistically significantly better compared to rofecoxib (p<or=0.02).


CONCLUSIONS
This dose-finding study identified naproxcinod 750 mg bid as the upper dose for further therapeutic confirmatory clinical trials. Naproxcinod at all doses decreased mean SBP compared to an increase with rofecoxib.
Karlsson
Jon
J
Sahlgrenska University Hospital/Ostra, Goteborg, Sweden.
Pivodic
Aldina
A
Aguirre
Diana
D
Schnitzer
Thomas J
TJ
D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D015207:Osteoarthritis, Hip / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D020030:Nitric Oxide Donors; C111751:naproxen-n-butyl nitrate; D009288:Naproxen