Efficacy, safety, and effects on blood pressure of naproxcinod 750 mg twice daily compared with placebo and naproxen 500 mg twice daily in patients with osteoarthritis of the hip: a randomized, double-blind, parallel-group, multicenter study

Arthritis Rheum. 2010 Dec;62(12):3635-44. doi: 10.1002/art.27694.

Abstract

Objective: To test the superiority of naproxcinod compared with placebo in relieving the signs and symptoms of hip osteoarthritis and to assess the safety of naproxcinod and its effects on blood pressure.

Methods: In a 13-week, randomized, double-blind, parallel-group, multicenter study, 810 patients were randomized to receive either naproxcinod 750 mg twice daily, placebo, or naproxen 500 mg twice daily (2:2:1). Primary efficacy analyses compared naproxcinod and placebo using an analysis of covariance for 3 co-primary end points (the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain and function subscales and patient's overall rating of disease status). Safety assessments included adverse events and in-office blood pressure measurements.

Results: The least squares mean changes from baseline were significantly greater with naproxcinod than with placebo (P < 0.0001) and were similar to those with naproxen at week 13 for the WOMAC pain score (-25.81, -17.97, and -24.31 mm, respectively), the WOMAC function score (-22.24, -13.45, and -21.67 mm, respectively), and patient's rating of disease status (0.86, 0.51, and 0.82, respectively). Changes from baseline in systolic blood pressure were similar in the naproxcinod and placebo groups at weeks 2, 6, and 13 (differences between groups of 0.25, -0.45, and -0.11 mm Hg, respectively). Changes in the naproxen group were greater than those in the placebo group (differences of 3.11, 3.03, and 2.00 mm Hg, respectively). Systolic blood pressure increases ≥10 mm Hg from baseline to week 13 occurred in 13.3%, 15.0%, and 20.3% of patients receiving naproxcinod, placebo, and naproxen, respectively. Naproxcinod and naproxen had similar adverse event and general safety profiles.

Conclusion: The efficacy of naproxcinod for treating the signs and symptoms of hip osteoarthritis was statistically superior to that of placebo and similar to that of naproxen. Naproxcinod was well tolerated, with effects on systolic blood pressure similar to those of placebo.

Trial registration: ClinicalTrials.gov NCT00541489.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naproxen / adverse effects
  • Naproxen / analogs & derivatives*
  • Naproxen / pharmacology*
  • Naproxen / therapeutic use*
  • Osteoarthritis, Hip / drug therapy*
  • Osteoarthritis, Hip / physiopathology
  • Pain Measurement
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • naproxen-n-butyl nitrate
  • Naproxen

Associated data

  • ClinicalTrials.gov/NCT00541489