Efficacy and safety of short-term use of a pelubiprofen CR and aceclofenac in patients with symptomatic knee osteoarthritis: A double-blinded, randomized, multicenter, active drug comparative, parallel-group, phase IV, non-inferiority clinical trial

INTRODUCTION: At present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis. MATERIALS AND METHODS: A total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit. RESULTS: At week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005). CONCLUSIONS: Pelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.