ANALGESIC EFFICACY OF SINGLE DOSE ROFECOXIB 50 MG AND MULTIDOSE OXYCODONE/PARACETAMOL IN PATIENTS WITH MODERATE VERSUS SEVERE PAIN

Background: Rofecoxib (ROF) 50 mg has demonstrated efficacy in the treatment of acute pain using a validated dental pain impaction model and in other postsurgical settings. In the dental pain model, ROF 50 mg demonstrated similar efficacy to naproxen 550 mg and ibuprofen 400 mg and greater overall efficacy than codeine/paracetamol 60/600 mg, all given as single doses. The pharmacokinetics of ROF are consistent with once daily dosing. NSAIDs and opioid analgesics generally require multiple daily dosing to provide pain relief over 24 hours. A recently completed double-blind, randomized study compared patient response to a single 50 mg dose of ROF and multidose oxycodone/paracetamol (OXY/PAR) using the dental pain model.Objectives: An analysis was performed that evaluated response to ROF and multidose OXY/PAR comparing patients with moderate pain and severe pain at baseline in this study.Methods: Patients experiencing moderate or severe pain after surgical extraction of ≥2 third molars were randomized to a single dose of ROF 50mg (N=118), OXY/PAR 10/650mg followed by 5/325mg q6hrs PRN (N=122), or placebo (N=30) for 24hrs. Key endpoints were overall analgesic efficacy over 6hrs (TOPAR6) and 24hrs (SPID24). To compare responses to ROF and OXY/PAR between patients with moderate and severe pain, TOPAR6, SPID24, patient global responders (percent with a good, very good, or excellent response), onset (time to confirmed perceptible pain relief), and duration (time to rescue medication) were analyzed for consistency of treatment effect by baseline pain intensity subgroups.Results: In the overall population, ROF demonstrated comparable efficacy to OXY/PAR on TOPAR6 and SPID24. Patients with moderate pain achieved numerically higher pain relief scores on TOPAR6 than patients with severe pain with ROF (mod:15.4 vs sev:13.9) and OXY/PAR (mod:13.9 vs sev:11.6). Patients with severe pain achieved numerically greater decreases in pain intensity on SPID24 than patients with moderate pain with ROF (sev:39.6 vs mod:21.8) and OXY/PAR (sev:33.0 vs mod:17.1). For the endpoints of TOPAR6 and SPID24, although the difference between the active treatment groups (ROF minus OXY/PAR) was numerically greater in the severe subgroup compared to the moderate subgroup, this difference was not statistically significant (treatment by subgroup interaction P>0.05). Patient global response scores were good, very good, or excellent among a numerically higher percentage of patients with moderate versus severe pain with ROF at 6hrs (mod:82.4% vs sev:78.7%) and at 24hrs (mod:84.5% vs sev:78.7%) as well as OXY/PAR [6hrs (mod:74.6% vs sev:70.8%) and 24hrs (mod:76.7% vs sev:71.4%)]. Within the treatment groups, patients with moderate and severe baseline pain achieved pain relief in a similar timeframe; the proportion of patients achieving onset was similar; and the duration of analgesia was similar.Conclusion: The results of the overall analgesic effect for the above endpoints support the conclusion that treatment effect was similar in the moderate and severe patient subgroups.References: 1. Morrison BW, et al. J AM Dent Assoc 2000;131: 1729-37.2. Chang DJ, et al. Clin Ther 2001; 23: 1446-55.Citation: , volume , supplement , year 2004, page Session: Psychology, measurements and management of pain