Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain

Objective: To assess the long-term efficacy, tolerability and safety of polymer-coated extended-release morphine sulfate (P-ERMS) (KADIAN*) compared with controlled-release oxycodone HCl (CRO) (OxyContin dagger) in treating chronic, nonmalignant, moderate to severe pain in a community-based outpatient population. Design: Phase IV, prospective, randomized, open-label. Participants: Adults (N = 112) with chronic, nonmalignant, moderate to severe pain with visual numeric scale (VNS) scores >= 4 (0 = no pain; 10 = worst pain). Interventions: Patients were randomized to receive either P-ERMS once-daily (QD) dosing or CRO twice-daily (BID) dosing for a 24-week treatment period. Upward titration of dose and switching P-ERMS to BID or CRO to thrice-daily (TID) dosing was allowed Weeks 2 - 24. Main outcome measures: Quality of life (Physical [PCS] and Mental [MCS] Component Summary scores of the SF-36v2 Health Survey), pain and sleep scores (0 - 10), and patient and clinician assessments of current therapy (-4 to +4). Results: Patients in both treatment groups experienced significant improvements in PCS scores (P-ERMS, +2.6; CRO, +3.1; p < 0.05 vs. baseline); patients taking CRO also demonstrated improvements in MCS scores (+4.7, p < 0.05 vs. baseline). Both groups attained significant reductions from baseline to 24 weeks in pain (P-ERMS, -2.0; CRO, -1.4; p <= 0.001 vs. baseline); the reduction with P-ERMS was clinically meaningful (as defined by at least a 2-point reduction in VNS score). Patients attained significant improvement in sleep scores (P-ERMS, -2.6; CRO, -1.6; p < 0.001 vs. baseline; p < 0.05, P-ERMS vs. CRO). At Week 24, both groups indicated significantly increased patient (P-ERMS, +2.6; CRO, +1.7; p < 0.001 vs. baseline) and clinician (P-ERMS, +4.0; CRO, +3.1; p < 0.001 vs. baseline) global assessments of therapy. After 24 weeks, all patients on P-ERMS were dosing within the FDA-approved frequencies (65% QD, 35% BID); 56% of patients on CRO dosed BID, but 38% dosed TID and 6% dosed four times daily (QID). Most common adverse events were constipation, nausea, and somnolence, with no significant difference between treatment groups. Conclusions: P-ERMS and CRO both relieved chronic nonmalignant pain in this community- based population; however, patients taking P-ERMS dosed in accordance with FDA-approved frequencies (QD/BID); 44% of those taking CRO dosed more frequently (TID/QID).