(205) Steady-State Pharmacokinetic Comparison of MorphelanR ROERR (Morphine Sulfate Rapid Onset Extended Release) Once-a-Day and Morphine Oral Solution Administered Q4H around-the-Clock in Healthy Volunteers

Abstract

Introduction: Controlled-release morphine formulations have been developed to decrease the dosing frequency needed to maintain pain control around-the-clock (ATC). Morphelan® ROER® (MROER), a novel, once-a-day, rapid onset extended release morphine formulation, was designed to rapidly reach target concentrations and to maintain therapeutic concentrations throughout a 24-hour dosing interval. Objective: To compare 24-hour steady-state pharmacokinetic profiles of morphine following MROER once-daily and morphine oral solution (MOS) administered q4h ATC. Methods: In an open-label, cross-over study, 12 healthy volunteers were randomized to MROER 60 mg once-daily or 10 mg q4h ATC MOS for 5 days with at least a 7-day washout before cross-over. Twenty-four-hour pharmacokinetic profiles were obtained on the last day of each study treatment. Results: Once-daily MROER rapidly releases morphine, providing plasma morphine concentrations at 30 minutes (C30min) similar to MOS following administration. Maximum concentrations (Cmax), total systemic exposure (AUC0-24h), peak-to-trough fluctuations (%FI) and plasma concentrations at 24 h (C24h) were similar between MROER once-a-day and MOS dosed q4h ATC over a 24 hour dosing interval (Table 1). Data are presented as mean ± SD. No statistical differences were observed (p < 0.05). # FL: Number of daily peak-to-trough fluctuations. Conclusions: MROER once-a-day rapidly reaches target plasma morphine concentrations and maintains similar therapeutic concentrations as MOS dosed q4h ATC over a 24-hour dosing interval with fewer peak-to-trough fluctuations. Therefore, MROER represents a true once-a-day controlled-release morphine formulation. Table 1. Parameter MROER (once-a-day) MOS (q4h ATC) AUC0-24h (ng×h /ml) 273 ± 81.2 279 ± 63.0 Cmax (ng/ml) 18.7 ± 7.13 20.0 ± 4.82 C30min (ng/ml) 12.9 ± 6.64 15.0 ± 4.05 C24h (ng/ml) 7.84 ± 2.99 9.45 ± 2.81 %FI 106 ± 78.1 116 ± 26.7 # FL 1 6