Poster 34: Extended-Release Morphine Sulfate With Sequestered Naltrexone is Effective in Treating the Pain of Osteoarthritis

Abstract

Objective: To assess the efficacy, tolerability, and pharmacokinetics of an extended-release morphine sulfate plus sequestered naltrexone compound (SNC) (naltrexone released if product tampering occurs) compared with polymer-coated extended-release morphine sulfate (P-ERMS; Kadian). Design: Prospective, randomized, double-blind crossover. Setting: Outpatient research sites. Participants: Adults (N=113) unable to control osteoarthritis (hip, knee) pain with nonopioid analgesics or received ≤40mg/d of oral morphine equivalents. Patients (median age, 57.0y) were mostly women (68.5%) and white (88.3%). Interventions: Washout from previous medication, P-ERMS dose titration to effective analgesia, two 14-day treatment periods (P-ERMS or SNC), 7 days P-ERMS after each treatment period. Main Outcome Measures: Average pain intensity (0−10 scale); daily Brief Pain Inventory (BPI) (worst, least, average, current; 0−10 scales); Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; Patient Global Assessment of Medication (1 [poor] to 5 [excellent]); morphine, naltrexone, and 6-β naltrexol pharmacokinetics. Results: Mean pain intensity after washout was 7.1; after P-ERMS titration, 2.1. For treatment days 7 and 14, intensities were: P-ERMS, 2.3 and 2.4; SNC, 2.4 and 2.3 (P=NS), respectively. For the BPI scales, P-ERMS and SNC were similar over the 14-day periods. WOMAC pain, physical function, and composite scores were similar between treatments. Most patients rated medications as good to excellent (P-ERMS, 78.9%; SNC, 91.5%). Steady-state morphine exposure area under the curve was similar between treatments. Most naltrexone levels were below limits of quantification; 6-β naltrexol levels were low or below limit of quantification. Adverse events were mostly mild to moderate; most common were: constipation (double-blind P-ERMS, 12.7%; SNC, 15.5%), nausea (8.5%; 9.9%), and somnolence (8.5%; 9.9%). Conclusions: SNC provided similar pain relief to P-ERMS; most patients rated P-ERMS and SNC as good to excellent. Naltrexone was adequately sequestered; low levels, when present, did not negatively impact patients’ pain scores or produce symptoms associated with opioid withdrawal.