Long-Term Safety and Efficacy of Morphine Sulfate and Naltrexone Hydrochloride Extended Release Capsules, a Novel Formulation Containing Morphine and Sequestered Naltrexone, in Patients with Chronic, Moderate to Severe Pain

Abstract

Morphine sulfate and naltrexone hydrochloride extended release capsules contain extended-release pellets of morphine with a sequestered naltrexone core (MS-sNT). Taken whole, as intended, morphine is released to provide pain relief; if tampered with by crushing, naltrexone is released to mitigate subjective effects of morphine. This open-label study assessed long-term (12-month) safety of MS-sNT in patients with chronic, moderate to severe pain. Safety assessments included determining adverse events (AEs), laboratory assessments, and the Clinical Opiate Withdrawal Scale (COWS). Analgesic efficacy was assessed (diary) as worst, least, average, and current pain using an 11-point numeric scale (0=none; 10=worst). Of 465 patients receiving one or more doses, 160 completed the study. Most patients (81.3%) experienced one or more AEs, most commonly constipation (31.8%) or nausea (25.2%). Thirty-three patients (7.1%) reported serious AEs; one patient's severe gastrointestinal inflammation and colitis were considered possibly study drug-related. Most discontinuations (30%) occurred in the first month, most often because of AEs (23.7%). There were no clinically relevant changes in laboratory results or vital signs, and no clinically significant electrocardiogram changes deemed study drug-related. During each visit after Week 1, 5% or fewer patients had COWS scores indicating mild withdrawal symptoms (range, 0%-4.8%). Five patients, who did not take the study drug as instructed, had scores consistent with moderate withdrawal. MS-sNT yielded statistically significant improvements from baseline in mean scores for all pain diary items for all visits, except Week 1 for least pain. In this study population, when MS-sNT was taken as directed for chronic, moderate to severe pain for up to 12 months, most AEs were typical opioid-related side effects. Mean COWS scores remained low, indicating lack ofwithdrawal symptoms and appropriate transition off the study drug at completion.