Safety profile of extended-release morphine sulfate with sequestered naltrexone hydrochloride in older patients: pooled analysis of three clinical trials

Abstract

Objective Clinical trial safety data following chronic administration of extended-release opioids within an older population is limited. Embeda* is an extended-release formulation of morphine sulfate surrounding sequestered naltrexone hydrochloride (MSN) and is designed to deter opioid misuse and abuse. The present analysis compared pooled safety outcomes among patients aged ≥65 years and those aged <65 years from three phase 2/3 studies (ranging from 2 weeks to 12 months) in patients treated with MSN.Research design and methods Subgroup analysis of patients aged ≥65 years and <65 years was performed on pooled data for adverse events (AEs), potentially clinically significant laboratory values (hematology/chemistry), and signs/symptoms of opioid withdrawal using the Clinical Opiate Withdrawal Scale (COWS) (phase 3 trials only) for patients who received at least one dose (short-term studies, maximum dose was 160 mg/d or 320 mg/d depending on study; long-term study, no maximum dose) of study medication during titration and maintenance phases.Clinical trial registration ClinicalTrials.gov: NCT00420992, NCT00415597.Results During titration, 173 (17.1%) of 1012 patients treated with MSN were aged ≥65 years, while during maintenance 76/564 (13.5%) patients were aged ≥65 years. Treatment-emergent AEs were similar in frequency and type between the two cohorts, with the most common being constipation, nausea, and somnolence; no consistent patterns relating to age and only one possibly treatment-related serious AE in patients ≥65 years was noted. No clinically significant differences in laboratory values or COWS scores (average maximum score ≤2.5) were observed between age groups.Conclusions Safety outcomes following daily administration of MSN (2 weeks–12 months) were similar between patients aged ≥65 years and <65 years. Key limitations include the variable study designs and length of treatment (2 weeks–12 months), small sample size, and the inclusion of only those patients who were otherwise in relatively good health with restrictions on concomitant medications.