title: 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.
  
  
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: a Pfizer Inc , Durham , NC , USA ;
authors.forename: Beatrice
authors.initials: B
authors.lastname: Setnik
authors.affiliation: a Pfizer Inc , Durham , NC , USA ;
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Pixton
authors.affiliation: b PRA Health Sciences , Salt Lake City , UT , USA.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Webster
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009292:Narcotic Antagonists; C550436:morphine, naltrexone combination; D009271:Naltrexone; D009020:Morphine
keywords: Abuse deterrent; age; chronic pain; extended-release; opioids