title: Morphine sulfate and naltrexone hydrochloride extended release capsules in patients with chronic osteoarthritis pain.
abstract: OBJECTIVE
  To assess the efficacy and safety of morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA; MS-sNT), which contain morphine sulfate pellets with a sequestered naltrexone core, in treating patients with chronic, moderate-to-severe osteoarthritis (hip or knee) pain.
  
  
  METHODS
  This phase 3 study had an enriched-enrollment, randomized-withdrawal, double-blind, multicenter design. Patients (N = 547) were titrated to an effective dose of MS-sNT (20-160 mg/day). Responders (n = 344) were randomized to 12 weeks maintenance with an effective MS-sNT dose or were tapered to placebo over 2 weeks. The primary efficacy measure was the change from baseline (CFB) in diary average-pain scores (0-10 scale, Brief Pain Inventory [BPI]) from randomization to the last 7 days of the maintenance period. Secondary efficacy measures included the remaining BPI scores and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. Opioid withdrawal symptoms were assessed by the Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Scale (SOWS). The study ran from January 10, 2007 through November 8, 2007.
  
  
  RESULTS
  MS-sNT maintained pain control better than placebo (mean CFB, diary average-pain score, -0.2 +/- 1.9 vs +/-0.3 +/- 2.1; P = 0.045). Change from baseline for MS-sNT pain-diary score (worst, least, average, current) was superior during the maintenance period visits, weeks 2 to 12 (P < 0.05). WOMAC composite score CFB was superior at most visits. MS-sNT was generally well tolerated, with a typical morphine safety profile. No patient taking MS-sNT as directed experienced withdrawal symptoms.
  
  
  CONCLUSIONS
  MS-sNT provided effective analgesia in patients with chronic, moderate-to-severe osteoarthritis pain, with a safety profile typical of morphine-containing products. Naltrexone sequestered in MS-sNT had no clinically relevant effect when MS-sNT was taken as directed.
authors.affiliation: Tufts University School of Medicine, Boston, MA, USA. nkatz@analgesicsolutions.com
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Katz
authors.forename: Martin
authors.initials: M
authors.lastname: Hale
authors.forename: David
authors.initials: D
authors.lastname: Morris
authors.forename: Joseph
authors.initials: J
authors.lastname: Stauffer
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002214:Capsules; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D010003:Osteoarthritis / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement; D010919:Placebos; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D010919:Placebos; D000082:Acetaminophen; D009271:Naltrexone; D009020:Morphine