title: New Formulation of Sustained Release Naloxone Can Reverse Opioid Induced Constipation Without Compromising the Desired Opioid Effects.
abstract: An international double-blind randomized placebo controlled study evaluated the safety and efficacy of four doses of a new sustained release naloxone capsule to treat Opioid Induced Constipation (OIC).
  
  
  METHODS
  Forty patients taking opioids for noncancer related pain, and experiencing OIC, were randomized into 4 cohorts of 10 patients. A multiple ascending dose design was used to evaluate the safety and efficacy of 2.5 mg, 5 mg, 10 mg, and 20 mg naloxone sustained release (NSR) capsules vs placebo. Drug was given once-daily for 3 weeks followed by twice daily (bid) dosing between weeks 4 and 6.
  
  
  RESULTS
  The incidence of treatment emergent adverse events was highest in the placebo group. The incidence of adverse events among the four active treatment groups were similar. There were no serious adverse events. The number of severe events was low overall but highest in the placebo group. Significant improvements were seen in Spontaneous Bowel Movements with 5 mg, 10 mg, and 20 mg NSR capsules. Mean change in SBMs from baseline of 2.21 (P = 0.052), 2.37 (P = 0.032); 4.11 (P = 0.0005); 5.19 (<0.0001) was noted with NSR 2.5 mg, 5 mg, 10 mg, and 20 mg, respectively, when taken once daily, compared with 1.38 (P = 0.2) for patients on placebo therapy. No changes in subjective or objective measures of opioid withdrawal as measured by the Subjective Opioid Withdrawal Scale or Clinical Opioid Withdrawal Scale were observed. There was no increase in patient reported pain as measured daily using a visual analogue scale.
  
  
  CONCLUSIONS
  This Phase II study has shown that using a new sustained release formulation to deliver oral naloxone to the colon allows successful treatment of OIC without comprising the desired opioid effects.
authors.affiliation: Norfolk and Norwich University Hospital, Norwich, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Sanders
authors.affiliation: Althean Pharma Limited, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jones
authors.affiliation: Gemeinschaftspraxis Lowenstein-Hesselbarth, Mainz, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Löwenstein
authors.affiliation: Schmerzzentrum Berlin, Berlin, Germany.
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Jansen
authors.affiliation: Schmerzzentrum Frankfurt, Frankfurt, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Miles
authors.affiliation: St. James's University Hospital, Leeds, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Simpson
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D003672:Defecation; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D017060:Patient Satisfaction; D011788:Quality of Life; D013375:Substance Withdrawal Syndrome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009270:Naloxone
keywords: Antagonist; Constipation; Naloxone; Opioid; Randomized Controlled Trial