title: Fixed-Dose Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: Results of a Randomized, Placebo-Controlled Study and Open-Label Extension.
abstract: BACKGROUND
  Subcutaneous methylnaltrexone (MNTX), dosed based on body weight, is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); however, fixed-dose administration of MNTX may improve ease of administration.
  
  
  OBJECTIVE
  The study objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4 trials.
  
  
  METHODS
  In a double-blind, randomized, placebo-controlled trial (RCT), patients with advanced illness and OIC received MNTX (8 mg or 12 mg by body weight [38 kg to <62 kg or ≥62 kg, respectively]) or placebo every other day (QOD) for two weeks. Patients completing the RCT could enroll in an open-label extension (OLE) study with MNTX administered as needed (PRN). The primary endpoint was percentage of patients with a rescue-free bowel movement (RFBM) within four hours after ≥2 of the first 4 doses in the first week.
  
  
  RESULTS
  In the RCT, 116 and 114 patients received MNTX and placebo, respectively, and 149 patients continued to the OLE study. The percentage of patients achieving primary endpoint was 62.9% and 9.6% for MNTX and placebo groups, respectively (p<0.0001). Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001). Efficacy results during the OLE study were consistent with the RCT. MNTX demonstrated a favorable safety profile in the RCT and OLE study.
  
  
  CONCLUSIONS
  Fixed-dose MNTX administered QOD in the RCT and PRN in the OLE study demonstrated robust efficacy and was well tolerated in treating OIC in patients with advanced illness.
authors.affiliation: 1 Four Seasons , Flat Rock, North Carolina.
authors.forename: Janet
authors.initials: J
authors.lastname: Bull
authors.affiliation: 2 Hospice of the Western Reserve , Cleveland, Ohio.
authors.forename: Charles V
authors.initials: CV
authors.lastname: Wellman
authors.affiliation: 3 Progenics Pharmaceuticals, Inc. , Tarrytown, New York.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Israel
authors.affiliation: 4 Salix Pharmaceuticals, Ltd. , Raleigh, North Carolina.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Barrett
authors.affiliation: 4 Salix Pharmaceuticals, Ltd. , Raleigh, North Carolina.
authors.forename: Craig
authors.initials: C
authors.lastname: Paterson
authors.affiliation: 4 Salix Pharmaceuticals, Ltd. , Raleigh, North Carolina.
authors.forename: William P
authors.initials: WP
authors.lastname: Forbes
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D061214:Patient Safety; D010919:Placebos; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010919:Placebos; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone