title: A 12-week extension study to assess the safety and tolerability of naloxegol in patients with noncancer pain and opioid-induced constipation.
abstract: To compare the long-term safety and tolerability of naloxegol with placebo in patients with opioid-induced constipation (OIC) and noncancer pain.
  
  
  
  Twelve-week, multicenter, randomized, double-blind, parallel-group phase 3 extension study (KODIAC-07, NCT01395524).
  
  
  
  Clinical investigation centers in the United States.
  
  
  
  Adult outpatients (N = 302) with confirmed OIC who had completed a 12-week pivotal phase 3 study (KODIAC-04, NCT01309841).
  
  
  
  Daily oral administration of naloxegol (12.5 and 25 mg) or placebo.
  
  
  
  Adverse events (AEs), including treatment-related AEs, serious AEs, and AEs of special interest; changes from baseline to week 12 in pain scores, daily opioid dose, and symptoms and quality-of-life measurements.
  
  
  
  No important new AEs occurred during this extension study compared with KODIAC-04. AEs occurred more frequently with naloxegol 25 mg (41.2 percent) versus naloxegol 12.5 mg (34.0 percent) and placebo (33.0 percent). Treatment-emergent AEs occurring in >5 percent of patients in either naloxegol group during the treatment period were arthralgia (25 mg; 5.2 percent) and diarrhea (12.5 mg; 5.3 percent); two reported AEs attributable to opioid withdrawal syndrome in naloxegol groups were deemed unrelated to study medication. None of the gastrointestinal serious AEs was adjudicated as bowel perforation; one patient (naloxegol 12.5 mg) had an event adjudicated as a major cardiovascular event and was unrelated to study medication. Pain scores and daily opioid dose were unchanged, and improvements in symptoms and quality-of-life observed in KODIAC-04 were maintained throughout the extension study.
  
  
  
  Naloxegol was generally safe and well tolerated in this 12-week extension study in patients with noncancer pain and OIC.
authors.affiliation: Vice President of Scientific Affairs, PRA Health Sciences, Salt Lake City, Utah.
authors.forename: Lynn
authors.initials: L
authors.lastname: Webster
authors.affiliation: Director of Clinical Research, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland.
authors.forename: Raj
authors.initials: R
authors.lastname: Tummala
authors.affiliation: Principal Statistician, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland; now with Ardea Biosciences, San Diego, California.
authors.forename: Ulysses
authors.initials: U
authors.lastname: Diva
authors.affiliation: Senior Director of Clinical Research, AstraZeneca Pharmaceuticals LP, Wilmington, Delaware; now with Marinus Pharmaceuticals, Radnor, Pennsylvania.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Lappalainen
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use*; D003248:Constipation / Q000139:chemically induced*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000009:adverse effects* / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects* / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use*; D011446:Prospective Studies; D014481:United States
chemical_list: D000701:Analgesics, Opioid; D009019:Morphinans; D009292:Narcotic Antagonists; D011092:Polyethylene Glycols; C000589308:naloxegol