PMID- 25112584
OWN - NLM
STAT- MEDLINE
DCOM- 20141229
LR  - 20220331
IS  - 1365-2036 (Electronic)
IS  - 0269-2813 (Linking)
VI  - 40
IP  - 7
DP  - 2014 Oct
TI  - Randomised clinical trial: the long-term safety and tolerability of naloxegol in 
      patients with pain and opioid-induced constipation.
PG  - 771-9
LID - 10.1111/apt.12899 [doi]
AB  - BACKGROUND: Opioid-induced constipation (OIC) is a common adverse effect of 
      opioid therapy. AIM: To evaluate the long-term safety and tolerability of 
      naloxegol, an oral, peripherally acting mu-opioid receptor antagonist (PAMORA), in 
      patients with noncancer pain and OIC. METHODS: A 52-week, multicenter, 
      open-label, randomised, parallel-group phase 3 study was conducted in 
      out-patients taking 30-1000 morphine-equivalent units per day for >/=4 weeks. 
      Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; 
      investigator-chosen laxative regimen) treatment for OIC. RESULTS: The safety set 
      comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration 
      was 268 days with naloxegol and 297 days with UC. Frequency of adverse events 
      (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment-emergent AEs 
      occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 
      3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 
      4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most 
      naloxegol-emergent gastrointestinal AEs occurred early, resolving during or after 
      naloxegol discontinuation and were mild or moderate in severity; 11 patients 
      discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain 
      scores and mean daily opioid doses remained stable throughout the study; no 
      attributable opioid withdrawal AEs were observed. Two patients in each group had 
      an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs 
      were reported nor adjudicated as bowel perforations. CONCLUSION: In patients with 
      noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 
      weeks was generally safe and well tolerated.
CI  - (c) 2014 The Authors. Alimentary Pharmacology & Therapeutics published by John 
      Wiley & Sons Ltd.
FAU - Webster, L
AU  - Webster L
AD  - PRA Health Sciences, Salt Lake City, UT, USA.
FAU - Chey, W D
AU  - Chey WD
FAU - Tack, J
AU  - Tack J
FAU - Lappalainen, J
AU  - Lappalainen J
FAU - Diva, U
AU  - Diva U
FAU - Sostek, M
AU  - Sostek M
LA  - eng
SI  - ClinicalTrials.gov/NCT01336205
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140812
PL  - England
TA  - Aliment Pharmacol Ther
JT  - Alimentary pharmacology & therapeutics
JID - 8707234
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Laxatives)
RN  - 0 (Morphinans)
RN  - 0 (Narcotic Antagonists)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 44T7335BKE (naloxegol)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analgesics, Opioid/adverse effects
MH  - Constipation/chemically induced/*drug therapy
MH  - Female
MH  - Humans
MH  - Laxatives/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Morphinans/adverse effects/*therapeutic use
MH  - Morphine/adverse effects
MH  - Narcotic Antagonists/adverse effects/*therapeutic use
MH  - Pain/*drug therapy
MH  - Polyethylene Glycols/adverse effects/*therapeutic use
EDAT- 2014/08/13 06:00
MHDA- 2014/12/30 06:00
CRDT- 2014/08/13 06:00
PHST- 2014/05/28 00:00 [received]
PHST- 2014/06/12 00:00 [revised]
PHST- 2014/07/10 00:00 [revised]
PHST- 2014/07/14 00:00 [accepted]
PHST- 2014/08/13 06:00 [entrez]
PHST- 2014/08/13 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
AID - 10.1111/apt.12899 [doi]
PST - ppublish
SO  - Aliment Pharmacol Ther. 2014 Oct;40(7):771-9. doi: 10.1111/apt.12899. Epub 2014 
      Aug 12.