PMID- 23726675
OWN - NLM
STAT- MEDLINE
DCOM- 20140321
LR  - 20220317
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Linking)
VI  - 154
IP  - 9
DP  - 2013 Sep
TI  - A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to 
      evaluate the efficacy, safety, and tolerability of naloxegol in patients with 
      opioid-induced constipation.
PG  - 1542-1550
LID - 10.1016/j.pain.2013.04.024 [doi]
AB  - Naloxegol (previously known as NKTR-118) is a peripherally acting mu-opioid 
      receptor antagonist engineered using polymer conjugate technology in development 
      as an oral, once-daily agent for the treatment of opioid-induced constipation 
      (OIC). Eligible patients with OIC (n=207), defined as <3 spontaneous bowel 
      movements (SBMs) per week with accompanying symptoms, on a stable opioid regimen 
      of 30-1000 mg/day morphine equivalents for >/= 2 weeks were randomized to receive 4 
      weeks of double-blind placebo or naloxegol (5, 25, or 50mg) once daily in 
      sequential cohorts after a 1-week placebo run-in. The primary end point, median 
      change from baseline in SBMs per week after week 1 of drug administration, was 
      statistically significant for the 25- and 50-mg naloxegol cohorts vs placebo (2.9 
      vs 1.0 [P=0.0020] and 3.3 vs 0.5 [P=0.0001], respectively). The increase in SBMs 
      vs placebo was maintained over 4 weeks for naloxegol 25mg (3.0 vs 0.8 [P=0.0022]) 
      and 50mg (3.5 vs 1.0 [P<0.0001]). Naloxegol was generally well tolerated across 
      all dosages. The most frequent adverse events (AEs) were abdominal pain, 
      diarrhea, and nausea. Most AEs at 5 and 25mg/day were mild and transient. Similar 
      AEs occurred with increased frequency and severity in the 50-mg cohort. There was 
      no evidence of a statistically significant increase from baseline in pain, opioid 
      use for the 25- and 50-mg cohorts, or centrally mediated opioid withdrawal signs 
      and/or symptoms with naloxegol. These data demonstrate that once-daily oral 
      naloxegol improves the frequency of SBMs compared with placebo and is generally 
      well tolerated in this population of patients with OIC.
CI  - Copyright (c) 2013 International Association for the Study of Pain. Published by 
      Elsevier B.V. All rights reserved.
FAU - Webster, Lynn
AU  - Webster L
AD  - CRI Lifetree Research, Salt Lake City, UT, USA Genentech Inc., San Francisco, CA, 
      USA Nektar Therapeutics, San Francisco, CA, USA Oakland, CA, USA AstraZeneca 
      Pharmaceuticals, Wilmington, DE, USA.
FAU - Dhar, Sunita
AU  - Dhar S
FAU - Eldon, Michael
AU  - Eldon M
FAU - Masuoka, Lorianne
AU  - Masuoka L
FAU - Lappalainen, Jaakko
AU  - Lappalainen J
FAU - Sostek, Mark
AU  - Sostek M
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130416
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Narcotic Antagonists)
RN  - 36B82AMQ7N (Naloxone)
SB  - IM
CIN - Pain. 2013 Sep;154(9):1491-2. PMID: 23953125
MH  - Adult
MH  - Analgesics, Opioid/adverse effects
MH  - Cohort Studies
MH  - Constipation/chemically induced/*drug therapy/psychology
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - International Cooperation
MH  - Male
MH  - Middle Aged
MH  - Naloxone/*administration & dosage
MH  - Narcotic Antagonists/*administration & dosage
MH  - Quality of Life
MH  - Surveys and Questionnaires
MH  - Time Factors
OTO - NOTNLM
OT  - Constipation
OT  - NKTR-118
OT  - Naloxegol
OT  - Naloxol
OT  - Naloxone
OT  - Opioid
EDAT- 2013/06/04 06:00
MHDA- 2014/03/22 06:00
CRDT- 2013/06/04 06:00
PHST- 2012/12/21 00:00 [received]
PHST- 2013/04/04 00:00 [revised]
PHST- 2013/04/09 00:00 [accepted]
PHST- 2013/06/04 06:00 [entrez]
PHST- 2013/06/04 06:00 [pubmed]
PHST- 2014/03/22 06:00 [medline]
AID - 00006396-201309000-00011 [pii]
AID - 10.1016/j.pain.2013.04.024 [doi]
PST - ppublish
SO  - Pain. 2013 Sep;154(9):1542-1550. doi: 10.1016/j.pain.2013.04.024. Epub 2013 Apr 
      16.