Efficacy and safety of oral lubiprostone in constipated patients with or without irritable bowel syndrome: a randomized, placebo-controlled and dose-finding study.

Abstract

BACKGROUND:

Lubiprostone is a prostone analog with a novel mechanism of action involving type-2 chloride channel activation. The aim of this work was to perform a dose-finding study for lubiprostone for the treatment of constipation with or without irritable bowel syndrome (IBS) in Japan.

METHODS:

A total of 170 patients (128 without IBS and 42 with IBS) with chronic idiopathic constipation (CIC) randomly received a placebo (n=42) or 16μg (n=41), 32μg (n=43), or 48μg (n=44) of lubiprostone daily for 2weeks.

KEY RESULTS:

There was a statistically significant and dose-dependent increase in change from baseline in the weekly average number of spontaneous bowel movements at week 1 (placebo: 1.5±0.4; 16μg: 2.3±0.4, 32μg: 3.5±0.5; and 48μg: 6.8±1.1, per week, mean±SE; P<0.0001). These primary endpoint results were significant on stratified analysis when patients were limited to those without IBS (P<0.0001). The primary endpoint in patients with IBS treated with 48μg of lubiprostone was significantly better than those given placebo (P=0.0086). Dose dependency was also seen for the secondary efficacy endpoints. Lubiprostone produced no serious side effects.

CONCLUSIONS & INFERENCES:

Our results suggest that lubiprostone produced a steady and effective improvement in the symptoms of CIC with or without IBS in a dose-dependent manner with a good safety profile and tolerability in a Japanese population.

• Authors: S Fukudo, M Hongo, H Kaneko, R Ueno
• Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (Neurogastroenterol Motil) Vol. 23 Issue 6 Pg. 544-e205 (Jun 2011) ISSN: 1365-2982 [Electronic] England
• PMID: 21303430 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Chloride Channels
• Placebos
• Lubiprostone
• Alprostadil

Topics

• Adult
• Alprostadil (analogs & derivatives, pharmacology, therapeutic use)
• Asian People
• Chloride Channels (metabolism)
• Constipation (drug therapy)
• Defecation (drug effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Irritable Bowel Syndrome (physiopathology)
• Lubiprostone
• Male
• Middle Aged
• Placebos
• Treatment Outcome