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Efficacy and safety of oral lubiprostone in constipated patients with or without irritable bowel syndrome: a randomized, placebo‐controlled and dose‐finding study
Author(s) -
Fukudo S.,
Hongo M.,
Kaneko H.,
Ueno R.
Publication year - 2011
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2011.01668.x
Subject(s) - lubiprostone , irritable bowel syndrome , medicine , tolerability , placebo , constipation , gastroenterology , clinical endpoint , adverse effect , population , randomized controlled trial , chronic constipation , pathology , alternative medicine , environmental health
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 16 μ g ( n = 41), 32 μ g ( n = 43), or 48 μ g ( n = 44) of lubiprostone daily for 2 weeks. 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; 16 μ g: 2.3 ± 0.4, 32 μ g: 3.5 ± 0.5; and 48 μ g: 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 48 μ g 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.