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Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double‐blind, placebo‐controlled, dose‐ranging study to evaluate efficacy and safety
Author(s) -
JOHANSON J. F.,
UENO R.
Publication year - 2007
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2007.03320.x
Subject(s) - lubiprostone , medicine , dose ranging study , activator (genetics) , placebo , constipation , double blind , chronic constipation , gastroenterology , pharmacology , pathology , receptor , alternative medicine
Summary Background Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion. Aim To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation. Methods A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked. Results Over the double‐blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant ( P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day ( P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo ( P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day ( P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea. Conclusions Lubiprostone improved SBM rates in a dose‐dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk‐to‐benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.