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
Article first published online: 20 MAR 2007
Alimentary Pharmacology & Therapeutics
Volume 25, Issue 11, pages 1351–1361, June 2007
How to Cite
JOHANSON, J. F. and UENO, R. (2007), 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. Alimentary Pharmacology & Therapeutics, 25: 1351–1361. doi: 10.1111/j.1365-2036.2007.03320.x
- Issue published online: 20 MAR 2007
- Article first published online: 20 MAR 2007
- Publication data Submitted 30 August 2006 First Decision 1 September 2006 Resubmitted 28 February 2007 Accepted 15 March 2007
Lubiprostone, a locally acting type-2 chloride channel activator, induces intestinal fluid secretion.
To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation.
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.
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.
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.