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

Authors


Dr J. F. Johanson, c/o Sucampo Pharmaceuticals Inc., 4733 Bethesda Avenue, Suite 450, Bethesda, MD 20814, USA.
E-mail: johnfj@uic.edu

Abstract

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 (= 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (≤ 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.

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