Initial and Sustained Effects of Lubiprostone, a Chloride Channel-2 (ClC-2) Activator for the Treatment of Constipation

Abstract

Purpose: To examine data on onset and persistence of effect from a 4-week Phase III study comparing lubiprostone with placebo in subjects with chronic idiopathic constipation. Methods: In a Phase III multicenter, parallel-group, DB trial comparing lubiprostone with placebo, subjects with a history of chronic idiopathic constipation were randomized to receive oral lubiprostone (24 μg bid) or placebo with food and water for 28 days after a 15-day drug-free period. Chronic constipation was defined as < 3 spontaneous bowel movements (SBMs) per week, with a minimum 6-month history of hard stools, sensation of incomplete evacuation, or straining during at least 25% of bowel movements (BM). An SBM was any BM that did not occur within 24 h of rescue medication use. Patients with mechanical obstruction, organic disorders of the large or small bowel were excluded, as were patients with conditions or treatments that could affect safety or data validity. Patients were evaluated at baseline, at weekly intervals during treatment, and at follow up. Patient diaries were used to record data on SBM frequency, global assessments, and symptom assessments. Results: Statistically significant differences in the timing of the first SBM following initiation of treatment were observed; 73 of the 119 subjects (61.3%) receiving lubiprostone vs 37 of the 118 subjects (31.4%) in the placebo group experienced an SBM within 24 h of first dose (p≤0.0001). Within 48 h, 79.3% of subjects receiving lubiprostone, versus 65.5% of subjects receiving placebo had experienced an SBM (p < 0.05). For the overall analysis of time to first SBM, there was a statistically significant (p < 0.001) treatment effect in favor of lubiprostone. The greater SBM frequency/week for patients receiving lubiprostone compared with those on placebo was statistically significant (p < 0.05) and sustained throughout the treatment period. [figure 1]FigureConclusions: Lubiprostone, 24 μg bid, provides rapid relief of chronic idiopathic constipation that is sustained over the 4-week treatment period.