Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation

OBJECTIVES: To assess the efficacy and safety of lubiprostone in adults with chronic constipation. METHODS: This multicenter, parallel-group, double-blind controlled trial enrolled 242 patients with constipation and randomized them to receive oral lubiprostone 24 mcg or placebo twice daily for 4 wk. The primary efficacy end point was the number of spontaneous bowel movements ( SBMs; those occurring without use of constipation relieving medications) after 1 wk of double-blind treatment. Other evaluations included SBMs at weeks 2, 3, and 4; bowel movement ( BM) characteristics (i.e., consistency and straining); constipation severity; abdominal bloating/ discomfort; global treatment effectiveness ratings; and safety assessments. RESULTS: The 120 lubiprostone-treated patients reported a greater mean number of SBMs at week 1 compared with the 122 placebo-treated patients ( 5.69 vs 3.46, P = 0.0001), with a greater frequency of SBMs also reported at weeks 2, 3, and 4 ( P <= 0.002). Within 24 h of the first dose of study drug, 56.7% of those given lubiprostone reported a SBM compared with 36.9% of those given placebo ( P = 0.0024); within 48 h, 80% and 60.7% of these patients reported a SBM ( P = 0.0013), respectively. Stool consistency, straining, and constipation severity, as well as patient-reported assessments of treatment effectiveness, were significantly improved with lubiprostone compared with placebo at all weeks ( P <= 0.0003). The two most common treatment-related adverse events were nausea ( 31.7%) and headache ( 11.7%). CONCLUSIONS: In patients with chronic constipation, treatment with lubiprostone produces a BM in the majority of individuals within 24 - 48 h of initial dosing and improves the frequency as well as other characteristics associated with BMs with short-term ( i. e., 4 wk) treatment. The most commonly reported adverse event was mild to moderate nausea, which resulted in treatment discontinuation in 5% of treated patients.