Lubiprostone Produces Spontaneous Bowel Movements within 24 and 48 Hours in Patients with Chronic Constipation

Abstract

Purpose: Constipation is a common gastrointestinal condition that frequently necessitates prompt relief of bothersome symptoms. Lubiprostone, a novel type-2 chloride channel (ClC-2) activator, has been shown to be efficacious – increasing spontaneous bowel movement (SBM) frequency – and has been well tolerated by patients with chronic idiopathic constipation in clinical trials of 3 to 4 weeks' duration. To assess the onset of action of lubiprostone, we examined individual and pooled results from two well-controlled Phase 3 trials. Methods: Data on time to first SBM and percentage of patients experiencing a SBM within 24 or 48 hours following initial study-drug administration were compared by study, pooled, and between treatment groups (placebo vs. lubiprostone 24 mcg BID). A SBM was defined as any bowel movement that did not occur within 24 hours of rescue medication use. Additionally, pooled adverse event (AE) incidence rates were compared between treatment groups. Results: The pooled analysis consisted of 240 placebo and 239 lubiprostone patients. Approximately 90% of patients were female, approximately 80% were Caucasian, and the mean patient age was 47.2 years. For the pooled group, baseline SBM frequencies were 1.52 and 1.35 SBMs/week for placebo and lubiprostone patients, respectively. For each study, the time to first SBM was significantly shorter for patients taking lubiprostone, compared with those taking placebo (P≤.006). In the individual studies, 57% to 63% of lubiprostone-treated patients and 32% to 37% of placebo patients had a SBM within 24 hours (P≤.0024). At the 48-hour timepoint in the individual studies, a SBM occurred in 79% to 80% of lubiprostone patients vs. 61% to 66% of placebo patients (P≤.0258). In the pooled analysis, 60% of lubiprostone patients had a SBM within 24 hours and 80% had a SBM within 48 hours, compared with 35% and 63% of placebo patients, respectively (P <.0001). Across the two well-controlled studies, 42.9% of placebo patients and 62.3% of patients taking lubiprostone reported at least one AE. Similarly, 18.8% of placebo patients and 46.9% of lubiprostone patients reported at least one treatment-related AE. The most common related AEs reported in ≥5% of patients were nausea, headache, and dizziness. Conclusions: In patients with chronic constipation, lubiprostone decreased the time to first SBM and increased the proportion of patients achieving SBMs within 24 and 48 hours compared to patients receiving placebo.