Efficacy and Safety of Lubiprostone in a Subgroup of Constipation Patients Diagnosed with Irritable Bowel Syndrome with Constipation (IBS-C)

Purpose: Lubiprostone is a novel type-2 chloride channel (ClC-2) activator that has been shown to be efficacious and well tolerated in a number of well-controlled clinical trials in patients with chronic idiopathic constipation. Pooled results from two Phase 3 constipation trials were examined to evaluate lubiprostone efficacy in patients with a history of IBS-C compared to placebo. Methods: To create an adequate pool of IBS-C patients, data were combined from two placebo-controlled clinical trials of 4 weeks' duration. Spontaneous bowel movement (SBM) frequency rates; stool consistency ratings (0 = very loose to 4 = very hard); and bowel straining, abdominal bloating, abdominal discomfort, and constipation severity assessments (0 = absent to 4 = very severe) were compared between treatment groups (placebo vs. lubiprostone 24 mcg BID). Subgroups of constipation patients with and without a prior diagnosis of IBS-C were also evaluated. Results: The pooled IBS-C subgroup consisted of 45 placebo and 46 lubiprostone-treated patients. Mean SBM rates were significantly greater among lubiprostone IBS-C patients (4.8–6.0/week) compared to their placebo counterparts (2.8–4.0/week) at all four weekly evaluations (P≤.0207). Mean stool consistency ratings were significantly better with lubiprostone treatment (1.6–1.7) vs. placebo (2.6–2.7) at all four weekly evaluations (P <.0001), and mean bowel straining ratings were also significantly better with lubiprostone (1.3–1.6) vs. placebo (2.1–2.2) at all four weekly evaluations (P≤.0119). Additionally, assessments of abdominal bloating and discomfort were significantly improved vs. placebo at Weeks 3 and 4 (P≤.0495), and constipation severity ratings were significantly improved vs. placebo at Weeks 1, 3, and 4 (P≤.0175) and nearly reached significance at Week 2 (P=.0509). Efficacy results were generally similar for both IBS-C and non-IBS-C patients. Fewer IBS-C patients receiving placebo (50%) experienced adverse events (AEs) compared with patients treated with lubiprostone (68.9%). The most common AE, nausea, had a slightly higher incidence in lubiprostone-treated IBS-C patients vs. their non-IBS-C counterparts (35.6% vs. 28.4%, respectively). Conclusions: In chronic constipation trials with lubiprostone, a subgroup of patients with a history of IBS-C treated with lubiprostone had more favorable symptom resolution compared to placebo.