Lubiprostone is a novel type-2 chloride channel activator for the treatment of chronic idiopathic constipation in adults. In a dose-ranging, double-blind, placebo-controlled phase 2 study, lubiprostone improved relief of IBS symptoms and was well-tolerated. To test these results, two 12-week, phase 3, multicenter, double-blind, randomized, placebo-controlled studies of lubiprostone in adults with IBS-C were conducted. Adults (n=1167) diagnosed with IBS-C (Rome II Criteria) were enrolled and received lubiprostone (8 mcg BID; n=780) or placebo (n=387) for 12 weeks. Most were female (91.6%) and aged 18-65 years (91.7%). Primary efficacy was determined by a unique question: "How would you rate your relief of IBS symptoms (abdominal discomfort/pain, bowel habits, and other IBS symptoms) over the past week compared to how you felt before you entered the study?" A 7-point balanced scale with a strict evaluation using the two highest scale points to qualify as a responder was used. Patients reporting at least moderate relief 4 out of 4 weeks or significant relief 2 out of 4 weeks were considered monthly responders. To qualify as an overall responder, patients had to be a monthly responder for at least 2 out of 3 months. During the evaluation period, patients discontinuing for any reason or reporting an increase in rescue medication use, lack of efficacy, or moderately or significantly worse relief were deemed non-responders. Patients receiving lubiprostone were nearly twice as likely to achieve overall response (LOCF) compared to those receiving placebo (lubiprostone 17.9% vs. placebo 10.1%; P=0.001). Individually, each study showed lubiprostone's superiority for overall response (P=0.009 and P=0.031). In combined studies, secondary endpoints included abdominal discomfort/pain, stool consistency, straining, constipation severity and QOL; these statistically significantly improved in patients receiving lubiprostone vs. placebo. Lubiprostone was well-tolerated, with a similar incidence of serious AEs (1% in each group) and related AEs (lubiprostone: 22% vs. placebo: 21%). The most common treatment-related AEs were nausea (8% vs. 4%, respectively) and diarrhea (6% vs. 4%, respectively). Abdominal pain was higher with placebo (5%) vs. lubiprostone (4%). Discontinuation rates for AEs were lower in the lubiprostone group (5%) vs. the placebo group (6%). Responder rates from this study may not be comparable to those in other studies since the new Phase 3 study definition is more restrictive than those previously reported. These results further demonstrate the efficacy and tolerability of 8 mcg BID lubiprostone for treatment of adults with IBS-C
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Drossman, D. A., Chey, W., Panas, R., Wahle, A., Scott, C., & Ueno, R. (2007). Lubiprostone Significantly Improves Symptom Relief Rates in Adults With Irritable Bowel Syndrome and Constipation (IBS-C): Data from Two Twelve-Week, Randomized, Placebo-Controlled, Double-Blind Trials. Gastroenterology, 132(7), 2586–2587. https://doi.org/10.1053/j.gastro.2007.04.022