Lubiprostone Improves Not Only Spontaneous Bowel Movement but Also Quality of Life in Patients With Chronic Idiopathic Constipation: Phase III Randomized, Double-Blind, and Placebo-Controlled Study and Long-Term Treatment Study in Japan

Abstract

Aim: Lubiprostone is a prostone analogue with a novel type-2 chloride channel activation process. We previously reported the efficacy of lubiprostone for chronic idiopathic constipation (CIC) with or without irritable bowel syndrome (IBS) as phase II trial in Japan (Gastroenterology 138: S226, 2010). However, report of phase a III randomized controlled trial and long-term efficacy of lubiprostone in Asian population was lacking. We tested the following hypotheses; (1) Lubiprostone is effective on spontaneous bowel movements (SBMs) in CIC patients in Japan. (2) Treatment with lubiprostone for long (but not short) term improves quality of life (QOL) in CIC patients.Methods: Essential feature of this studywas randomized, double-blind, placebo-controlled, phase III trial of lubiprostone. Patients with CIC (n = 124) were randomly allocated for treatments using a placebo (n = 62) or 24 μg twice daily dose of lubiprostone (n = 62) for 4 weeks. The primary efficacy endpoint was the change from baseline in the weekly average number of SBMs at week 1. The secondary efficacy endpoints included the change from baseline in the weekly average number of SBMs at week 2-4, gastrointestinal symptoms, SF-36, and IBS-QOL. In the long-term treatment study, 209 patients with CICwere enrolled. Twice daily dose of lubiprostone 24 μgwas administered for 48 weeks. Efficacy and safety were checked at visits. Results: Administration of 48 μg of lubiprostone induced significantly more average number of SBMs at week 1 (3.7 ± 2.8) than that of placebo (1.3 ± 1.8, p < 0.001). SBMs at week 2, 3, and 4 in lubiprostone 48 μg/day arm were significantly superior to those in placebo arm. Stool form at week 1, 2, 3, and 4 in lubiprostone arm was also significantly better than in placebo arm. There was significantly more global improvement during the treatment period with lubiprostone than placebo. However, changes in SF-36 or IBS-QOL in lubiprostone arm did not differ from those in placebo arm. In the long-term treatment study, SBMs during administration of lubiprostone were significantly more than those at baseline (p < 0.001). Lubiprostone significantly maintained better stool form, straining, incomplete evacuation, abdominal discomfort, abdominal distention, and global improvement during treatment period than baseline. Lubiprostone for long-term therapy induced significantly better SF-36 and IBS-QOL than baseline. Conclusion: Our results confirmed effect of lubiprostone on constipation regardless of different culture. This study also suggests that improvement of QOL may follow better bowel movements for certain duration in patients with CIC.