Clinical trial: renzapride treatment of women with irritable bowel syndrome and constipation - a double-blind, randomized, placebo-controlled, study

Abstract

Background: Renzapride, a 5-hydroxytryptamine type-4 (5-HT(4)) receptor agonist and 5-HT(3) receptor antagonist, has been proposed as a new treatment of irritable bowel syndrome with constipation (IBS-C).

Aim: To assess the efficacy and safety of renzapride in women with IBS-C.

Methods: Women with IBS-C were randomized to renzapride 4 mg daily, 2 mg b.d. or placebo for 12 weeks. The primary outcome measure was global relief of IBS symptoms. A subset of patients were enrolled in a 12-month, open-label study of renzapride 4 mg daily.

Results: A total of 1798 patients were included in the efficacy analysis and 971 patients entered the long-term study. The mean (S.E.M.) number of months with relief of overall IBS symptoms was 0.55 (0.04), 0.60 (0.04) and 0.44 (0.04) in the renzapride 4 mg daily, 2 mg b.d. and placebo groups (P = 0.027 and P = 0.004 respectively). Small yet statistically significant differences in favour of renzapride were observed on stool consistency and frequency, and bloating/abdominal distension scores. Renzapride was generally well tolerated; however, three episodes of ischaemic colitis were reported in the long-term study.

Conclusion: Given the limited increase in efficacy over placebo and the incidence of ischaemic colitis observed, our data suggest that the benefit/risk ratio of renzapride is not sufficient to warrant further study in IBS-C.