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


OBJECTIVE
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.


CONCLUSIONS
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.
Lembo
A J
AJ
Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA 02215, USA. alembo@bidmc.harvard.edu
Cremonini
F
F
Meyers
N
N
Hickling
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides / Q000008:administration & dosage*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage*; D003248:Constipation / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D011788:Quality of Life; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005765:Gastrointestinal Agents; D012702:Serotonin Antagonists; C053006:renzapride