Randomized Controlled Trial
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2014; 20(34): 12283-12291
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12283
Otilonium bromide in irritable bowel syndrome: A dose-ranging randomized double-blind placebo-controlled trial
Danuta Chmielewska-Wilkoń, Giorgio Reggiardo, Colin Gerard Egan
Danuta Chmielewska-Wilkoń, Department of Gastrointestinal Endoscopy, Gabinet Endoskopii Przewodu Pokarmowego, Szewska, 31-009 Krakow, Poland
Giorgio Reggiardo, Medi Service, World Trade Center, 16149 Genoa, Italy
Colin Gerard Egan, Primula Multimedia SRL, 56121 Pisa, Italy
Author contributions: Chmielewska-Wilkoń D designed the trial and recruited the patients; Reggiardo G performed statistical analysis; Egan CG performed data analysis, prepared tables and figures and wrote the manuscript; all authors critically revised the final version of the manuscript.
Supported by Menarini Group, Florence, Italy
Correspondence to: Colin Gerard Egan, PhD, Primula Multimedia SRL, Via G. Ravizza 22/b Ospedaletto, 56121 Pisa, Italy. cegan@primulaedizioni.it
Telephone: +39-50-9656242 Fax: +39-50-3163810
Received: February 10, 2014
Revised: April 29, 2014
Accepted: June 2, 2014
Published online: September 14, 2014

AIM: To examine the efficacy and safety of otilonium bromide (OB) in treatment-sensitive functional irritable bowel syndrome (IBS) clinical parameters.

METHODS: Ninety-three patients (44.8 ± 12.6 years, 69% female) with IBS symptoms complying with Rome II criteria participated in this double-blind, placebo-controlled, randomised, dose-ranging phase I/II study. Patients were administered OB 20 mg (n = 24), 40mg (n = 23) and 80 mg (n = 23) tid or placebo (n = 23) in 4 parallel groups for 4 wk. Primary efficacy variables included abdominal discomfort, intestinal habits, number of daily evacuations and stool consistency. Secondary efficacy measures included return to regular intestinal habits and global discomfort. Safety was also assessed.

RESULTS: Baseline clinical characteristics were similar among the 4 groups. Although individual parameters such as intensity and frequency of abdominal discomfort, bloating or pain were reduced by OB over the 4 wk, no significant differences were observed between groups. Similarly, no difference was observed between OB treatment or placebo for mucus in stool and incomplete or difficulty of evacuation. However, evacuation frequency was significantly reduced after 4 wk by 80 mg OB compared to placebo (-8.36% for placebo vs -41.9% for 80 mg OB, P < 0.01). While 21.7% of patients in the placebo group experienced regular intestinal habits after 4 wk, this improvement was greater for patients treated with 40 mg OB (P < 0.01 vs placebo). Furthermore, a dose-dependent reduction in frequency of diarrhoea (χ2-test for trend = 11.5, P < 0.001) and an increase in normal stool frequency was observed. Combining individual variables into a global discomfort index revealed significant improvement among increasing OB doses, favouring 40 mg (P = 0.013) and 80mg OB (P = 0.001) over placebo. No difference was observed between frequency of adverse events for placebo vs OB.

CONCLUSION: This dose-ranging study demonstrates that OB at 40 and 80 mg can improve individual and global clinical symptoms of IBS compared to placebo over a 4-wk period.

Keywords: Otilonium bromide, Irritable bowel syndrome, Spasmolytic, Acute treatment

Core tip: Although previous trials have confirmed the efficacy of a single dose of otilonium bromide (OB) on well-defined endpoints in patients with irritable bowel syndrome (IBS), no study has specifically defined the optimal dosage of OB on standard IBS efficacy measures in a controlled cross-over design. Findings from this dose-ranging study demonstrate that OB at 40 and 80 mg can improve both individual and global clinical IBS symptoms compared to placebo over 4 wk. All doses of OB were well tolerated compared to placebo. Future long-term controlled trials on global efficacy measures will help reinforce findings from the present trial.