Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12283
Revised: April 29, 2014
Accepted: June 2, 2014
Published online: September 14, 2014
Processing time: 220 Days and 2 Hours
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.
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.