Otilonium bromide in irritable bowel syndrome: a dose-ranging randomized double-blind placebo-controlled trial.
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), 40 mg (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 (χ(2)-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 80 mg 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.
['Chmielewska-Wilkoń|Danuta|D|', 'Reggiardo|Giorgio|G|', 'Egan|Colin Gerard|CG|']
D015746:Abdominal Pain D000328:Adult D003672:Defecation D004305:Dose-Response Relationship, Drug D004311:Double-Blind Method D054796:Drug Dosage Calculations D005260:Female D005765:Gastrointestinal Agents D006801:Humans D043183:Irritable Bowel Syndrome D008297:Male D008875:Middle Aged D010147:Pain Measurement D011044:Poland D000644:Quaternary Ammonium Compounds D013997:Time Factors D016896:Treatment Outcome
Otilonium bromide Irritable bowel syndrome Acute treatment Spasmolytic