Otilonium bromide in irritable bowel syndrome: a dose-ranging randomized double-blind placebo-controlled trial

Abstract

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.

Keywords: Acute treatment; Irritable bowel syndrome; Otilonium bromide; Spasmolytic.

Figure 1

Patient disposition. OB: Otilonium bromide.

Figure 2

Effect of otilonium bromide (20, 40, 80 mg) and placebo on the intensity (A) and frequency (B) of abdominal discomfort, bloating or pain. Data are presented as % change from baseline values. Asterix denotes level of statistical significance (^aP < 0.05) for placebo vs 80 mg otilonium bromide at 1 wk.

Figure 3

Effect of otilonium bromide (20, 40, 80 mg) and placebo on the frequency of evacuations (A) and the presence of mucus in stool, incomplete evacuation or difficulty of evacuation (B). Data are presented as % change from baseline values. Asterix denotes level of statistical significance (^bP < 0.01) for placebo vs 80 mg OB at 4 wk.

Figure 4

Effect of otilonium bromide (20, 40, 80 mg) and placebo on change in regular stool rate (A), regular intestinal habits (B) and frequency of stool type (C). Data are presented as % change from baseline values (A + B) or % patients (C). Asterix denotes level of statistical significance (^bP < 0.01) for placebo vs 40 mg otilonium bromide at 4 wk (B) and a dose dependent reduction in frequency of diarrhoea (^dP < 0.001) (C).

Figure 5

Effect of otilonium bromide (20, 40, 80 mg) and placebo on global discomfort index (A, B, C, D). Data are presented by scatterplot for individual global discomfort index values. Mean values over time are represented by trendlines for different treatment.