title: Otilonium bromide in irritable bowel syndrome: a dose-ranging randomized double-blind placebo-controlled trial.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Danuta Chmielewska-Wilkoń, Department of Gastrointestinal Endoscopy, Gabinet Endoskopii Przewodu Pokarmowego, Szewska, 31-009 Krakow, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Chmielewska-Wilkoń
authors.affiliation: Danuta Chmielewska-Wilkoń, Department of Gastrointestinal Endoscopy, Gabinet Endoskopii Przewodu Pokarmowego, Szewska, 31-009 Krakow, Poland.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Reggiardo
authors.affiliation: Danuta Chmielewska-Wilkoń, Department of Gastrointestinal Endoscopy, Gabinet Endoskopii Przewodu Pokarmowego, Szewska, 31-009 Krakow, Poland.
authors.forename: Colin Gerard
authors.initials: CG
authors.lastname: Egan
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D000328:Adult; D003672:Defecation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D054796:Drug Dosage Calculations; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011044:Poland; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D000644:Quaternary Ammonium Compounds; C013934:octylonium
keywords: Acute treatment; Irritable bowel syndrome; Otilonium bromide; Spasmolytic