Allen W. Mangel

Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial

BACKGROUND Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with symptoms of abdominal pain, discomfort, and altered bowel function. Antagonists of the type 3 serotonin receptor (5-HT3) have shown promising results in the relief of IBS-associated symptoms. We aimed to confirm these findings by doing a randomised, placebo-controlled trial. METHODS We studied 647 female IBS patients with diarrhoea-predominant or alternating bowel patterns (diarrhoea and constipation). 324 patients were assigned 1 mg alosetron and 323 placebo orally twice daily for 12 weeks, followed by a 4-week post-treatment period. Adequate relief of abdominal pain and discomfort was the primary endpoint; secondary endpoints included improvements in urgency, stool frequency, and stool consistency. Analysis was by intention to treat. FINDINGS 79 (24%) of patients in the alosetron group and 53 (16%) in the placebo group dropped out. The difference in the drop-out rate between groups was mainly due to a greater occurrence of constipation in the alosetron group. A greater proportion of alosetron-treated patients than placebo-treated patients (133 [41%] vs 94 [29%], respectively) reported adequate relief for all 3 months of treatment (difference 12% [4.7-19.2]). Alosetron also significantly decreased urgency and stool frequency, and increased stool firmness. Constipation occurred in 30% and 3% of patients in the alosetron and placebo groups, respectively. INTERPRETATION Alosetron was well tolerated and clinically effective in alleviating pain and bowel-related symptoms in this population of women with IBS.

Prevalence and demographics of irritable bowel syndrome: results from a large web‐based survey

Background : Irritable bowel syndrome is a common gastrointestinal disorder, and its prevalence and demographics have been evaluated by different methodologies with varying results.

Clinical trial : asimadoline in the treatment of patients with irritable bowel syndrome

Background  In models of irritable bowel syndrome (IBS), asimadoline, a kappa‐opioid agonist, improves pain and abnormal bowel function.

A dose-ranging, placebo-controlled, randomized trial of alosetron in patients with functional dyspepsia:

Functional dyspepsia is characterized by upper abdominal pain or discomfort.

Gastrointestinal side effects in chronic opioid users: results from a population-based survey.

Background  Gastrointestinal side effects are commonly associated with opioid treatment for pain.

Alosetron improves quality of life in women with diarrhea-predominant irritable bowel syndrome

OBJECTIVES:The aim of this study was to assess the impact of alosetron, a treatment recently approved in the United States for irritable bowel syndrome in diarrhea-predominant female patients, on health-related quality of life.METHODS:Quality of life was assessed as part of two 12-wk randomized, double-blind, placebo-controlled irritable bowel syndrome studies comparing alosetron 1 mg b.i.d. with placebo (S3BA3001 and S3BA3002). Patients completed a validated disease-specific quality of life questionnaire, the Irritable Bowel Syndrome Quality of Life Questionnaire (IBSQOL), at baseline and at the 12-wk or final visit. The clinical relevance of data were also evaluated by a minimal meaningful difference instrument.RESULTS:A total of 626 and 647 patients were enrolled in studies S3BA3001 and S3BA3002, respectively. Approximately 70% of patients in each study had diarrhea-predominant IBS. In diarrhea-predominant patients enrolled in S3BA3001, statistically significant (p < 0.05) improvements with alosetron versus placebo were observed on all nine IBSQOL scales (emotional health, mental health, sleep, energy, physical functioning, food/diet, social functioning, role–physical, and sexual relations) and for all but one scale (mental health) in S3BA3002. In both studies, a significantly greater percentage of patients treated with alosetron (p < 0.05) experienced clinically meaningful improvement on three of the nine IBSQOL scales (food/diet, social functioning, and role–physical) compared with patients treated with placebo. Patients treated with alosetron did not show worsening in any quality of life domain compared with patients treated with placebo.CONCLUSIONS:These results in women with diarrhea-predominant IBS demonstrate that alosetron significantly improves health-related quality of life.

Clinical trial: the efficacy and tolerability of velusetrag, a selective 5‐HT4 agonist with high intrinsic activity, in chronic idiopathic constipation – a 4‐week, randomized, double‐blind, placebo‐controlled, dose–response study

Aliment Pharmacol Ther 2010; 32: 1102–1112

Review article: the safety and efficacy of alosetron, a 5-HT3 receptor antagonist, in female irritable bowel syndrome patients.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal‐related conditions. In this review, the safety and efficacy of alosetron, a potent and selective 5‐HT3 receptor antagonist, in the treatment of IBS are discussed.

Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome.

Background  Dextofisopam modulates stimulated activity in animal models of stress, altered bowel motility, and visceral hypersensitivity.

Determinants of healthcare-seeking behaviour among subjects with irritable bowel syndrome.

Doctor visits for irritable bowel syndrome are associated with high medical costs. Predictors of medical consultation for irritable bowel syndrome remain poorly understood.