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

Lancet. 2000 Mar 25;355(9209):1035-40. doi: 10.1016/S0140-6736(00)02033-X.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Carbolines / adverse effects
  • Carbolines / therapeutic use*
  • Colonic Diseases, Functional / diagnosis
  • Colonic Diseases, Functional / drug therapy*
  • Drug Administration Schedule
  • Female
  • Gastrointestinal Transit / drug effects
  • Humans
  • Middle Aged
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / adverse effects
  • Serotonin Antagonists / therapeutic use*
  • Treatment Outcome

Substances

  • Carbolines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • alosetron