A randomized, double-blind, placebo-controlled study to assess efficacy and safety of 0.5 mg and 1 mg alosetron in women with severe diarrhea-predominant IBS

Am J Gastroenterol. 2007 Aug;102(8):1709-19. doi: 10.1111/j.1572-0241.2007.01282.x. Epub 2007 May 17.


Objective: Alosetron is indicated for women with chronic, severe diarrhea-predominant IBS (d-IBS) who have not responded adequately to conventional therapy. Constipation is the most common adverse event with alosetron treatment. Multiple dosing regimens were assessed in a randomized, double-blind, placebo-controlled study (S3B30040) to determine efficacy, tolerability, and evaluate constipation rate.

Methods: 705 women with severe d-IBS were randomized to placebo, alosetron 0.5 mg once daily, 1 mg once daily, or 1 mg twice daily for 12 wk. The primary end point was the proportion of week 12 responders (patients with moderate or substantial improvement in IBS symptoms) on the 7-point Likert Global Improvement Scale (GIS). Secondary end points were average rate of adequate relief of IBS pain and discomfort, and bowel symptom improvements.

Results: The proportion of GIS responders at week 12 (primary time point) was significantly greater in all alosetron groups compared with placebo (54/176 [30.7%], 90/177 [50.8%], 84/175 [48%], and 76/177 [42.9%] for placebo, 0.5, 1 mg once daily, and 1 mg twice daily alosetron groups, respectively; P< or = 0.02). Results were similar for the average adequate relief rate (treatment effects > or =12%, P< or = 0.038). Bowel symptoms were improved in all alosetron groups. Constipation was the most common adverse event (9%, 16%, and 19% patients in the 0.5 mg, 1 mg once daily, and 1 mg twice daily groups, respectively). One event of intestinal obstruction and one of ischemic colitis occurred in the 0.5 mg group, and one event of fecal impaction occurred in the 1 mg twice-daily group. All were self-limited and resolved without sequelae.

Conclusion: Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a decreased constipation rate.

Publication types

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

MeSH terms

  • Carbolines / administration & dosage*
  • Carbolines / adverse effects
  • Constipation / chemically induced
  • Diarrhea / drug therapy
  • Double-Blind Method
  • Drug Tolerance
  • Female
  • Gastrointestinal Agents / administration & dosage*
  • Gastrointestinal Agents / adverse effects
  • Humans
  • Irritable Bowel Syndrome / drug therapy*
  • Middle Aged
  • Serotonin Antagonists / administration & dosage*
  • Serotonin Antagonists / adverse effects
  • Treatment Outcome


  • Carbolines
  • Gastrointestinal Agents
  • Serotonin Antagonists
  • alosetron