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Michael Camilleri, MD; William Y. Chey, MD, DSci; Emeran A. Mayer, MD; Allison R. Northcutt, MS; Amy Heath, MS; George E. Dukes, PharmD; David McSorley, MPH; Allen M. Mangel, MD, PhD

Arch Intern Med. 2001;161:1733-1740.

Background  Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen in primary care practice. The symptoms of IBS, including abdominal pain, discomfort, and abnormal bowel function, may be modulated by activity of the serotonin type 3 receptor (5-HT₃). The efficacy and tolerability of the 5-HT₃ receptor antagonist alosetron hydrochloride in nonconstipated female patients with IBS were evaluated in a double-blind, randomized, placebo-controlled trial.

Methods  Patients received either 1 mg of alosetron hydrochloride (n = 309) or placebo (n = 317) twice daily for 12 weeks, followed by a 4-week posttreatment period. Adequate relief of IBS pain and discomfort was the primary end point. Secondary end points included improvements in urgency, stool frequency, stool consistency, incomplete evacuation, and bloating.

Results  Seventy-one percent of patients were classified as having diarrhea-predominant IBS. Forty-three percent of alosetron-treated patients with diarrhea-predominant IBS reported adequate relief for all 3 months compared with 26% of placebo-treated patients (P<.001; percentage point difference = 17; 95% confidence interval, 8.0-25.4). Improvement with alosetron compared with placebo was observed by the end of the fourth week of treatment and persisted throughout the remainder of treatment. Alosetron significantly decreased urgency and stool frequency and caused firmer stools within 1 week of starting treatment. Effects were sustained throughout treatment and symptoms returned following treatment cessation. No significant improvement in the percentage of days with sense of incomplete evacuation or bloating was observed compared with placebo during the first month of treatment. Constipation was the most commonly reported adverse event.

Conclusion  Alosetron hydrochloride, 1 mg twice daily for 12 weeks, is effective in relieving pain and some bowel-related symptoms in diarrhea-predominant female patients with IBS.

From the Gastroenterology Research Unit, Mayo Clinic, Rochester, Minn (Dr Camilleri); Rochester Institute for Digestive Diseases and Science Inc, Rochester, NY (Dr Chey); Division of Gastroenterology, University of California at Los Angeles Medical Center (Dr Mayer); and Departments of Gastroenterology Clinical Development (Ms Northcutt and Drs Dukes and Mangel) and Clinical Statistics (Ms Heath and Mr McSorley), Glaxo Wellcome Inc, Research Triangle Park, NC. Dr Camilleri has performed research that has been supported in part by Glaxo Wellcome Inc, has served as a consultant to Glaxo Wellcome Inc, received honoraria, and testified before the Food and Drug Advisory Committee on the mechanism of action of alosteron. Drs Chey and Mayer have served as consultants to Glaxo Wellcome Inc and have performed research that has been supported in part by Glaxo Wellcome Inc. Drs Dukes and Mangel, Mss Northcutt and Heath, and Mr McSorley are employees of Glaxo Wellcome Inc.

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