Abstract | 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.
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Authors | Richard Krause, Vanessa Ameen, Susan H Gordon, Marquita West, Amy T Heath, Teresa Perschy, Eric G Carter |
Journal | The American journal of gastroenterology
(Am J Gastroenterol)
Vol. 102
Issue 8
Pg. 1709-19
(Aug 2007)
ISSN: 0002-9270 [Print] United States |
PMID | 17509028
(Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carbolines
- Gastrointestinal Agents
- Serotonin Antagonists
- alosetron
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Topics |
- Carbolines
(administration & dosage, adverse effects)
- Constipation
(chemically induced)
- Diarrhea
(drug therapy)
- Double-Blind Method
- Drug Tolerance
- Female
- Gastrointestinal Agents
(administration & dosage, adverse effects)
- Humans
- Irritable Bowel Syndrome
(drug therapy)
- Middle Aged
- Serotonin Antagonists
(administration & dosage, adverse effects)
- Treatment Outcome
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