Effect of Alosetron on Bowel Urgency and Global Symptoms in Women With Severe, Diarrhea-Predominant Irritable Bowel Syndrome: Analysis of Two Controlled Trials

Background & Aims: The aim of this study was to assess the effect of alosetron on bowel urgency and irritable bowel syndrome (IBS) global improvement in diarrhea-predominant IBS (D-IBS). Methods: Women with a lack of satisfactory bowel urgency control at least 50% of the time during screening were randomized to receive alosetron 1 mg (n = 246) or placebo (n = 246) twice daily. The primary end point was the percentage of days with satisfactory control of bowel urgency. The response rate for the IBS global improvement scale (GIS) was a secondary end point. GIS responders were patients who recorded either moderate or substantial improvement in IBS symptoms relative to the way they felt before entering the study. Other end points included improvement in stool frequency, stool consistency, and percentage of days with incomplete evacuation. Further analyses were performed on a subset of patients who had at least 10 of 14 days during screening (>= 71% of days) with a lack of satisfactory control of bowel urgency. Results: Patients had severe chronic IBS symptoms, and 89% of patients had D-IBS. Alosetron resulted in a greater percentage of days with satisfactory control of urgency compared with placebo (69% vs. 56%, respectively, P < 0.001). Greater percentages of alosetron-treated patients were GIS responders at 4, 8, and 12 weeks compared with placebo (59% vs. 41%, 63% vs. 41%, and 68% vs. 46%, respectively, P < 0.001). Patients with more frequent urgency had similar results. Constipation occurred in 28% and 9% of subjects in the alosetronand placebo-treated groups, respectively. No cases of ischemic colitis were reported. Conclusions: Alosetron effectively manages bowel urgency and improves global symptoms in women with severe chronic D-IBS.