Original Contribution
The American Journal of Gastroenterology (2004) 99, 2195–2203; doi:10.1111/j.1572-0241.2004.30509.x
Long-Term Safety and Efficacy of Alosetron in Women with Severe Diarrhea-Predominant Irritable Bowel Syndrome
Results of this study have been presented in part in the Program and Abstracts of Digestive Disease 2001; May 20–23, 2001; Atlanta, Georgia.
William D Chey MD, FACG1, William Y Chey MD, FACG1, Amy T Heath MS1, George E Dukes PharmD1, Eric G Carter MD, PhD1, Allison Northcutt MS1 and Vanessa Z Ameen MD1
1University of Michigan Medical Center, Ann Arbor, Michigan; Rochester Inst Digestive Diseases, Rochester, New York; and GlaxoSmithKline, Research Triangle Park, North Carolina
Correspondence: Vanessa Z Ameen, MD, Clinical Development and Medical Affairs, GlaxoSmithKline, 5 Moore Dr., Research Triangle Park, NC 27709
Received 11 May 2004; Revised 0000; Accepted 25 May 2004.
Abstract
OBJECTIVES
To assess long-term safety and efficacy of alosetron in women with severe, chronic diarrhea-predominant IBS and in a subset having more frequent urgency (i.e., bowel urgency at least 10 of 14 days during screening).
METHODS
Randomized patients received either alosetron 1 mg (n = 351) or placebo (n = 363) twice daily during a 48-wk, double-blind study. The primary endpoint was the 48-wk average rate of adequate relief of IBS pain and discomfort. Secondary endpoints included 48-wk average satisfactory control rates of urgency, stool frequency, stool consistency, and bloating. Other efficacy endpoints were average monthly adequate relief and urgency control rates and impact of provided rescue medication.
RESULTS
Alosetron-treated patients had significantly greater 48-wk average adequate relief (p= 0.01) and urgency control (p < 0.001) rates, regardless of rescue medication use, compared with placebo. Results in subjects with more frequent urgency were more robust than those in the overall population (p= 0.005). In weeks without rescue medication use, satisfactory control rates for stool frequency and stool consistency were significantly greater in alosetron-treated patients than placebo. Alosetron-treated patients had significantly greater adequate relief than placebo-treated patients (p < 0.05) in 9 of 12 months and significantly greater urgency control (p < 0.001) in all months. Adequate relief and urgency control were maintained throughout the treatment. Adverse events and serious adverse events were similar between treatment groups, except for constipation. Neither ischemic colitis nor serious events related to bowel motor dysfunction was reported.
CONCLUSIONS
Long-term use of alosetron is effective and well-tolerated in women with chronic, diarrhea-predominant IBS, including those with more frequent urgency.
