A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS.
BACKGROUND
A randomized, double blind, placebo-controlled dose-ranging study was conducted to assess the efficacy of alosetron in men with diarrhea-predominant irritable bowel syndrome (IBS).


METHODS
Six hundred and sixty-two men were randomized to treatment with alosetron 0.5, 1.0, 2.0, 4.0 mg, or placebo twice daily for 12 wk, followed by a 4-wk posttreatment period. Adequate relief of IBS pain and discomfort during week 5-12 of the treatment phase was the primary endpoint; secondary endpoints included bowel urgency, stool frequency, and consistency, incomplete evacuation, bloating, and abdominal pain or discomfort.


RESULTS
Subjects ranked urgency and abdominal pain as their most bothersome IBS symptoms. The average rate of adequate relief during week 5-12 was significantly higher in the alosetron 1.0 mg twice-daily group compared to placebo (53%vs 40%, p= 0.04), and all doses of alosetron significantly reduced stool consistency scores (p < 0.001) indicating firmer stools. No significant effects of alosetron were seen with regard to urgency, number of bowel movements, bloating, and incomplete evacuation. Constipation was the most common adverse event and occurred in a dose-related manner among subjects receiving alosetron, 9% (0.5 mg twice daily), 15% (1.0 mg twice daily), 11% (2.0 mg twice daily), and 21% (4.0 mg twice daily). No serious adverse events of constipation were reported. One subject in the 0.5 mg twice-daily group had an episode of rectal bleeding suggestive of a possible diagnosis of ischemic colitis.


CONCLUSIONS
Alosetron 1 mg twice daily provided adequate relief of IBS pain and discomfort, and improved stool consistency in men with diarrhea-predominant IBS.
Chang
Lin
L
Center for Neurovisceral Sciences and Women's Health, UCLA Division of Digestive Diseases, Los Angeles, California, USA.
Ameen
Vanessa Z
VZ
Dukes
George E
GE
McSorley
David J
DJ
Carter
Eric G
EG
Mayer
Emeran A
EA
D015746:Abdominal Pain / Q000188:drug therapy* / Q000209:etiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002243:Carbolines / Q000008:administration & dosage* / Q000009:adverse effects; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D002243:Carbolines; D005765:Gastrointestinal Agents; C090840:alosetron