Tolerability and safety of alosetron during long-term administration in female and male irritable bowel syndrome patients.
OBJECTIVE
Alosetron (Lotronex) is a new therapeutic agent for irritable bowel syndrome (IBS) in women with diarrhea-predominant IBS. This multicenter randomized, double-blind, placebo-controlled study assessed the safety and tolerability of alosetron during long-term (< or = 12 months) treatment.


METHODS
A total of 859 subjects (637 female and 222 male) with IBS were enrolled from 130 sites in the United States and were randomized 3:1 to receive 1 mg alosetron or placebo b.i.d. for 48 wk; of the subjects, 649 (76%) were randomized to the alosetron group and 212 (24%) to the placebo group. Of the original group, 850 subjects received at least one dose of alosetron (n = 640) or placebo (n = 210).


RESULTS
In all, 59% of the subjects completed the study. Safety data were similar in treatment groups and within age, sex, racial origin, and hormone use. Adverse events were reported by 83% (530/640) and 76% (159/210) of subjects in the alosetron and placebo groups, respectively, (p < 0.05) and were similar with the exception of constipation; 32% of subjects receiving alosetron reported constipation, compared to 5% in the placebo group (p < 0.001). Most reports (72%) of constipation were of mild or moderate severity, and 66% of subjects with constipation had single episode of 8 days median duration. Constipation occurred a median of 13 days after initiating treatment and resolved spontaneously, with laxative, or after a brief interruption of therapy. Of the subjects, 4% (11/210) in the alosetron and 5% (28/ 640) in the placebo group experienced serious adverse events. Two deaths occurred in subjects with pre-existing cardiovascular risk factors; neither death was attributed to the study drug.


CONCLUSIONS
Alosetron 1 mg b.i.d. for 12 months was well tolerated. Constipation is the most frequent adverse event, with a higher incidence of transient constipation in alosetron-treated patients, typically occurring in the first month of treatment.
Wolfe
S G
SG
Gastroenterology Clinical Development, Glaxo Wellcome, Research Triangle Park, North Carolina, USA.
Chey
W Y
WY
Washington
M K
MK
Harding
J
J
Heath
A T
AT
McSorley
D J
DJ
Dukes
G E
GE
Hunt
C M
CM
D002243:Carbolines / Q000009:adverse effects / Q000627:therapeutic use*; D003109:Colonic Diseases, Functional / Q000188:drug therapy*; D003248:Constipation / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D012449:Safety; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D002243:Carbolines; D012702:Serotonin Antagonists; C090840:alosetron