Safety and Efficacy Study of GR68755 (Alosetron hydrochloride) to Treat Severe Diarrhea-Predominant Irritable Bowel Syndrome (IBS)

A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1.Does not have severe d-IBS 2.Has current evidence of or history of chronic or severe constipation, or a history of sequelae from constipation. 3.Is currently constipated or did report no stool for three or more consecutive days during the screening phase. 4.Has evidence of bloody diarrhea or abdominal pain with lower gastrointestinal hemorrhage. 5.Has current evidence of uncontrollable cardiovascular, renal, hepatic, pulmonary, endocrine, metabolic, hematologic, or digestive condition (excluding IBS). 6.Has evidence of biochemical or structural abnormality of the digestive tract. These conditions include the evidence or history of the following: •Ischemic colitis •Impaired intestinal circulation •gastrointestinal perforation •gastrointestinal obstruction and/or stricture •diverticulitis •Inflammatory bowel disease (Crohn’s disease or ulcerative colitis) •Microscopic colitis (lymphocytic colitis, collagenous colitis), or celiac sprue •Laxative abuse (in the clinical judgement of the investigator/subinvestigator) or melanosis coli. •Gastroparesis •GI malignancy •Carcinoid syndrome •Amyloidosis •Chronic pancreatitis •Abdominal adhesions •Toxic megacolon •Acute proctitis •Fecal impaction •Symptomatic cholelithiasis 7.Has performed gastrointestinal surgery (except six months post-surgery appendectomy, cholecystectomy, benign polypectomy, fundoplication (not have gas bloat), and hiatal hernia repair; three months post-surgery herniorrhaphy without bowel resection) 8.Has a history of thrombophlebitis or hypercoagulable state. 9.Has been diagnosed with a psychiatric disorder that required hospitalization and/or involved a suicide attempt (however, if a subject has a history of severe psychiatric disorder other than above within the past two years, the subject may enter into the study if the symptom is controlled with a stable dose of medicine for at least six months prior to the screening visit) 10.Has a history of alcohol and/or drug abuse within the past two years. 11.Exhibits evidence of hepatic dysfunction (AST [GOP] or ALT [GPT] values >2.5 times the upper limit of normal or alkaline phosphatase or serum bilirubin values >2.0 times the upper limit of normal) 12.Exhibits evidence of renal impairment (a serum creatinine value >2.0 mg/dl) 13.Exhibits an abnormal serum thyroid-stimulating hormone (TSH) (TSH value exceeds the limit of normal at the clinical laboratory). 14.Has current evidence of, or has been treated for a malignancy within the past five years (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected). 15.Has used GR68755 tablets or has been participated in other clinical study of 5HT3 antagonists in IBS patients within three years prior to the screening visit. 16.Has been enrolled in other clinical study within four months prior to the screening visit. 17.Has used any prohibited concomitant medicine within seven days prior to the screening visit. However loperamin hydrochloride and butylscopolamine bromide may be taken until 24 hours before starting the screening period. 18.Has used a permitted concomitant medication within 30 days prior to the screening visit and adjusted the dose. 19.Is hypersensitive to 5-HT3 antagonists. 20.Is pregnant or breastfeeding. 21.Is not eligible to participate this study in the opinion of the investigator/subinvestigator.