Patient description: The patient is a 57-year-old man with abdominal pain and vomiting. The pain started gradually about 20 hours ago in the epigastric and periumbilical regions, radiating to his back. He drinks around 60 units of alcohol per week and smokes 22 cigarettes per day. He is healthy with no history of allergies or using any medications. His family history is positive for type 2 diabetes (his father and sister). He lives alone and has no children. The abdomen is tender and soft. His bowel sounds are normal. His heart rate is 115/min and blood pressure 110/75 mmHg. The lab results are remarkable for leukocytosis (19.5), urea of 8.5, high CRP (145), high amylase (1200) and Glc level of 15. Cross-sectional imaging was negative for obstructive pancreatitis.

Clinical trial eligibility criteria: eligible ages (years): 18.0-80.0,  Irritable Bowel Syndrome With Diarrhea Male and female patients age≥18 years (with a minimum of 35% males in the study) 2. Patient meets FDA guidance and Rome III for IBS-D: a. Recurrent abdominal pain or discomfort over ≥6 months, with frequency ≥3 days/month in the last 3 months associated with ≥2 of the following: i. Improvement with defecation ii. Onset associated with a change in frequency of stool iii. Onset associated with a change in the form of stool b. Loose or watery stools (Bristol stool form scale 6 or 7) ≥2 days per week 3. Average worst daily pain intensity ≥3.0 for each of the two baseline weeks 4. Major laboratory parameters within the following limits (no worse than grade 1 abnormalities per NCI-CTCAE v4): a. Adequate hematologic function, as demonstrated by i. Hemoglobin ≥10 g/dL ii. Absolute neutrophil count (ANC) 1.5-10 x 10^9/L iii. Platelets ≥100 x 10^9/L b. Adequate liver and renal function as demonstrated by i. Aspartate transaminase (AST) and Alanine transaminase (ALT) each ≤ 3.0 x upper limit of normal (ULN) ii. Total bilirubin ≤1.5 x ULN iii. Creatinine ≤1.5 X ULN c. Euthyroid based on thyroid-stimulating hormone (TSH) and free T4 levels 5. Patients on thyroid hormone replacement must be on a stable dose for at least one month prior to study entry. 6. C-reactive protein ≤2 x ULN for lab 7. Patients of childbearing potential and male patients with partners of childbearing potential must utilize effective contraceptive measures Women of childbearing potential are women who have menstruated in the past 12 months, with the exception of women who have undergone surgical sterilization 8. All patients must sign informed consent  Evidence of other cause for bowel disease: 1. Relevant abnormalities seen on colonoscopy if previously performed or if required per this protocol. These but are not limited to Crohn's disease, ulcerative colitis, diverticulitis, ischemic colitis, microscopic colitis. 2. History of and/or positive serologic test for celiac disease 3. Known or suspected lactose intolerance. 2. History of abdominal surgery other than appendectomy or cholecystectomy at any time 3. Any elective major surgery (of any organ) planned for the period of the study, including follow-up 4. History of organic abnormalities of the GI tract including but not limited to intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, adhesions or impaired intestinal circulation (e.g., aortoiliac disease) 5. Current or previous diagnosis of neoplasia (except non-GI neoplasia in complete remission ≥5 years, squamous and basal cell carcinomas). With approval of the medical monitor patients with curatively treated neoplasm in complete remission <5 years may be entered in the study. 6. Patients with a history of positive tests for ova or parasites or Clostridium difficile must be retested during the screening period and tests for the relevant agents must be negative 7. Use of any 5-HT3 antagonist (5hydroxytryptamine receptor antagonists) within 4 weeks of the start of baseline data collection. 8. Use of rifaximin within 4 months of the start of baseline data collection. 9. Use of any other agent specific for IBS (such as alosetron or eluxadoline) or for symptomatic treatment of IBS (such as antispasmotics and antidiarrheals other than loperamide) within 2 weeks of the start of baseline data collection. 10. Uses of any investigational agent for any indication within 4 weeks of the start of baseline data collection. 11. Congestive heart failure, bradyarrhythmia (baseline pulse<55/min), known long QT syndrome 12. Patients who have Corrected QT interval (QTc) prolongation>450 msec noted on screening ECG, or who are taking medication known to cause QT prolongation Note: For current list of medications known to cause QT prolongation see: https://www.crediblemeds.org/healthcare-providers/drug-list/ There are several risk categories. Use the list showing those drugs known to cause torsade de pointes (TdP) 13. Hypersensitivity or other known intolerance to ondansetron or other 5-HT3 antagonists 14. Patient has taken apomorphine within 24 hours of screening 15. Pregnant or lactating 16. Patients with other major illnesses, either physical or psychiatric, or social situations which may interfere with participation in the study or interpretation of results 17. Patients with severe hepatic impairment, defined as Child-Pugh score ≥10 at baseline