Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of BEKINDA (Ondansetron 12 mg Bimodal Release Tablets) for Diarrhea Predominant Irritable Bowel Syndrome (IBS-D)

1. Evidence of other cause for bowel disease:

1. Relevant abnormalities seen on colonoscopy if previously performed or if required per this protocol. These include 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

What this study is about