- Inclusion Criteria:

1. Are adult male and female subjects ≥ 18 years of age;

2. Have a body mass index between 18 and 40 kg/m2, inclusive at Screening;

3. Meet Rome IV Criteria for IBS-D by subject self-report of recurrent abdominal
pain that is associated with ≥ 2 of the following over the last ≥ 6 months, with
frequency of at least 1 day per week over the last 3 months (on average) before
enrollment:

1. Related to defecation;

2. Associated with a change in frequency of stool; and/or

3. Associated with a change in form (appearance of stool).

4. Based on Investigator interview of subject's symptoms over the last 3 months,
have ≥ 25% of bowel movements (BMs) with Bristol Stool Scale (BSS) types 6 or 7
(loose or watery stools) and < 25% of BMs with BSS Type 1 or 2 (lumpy or hard
stools) per the Rome IV Criteria for IBS-D;

5. In the opinion of the Investigator, are on a stable diet for ≥ 4 weeks prior to
Screening and are not planning to change lifestyle, exercise, and/or diet that
may impact symptoms of IBS-D during study participation;

6. Have a fecal calprotectin < 50 mcg/g at the Screening Visit or Visit 2;

7. Have a serum tTG-IgA (tissue transglutaminase immunoglobulin A) ≤ 3 U/mL at the
Screening Visit;

8. Have undergone a colonoscopy examination within the designated time interval
prior to randomization, if they meet any of the following criteria:

1. Average risk, based on US Preventive Services Task Force Recommendation
Statement for screening of colorectal cancer, with age ≥ 45 years
(colonoscopy within 10 years);

2. Personal history of completely removed adenomatous colorectal polyps
(colonoscopy within 5 years for polyps >1 cm, within 10 years for polyps <1
cm);

3. History of colorectal cancer or adenomatous polyps in a first-degree
relative before age 60 (colonoscopy within 5 years);

4. History of colorectal cancer or adenomatous polyps in ≥ 2 first-degree
relatives at any age, or family history of hereditary colorectal cancer or
polyposis (colonoscopy within 5 years); or

5. History of or active inflammatory bowel disease in first-degree relative
(colonoscopy any time).

- Exclusion Criteria:

1. Have a diagnosis or suspected diagnosis of IBS with a subtype of constipation,
IBS with mixed or alternating bowel habits, un-subtyped IBS, or functional
constipation by the Rome IV Criteria;

2. Have a history of or current inflammatory bowel disease (ie, Crohn's disease,
ulcerative colitis, indeterminate colitis), microscopic colitis, lymphocytic
colitis, celiac disease, non-celiac gluten sensitivity and non-compliant on a
gluten-free diet, untreated lactose intolerance, carcinoid syndrome, Lynch
syndrome, or familial polyposis;

Note: Lactose intolerance and non-celiac gluten sensitivity will not exclude a
subject from participation if the Investigator documents that the subject is
compliant on a special diet (lactose-free diet or gluten-free diet, respectively)
and/or for lactose intolerance is successfully treated with commercial lactase
supplement(s).

3. Have a known history of a pelvic floor disorder (unless successful treatment has
been documented by a normal balloon expulsion test), refractory constipation not
responsive to standard medical therapy, fecal impaction that required
hospitalization, cathartic colon, and/or active proctological condition;

4. Have a history of or current non-IBS chronic condition(s) with ongoing symptoms
associated with abdominal pain or GI discomfort (eg, gastroparesis, functional
dyspepsia, uncontrolled gastroesophageal reflux disease, polycystic kidney
disease, ovarian cysts, urological pain, or endometriosis);

5. Have a history of or current clinically significant arrhythmias as judged by the
Investigator, including ventricular tachycardia, ventricular fibrillation, and
Torsades de pointes. Subjects with any abnormal electrocardiogram (ECG) not
considered clinically significant by the Investigator are not necessarily
excluded;

6. Have current or a history of diverticulitis, heme positive stool, or unexplained
GI bleeding within 3 months prior to Screening

Note: Surgically repaired diverticulitis > 3 months prior to Screening is
permitted.

7. Have a history of surgical resection of the stomach, small, or large intestine;

8. Have had any major abdominal surgery within the 3 months prior to Screening;

Note: Permitted procedures are uncomplicated appendectomy, cholecystectomy, and
resection of benign polyps within the 3 months prior to Screening. Subjects who
had an appendectomy that was associated with any related complications or
sequelae are eligible if the procedure was performed at least 6 months prior to
Screening.

9. Have a history of intestinal obstruction, stricture, toxic megacolon, solitary
rectal ulcer syndrome, GI perforation, intra-abdominal or pelvic adhesions,
ischemic colitis, radiation proctitis, enteritis, colitis, or impaired intestinal
circulation (eg, aortoiliac disease);

10. Are currently undergoing or planning to initiate treatment with weight loss
medication during study participation or prior weight loss surgery (eg, gastric
bypass surgery, gastric banding);

11. Have a planned invasive elective surgery during the period of anticipated study
participation from the time of informed consent through the last study visit;

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/25/24. Questions regarding updates should be directed to the study team contact.