Inclusion Criteria:

1. Are adult male and female subjects ≥ 18 years of age;
2. Have a body mass index between 18 and 45 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) Type 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 ≤ 100 mcg/g at the Screening Visit or Visit 2; Note: A single normal test result is adequate for study eligibility. If subjects are rescreened within 6 months, there is no need for repeat fecal calprotectin sample collection and testing. However, subjects who fail screening due to a fecal calprotectin level \>100 mcg/g are not eligible for re-screening. Note: Repeat Fecal calprotectin may be considered with prior Sponsor approval.
7. Have a serum tTG-IgA (tissue transglutaminase immunoglobulin A) ≤ 4.99 FLU (fluorescent light units) 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. Note: A negative Cologuard® test result is an acceptable alternative to colonoscopy for subjects ≥ 45 years and at average risk for colon cancer.

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 or negative test results on Cologuard within 3 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); or
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).

Exclusion Criteria:

1. Have a diagnosis or suspected diagnosis of non-diarrhea predominant IBS (eg, 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. Non-infectious chronic lower gastrointestinal conditions including a history of or current inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis, indeterminate colitis), recurrent diverticulosis, 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, intestinal obstruction, stricture, toxic megacolon, solitary rectal ulcer syndrome, GI perforation, intra-abdominal or pelvic adhesions, ischemic colitis, radiation proctitis, chronic enteritis, non-infectious colitis, or impaired intestinal circulation (eg, aortoiliac disease);

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. Infectious lower gastrointestinal conditions requiring antibiotics or microbiome therapy; any microbiologically documented acute lower gastrointestinal colitis or enteritis requiring antibiotic treatment including successfully treated Clostridioides difficile colitis within 3 months prior to Screening, or a history of recurrent C. difficile colitis at any time in the past;
4. Have a known family history of inflammatory bowel disease in at least 1 first-degree relative;
5. Have a known history of a pelvic floor disorder associated with constipation (unless successful treatment has been documented by a normal balloon expulsion test or anorectal manometry), refractory constipation not responsive to standard medical therapy, fecal impaction that required hospitalization, cathartic colon, and/or active proctological condition;
6. 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);
7. 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 excluded;
8. 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.
9. Have a history of surgical resection of the stomach, small, or large intestine;
10. 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.
11. 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);
12. 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 08/07/2024. Questions regarding updates should be directed to the study team contact.