Inclusion Criteria:

• Adult men or women aged 18 to 75 years inclusive with a diagnosis of IBS-D per Rome IV criteria.
• Participants with evidence of BAM must have at least one of the following at screening or within 1 calendar year prior to screening:
  • Fasting serum 7a-hydroxy-4-cholesten-3-at least one (7αC4) level ≥ 52.5 ng/mL;
  • Total fecal bile acid (BA) > 2337 micromoles/48 hours;
  • Primary bile acids (fecal CA and CDCA) > 10% in a 48-hour fecal collection;
  • Primary bile acids (fecal CA and CDCA)  ≥ 4% with total fecal bile acid  ≥ 1,000 micromoles/48 hours.
• Participants without BAM must have at least one of the following at screening or within 1 calendar year prior to screening:
  • Fasting serum 7a-hydroxy-4-cholesten-3-one (7αC4) level ≤ 47.1;
  • Fasting serum 7a-hydroxy-4-cholesten-3-one (7αC4) level  ≥ 47.1 but ≤ 52.5 ng/mL with fecal bile acids that are negative for bile acid malabsorption (i.e., do not meet criteria 2.03 based on fecal bile acids level);
  • Total fecal bile acids (BA) ≤  2337 micromoles/48 hours;
  • Primary bile acids (fecal CA and CDCA) < 10% in a 48-hour fecal collection;
  • Primary bile acids (fecal CA and CDCA) < 4% with total fecal bile acid < 1,000 micromoles/48 hours.
• An average daily Bristol Stool Form Scale (BSFS) score ≥ 5.0 or ≥ 25% of diary entry days with a BSFS score of 6 or 7 during the 14 days prior to Day 1.
• Women of childbearing potential must use hormonal or double barrier contraception or maintain a monogamous relationship with a vasectomized male partner from the date of informed consent until 24 hours after final dose of study drug.
• Completed the electronic diary (eDiary) on ≥ 10 of the 14 days prior to Day 1.
• Has not used loperamide rescue medication on > 3 of the 14 days prior to Day 1.

Key Exclusion Criteria:

• A diagnosis of IBS with a subtype of irritable bowel syndrome with constipation (IBS-C), mixed IBS, or unsubtyped IBS per Rome IV criteria.
• Does not have a gallbladder.
• Known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction. (Participants with a history of gallstones may be enrolled).
• History of alcoholism, alcohol abuse or alcohol addiction, or drinks more than 3 alcoholic beverages per day.
• History of pancreatitis; structural diseases of the pancreas, including known or suspected pancreatic duct obstruction.
• History of mild, moderate, or severe hepatic impairment according to Child-Pugh classification. History or current diagnosis of inflammatory or immune-mediated gastrointestinal (GI) disorders.
• Celiac disease or a positive serological test for celiac disease.
• Known lactose or fructose intolerance associated with diarrhea, abdominal pain or discomfort, that could confound assessments in the study.
• Women who are currently pregnant or nursing, or plan to become pregnant or nurse during the study.
• Known allergies or hypersensitivity to opioids.