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 a fasting serum 7a-hydroxy-4-cholesten-3-one (7αC4) level ≥ 52.5 ng/mL or total fecal bile acid (BA) \> 2337 micromoles/48 hours (positive result) at screening or within 1 calendar year prior to screening.
* Participants without BAM must have a fasting serum 7αC4 level ≤ 47.1 ng/mL or total fecal BA \< 2200 micromoles/48 hours (negative result) at screening or within 1 calendar year prior to screening.
* Has 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.
Exclusion Criteria:
* Has 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.
* Has known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction. (Participants with a history of gallstones may be enrolled).
* Has a history of alcoholism, alcohol abuse or alcohol addiction, or drinks more than 3 alcoholic beverages per day.
* Has a history of pancreatitis; structural diseases of the pancreas, including known or suspected pancreatic duct obstruction.
* Has a 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.
* Has Celiac disease or a positive serological test for celiac disease.
* Has 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.
* Has known allergies or hypersensitivity to opioids.
