• 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
  To evaluate in participants with diarrhea-predominant irritable bowel syndrome (IBS-D) the abdominal pain response to BOS-589 after 4 weeks of treatment, relative to placebo. Throughout the 4 weeks of the double blind treatment phase, participants were asked to rate their WAP in the past 24 hours. The participant-reported WAP in the past 24 hours was recorded on a 0 to 10 scale, where 0 corresponded to no pain and 10 corresponded to worst imaginable pain. Higher scores indicated worse outcome.
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs [ Time Frame: Up to Day 43/end-of-study follow up visit ]
  To evaluate the overall safety and tolerability of BOS-589 in the treatment of IBS-D during 4 weeks of treatment, relative to placebo.

• 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
• Number of participants with any adverse event and any serious adverse event [ Time Frame: up to 10 weeks ]
• Number of participants who discontinued the study because of an adverse event [ Time Frame: up to 10 weeks ]
• Number of participants with any treatment-related severe adverse event [ Time Frame: up to 10 weeks ]

• Change in Stool Consistency, Measured by the Daily Bristol Stool Form Score (BSFS) Most Representative Stool Consistency Scores at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
  To evaluate the treatment effect of BOS-589 on defecation after 4 weeks, relative to placebo. Participants were asked to record daily stool consistency according to the BSFS most representative of the past 24 hours. The participant-reported BSFS consistency score was based on a 1 to 7 scale where 1 corresponded to a hard stool and 7 corresponded to watery diarrhea. Higher scores indicated worse outcome.
• Change in Stool Consistency, Measured by the Daily BSFS Worst (Loosest) Stool Consistency Scores at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
  To evaluate the treatment effect of BOS-589 on defecation after 4 weeks, relative to placebo. Participants were asked to record daily stool consistency according to the BSFS worst stool consistency (defined as the loosest stool with the highest BSFS score) in the past 24 hours. The participant-reported BSFS consistency score was based on a 1 to 7 scale where 1 corresponded to a hard stool and 7 corresponded to watery diarrhea. Higher scores indicated worse outcome.
• Change in Stool Frequency, Measured by the Total Number of Spontaneous Bowel Movements in 24 Hours at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
  To evaluate the treatment effect of BOS-589 on defecation after 4 weeks, relative to placebo. Participants were asked to record stool frequency based on the total number of spontaneous bowel movements in the past 24 hours.
• Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline [ Time Frame: Baseline; Day 29 ]
  To evaluate the treatment effect of BOS-589 on IBS-related signs and symptoms. Participants were asked to complete 5 questions regarding the severity of their IBS. Each of the 5 questions generated a maximum score of 100, leading to a total possible IBS-SS of 500. The IBS-SS scale ranges from 0 to 500. A higher score indicated greater severity.
• Change in the IBS Global Scale (IBS-GS) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
  To evaluate the treatment effect of BOS-589 on IBS related signs and symptoms. Participants were asked to record daily their overall diarrhea-predominant Irritable Bowel Syndrome (IBS-D) global symptoms in the prior 24 hours. The participant-reported daily IBS-GS was based on a 0 to 4 scale where: 0 corresponded to no symptoms; 1 corresponded to mild symptoms; 2 corresponded to moderate symptoms; 3 corresponded to severe symptoms; and 4 corresponded to very severe symptoms. Higher scores indicated severe symptoms.
• Maximum Observed Plasma Concentration (Cmax) for BOS-589 [ Time Frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose ]
  To evaluate the steady state pharmacokinetics (PK) of BOS-589.
• Time to Reach Cmax (Tmax) for BOS-589 [ Time Frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose ]
  To evaluate the steady state PK of BOS-589.
• Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589 [ Time Frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose ]
  To evaluate the steady state PK of BOS-589.
• AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589 [ Time Frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose ]
  To evaluate the steady state PK of BOS-589.

• Change in stool consistency, measured by the daily Bristol Stool Form Score (BSFS) at Day 29 compared to baseline (averaged over the week prior to each respective time point) [ Time Frame: Baseline; Day 29 ]
• Change in Stool Frequency, Measured by the Total Number of Spontaneous Bowel Movements in 24 Hours at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
• Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline [ Time Frame: Baseline; Day 29 ]
• Change in the IBS Global Scale (IBS-GS) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) [ Time Frame: Baseline; Day 29 ]
• Maximum observed plasma concentration (Cmax) [ Time Frame: predose and 0.5, 1, 2, and 4 hours postdose on Days 1 and 15 (samples should be collected on Day 22 if they cannot be collected on Day 15); predose on Days 8, 22, and 29 ]
• Time to Cmax (Tmax) [ Time Frame: predose and 0.5, 1, 2, and 4 hours postdose on Days 1 and 15 (samples should be collected on Day 22 if they cannot be collected on Day 15); predose on Days 8, 22, and 29 ]
• Minimum plasma concentration (Cmin) [ Time Frame: predose and 0.5, 1, 2, and 4 hours postdose on Days 1 and 15 (samples should be collected on Day 22 if they cannot be collected on Day 15); predose on Days 8, 22, and 29 ]
• Area under the concentration versus time curve (AUC) from time zero to 4 hours post dose (AUC0-4) [ Time Frame: predose and 0.5, 1, 2, and 4 hours postdose on Days 1 and 15 (samples should be collected on Day 22 if they cannot be collected on Day 15); predose on Days 8, 22, and 29 ]
• AUC from time zero to the last quantifiable concentration (AUC0-t) [ Time Frame: predose and 0.5, 1, 2, and 4 hours postdose on Days 1 and 15 (samples should be collected on Day 22 if they cannot be collected on Day 15); predose on Days 8, 22, and 29 ]

• Drug: BOS-589
  oral tablets
• Drug: Placebo
  oral tablets

• Experimental: High dose of BOS-589
  Participants will receive a high dose of BOS-589 orally twice a day (BID).
  Intervention: Drug: BOS-589
• Experimental: Low dose of BOS-589
  Participants will receive a low dose of BOS-589 orally BID.
  Intervention: Drug: BOS-589
• Placebo Comparator: Placebo
  Participants will receive matching placebo orally BID.
  Intervention: Drug: Placebo

Inclusion Criteria:

• Participant meets the diagnosis of diarrhea-predominant IBS (IBS-D) subtype based on Rome IV diagnostic criteria within 3 months prior to randomization. On days when the participant experiences IBS symptoms

  • At least 25% of stools are loose or watery; and
  • Fewer than 25% of stools are hard.

• Recurrent abdominal pain occurring, on average, at least 1 day per week and associated with 2 or more of the following:

  • Related to defecation;
  • Associated with a change in frequency of bowel movements;
  • Associated with a change in form (appearance) of stool.

• Over the week prior to randomization, the participant has

  • An average of worst abdominal pain (WAP) scores in the prior 24 hours of 4.0 to 8.0 on a 0 to 10 numerical rating scale;
  • An average daily Bristol Stool Form Scale (BSFS) score ≥ 5.0 (and at least 5 days with a BSFS score ≥ 5.0;
  • An average daily IBS-Global Scale (IBS-GS) score of ≥ 2.0.
• Participant must undergo or previously have undergone (a) an appropriate evaluation for their IBS symptoms, including an evaluation for organic/structural etiologies (if in the presence of alarm symptoms); and (b) age-appropriate screening for colorectal cancer, if applicable.
• Participant is negative for serum tissue transglutaminase immunoglobulin A antibody (tTG-IgA) plus has evidence of detectable serum IgA within the normal reference range.

Exclusion Criteria:

• At the time of screening, participant has a diagnosis of an IBS subtype other than IBS-D, based on Rome IV criteria.
• Participant has a history of inflammatory or immune-mediated gastrointestinal (GI) disorders including (but not limited to) inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis, microscopic colitis, and celiac disease).
• Participant has had an episode of diverticulitis within 3 months prior to Screening.
• Participant has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (e.g., aortoiliac occlusive disease).

• Participant has any of the following surgical history:

  • Cholecystectomy with any history of post-cholecystectomy biliary tract pain;
  • Any abdominal surgery within the 3 months prior to Screening;
  • Major gastric, esophageal, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed).
• Confirmed alanine aminotransferase (ALT) > 2 upper limit of normal (ULN)
• Confirmed total bilirubin > ULN, unless the participant has a documented history of Gilbert's syndrome
• Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or Human immunodeficiency virus (HIV)-1 or HIV-2 antibody positive
• Evidence of HCV infection based on a positive HCV antibody screen (Participants who have been successfully treated for HCV are eligible if an undetectable HCV viral load at least 6 months after completion of treatment can be demonstrated.)