Study to Evaluate the Efficacy, Safety, and Tolerability of BOS-589 in the Treatment of Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)
Condition: Diarrhea-predominant Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea
Intervention: BOS-589; Placebo
Intervention description: oral tablets; oral tablets
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 133.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Irritable Bowel Syndrome; diarrhea; BOS-589

Summary:

      This study is being conducted to evaluate in participants with diarrhea-predominant Irritable
      Bowel Syndrome (IBS-D) the abdominal pain response to BOS-589 after 4 weeks of treatment and
      to evaluate the overall safety and tolerability of BOS-589 in the treatment of IBS-D during 4
      weeks of treatment, relative to placebo (PBO).
    

Eligibility criteria:

        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.)