A Phase 2a, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of BOS-589 in the Treatment of Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Boston Pharmaceuticals
- Enrollment
- 133
- Locations
- 51
- Primary Endpoint
- 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point)
Study Overview
Brief 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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •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.)
Arms & Interventions
High dose of BOS-589
Participants will receive a high dose of BOS-589 orally twice a day (BID).
Intervention: BOS-589 (Drug)
Low dose of BOS-589
Participants will receive a low dose of BOS-589 orally BID.
Intervention: BOS-589 (Drug)
Placebo
Participants will receive matching placebo orally BID.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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)(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)(Baseline; Day 29)
- AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589(Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose)
- Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline(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)(Baseline; Day 29)
- Time to Reach Cmax (Tmax) for BOS-589(Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose)
- Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589(Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose)
- 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)(Baseline; Day 29)
- Maximum Observed Plasma Concentration (Cmax) for BOS-589(Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose)