Study to Evaluate the Efficacy, Safety, and Tolerability of BOS-589 in the Treatment of Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)

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)

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 Overview

• Status: Completed
• Conditions: Diarrhea-predominant Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: BOS-589

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
    • Huntsville, Alabama, United States, 35801
      • Clinical Research Associates
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synexus Clinical Research US, Inc. - East Valley Family Physicians, PLC
    • Chandler, Arizona, United States, 85224
      • Synexus Clinical Research US, Inc. - Phoenix Southeast
    • Mesa, Arizona, United States, 85018
      • Synexus Clinical Research US, Inc. - Desert Clinical Research, LLC
    • Mesa, Arizona, United States, 85213
      • Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC
    • Peoria, Arizona, United States, 85381
      • Hope Research Institute LLC
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
    • Phoenix, Arizona, United States, 85050
      • Synexus Clinical Research US, Inc. - Tatum Highlands Medical Associates, PLLC
    • Phoenix, Arizona, United States, 85206
      • Hope Research Institute LLC
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Carlsbad, California, United States, 95821
      • Synexus Clinical Research US, Inc.
    • Garden Grove, California, United States, 92683
      • Paragon Rx Clinical, Inc.
    • La Mesa, California, United States, 91942
      • eStudySite
    • La Mesa, California, United States, 92008
      • Grossmont Center for Clinical Research
    • Sacramento, California, United States, 91942
      • Clinical Trials Research
    • San Diego, California, United States, 92114
      • Precision Research Institute
    • San Diego, California, United States, 92105
      • Research and Education Inc
    • Sherman Oaks, California, United States, 91403
      • Shahram Jacobs MD Inc
    • Thousand Oaks, California, United States, 92840
      • Millennium ClinicalTrials
    • Westminster, California, United States, 91360
      • Advanced Rx Clinical Research
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research LLC
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research-ClinEdge-PPDS
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research LLC - ERN-PPDS
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Jupiter, Florida, United States, 33458
      • Health Awareness INC
    • Miami, Florida, United States, 33135
      • Suncoast Research Group LLC - ERN-PPDS
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research, LLC
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials-ClinEdge-PPDS
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Synexus Clinical Research US, Inc. - Allaw
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials Inc
  • Michigan
    • Wyoming, Michigan, United States, 49519
      • West Michigan Clinical Research
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research - ClinEdge - PPDS
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials Inc - BTC - PPDS
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research, LLC
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh, LLC
  • Ohio
    • Akron, Ohio, United States, 44311
      • Synexus Clinical Research US, Inc.
    • Cincinnati, Ohio, United States, 45215
      • Hometown Urgent Care and Research
    • Columbus, Ohio, United States, 45424
      • Synexus Clinical Research US, Inc.
    • Dayton, Ohio, United States, 43212
      • Hometown Urgent Care and Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Founders Research Corporation
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Safe Harbor Clinical Research
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Synexus Clinical Research US, Inc.
    • Fort Mill, South Carolina, United States, 29707
      • Pledmont Research Partners LLC
    • Greer, South Carolina, United States, 29651
      • Synexus Clinical Research US, Inc.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37909
      • WR-Clinsearch, LLC
    • Knoxville, Tennessee, United States, 37421
      • New Phase Research & Development
  • Texas
    • Dallas, Texas, United States, 75219
      • L12 Clinical Research
    • Dallas, Texas, United States, 78209
      • Synexus Clinical Research US, Inc.
    • Houston, Texas, United States, 77074
      • Southwest Clinical Trials
    • San Antonio, Texas, United States, 75234
      • Quality Research Inc.
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Blue Ridge Medical Research
    • Richmond, Virginia, United States, 23235
      • Clinical Research Partners Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose of BOS-589; Participants will receive a high dose of BOS-589 orally twice a day (BID).	Drug: BOS-589; oral tablets
Experimental: Low dose of BOS-589; Participants will receive a low dose of BOS-589 orally BID.	Drug: BOS-589; oral tablets
Placebo Comparator: Placebo; Participants will receive matching placebo orally BID.	Drug: Placebo; oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point)	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.	Baseline; Day 29
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs	To evaluate the overall safety and tolerability of BOS-589 in the treatment of IBS-D during 4 weeks of treatment, relative to placebo.	Up to Day 43/end-of-study follow up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline; Day 29
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)	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.	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)	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.	Baseline; Day 29
Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline	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.	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)	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.	Baseline; Day 29
Maximum Observed Plasma Concentration (Cmax) for BOS-589	To evaluate the steady state pharmacokinetics (PK) of BOS-589.	Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
Time to Reach Cmax (Tmax) for BOS-589	To evaluate the steady state PK of 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	To evaluate the steady state PK of BOS-589.	Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589	To evaluate the steady state PK of BOS-589.	Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose

Collaborators and Investigators

• Sponsor: Boston Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Actual): May 6, 2020
• Study Completion (Actual): May 6, 2020

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; diarrhea; BOS-589
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea
• Other Study ID Numbers: BOS-589-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No