Clinical trial NCT03977155: Study to Evaluate the Efficacy, Safety, and Tolerability of BOS-589 in the Treatment of Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diarrhea-predominant Irritable Bowel Syndrome
Keywords: Irritable Bowel Syndrome
diarrhea
BOS-589
Lead sponsor: Boston Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-06-06
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.)

Primary outcomes:
measure: 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point)
timeFrame: Baseline; Day 29
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs
timeFrame: Up to Day 43/end-of-study follow up visit
Secondary outcomes:
measure: 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)
timeFrame: Baseline; Day 29
measure: 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)
timeFrame: Baseline; Day 29
measure: 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)
timeFrame: Baseline; Day 29
measure: Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline
timeFrame: Baseline; Day 29
measure: Change in the IBS Global Scale (IBS-GS) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point)
timeFrame: Baseline; Day 29
measure: Maximum Observed Plasma Concentration (Cmax) for BOS-589
timeFrame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
measure: Time to Reach Cmax (Tmax) for BOS-589
timeFrame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
measure: Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589
timeFrame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
measure: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589
timeFrame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Huntsville
country: United States
facility: Clinical Research Associates
state: Alabama
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. - East Valley Family Physicians, PLC
state: Arizona
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. - Phoenix Southeast
state: Arizona
city: Mesa
country: United States
facility: Synexus Clinical Research US, Inc. - Desert Clinical Research, LLC
state: Arizona
city: Mesa
country: United States
facility: Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC
state: Arizona
city: Peoria
country: United States
facility: Hope Research Institute LLC
state: Arizona
city: Phoenix
country: United States
facility: Elite Clinical Studies
state: Arizona
city: Phoenix
country: United States
facility: Synexus Clinical Research US, Inc. - Tatum Highlands Medical Associates, PLLC
state: Arizona
city: Phoenix
country: United States
facility: Hope Research Institute LLC
state: Arizona
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Carlsbad
country: United States
facility: Synexus Clinical Research US, Inc.
state: California
city: Garden Grove
country: United States
facility: Paragon Rx Clinical, Inc.
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: La Mesa
country: United States
facility: Grossmont Center For Clinical Research
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research
state: California
city: San Diego
country: United States
facility: Research and Education Inc
state: California
city: San Diego
country: United States
facility: Precision Research Institute
state: California
city: Sherman Oaks
country: United States
facility: Shahram Jacobs MD Inc
state: California
city: Thousand Oaks
country: United States
facility: Millennium ClinicalTrials
state: California
city: Westminster
country: United States
facility: Advanced Rx Clinical Research
state: California
city: Waterbury
country: United States
facility: Chase Medical Research LLC
state: Connecticut
city: Brandon
country: United States
facility: PAB Clinical Research-ClinEdge-PPDS
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research LLC - ERN-PPDS
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Jupiter
country: United States
facility: Health Awareness Inc
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group LLC - ERN-PPDS
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Medical Arts Pharmaceutical
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research, LLC
state: Florida
city: Boise
country: United States
facility: Northwest Clinical Trials-ClinEdge-PPDS
state: Idaho
city: Evansville
country: United States
facility: Synexus Clinical Research US, Inc. - Allaw
state: Indiana
city: Boston
country: United States
facility: Boston Clinical Trials Inc
state: Massachusetts
city: Wyoming
country: United States
facility: West Michigan Clinical Research
state: Michigan
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research - ClinEdge - PPDS
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials Inc - BTC - PPDS
state: New Mexico
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: High Point
country: United States
facility: Peters Medical Research, LLC
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh, LLC
state: North Carolina
city: Akron
country: United States
facility: Synexus Clinical Research US, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Columbus
country: United States
facility: Synexus Clinical Research US, Inc.
state: Ohio
city: Dayton
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Philadelphia
country: United States
facility: Founders Research Corporation
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: East Providence
country: United States
facility: Safe Harbor Clinical Research
state: Rhode Island
city: Anderson
country: United States
facility: Synexus Clinical Research US, Inc.
state: South Carolina
city: Fort Mill
country: United States
facility: Pledmont Research Partners LLC
state: South Carolina
city: Greer
country: United States
facility: Synexus Clinical Research US, Inc.
state: South Carolina
city: Chattanooga
country: United States
facility: WR-ClinSearch, LLC
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Dallas
country: United States
facility: L12 Clinical Research
state: Texas
city: Dallas
country: United States
facility: Synexus Clinical Research US, Inc.
state: Texas
city: Houston
country: United States
facility: Southwest Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: Quality Research Inc.
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners LLC
state: Virginia
Study officials:
References: