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

Diarrhea-predominant Irritable Bowel Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03977155
• Other study ID #: BOS-589-201
• Status: Completed
• Phase: Phase 2
• Start date: June 4, 2019
• Est. completion date: May 6, 2020

Study information

• Verified date: June 2021
• Source: Boston Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: May 6, 2020
• Est. primary completion date: May 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Diarrhea
• Diarrhea-predominant Irritable Bowel Syndrome
• Irritable Bowel Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Synexus Clinical Research US, Inc.	Akron	Ohio
United States	Albuquerque Clinical Trials Inc - BTC - PPDS	Albuquerque	New Mexico
United States	Synexus Clinical Research US, Inc.	Anderson	South Carolina
United States	Pinnacle Research Group	Anniston	Alabama
United States	Northwest Clinical Trials-ClinEdge-PPDS	Boise	Idaho
United States	Boston Clinical Trials Inc	Boston	Massachusetts
United States	PAB Clinical Research-ClinEdge-PPDS	Brandon	Florida
United States	NY Scientific	Brooklyn	New York
United States	Synexus Clinical Research US, Inc.	Carlsbad	California
United States	Synexus Clinical Research US, Inc. - East Valley Family Physicians, PLC	Chandler	Arizona
United States	Synexus Clinical Research US, Inc. - Phoenix Southeast	Chandler	Arizona
United States	WR-ClinSearch, LLC	Chattanooga	Tennessee
United States	Hometown Urgent Care and Research	Cincinnati	Ohio
United States	Synexus Clinical Research US, Inc.	Columbus	Ohio
United States	L12 Clinical Research	Dallas	Texas
United States	Synexus Clinical Research US, Inc.	Dallas	Texas
United States	Hometown Urgent Care and Research	Dayton	Ohio
United States	Safe Harbor Clinical Research	East Providence	Rhode Island
United States	Synexus Clinical Research US, Inc. - Allaw	Evansville	Indiana
United States	Pledmont Research Partners LLC	Fort Mill	South Carolina
United States	Paragon Rx Clinical, Inc.	Garden Grove	California
United States	Synexus Clinical Research US, Inc.	Greer	South Carolina
United States	Peters Medical Research, LLC	High Point	North Carolina
United States	Southwest Clinical Trials	Houston	Texas
United States	Clinical Research Associates	Huntsville	Alabama
United States	Nature Coast Clinical Research LLC - ERN-PPDS	Inverness	Florida
United States	Mayo Clinic	Jacksonville	Florida
United States	Health Awareness Inc	Jupiter	Florida
United States	New Phase Research & Development	Knoxville	Tennessee
United States	eStudySite	La Mesa	California
United States	Grossmont Center For Clinical Research	La Mesa	California
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC	Mesa	Arizona
United States	Synexus Clinical Research US, Inc. - Desert Clinical Research, LLC	Mesa	Arizona
United States	Suncoast Research Group LLC - ERN-PPDS	Miami	Florida
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Advanced Research Institute	Ogden	Utah
United States	Quality Clinical Research - ClinEdge - PPDS	Omaha	Nebraska
United States	Ormond Medical Arts Pharmaceutical	Ormond Beach	Florida
United States	Hope Research Institute LLC	Peoria	Arizona
United States	Founders Research Corporation	Philadelphia	Pennsylvania
United States	Elite Clinical Studies	Phoenix	Arizona
United States	Hope Research Institute LLC	Phoenix	Arizona
United States	Synexus Clinical Research US, Inc. - Tatum Highlands Medical Associates, PLLC	Phoenix	Arizona
United States	PMG Research of Raleigh, LLC	Raleigh	North Carolina
United States	Clinical Research Partners LLC	Richmond	Virginia
United States	Clinical Trials Research	Sacramento	California
United States	Sundance Clinical Research	Saint Louis	Missouri
United States	Quality Research Inc.	San Antonio	Texas
United States	Precision Research Institute	San Diego	California
United States	Research and Education Inc	San Diego	California
United States	Shahram Jacobs MD Inc	Sherman Oaks	California
United States	Precision Clinical Research, LLC	Sunrise	Florida
United States	Millennium ClinicalTrials	Thousand Oaks	California
United States	Preferred Primary Care Physicians	Uniontown	Pennsylvania
United States	Chase Medical Research LLC	Waterbury	Connecticut
United States	Advanced Rx Clinical Research	Westminster	California
United States	West Michigan Clinical Research	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Boston Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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