Diarrhea-predominant Irritable Bowel Syndrome
Conditions
Keywords
Irritable Bowel Syndrome, diarrhea, BOS-589
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).
Interventions
DRUGBOS-589
oral tablets
DRUGPlacebo
oral tablets
Sponsors
Boston Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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 ≥ 2.0. * 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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline | Baseline; Day 29 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | To evaluate the steady state PK of BOS-589. |
| 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 | To evaluate the steady state PK of BOS-589. |
| 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 | To evaluate the steady state PK of BOS-589. |
| 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 | To evaluate the steady state pharmacokinetics (PK) of BOS-589. |
| 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 | 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 47 study centers in the United States.
Pre-assignment details
During the pretreatment phase, participants were evaluated for up to 5 weeks to assess eligibility. The pretreatment phase consisted of initial screening assessments and a run in period.
Participants by arm
| Arm | Count |
|---|---|
| High Dose of BOS-589 Randomized participants received a high dose of BOS-589 tablets orally BID. | 43 |
| Low Dose of BOS-589 Randomized participants received a low dose of BOS-589 tablets orally BID. | 48 |
| Placebo Randomized participants received matching placebo tablets orally BID. | 42 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Participant was unable to come in for the Visit | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | High Dose of BOS-589 | Low Dose of BOS-589 | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 41.0 Years STANDARD_DEVIATION 13.15 | 39.9 Years STANDARD_DEVIATION 13.26 | 40.0 Years STANDARD_DEVIATION 12.84 | 40.3 Years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 7 Participants | 7 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 41 Participants | 35 Participants | 113 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 6 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 8 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 33 Participants | 34 Participants | 103 Participants |
| Sex: Female, Male Female | 30 Participants | 31 Participants | 26 Participants | 87 Participants |
| Sex: Female, Male Male | 13 Participants | 17 Participants | 16 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 48 | 0 / 42 |
| other Total, other adverse events | 23 / 43 | 23 / 48 | 15 / 42 |
| serious Total, serious adverse events | 0 / 43 | 0 / 48 | 0 / 42 |
Outcome results
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.
Time frame: Baseline; Day 29
Population: The Intent to Treat (ITT) Analysis Set included all randomized participants. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose of BOS-589 | 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -1.64 Score on a scale | Standard Deviation 1.684 |
| Low Dose of BOS-589 | 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -2.30 Score on a scale | Standard Deviation 1.933 |
| BOS-589: Active Treatment | 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -2.00 Score on a scale | Standard Deviation 1.842 |
| Placebo | 24-hour Worst Abdominal Pain Scores (WAP) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -1.69 Score on a scale | Standard Deviation 1.783 |
Comparison: Statistical Analysis 1p-value: 0.377695% CI: [-1, 0.38]t test
Comparison: Statistical Analysis 295% CI: [-0.73, 0.82]
Comparison: Statistical Analysis 395% CI: [-1.41, 0.19]
Comparison: Statistical Analysis 495% CI: [-0.13, 1.44]
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.
Time frame: Up to Day 43/end-of-study follow up visit
Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Moderate or Severe TEAE | 10 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE with Outcome of Death | 0 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Moderate or Severe TEAE Related to Study Drug | 3 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Leading to Withdrawal from the Study | 3 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Related to Study Drug | 8 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-Emergent SAE | 0 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-Emergent SAE Related to Study Drug | 0 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-emergent adverse event (TEAE) | 23 Participants |
| High Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Causing Discontinuation of Study Drug | 3 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Related to Study Drug | 5 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Causing Discontinuation of Study Drug | 0 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-emergent adverse event (TEAE) | 23 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Leading to Withdrawal from the Study | 0 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE with Outcome of Death | 0 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Moderate or Severe TEAE | 10 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-Emergent SAE | 0 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Moderate or Severe TEAE Related to Study Drug | 3 Participants |
| Low Dose of BOS-589 | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-Emergent SAE Related to Study Drug | 0 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE with Outcome of Death | 0 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-Emergent SAE | 0 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-emergent adverse event (TEAE) | 15 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Related to Study Drug | 4 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Moderate or Severe TEAE | 6 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Moderate or Severe TEAE Related to Study Drug | 1 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any Treatment-Emergent SAE Related to Study Drug | 0 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Causing Discontinuation of Study Drug | 0 Participants |
| BOS-589: Active Treatment | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Because of AEs, and Any Treatment-related Severe AEs | Any TEAE Leading to Withdrawal from the Study | 0 Participants |
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.
Time frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
Population: The PK population included all participants who took any amount of BOS-589 and had sufficient concentration time data to report at least a maximum concentration (Cmax). Here, number analyzed in each row signifies only the participants with available data that were analyzed for that day.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose of BOS-589 | Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589 | Day 1 | 4250 h*pg/mL | Geometric Coefficient of Variation 90.5 |
| High Dose of BOS-589 | Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589 | Day 15 | 6080 h*pg/mL | Geometric Coefficient of Variation 85.4 |
| High Dose of BOS-589 | Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589 | Day 22 | 2210 h*pg/mL | Geometric Coefficient of Variation 85.9 |
| Low Dose of BOS-589 | Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589 | Day 1 | 2460 h*pg/mL | Geometric Coefficient of Variation 65.3 |
| Low Dose of BOS-589 | Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589 | Day 15 | 3090 h*pg/mL | Geometric Coefficient of Variation 91.5 |
| Low Dose of BOS-589 | Area Under the Concentration-versus-time Curve (AUC) From Time Zero to 4 Hours Post Dose (AUC0-4) for BOS-589 | Day 22 | 7360 h*pg/mL | Geometric Coefficient of Variation 38.9 |
Secondary
AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589
To evaluate the steady state PK of BOS-589.
Time frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
Population: The PK population included all participants who took any amount of BOS-589 and had sufficient concentration time data to report at least a maximum concentration (Cmax). Here, number analyzed in each row signifies only the participants with available data that were analyzed for that day.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose of BOS-589 | AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589 | Day 1 | 4330 h*pg/mL | Geometric Coefficient of Variation 90.3 |
| High Dose of BOS-589 | AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589 | Day 15 | 6080 h*pg/mL | Geometric Coefficient of Variation 85.4 |
| High Dose of BOS-589 | AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589 | Day 22 | 2480 h*pg/mL | Geometric Coefficient of Variation 78.5 |
| Low Dose of BOS-589 | AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589 | Day 1 | 2470 h*pg/mL | Geometric Coefficient of Variation 63.7 |
| Low Dose of BOS-589 | AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589 | Day 15 | 3220 h*pg/mL | Geometric Coefficient of Variation 96.9 |
| Low Dose of BOS-589 | AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589 | Day 22 | 4640 h*pg/mL | Geometric Coefficient of Variation 149 |
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.
Time frame: Baseline; Day 29
Population: The ITT Analysis Set included all randomized participants. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose of BOS-589 | 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) | -1.11 Score on a scale | Standard Deviation 1.179 |
| Low Dose of BOS-589 | 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) | -0.97 Score on a scale | Standard Deviation 1.087 |
| BOS-589: Active Treatment | 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) | -1.04 Score on a scale | Standard Deviation 1.125 |
| Placebo | 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) | -1.01 Score on a scale | Standard Deviation 1.034 |
Comparison: Statistical Analysis 1p-value: 0.88495% CI: [-0.45, 0.39]t test
Comparison: Statistical Analysis 295% CI: [-0.6, 0.39]
Comparison: Statistical Analysis 395% CI: [-0.43, 0.49]
Comparison: Statistical Analysis 495% CI: [-0.63, 0.36]
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.
Time frame: Baseline; Day 29
Population: The ITT Analysis Set included all randomized participants. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose of BOS-589 | 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) | -1.13 Score on a scale | Standard Deviation 1.167 |
| Low Dose of BOS-589 | 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) | -1.06 Score on a scale | Standard Deviation 1.132 |
| BOS-589: Active Treatment | 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) | -1.09 Score on a scale | Standard Deviation 1.142 |
| Placebo | 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) | -0.93 Score on a scale | Standard Deviation 0.926 |
Comparison: Statistical Analysis 1p-value: 0.472595% CI: [-0.62, 0.29]t test
Comparison: Statistical Analysis 295% CI: [-0.71, 0.31]
Comparison: Statistical Analysis 395% CI: [-0.62, 0.37]
Comparison: Statistical Analysis 495% CI: [-0.6, 0.45]
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.
Time frame: Baseline; Day 29
Population: The ITT Analysis Set included all randomized participants. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose of BOS-589 | 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) | -0.69 Number of spontaneous bowel movements | Standard Deviation 1.19 |
| Low Dose of BOS-589 | 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) | -0.74 Number of spontaneous bowel movements | Standard Deviation 0.944 |
| BOS-589: Active Treatment | 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) | -0.71 Number of spontaneous bowel movements | Standard Deviation 1.057 |
| Placebo | 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) | -0.83 Number of spontaneous bowel movements | Standard Deviation 1.006 |
Comparison: Statistical Analysis 1p-value: 0.569395% CI: [-0.28, 0.51]t test
Comparison: Statistical Analysis 295% CI: [-0.35, 0.63]
Comparison: Statistical Analysis 395% CI: [-0.33, 0.51]
Comparison: Statistical Analysis 495% CI: [-0.41, 0.51]
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.
Time frame: Baseline; Day 29
Population: The ITT Analysis Set included all randomized participants. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose of BOS-589 | Change in the IBS Global Scale (IBS-GS) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -0.56 Score on a scale | Standard Deviation 0.629 |
| Low Dose of BOS-589 | Change in the IBS Global Scale (IBS-GS) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -0.89 Score on a scale | Standard Deviation 0.815 |
| BOS-589: Active Treatment | Change in the IBS Global Scale (IBS-GS) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -0.74 Score on a scale | Standard Deviation 0.75 |
| Placebo | Change in the IBS Global Scale (IBS-GS) at Day 29 Compared to Baseline (Averaged Over the Week Prior to Each Respective Time Point) | -0.57 Score on a scale | Standard Deviation 0.626 |
Comparison: Statistical Analysis 1p-value: 0.214995% CI: [-0.44, 0.1]t test
Comparison: Statistical Analysis 295% CI: [-0.27, 0.29]
Comparison: Statistical Analysis 395% CI: [-0.64, -0.01]
Comparison: Statistical Analysis 495% CI: [0.02, 0.65]
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.
Time frame: Baseline; Day 29
Population: The ITT Analysis Set included all randomized participants. Here, overall number of participants analyzed signifies only the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose of BOS-589 | Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline | -89.3 Score on a scale | Standard Deviation 116.65 |
| Low Dose of BOS-589 | Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline | -146.8 Score on a scale | Standard Deviation 113.06 |
| BOS-589: Active Treatment | Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline | -121.0 Score on a scale | Standard Deviation 117.38 |
| Placebo | Changes in the Irritable Bowel Syndrome-Severity Score (IBS-SS) at Day 29 Compared to Baseline | -113.3 Score on a scale | Standard Deviation 108.51 |
Comparison: Statistical Analysis 1p-value: 0.760395% CI: [-57.76, 42.33]t test
Comparison: Statistical Analysis 295% CI: [-34.22, 82.22]
Comparison: Statistical Analysis 395% CI: [-87.91, 21.07]
Comparison: Statistical Analysis 495% CI: [1.16, 113.69]
Secondary
Maximum Observed Plasma Concentration (Cmax) for BOS-589
To evaluate the steady state pharmacokinetics (PK) of BOS-589.
Time frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
Population: The PK population included all participants who took any amount of BOS-589 and had sufficient concentration time data to report at least a maximum concentration (Cmax). Here, number analyzed in each row signifies only the participants with available data that were analyzed for that day.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| High Dose of BOS-589 | Maximum Observed Plasma Concentration (Cmax) for BOS-589 | Day 1 | 1840 pg/mL | Geometric Coefficient of Variation 90.4 |
| High Dose of BOS-589 | Maximum Observed Plasma Concentration (Cmax) for BOS-589 | Day 15 | 2050 pg/mL | Geometric Coefficient of Variation 109 |
| High Dose of BOS-589 | Maximum Observed Plasma Concentration (Cmax) for BOS-589 | Day 22 | 984 pg/mL | Geometric Coefficient of Variation 105 |
| Low Dose of BOS-589 | Maximum Observed Plasma Concentration (Cmax) for BOS-589 | Day 1 | 999 pg/mL | Geometric Coefficient of Variation 72 |
| Low Dose of BOS-589 | Maximum Observed Plasma Concentration (Cmax) for BOS-589 | Day 15 | 1280 pg/mL | Geometric Coefficient of Variation 91.2 |
| Low Dose of BOS-589 | Maximum Observed Plasma Concentration (Cmax) for BOS-589 | Day 22 | 1620 pg/mL | Geometric Coefficient of Variation 117 |
Secondary
Time to Reach Cmax (Tmax) for BOS-589
To evaluate the steady state PK of BOS-589.
Time frame: Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose
Population: The PK population included all participants who took any amount of BOS-589 and had sufficient concentration time data to report at least a maximum concentration (Cmax). Here, number analyzed in each row signifies only the participants with available data that were analyzed for that day.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| High Dose of BOS-589 | Time to Reach Cmax (Tmax) for BOS-589 | Day 1 | 1.02 Hour |
| High Dose of BOS-589 | Time to Reach Cmax (Tmax) for BOS-589 | Day 15 | 1.44 Hour |
| High Dose of BOS-589 | Time to Reach Cmax (Tmax) for BOS-589 | Day 22 | 1.00 Hour |
| Low Dose of BOS-589 | Time to Reach Cmax (Tmax) for BOS-589 | Day 1 | 1.21 Hour |
| Low Dose of BOS-589 | Time to Reach Cmax (Tmax) for BOS-589 | Day 15 | 1.05 Hour |
| Low Dose of BOS-589 | Time to Reach Cmax (Tmax) for BOS-589 | Day 22 | 1.92 Hour |