Study to Evaluate the Efficacy, Safety, and Tolerability... | NCT03977155

Label	Type	Description	Intervention Names
High dose of BOS-589	Experimental	Participants will receive a high dose of BOS-589 orally twice a day (BID).	Drug: BOS-589
Low dose of BOS-589	Experimental	Participants will receive a low dose of BOS-589 orally BID.	Drug: BOS-589
Placebo	Placebo Comparator	Participants will receive matching placebo orally BID.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
BOS-589	Drug	oral tablets	High dose of BOS-589 Low dose of BOS-589

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

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.)

Facility	Status	City	State	ZIP	Country	Contacts
Pinnacle Research Group		Anniston	Alabama	36207	United States
Clinical Research Associates

ID	Title	Description
FG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally twice a day (BID).
FG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 12, 2019	Apr 29, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Mean

Standard Deviation

Score on a scale

Baseline; Day 29

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
OG002	BOS-589: Active Treatment	High Dose of BOS-589: Randomized participants received a high dose of BOS-589 tablets orally BID. Low Dose of BOS-589: Randomized participants received a low dose of BOS-589 tablets orally BID. Data were pooled from the above mentioned doses for analysis.
OG003	Placebo	Randomized participants received matching placebo tablets orally BID.

Units	Counts
Participants	OG00039 OG00146 OG00285 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.64± 1.684 OG001-2.30± 1.933 OG002-2.00± 1.842 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG002 OG003	Statistical Analysis 1	t test	P-values were calculated from the independent two-sample t test with equal variance.	0.3776		Mean Difference (Net)	-0.31	Standard Error of the Mean	0.350	2-Sided	95	-1.00	0.38					Superiority	Individual BOS-589 dose levels versus placebo were only to be tested if pooled BOS-589 doses versus placebo was significant at p<0.05.

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.

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Posted

Number

Participants

Up to Day 43/end-of-study follow up visit

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
OG002	Placebo	Randomized participants received matching placebo tablets orally BID.

Units	Counts
Participants

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.

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.

Posted

Mean

Standard Deviation

Score on a scale

Baseline; Day 29

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
OG002	BOS-589: Active Treatment	High Dose of BOS-589: Randomized participants received a high dose of BOS-589 tablets orally BID. Low Dose of BOS-589: Randomized participants received a low dose of BOS-589 tablets orally BID. Data were pooled from the above mentioned doses for analysis.

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.

Posted

Mean

Standard Deviation

Score on a scale

Baseline; Day 29

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
OG002	BOS-589: Active Treatment	High Dose of BOS-589: Randomized participants received a high dose of BOS-589 tablets orally BID. Low Dose of BOS-589: Randomized participants received a low dose of BOS-589 tablets orally BID. Data were pooled from the above mentioned doses for analysis.

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.

Posted

Mean

Standard Deviation

Number of spontaneous bowel movements

Baseline; Day 29

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
OG002	BOS-589: Active Treatment	High Dose of BOS-589: Randomized participants received a high dose of BOS-589 tablets orally BID. Low Dose of BOS-589: Randomized participants received a low dose of BOS-589 tablets orally BID. Data were pooled from the above mentioned doses for analysis.

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.

Posted

Mean

Standard Deviation

Score on a scale

Baseline; Day 29

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
OG002	BOS-589: Active Treatment	High Dose of BOS-589: Randomized participants received a high dose of BOS-589 tablets orally BID. Low Dose of BOS-589: Randomized participants received a low dose of BOS-589 tablets orally BID. Data were pooled from the above mentioned doses for analysis.

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.

Posted

Mean

Standard Deviation

Score on a scale

Baseline; Day 29

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
OG002	BOS-589: Active Treatment	High Dose of BOS-589: Randomized participants received a high dose of BOS-589 tablets orally BID. Low Dose of BOS-589: Randomized participants received a low dose of BOS-589 tablets orally BID. Data were pooled from the above mentioned doses for analysis.

Secondary

Maximum Observed Plasma Concentration (Cmax) for BOS-589

To evaluate the steady state pharmacokinetics (PK) of BOS-589.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pg/mL

Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.

Units	Counts
Participants	OG000

Secondary

Time to Reach Cmax (Tmax) for BOS-589

To evaluate the steady state PK of BOS-589.

Posted

Median

Full Range

Hour

Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.

Units	Counts
Participants	OG000

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*pg/mL

Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.

Units	Counts
Participants	OG000

Secondary

AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) for BOS-589

To evaluate the steady state PK of BOS-589.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*pg/mL

Day 1, Day 15 and Day 22 at pre-dose and at 0.5, 1, 2, and 4 hours post-dose

ID	Title	Description
OG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
OG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0014 affected48 at risk EG0021 affected42 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0012 affected48 at risk EG0021 affected42 at risk
Urinary tract infection	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0012 affected48 at risk EG0020 affected42 at risk
Influenza	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0012 affected48 at risk EG0021 affected42 at risk
Gastroenteritis viral	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Atypical pneumonia	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Pneumonia	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Sinusitis	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Nausea	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0012 affected48 at risk EG0022 affected42 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0004 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Vomiting	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0012 affected48 at risk EG0020 affected42 at risk
Constipation	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0012 affected48 at risk EG0020 affected42 at risk
Flatulence	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Food poisoning	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0012 affected48 at risk EG0021 affected42 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Abdominal rigidity	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Aphthous ulcer	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Dry mouth	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Gastrointestinal sounds abnormal	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Toothache	Gastrointestinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Headache	Nervous system disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0014 affected48 at risk EG0024 affected42 at risk
Dizziness	Nervous system disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0011 affected48 at risk EG0022 affected42 at risk
Migraine	Nervous system disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Paraesthesia	Nervous system disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA, Version 22.0	Non-systematic Assessment	EG0002 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Post procedural contusion	Injury, poisoning and procedural complications	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Wound	Injury, poisoning and procedural complications	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Catheter site bruise	General disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Catheter site pain	General disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Fatigue	General disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Anxiety	Psychiatric disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Mental status changes	Psychiatric disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Tachycardia	Cardiac disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected48 at risk EG0020 affected42 at risk
Eye irritation	Eye disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
C-reactive protein increased	Investigations	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Red blood cell sedimentation rate increased	Investigations	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk
Pollakiuria	Renal and urinary disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0000 affected43 at risk EG0010 affected48 at risk EG0021 affected42 at risk
Hypertension	Vascular disorders	MedDRA, Version 22.0	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected48 at risk EG0020 affected42 at risk

ID	Term
D003109	Colonic Diseases, Functional
D003108	Colonic Diseases
D007410	Intestinal Diseases
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.
BG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.
BG002	Placebo	Randomized participants received matching placebo tablets orally BID.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	High Dose of BOS-589	Randomized participants received a high dose of BOS-589 tablets orally BID.	43	43	23	43
EG001	Low Dose of BOS-589	Randomized participants received a low dose of BOS-589 tablets orally BID.	48	48	23	48
EG002	Placebo	Randomized participants received matching placebo tablets orally BID.	42	42	15	42