Study to Evaluate the Efficacy and Safety of Vibegron Administered Orally for 12 Weeks to Women With Irritable Bowel Syndrome

• Sponsor: Urovant Sciences GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03806127
• Collaborator: (none)
• Enrollment: 222
• Locations: 41
• Arms: 2
• Actual Duration (Months): 21.2
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of vibegron, a beta-3 adrenergic receptor (β3-AR) agonist, in the treatment of pain associated with irritable bowel syndrome (IBS) due to IBS with predominant diarrhea (IBS-D) or mixed episodes of diarrhea and constipation (IBS-M).

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome	Drug: Vibegron; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 222 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Vibegron Administered Orally for 12 Weeks to Women With Irritable Bowel Syndrome
• Actual Study Start Date: Dec 31, 2018
• Actual Primary Completion Date: Sep 25, 2020
• Actual Study Completion Date: Oct 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vibegron 75 mg Participants will receive vibegron 75 milligrams (mg) orally once daily for 12 weeks.	Drug: Vibegron; oral administration; Other Names: RVT-901 MK-4618 KRP-114V URO-901
Placebo Comparator: Placebo Participants will receive matching placebo orally once daily for 12 weeks.	Drug: Placebo; oral administration

Outcome Measures

Primary Outcome Measures

1. Number of Irritable Bowel Syndrome (IBS) With Predominantly Diarrhea (IBS-D) Participants Who Were Abdominal Pain Intensity (API) Weekly Responders at Week 12 [Baseline; Week 12]

   An API Weekly Responder was defined as a participant who experienced a decrease in the weekly average of "worst abdominal pain in the past 24 hours" scores of at least 30% compared with the Baseline weekly average. A participant was considered a responder over Weeks 1 to 12 if they met the criteria for at least 50% of the weeks assessed (i.e., ≥6 weeks).

Secondary Outcome Measures

1. Number of Global Improvement Scale (GIS) Responders at Week 12 for All IBS Participants, Including IBS-D and IBS-M Participants [Week 12]

   Global improvement assessment asks participants to evaluate their current IBS status by asking the following question: How would you rate your IBS signs or symptoms overall over the past 7 days?: (1) significantly relieved; (2) moderately relieved; (3) slightly relieved; (4) unchanged; (5) slightly worse; (6) moderately worse; (7) significantly worse. A responder was defined as a participant who answered that their symptoms were either moderately relieved or significantly relieved. A participant with a missing GIS response was considered to be a non-responder.

2. Number of IBS-D Participants Who Were API Weekly Responders With ≥ 40% Improvement Over 12 Weeks [Baseline; 12 weeks]

   An API Weekly Responder was defined as a participant who experienced a decrease in the weekly average of "worst abdominal pain in the past 24 hours" scores of at least 40% compared with the Baseline weekly average. A participant was considered a responder over Weeks 1 to 12 if they met the criteria for at least 50% of the weeks assessed (i.e., ≥6 weeks).

3. Number of IBS-D Participants Who Were API Weekly Responders With ≥ 50% Improvement Over 12 Weeks [Baseline; 12 weeks]

   An API Weekly Responder was defined as a participant who experienced a decrease in the weekly average of "worst abdominal pain in the past 24 hours" scores of at least 50% compared with the Baseline weekly average. A participant was considered a responder over Weeks 1 to 12 if they met the criteria for at least 50% of the weeks assessed (i.e., ≥6 weeks).

4. Number of Participants With Any Treatment-emergent Adverse Event (TEAE) [from the time the participant provided informed consent to participate in the study at the Screening Visit until completion of the Safety Follow-up Call (up to Day 113 or Early Withdrawal plus 28 days)]

   TEAEs are defined as events that began or worsened in severity after the first dose of the double-blind study treatment through 14 days after the last dose of study treatment.

5. Number of Participants With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values at Week 12 [Baseline; Week 12]

   The investigator determined whether a change was clinically meaningful.

6. Number of Participants With Clinically Relevant Changes From Baseline in Vital Sign Values at Week 12 [Baseline; Week 12]

   Clinical relevance was determined by the investigator.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of irritable bowel syndrome (IBS) with predominantly diarrhea (IBS-D) or IBS with mixed episodes of diarrhea and constipation (IBS-M) according to the Rome IV criteria

• Has completed a colonoscopy according to the American Gastroenterological Association criteria, with no clinically significant findings in the last 5 years

• Has no clinically significant findings on a physical examination or clinical laboratory tests that could interfere with study participation or confound study assessments, in the opinion of the Investigator. Serum tissue transglutaminase antibody (IgA) must be negative. Fecal calprotectin testing is optional and should only be considered if there is a strong suspicion that the participant has inflammatory bowel disease (IBD) (eg, family history in a 1st degree relative, other genetic factors, etc.) or other organic disease, according to the clinical judgement of the investigator.

Exclusion Criteria:

• Diagnosis of IBS-C or IBS-U per Rome IV criteria

• History of chronic idiopathic constipation or functional constipation

• Structural abnormality of the gastrointestinal tract or a disease (e.g., known small intestine bacterial overgrowth) or condition that can affect gastrointestinal motility

• History of a gastrointestinal motility disorder other than IBS (e.g., gastroparesis, intestinal pseudo-obstruction, achalasia, Parkinsons disease, multiple sclerosis, spinal cord injury)

• Prior history of a gastrointestinal malignancy, inflammatory bowel disease, celiac disease

• Planned gastrointestinal or abdominal surgery within the next 6 months

• Co-existing gastroesophageal reflux disease or functional dyspepsia with symptoms predominant to IBS symptoms

• Symptoms or diagnosis of a medical condition other than IBS that may contribute to abdominal pain (e.g., interstitial cystitis; fibromyalgia currently being treated with pregabalin or gabapentin; and endometriosis with uncontrolled abdominal pain)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Synexus Clinical Research US, Inc.-Simon Williamson Clinic	Birmingham	Alabama	United States	35211
2	Clinical Research Associates	Huntsville	Alabama	United States	35801
3	Alabama Medical Group, PC	Mobile	Alabama	United States	36693
4	Hope Research Institute	Chandler	Arizona	United States	85224
5	Synexus Clinical Research US, Inc. - East Valley Family Physicians, PLC	Chandler	Arizona	United States	85224
6	Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC	Mesa	Arizona	United States	85206
7	Synexus Clinical Research US, Inc. - Desert Clinical Research, LLC	Mesa	Arizona	United States	85213
8	Synexus - Clinical Research Advantage, Inc. - Central Phoenix Medical Clinic LLC	Phoenix	Arizona	United States	85020
9	GW Research Inc - ClinEdge-PPDS	Chula Vista	California	United States	91910
10	Triwest Research Associates, LLC	La Mesa	California	United States	91942
11	VA Long Beach Healthcare System - NAVREF	Long Beach	California	United States	90822
12	Southern California Research Institute Medical Group, Inc.	Los Angeles	California	United States	90045
13	Desta Digestive Disease Medical Center	San Diego	California	United States	92114
14	Medical Associates Research Group, Inc.	San Diego	California	United States	92123
15	Torrance Clinical Research	Torrance	California	United States	90505
16	Medical Research Center of Connecticut LLC	Hamden	Connecticut	United States	06518
17	Mayo Clinic - Division of Gastroenterology	Jacksonville	Florida	United States	32224
18	Florida Center For Gastroenterology	Largo	Florida	United States	33777
19	Clinical Research Center of Florida	Pompano Beach	Florida	United States	33060
20	Palm Beach Research - ClinEdge - PPDS	West Palm Beach	Florida	United States	33409
21	RNA America, LLC	Sugar Hill	Georgia	United States	30518
22	Investigators Research Group, LLC	Indianapolis	Indiana	United States	46268
23	Mandeville Private Physician Group, LLC	Mandeville	Louisiana	United States	70471
24	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
25	University of Michigan	Ann Arbor	Michigan	United States	48109
26	Clinical Research Institute of Michigan	Chesterfield	Michigan	United States	48047
27	Synexus Clinical Research US, Inc. - Rita B. Chuang, MD, LLC	Henderson	Nevada	United States	89502
28	Advanced Research Institute	Reno	Nevada	United States	89511
29	Atrium Healthcare Center for Digestive Health	Charlotte	North Carolina	United States	28204
30	Carolina Digestive Diseases	Greenville	North Carolina	United States	27834
31	East Carolina Gastroenterology	Jacksonville	North Carolina	United States	28546
32	Dayton Gastroenterology, Inc.	Beavercreek	Ohio	United States	45440
33	Central Sooner Research	Norman	Oklahoma	United States	73071
34	Synexus Clinical Research US, Inc. - Anderson	Anderson	South Carolina	United States	29621
35	Chattanooga Medical Research Inc	Chattanooga	Tennessee	United States	37404
36	Clinical Research Solutions PC	Jackson	Tennessee	United States	38305
37	DHAT Research Institute	Garland	Texas	United States	75044
38	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
39	Synexus Clinical Research US, Inc.-Plano	Plano	Texas	United States	75093
40	Synexus Clinical Research US, Inc. - Wasatch Peak Family Practice	Layton	Utah	United States	84041
41	Advanced Research Institute	South Ogden	Utah	United States	84405

Sponsors and Collaborators

• Urovant Sciences GmbH

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 19, 2019
• Statistical Analysis Plan - Sep 22, 2020

More Information

Publications

None provided.

• Responsible Party: Urovant Sciences GmbH
• ClinicalTrials.gov Identifier: NCT03806127
• Other Study ID Numbers: URO-901-2001
• First Posted: Jan 16, 2019
• Last Update Posted: Aug 2, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Urovant Sciences GmbH: Irritable Bowel Syndrome; Irritable Bowel Syndrome with predominantly diarrhea (IBS-D); Irritable Bowel Syndrome with mixed episodes of diarrhea and constipation (IBS-M); Vibegron; Beta-3 adrenergic receptor (β3-AR); Pain
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome

Study Results

Participant Flow

Pre-assignment Detail	Of 806 participants screened for this study, 222 were randomized (after a 2-week, single-blind placebo Run-in Period), and 222 received 1 dose of double-blind study drug in the Treatment Period (Safety Set: placebo, N = 111; vibegron, N = 111).

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Period Title: Overall Study
STARTED	111	111
COMPLETED	90	99
NOT COMPLETED	21	12

Baseline Characteristics

Arm/Group Title	Placebo	Vibegron 75 mg	Total
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).	Total of all reporting groups
Overall Participants	108	111	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.6 (13.10)	40.5 (13.88)	40.1 (13.48)
Sex: Female, Male (Count of Participants)
Female	108 100%	111 100%	219 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	82 75.9%	80 72.1%	162 74%
Black or African American	24 22.2%	25 22.5%	49 22.4%
Captured as Other	1 0.9%	3 2.7%	4 1.8%
American Indian or Alaska Native	1 0.9%	1 0.9%	2 0.9%
Asian	0 0%	1 0.9%	1 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.9%	1 0.5%
Abdominal Pain Intensity Score (Stratified Strata) (Count of Participants)
< 6	77 71.3%	78 70.3%	155 70.8%
≥ 6	31 28.7%	33 29.7%	64 29.2%
IBS Subtype (Stratified Strata) (Count of Participants)
IBS-D	63 58.3%	66 59.5%	129 58.9%
IBS-M	45 41.7%	45 40.5%	90 41.1%

Outcome Measures

1. Primary Outcome

Title	Number of Irritable Bowel Syndrome (IBS) With Predominantly Diarrhea (IBS-D) Participants Who Were Abdominal Pain Intensity (API) Weekly Responders at Week 12
Description	An API Weekly Responder was defined as a participant who experienced a decrease in the weekly average of "worst abdominal pain in the past 24 hours" scores of at least 30% compared with the Baseline weekly average. A participant was considered a responder over Weeks 1 to 12 if they met the criteria for at least 50% of the weeks assessed (i.e., ≥6 weeks).
Time Frame	Baseline; Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set for IBS-D participants: all randomized participants with IBS-D who who took at least one dose of double-blind study medication and had at least one evaluable post-randomization weekly API score (i.e., where evaluable was considered a minimum of 5 diary entries in a week)

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Measure Participants	63	66
Count of Participants [Participants]	27 25%	27 24.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vibegron 75 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cochran-Mantel-Haenszel (CMH) Difference
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 90%; -16.1 to 12.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportion and corresponding confidence interval were calculated using the CMH risk difference estimate stratified by randomized Baseline abdominal pain (< 6 versus ≥ 6) strata, with weights proposed by Greenland and Robins.

2. Secondary Outcome

Title	Number of Global Improvement Scale (GIS) Responders at Week 12 for All IBS Participants, Including IBS-D and IBS-M Participants
Description	Global improvement assessment asks participants to evaluate their current IBS status by asking the following question: How would you rate your IBS signs or symptoms overall over the past 7 days?: (1) significantly relieved; (2) moderately relieved; (3) slightly relieved; (4) unchanged; (5) slightly worse; (6) moderately worse; (7) significantly worse. A responder was defined as a participant who answered that their symptoms were either moderately relieved or significantly relieved. A participant with a missing GIS response was considered to be a non-responder.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants who took at least one dose of double-blind study medication and had at least one evaluable post-randomization weekly API score (i.e., where evaluable was considered a minimum of 5 diary entries in a week)

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Measure Participants	108	111
IBS-D Participants	21 19.4%	28 25.2%
IBS-M Participants	16 14.8%	16 14.4%
All Participants	37 34.3%	44 39.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vibegron 75 mg
	Comments	IBS-D Participants
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CMH Difference
	Estimated Value	9.1
	Confidence Interval	(2-Sided) 90%; -4.8 to 22.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportion and corresponding confidence interval were calculated using the CMH risk difference estimate stratified by randomized Baseline abdominal pain (< 6 versus >= 6) strata, with weights proposed by Greenland and Robins.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vibegron 75 mg
	Comments	IBS-M Participants
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CMH Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 90%; -16.7 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportion and corresponding confidence interval were calculated using the CMH risk difference estimate stratified by randomized Baseline abdominal pain (< 6 versus >= 6) strata, with weights proposed by Greenland and Robins.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vibegron 75 mg
	Comments	All Participants
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CMH Difference
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 90%; -5.4 to 15.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportion and corresponding confidence interval were calculated using the CMH risk difference estimate stratified by randomized Baseline abdominal pain (< 6 versus >= 6) strata, with weights proposed by Greenland and Robins.

3. Secondary Outcome

Title	Number of IBS-D Participants Who Were API Weekly Responders With ≥ 40% Improvement Over 12 Weeks
Description	An API Weekly Responder was defined as a participant who experienced a decrease in the weekly average of "worst abdominal pain in the past 24 hours" scores of at least 40% compared with the Baseline weekly average. A participant was considered a responder over Weeks 1 to 12 if they met the criteria for at least 50% of the weeks assessed (i.e., ≥6 weeks).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set for IBS-D participants

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Measure Participants	63	66
Count of Participants [Participants]	20 18.5%	22 19.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vibegron 75 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CMH Difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 90%; -11.7 to 14.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportion and corresponding confidence interval were calculated using the CMH risk difference estimate stratified by randomized Baseline abdominal pain (< 6 versus >= 6) strata, with weights proposed by Greenland and Robins.

4. Secondary Outcome

Title	Number of IBS-D Participants Who Were API Weekly Responders With ≥ 50% Improvement Over 12 Weeks
Description	An API Weekly Responder was defined as a participant who experienced a decrease in the weekly average of "worst abdominal pain in the past 24 hours" scores of at least 50% compared with the Baseline weekly average. A participant was considered a responder over Weeks 1 to 12 if they met the criteria for at least 50% of the weeks assessed (i.e., ≥6 weeks).
Time Frame	Baseline; 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set for IBS-D participants

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Measure Participants	63	66
Count of Participants [Participants]	13 12%	18 16.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vibegron 75 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CMH Difference
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 90%; -5.5 to 18.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportion and corresponding confidence interval were calculated using the CMH risk difference estimate stratified by randomized Baseline abdominal pain (< 6 versus ≥ 6) strata, with weights proposed by Greenland and Robins.

5. Secondary Outcome

Title	Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Description	TEAEs are defined as events that began or worsened in severity after the first dose of the double-blind study treatment through 14 days after the last dose of study treatment.
Time Frame	from the time the participant provided informed consent to participate in the study at the Screening Visit until completion of the Safety Follow-up Call (up to Day 113 or Early Withdrawal plus 28 days)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all participants who received at least 1 dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Measure Participants	111	111
Count of Participants [Participants]	37 34.3%	37 33.3%

6. Secondary Outcome

Title	Number of Participants With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values at Week 12
Description	The investigator determined whether a change was clinically meaningful.
Time Frame	Baseline; Week 12

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Measure Participants	111	111
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Clinically Relevant Changes From Baseline in Vital Sign Values at Week 12
Description	Clinical relevance was determined by the investigator.
Time Frame	Baseline; Week 12

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Placebo	Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).	Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
Measure Participants	111	111
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	from the time the participant provided informed consent to participate in the study at the Screening Visit until completion of the Safety Follow-up Call (up to Week 14)
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs), defined as events that began or worsened in severity after the first dose of the double-blind study treatment through 14 days after the last dose of study treatment, are reported for members of the Safety Analysis Set, comprised of all participants who received at least 1 dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Arm/Group Title	Placebo		Vibegron 75 mg
Arm/Group Description	Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline abdominal pain intensity (API) score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and irritable bowel syndrome (IBS) subtype (IBS with predominant diarrhea [IBS-D] versus IBS with mixed episodes of diarrhea and constipation [IBS-M]).		Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline API score (< 6 versus ≥ 6 on a 0- to 10-point numeric rating scale) and IBS subtype (IBS-D versus IBS-M).
All Cause Mortality
	Placebo		Vibegron 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/111 (0%)		0/111 (0%)
Serious Adverse Events
	Placebo		Vibegron 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/111 (0.9%)		2/111 (1.8%)
Infections and infestations
COVID-19	0/111 (0%)		1/111 (0.9%)
Metabolism and nutrition disorders
Hyperkalaemia	1/111 (0.9%)		0/111 (0%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/111 (0%)		1/111 (0.9%)
Other (Not Including Serious) Adverse Events
	Placebo		Vibegron 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/111 (17.1%)		13/111 (11.7%)
Gastrointestinal disorders
Constipation	3/111 (2.7%)		1/111 (0.9%)
Irritable bowel syndrome	3/111 (2.7%)		3/111 (2.7%)
Infections and infestations
Bacteriuria	5/111 (4.5%)		3/111 (2.7%)
Gastroenteritis	0/111 (0%)		3/111 (2.7%)
Nasopharyngitis	3/111 (2.7%)		0/111 (0%)
Upper respiratory tract infection	5/111 (4.5%)		1/111 (0.9%)
Nervous system disorders
Headache	3/111 (2.7%)		3/111 (2.7%)
Renal and urinary disorders
Leukocyturia	3/111 (2.7%)		0/111 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor does not object to publication by Institution or Principal Investigator (PI) of results of the Trial based on information collected or generated by the Institution or PI. However, the Institution and PI are required to provide the Sponsor with an opportunity to review any proposed publication or other type of disclosure before it is submitted or otherwise disclosed to ensure against any inadvertent disclosure of Sponsor Confidential Information or unprotected Sponsor Inventions.