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

Study Overview
=================
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).

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

Conditions
-----------------
Irritable Bowel Syndrome

Intervention / Treatment
-----------------
* Drug: Vibegron
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vibegron 75 mg<br>Participants will receive vibegron 75 milligrams (mg) orally once daily for 12 weeks. | Drug: Vibegron<br>* oral administration<br>* Other names: URO-901;|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo orally once daily for 12 weeks. | Drug: Placebo<br>* oral administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Irritable Bowel Syndrome (IBS) With Predominantly Diarrhea (IBS-D) Participants Who Were Abdominal Pain Intensity (API) Weekly Responders at 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). | Baseline; Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Global Improvement Scale (GIS) Responders at Week 12 for All IBS Participants, Including IBS-D and IBS-M Participants | 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. | Week 12 | 
| Number of IBS-D Participants Who Were API Weekly Responders With ≥ 40% Improvement Over 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). | Baseline; 12 weeks | 
| Number of IBS-D Participants Who Were API Weekly Responders With ≥ 50% Improvement Over 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). | Baseline; 12 weeks | 
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 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. | 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) | 
| Number of Participants With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values at Week 12 | The investigator determined whether a change was clinically meaningful. | Baseline; Week 12 | 
| Number of Participants With Clinically Relevant Changes From Baseline in Vital Sign Values at Week 12 | Clinical relevance was determined by the investigator. | Baseline; Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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