A Study to Evaluate Once Daily Low Dose and High Dose Solabegron or Placebo Given for 12 Weeks to Treat Women With Symptoms of Overactive Bladder: Sudden Urge to Urinate, Frequent Urination Associated With Wetting Episodes (VEL-2001)

Study Overview
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Brief Summary
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This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety, and tolerability of solabegron modified release low dose or high dose tablets, compared to matched placebo, administered once daily for 12 weeks to adult female subjects with overactive bladder symptoms (frequency, urgency, and predominantly urgency incontinence) for at least 6 months.

Official Title
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A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Oral Solabegron Modified Release Tablets in the Treatment of Overactive Bladder (OAB) in Adult Female Subjects

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: Solabegron modified release tablets, low dose
* Drug: Solabegron modified release tablets, high dose
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult female subjects 18 to 80 years of age, with a ≥ 6-month history of symptoms of overactive bladder including: frequency, urgency, urgency urinary incontinence, and mixed incontinence. Subjects must provide written informed consent and either be of non-childbearing potential or of childbearing potential meeting specific criteria (e.g., negative pregnancy test, sexual inactivity, acceptable methods of birth control, and use of hormonal contraceptives). Exclusion Criteria: Subjects must have no history of pelvic or bladder disease, e.g., uterine prolapse, malignancy, prior surgery, or treatment with botulinum toxin. Diabetes insipidus or poorly controlled Type 1 or Type 2 diabetes mellitus Cardiac conditions: prior cardiovascular events or procedures within 6 months of screening congestive heart failure abnormal ECG findings, including ECG QT correction interval (QTc) > 470 msec at the Screening Visit systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg, or heart rate > 100 beats per minute Abnormal tests of liver function History of prior infection due to HIV or hepatitis B or hepatitis C virus Allergy or hypersensitivity to solabegron or mirabegron Women of childbearing potential: breastfeeding, pregnant, or actively trying to become pregnant Participation in a trial of an investigational or marketed drug ≤ 30 days prior to the Screening Visit or in any clinical trial of an investigational drug that may affect urinary function within 3 months prior to Screening Visit. Inability to read, understand, or complete study-related materials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Eligible female subjects (N=1200) with symptoms of overactive bladder for at least 6 months will enter a 14-day single-blind Run-in Period. Subjects (N=375) who meet prespecified criteria based on data entered into an electronic diary over 3 days will be randomized 1:1:1 (125 subjects per arm) to receive solabegron modified release tablets, low dose or high dose, or matching placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solabegron modified release tablets low dose<br> | Drug: Solabegron modified release tablets, low dose<br>* Solabegron modified release tablets low dose or high dose or matching placebo once daily for 12 weeks.<br>|
| Experimental: Solabegron modified release tablets high dose<br> | Drug: Solabegron modified release tablets, high dose<br>* Solabegron modified release tablets low dose or high dose or matching placebo once daily for 12 weeks.<br>|
| Placebo Comparator: Placebo Comparator<br> | Drug: Matching Placebo<br>* Solabegron modified release tablets low dose or high dose or matching placebo once daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in mean number of micturitions per 24 hours at Week 12 | Micturition events will be recorded by subjects in an eDiary using a smartphone device during 3-day diary periods prior to randomization and at 12 weeks. | Micturtions will be assessed prior to randomization and at Week 12 (Visit 6). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Incontinence (1) | Change from Baseline in mean number of urgency urinary incontinence episodes per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urinary Incontinence (2) | Percentage change from Baseline in mean number of urgency urinary incontinence episodes per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urinary Incontinence (3) | Proportion of subjects with no episodes of urgency urinary incontinence per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urinary Incontinence (4) | Proportion of subjects with no episodes of urinary incontinence (urgency and non-urgency) per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urinary Incontinence (5) | Change from Baseline in total urinary incontinence episodes (urgency and non-urgency) per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Micturitions (1) | Change from Baseline in mean number of micturitions per 24 hours | Prior to Randomization (Baseline) and at Weeks 4 and 8 | 
| Micturitions (2) | Percentage change from Baseline in mean number of micturitions per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Micturitions (3) | Percentage of subjects with < 8 micturitions per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Micturitions (4) | Change from Baseline in mean number of nocturnal voids per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urine Void Volume (1) | Change from Baseline in average void volume over 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urine Void Volume (2) | Percentage change from Baseline in average void volume over 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urine Void Volume (3) | Change from Baseline in maximum individual void volume over 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urine Void Volume (4) | Percentage change from Baseline in maximum individual void volume over 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urgency (1) | Proportion of subjects with urges with a mean grade of 3 of 4 per 24 hours | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Urgency (2) | Change from Baseline in mean urgency assessments per 24 hours associated with micturitions or incontinence | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Patient Reported Outcomes (1) | Patient Perception of Bladder Control. This patient-reported questionnaire assesses the patient's perception of current urinary problems, where higher score (on a scale of 1 to 6) indicates more severe problems. | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Patient Reported Outcomes (2) | Change from Baseline in Symptom Bother Score (Overactive Bladder Questionnaire [OAB-q] short form). The OAB-q short form is completed as a 4-week recall where a higher score (on a scale of 1 to 6) indicates greater symptoms. | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 
| Patient Reported Outcomes (3) | Change from Baseline in health-related quality of life (Overactive Bladder Questionnaire [OAB-q] short form). The OAB-q short form is completed as a 4-week recall where a higher score (on a scale of 1 to 6) indicates worse health-related quality of life. | Prior to Randomization (Baseline) and at Weeks 4, 8, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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overactive bladder, urinary conditions, urgency urinary incontinence, urgency, micturitions