BOTOX® Intravesical Instillation in Participants With Overactive Bladder and Urinary Incontinence

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of BOTOX® intravesical instillation in participants with overactive bladder and urinary incontinence.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Single-treatment, 2-stage, Dose-finding Study Evaluating the Efficacy and Safety of BOTOX® Intravesical Instillation in Participants With Overactive Bladder and Urinary Incontinence

Conditions
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Urinary Incontinence, Overactive Bladder With Urinary Incontinence

Intervention / Treatment
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* Drug: OnabotulinumtoxinA and Hydrogel admixture
* Drug: Placebo and Hydrogel admixture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of OAB (frequency/urgency) with urinary incontinence for at least 6 months Inadequate response or limiting side effects with pharmacotherapy for the treatment of OAB Exclusion Criteria: Overactive Bladder caused by neurological condition Patient has predominance of stress incontinence History or evidence of pelvic or urological abnormality Prior use of BOTOX for any urological condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100U cohort - BOTOX® plus Hydrogel admixture<br>100U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: OnabotulinumtoxinA and Hydrogel admixture<br>* BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation<br>* Other names: Botulinum Toxin Type A;|
| Placebo Comparator: 100U cohort - Placebo plus Hydrogel admixture<br>Placebo and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: Placebo and Hydrogel admixture<br>* Placebo and Hydrogel admixture administered as a single intravesical instillation<br>|
| Experimental: 300U cohort - BOTOX® plus Hydrogel admixture<br>300U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: OnabotulinumtoxinA and Hydrogel admixture<br>* BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation<br>* Other names: Botulinum Toxin Type A;|
| Placebo Comparator: 300U cohort - Placebo plus Hydrogel admixture<br>Placebo and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: Placebo and Hydrogel admixture<br>* Placebo and Hydrogel admixture administered as a single intravesical instillation<br>|
| Experimental: 400U cohort - BOTOX® plus Hydrogel admixture<br>400U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: OnabotulinumtoxinA and Hydrogel admixture<br>* BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation<br>* Other names: Botulinum Toxin Type A;|
| Placebo Comparator: 400U cohort - Placebo plus Hydrogel admixture<br>Placebo and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: Placebo and Hydrogel admixture<br>* Placebo and Hydrogel admixture administered as a single intravesical instillation<br>|
| Experimental: 500U cohort - BOTOX® plus Hydrogel admixture<br>500U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: OnabotulinumtoxinA and Hydrogel admixture<br>* BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation<br>* Other names: Botulinum Toxin Type A;|
| Placebo Comparator: 500U cohort - Placebo plus Hydrogel admixture<br>Placebo and Hydrogel admixture administered as a single intravesical instillation on Day 1 | Drug: Placebo and Hydrogel admixture<br>* Placebo and Hydrogel admixture administered as a single intravesical instillation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day | The participant recorded urinary incontinence (lack of voluntary control over urination) in a 3-day bladder diary. The average number of UIEs per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. An analysis of covariance (ANCOVA) model was used for analyses. | Baseline (3 consecutive days during Day -14 to Day -1) to 3 consecutive days in the Week prior to Week 12 | 
| Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period | An adverse event (AE) is any untoward medical occurrence in a participants or clinical study investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug. | Up to End of Study (Stage 1: Up to 114 days and Stage 2: Up to 35.1 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day | The participant recorded the number of micturition (urination in toilet or catherization) episodes per day in a 3-day bladder diary. The average number of micturition episodes per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses. | Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12 | 
| Stage 2: Change From Baseline in the Average Volume Voided Per Micturition | Volume voided per micturition was recorded over one 24-hour period during the 3-day bladder diary. The volume voided during each 24-hour period was divided by the number of micturitions during the period. The average volume voided per micturition is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses. | Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12 |