Safety and Efficacy Study of OnabotulinumtoxinA for the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity (NDO) in Non-Catheterizing Patients With Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of OnabotulinumtoxinA (BOTOX®) for the treatment of urinary incontinence due to NDO in non-catheterizing patients with MS.

Conditions
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Urinary Incontinence, Multiple Sclerosis, Neurogenic Bladder

Intervention / Treatment
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* Biological: OnabotulinumtoxinA
* Drug: Placebo (Normal Saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 3 episodes of urinary incontinence over a 3-day period History of Multiple Sclerosis (MS) Urinary incontinence not adequately controlled by anticholinergic medication Exclusion Criteria: Current use of intermittent catheter or indwelling catheter to manage urinary incontinence Previous or current botulinum toxin therapy of any serotype for any urological condition Previous or current botulinum toxin therapy of any serotype for any non-urological condition within the last 12 weeks Diagnosis of myasthenia gravis, Eaton-Lambert Syndrome, or Amyotrophic Lateral Sclerosis

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OnabotulinumtoxinA<br>OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA 100 U injection. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1 in the onabotulinumtoxinA 100 U arm. After a minimum of 12 weeks, patients in both the onabotulinumtoxinA 100 U arm and the placebo arm could request/qualify for an onabotulinumtoxinA injection.<br>* Other names: botulinum toxin Type A;|
| Other: Placebo (Normal Saline)<br>Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1 in the onabotulinumtoxinA 100 U arm. After a minimum of 12 weeks, patients in both the onabotulinumtoxinA 100 U arm and the placebo arm could request/qualify for an onabotulinumtoxinA injection.<br>* Other names: botulinum toxin Type A;Drug: Placebo (Normal Saline)<br>* Placebo (normal saline) is administered into the detrusor at Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes | Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. The number of episodes of urinary incontinence is recorded over a 3-day period the week of the study visit. A negative number change from baseline indicates a reduction in incontinence episodes (improvement) and a positive number change indicates an increase in incontinence episodes (worsening). | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Maximum Cystometric Capacity (MCC) | MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in the maximum volume of urine the bladder holds and a negative number change from baseline represents a worsening (decrease) in the maximum volume of urine the bladder holds. | Baseline, Week 6 | 
| Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) | Maximum detrusor pressure represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. A negative number change from baseline indicates an improvement in pressure and a positive number change from baseline indicates a worsening in pressure. | Baseline, Week 6 | 
| Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score | The I-QOL is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL, and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0=worst QOL and 100=best QOL). A positive change from baseline represents an improvement and a negative change from baseline represents a worsening. | Baseline, Week 6 |