Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and effectiveness of botulinum toxin type A in treating overactive bladder in spinal cord injury or multiple sclerosis patients

Conditions
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Overactive Bladder

Intervention / Treatment
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* Biological: botulinum toxin Type A (200U)
* Biological: botulinum toxin Type A (300U)
* Other: Normal saline (Placebo); botulinum toxin Type A (200U)
* Other: Normal saline (Placebo); botulinum toxin Type A (300U)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Urinary incontinence as a result of neurogenic overactive bladder due to spinal cord injury or multiple sclerosis Inadequate response to anticholinergic medication used to treat overactive bladder Exclusion Criteria: History or evidence of pelvic or urologic abnormality Previous or current diagnosis of bladder or prostate cancer Urinary tract infection at time of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: 1<br>botulinum toxin Type A (200U) | Biological: botulinum toxin Type A (200U)<br>* botulinum toxin Type A 200 U injection at Day 1 followed by botulinum toxin Type A 200 U injection > Week 12; injections into detrusor<br>* Other names: BOTOX®;|
| Experimental: 2<br>botulinum toxin Type A (300U) | Biological: botulinum toxin Type A (300U)<br>* botulinum toxin Type A 300 U injection on Day 1 followed by botulinum toxin Type A 300 U injection > Week 12; injections into detrusor<br>* Other names: BOTOX®;|
| Other: 3<br>placebo; botulinum toxin Type A (200U) | Other: Normal saline (Placebo); botulinum toxin Type A (200U)<br>* Placebo injection on Day 1 followed by botulinum toxin Type A 200 U injection > 12 weeks; injections into detrusor<br>* Other names: BOTOX®;|
| Other: 4<br>placebo; botulinum toxin Type A (300U) | Other: Normal saline (Placebo); botulinum toxin Type A (300U)<br>* Placebo injection on Day 1 followed by botulinum toxin Type A 300 U injection > Week 12; injections into detrusor<br>* Other names: BOTOX®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Number of Weekly Episodes of Urinary Incontinence | Change from baseline in the weekly frequency of incontinence episodes at Week 6 after the first treatment. Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. A negative number change from baseline indicates a reduction in incontinence episodes (improvement). | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Maximum Cystometric Capacity (MCC) | Change from baseline in MCC at Week 6. MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in maximum volume of urine the bladder holds. | Baseline, Week 6 | 
| Change From Baseline in Maximum Detrusor Pressure (MDP) | Change from baseline in MDP during the first involuntary detrusor contraction at week 6. MDP represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. The greater the negative number change from baseline, the better the improvement. | Baseline, Week 6 | 
| Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire | Change from baseline in I-QOL questionnaire total score at Week 6, as completed by the patient. 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. | Baseline, Week 6 |