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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This study will assess the safety and efficacy of botulinum toxin Type A for the treatment of urinary incontinence overactive bladder in patients with a spinal cord injury or multiple sclerosis.

Detailed Description
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Botulinum toxin Type A 300U has been discontinued from the study after regulatory approval of botulinum toxin Type A 200U. Patients remaining in the study who were allocated to receive botulinum toxin Type A 300U at treatment 2 (and had not yet received it) will receive botulinum toxin Type A 200U instead.

Conditions
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Overactive Bladder

Intervention / Treatment
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* Biological: botulinum toxin Type A
* Drug: Normal Saline (Placebo)


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. Neurological respiratory impairment and abnormal pulmonary function test results Exclusion Criteria: History or evidence of pelvic or urologic abnormality Previous or current diagnosis of bladder or prostate cancer Symptomatic or untreated 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: botulinum toxin Type A 200U<br>Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable). | Biological: botulinum toxin Type A<br>* Botulinum toxin Type A injection into the detrusor.<br>* Other names: onabotulinumtoxinA;|
| Experimental: botulinum toxin Type A 300U<br>Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable). | Biological: botulinum toxin Type A<br>* Botulinum toxin Type A injection into the detrusor.<br>* Other names: onabotulinumtoxinA;|
| Other: Placebo/botulinum toxin Type A 200U<br>Placebo (Normal Saline) injection into the detrusor on Day 1 followed by a botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable). | Biological: botulinum toxin Type A<br>* Botulinum toxin Type A injection into the detrusor.<br>* Other names: onabotulinumtoxinA;Drug: Normal Saline (Placebo)<br>* Placebo (Normal Saline) injection into the detrusor.<br>|
| Other: Placebo/botulinum toxin Type A 300U<br>Placebo (Normal Saline) injection into the detrusor on Day 1 followed by a botulinum toxin Type A 300U injection (200U after discontinuation of 300U) after a minimum of 12 weeks (if applicable). | Biological: botulinum toxin Type A<br>* Botulinum toxin Type A injection into the detrusor.<br>* Other names: onabotulinumtoxinA;Drug: Normal Saline (Placebo)<br>* Placebo (Normal Saline) injection into the detrusor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Vital Capacity (FVC) | Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible, at Baseline and Week 6. A positive change from Baseline indicated improvement. | Baseline, Week 6 | 
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FEV1, the maximum amount of air exhaled in one second, at Baseline and Week 6. The highest value at each time-point was recorded. A positive change from Baseline indicated improvement. | Baseline, Week 6 | 
| Change From Baseline in FEV1/FVC Ratio | The FEV1/FVC ratio was calculated by dividing the FEV1 value by the FVC value representing the portion (or ratio) of FVC exhaled in one second. A positive change from Baseline indicated improvement. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Number of Urinary Incontinence Episodes | The number of urinary incontinence episodes or leakage occurring over the previous 3 days was recorded in the patient bladder diary at Baseline and prior to Week 6. A negative change from Baseline indicated improvement (less incontinence/leakage). | Baseline, Week 6 | 
| Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP) | MDP was measured at the first involuntary detrusor contraction using urodynamic testing. A catheter was inserted into the bladder at Baseline and Week 6 and the pressure [measured in centimeters water (cm H20)] was determined as the bladder filled. A negative change from Baseline indicated improvement (less Detrusor pressure). | Baseline, Week 6 | 
| Change From Baseline in Maximum Cystometric Capacity (MCC) | MCC (the maximum amount of urine the bladder could hold) was measured using urodynamic testing. The amount of urine collected was subtracted from the total volume infused measured as milliliters (mL) of urine. A positive change from Baseline indicated improvement (fuller bladder/ less incontinence). | Baseline, Week 6 |