Study of OnabotulinumtoxinA (BOTOX®) for Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Pediatric Patients

Study Overview
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Brief Summary
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This study will evaluate the 3 doses of onabotulinumtoxinA (botulinum toxin Type A) for the treatment of urinary incontinence due to neurogenic detrusor overactivity in pediatric participants between the ages of 5 to 17 years to determine if 1 or more doses were safe and effective.

Official Title
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BOTOX® in the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Patients 5 to 17 Years of Age

Conditions
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Urinary Incontinence

Intervention / Treatment
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* Biological: OnabotulinumtoxinA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Urinary incontinence due to neurogenic detrusor overactivity Regularly using clean intermittent catheterization to empty the bladder Exclusion Criteria: Surgery of the spinal cord within 6 months Diagnosis of cerebral palsy Current or planned use of a baclofen pump Current or planned use of an electrostimulation/neuromodulation device for urinary incontinence Use of an indwelling catheter for urinary incontinence instead of using clean intermittent catheterization to empty the bladder Previous or current use of botulinum toxin therapy of any serotype for any urological condition, or treatment with botulinum toxin of any serotype within 3 months for any other condition or use Myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 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 50 U<br>OnabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1. Participants were eligible for retreatment in study 191622-121 (NCT01852058) if qualified. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into the detrusor wall on Day 1.<br>* Other names: botulinum toxin Type A;|
| Experimental: OnabotulinumtoxinA 100 U<br>OnabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1. Participants were eligible for retreatment in study 191622-121 if qualified. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into the detrusor wall on Day 1.<br>* Other names: botulinum toxin Type A;|
| Experimental: OnabotulinumtoxinA 200 U<br>OnabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1. Participants were eligible for retreatment in study 191622-121 if qualified. | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into the detrusor wall on Day 1.<br>* Other names: botulinum toxin Type A;|

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 Daytime Urinary Incontinence Episodes | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during the 2 consecutive days (normalized to a 12-hour daytime period) prior to the study visit. Daytime was defined as the time between waking up to start the day and first morning catheterization and going to bed to sleep for the night. The number of incontinence episodes were averaged daily during this period. A negative change from Baseline indicates improvement. Least squares estimates were based on an Analysis of Covariance (ANCOVA) model. | Baseline (Day -28 to Day -1) to 2 consecutive days prior to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | An adverse event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is defined as any new adverse event or worsening of an existing condition after initiation of treatment. | First study treatment to 12 weeks after last treatment (Up to 48 weeks after first study injection) | 
| Change From Baseline in Average Urine Volume at First Morning Catheterization | The change in urine volume at first morning catherization was recorded by the participant in a bladder diary in the 2 consecutive days during the week prior to the study visit. A positive change from Baseline indicates improvement. Least squares estimates were based on an ANCOVA model. | Baseline (Day -28 to Day -1) to 2 consecutive days prior to Week 6 | 
| Percentage of Participants With Night Time Urinary Incontinence | Urinary incontinence was defined as involuntary loss of urine and the presence or absence of night time urinary incontinence was recorded by the participant in a bladder diary in the 2 consecutive days (normalized to a 12-hour daytime period) during the week prior to the study visit. Night time was defined as the time between going to bed to sleep for the night and waking up to start the day. The percentage of participants with night time urinary incontinence is presented in categories (0, 1, 2 nights). | Baseline (Day -28 to Day -1), Week 6 | 
| Change From Baseline in Maximum Cystometric Capacity (MCC) | The MCC was defined by urodynamics, as the volume infused before the participant felt they could no longer delay micturition (has a strong desire to void), had a leakage, or 500 mL was instilled. A positive change from Baseline indicates improvement (increase) in the maximum volume of urine the bladder holds. Least squares estimates were based on an ANCOVA model. | Baseline (Day -28 to Day -1) to Week 6 | 
| Percentage of Participants With Involuntary Detrusor Contractions (IDC) | Urodynamic tests were performed by site personnel qualified for performing pressure/flow cystometry. The results were verified by an independent central reviewer. Cystometry was used to measures the presence of involuntary detrusor contractions upon filling. A reduction in IDCs from Baseline to Week 6 indicates improvement. | Baseline (Day -28 to -1) and Week 6 | 
| Change From Baseline in Maximum Detrusor Pressure During the First IDC (PdetMax1stIDC) in Participants With IDC | Urodynamic tests were performed by site personnel qualified for performing pressure/flow cystometry. The results were verified by an independent central reviewer. Cystometry was used to measures the pressure inside of the bladder to see how well the bladder was working. A negative change from Baseline indicates improvement. Least squares estimates were based on an ANCOVA model. | Baseline (Day-28 to Day-1) to Week 6 | 
| Change From Baseline in Maximum Detrusor Pressure (PdetMax) During the Storage Phase | Urodynamic tests were performed by site personnel qualified for performing pressure/flow cystometry. The results were verified by an independent central reviewer. Cystometry was used to measures the pressure inside of the bladder to see how well the bladder was working. A negative change from Baseline indicates improvement. Least squares estimates were based on an ANCOVA model. | Baseline (Day 1) to Week 6 | 
| Change From Baseline in Detrusor Leak Point Pressure (DLPP) During the Storage Phase | DLPP was defined as the lowest detrusor pressure at which urine leakage occurs in the absence of either a detrusor contraction or increased intra-abdominal pressure. Urodynamic tests were performed by site personnel qualified for performing pressure/flow cystometry. The results were verified by an independent central reviewer. Cystometry was used to measures the pressure inside of the bladder to see how well the bladder was working. A negative change from Baseline indicates improvement. Least squares estimates are based on an ANCOVA model. | Baseline (Day -28 to -1) to Week 6 | 
| Time to Participant Request for Retreatment | Time from treatment on Day 1 to request for retreatment was estimated. For those participants who did not request retreatment, their data was censored using the date of their last study visit. | 48 weeks | 
| Time to Participant Qualification for Retreatment | In order to qualify for retreatment, the criteria listed below must be fulfilled at the qualification for retreatment visit: Participant/parent/caregiver requests retreatment, participant has a total of at least 2 daytime urinary incontinence episodes over the 2-day bladder diary collection period, at least 12 weeks has elapsed since treatment 1 and participant has not experienced a serious treatment-related adverse event at any time. | 48 weeks |