A Long-Term Extension Study of OnabotulinumtoxinA (BOTOX®) for Urinary Incontinence Due to Neurogenic Detrusor Overactivity

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the long-term safety and efficacy of onabotulinumtoxinA (botulinum toxin Type A; BOTOX®) for the treatment of urinary incontinence due to neurogenic detrusor overactivity in participants who successfully completed Study 191622-120 (NCT01852045).

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

Conditions
-----------------
Urinary Incontinence

Intervention / Treatment
-----------------
* Biological: OnabotulinumtoxinA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Successfully completed participation in Study 191622-120 Aged ≥ 5 years to ≤ 17 years at the time of entry into Study 191622-120 Regularly using clean intermittent catheterization to empty the bladder Exclusion Criteria: Myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis 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 for any other condition since entering study 191622-120

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OnabotulinumtoxinA 50 U<br>Following treatment with onabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg). | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into the detrusor wall. Treatments were administered as needed with a minimum of a 12-week interval between doses.<br>* Other names: botulinum toxin Type A;|
| Experimental: OnabotulinumtoxinA 100 U<br>Following treatment with onabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg). | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into the detrusor wall. Treatments were administered as needed with a minimum of a 12-week interval between doses.<br>* Other names: botulinum toxin Type A;|
| Experimental: OnabotulinumtoxinA 200 U<br>Following treatment with onabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg). | Biological: OnabotulinumtoxinA<br>* OnabotulinumtoxinA injected into the detrusor wall. Treatments were administered as needed with a minimum of a 12-week interval between doses.<br>* Other names: botulinum toxin Type A;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1 | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1 | 
| Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 2 | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2 | 
| Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 3 | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (STEAEs) | 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 use of a medicinal (investigational) product, whether or not related to medicinal (investigational) product. A serious adverse event (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life threatening, a congenital anomaly/birth defect, or an important medical event. A TEAE or STEAE is defined as any new AE or worsening of an existing condition after initiation of treatment. Data are summarized under the respective treatments that participants received in the corresponding treatment cycles. | First injection on Day 1 in Study 120 through completion of Study 121 (Up to 108 weeks) | 
| Percentage of Participants With ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction From Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 1 | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily incontinence episodes were averaged during the 2-day period. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1 | 
| Percentage of Participants With ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction From Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 2 | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily incontinence episodes were averaged during the 2-day period. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2 | 
| Percentage of Participants With ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction From Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 3 | Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily incontinence episodes were averaged during the 2-day period. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3 | 
| Change From Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 1 | 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. The daily values were averaged during the 2-day period. A positive change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1 | 
| Change From Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 2 | 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. The daily values were averaged during the 2-day period. A positive change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2 | 
| Change From Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 3 | 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. The daily values were averaged during the 2-day period. A positive change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3 | 
| Percentage of Participants With Night Time Urinary Incontinence in Treatment Cycle 1 | Urinary incontinence was defined as involuntary loss of urine. Night time urinary incontinence was recorded by the participant on the bladder diary as a presence or absence of urinary leakage upon waking, for 2 consecutive days in the week prior to the week 6 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, and 2 nights. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Baseline (Prior to Day 1 in Study 120) and 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1 | 
| Percentage of Participants With Night Time Urinary Incontinence in Treatment Cycle 2 | Urinary incontinence was defined as involuntary loss of urine. Night time urinary incontinence was recorded by the participant on the bladder diary as a presence or absence of urinary leakage upon waking, for 2 consecutive days in the week prior to the week 6 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, and 2 nights. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Baseline (Prior to Day 1 in Study 120) and 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2 | 
| Percentage of Participants With Night Time Urinary Incontinence in Treatment Cycle 3 | Urinary incontinence was defined as involuntary loss of urine. Night time urinary incontinence was recorded by the participant on the bladder diary as a presence or absence of urinary leakage upon waking, for 2 consecutive days in the week prior to the week 6 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, and 2 nights. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Baseline (Prior to Day 1 in Study 120) and 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3 | 
| Average Time to Participant's Request for Retreatment | Time to request for re-treatment is the time in weeks between last injection and request for next injection, regardless of fulfillment of the re-treatment criteria. Data are summarized under the respective treatments that participants received across entire study. Data is reported for only participants that had at least one request for retreatment while on a specified BOTOX dose. | First injection on Day 1 in Study 120 through to the date of completion of Study 121 (Up to 108 weeks) | 
| Average Time to Participant's Qualification for Retreatment | The criteria for qualification of retreatment included 1) Participant/parent/caregiver requests retreatment; 2) Participant has a total of at least 2 daytime urinary incontinence episodes over the 2-day bladder diary collection period; 3) At least 12 weeks has elapsed since treatment 1 and 4) Participant has not experienced a serious treatment-related adverse event at any time. Data are summarized under the respective treatments that participants received across entire study. Data is reported for only participants that had at least one request for retreatment while on a specified BOTOX dose. | First injection on Day 1 in Study 120 through to the date of completion of Study 121 (Up to 108 weeks) | 
| Percentage of Participants With Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 1 | The Modified TBS is a single-item scale which assesses the participant's condition (urinary problems, urinary incontinence) on a 4-point scale where 1 = greatly improved; 2 = improved; 3 = not changed; and 4 = worsened. A participant was considered to have a positive treatment response if they responded to the TBS question as either greatly improved or improved. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Week 6 in Treatment Cycle 1 | 
| Percentage of Participants With Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 2 | The Modified TBS is a single-item scale which assesses the participant's condition (urinary problems, urinary incontinence) on a 4-point scale where 1 = greatly improved; 2 = improved; 3 = not changed; and 4 = worsened. A participant was considered to have a positive treatment response if they responded to the TBS question as either greatly improved or improved. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Week 6 in Treatment Cycle 2 | 
| Percentage of Participants With Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 3 | The Modified TBS is a single-item scale which assesses the participant's condition (urinary problems, urinary incontinence) on a 4-point scale where 1 = greatly improved; 2 = improved; 3 = not changed; and 4 = worsened. A participant was considered to have a positive treatment response if they responded to the TBS question as either greatly improved or improved. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. | Week 6 in Treatment Cycle 3 |