OnabotulinumtoxinA for the Treatment of Urinary Incontinence Due to Overactive Bladder in Pediatric Patients (12 to 17)

Study Overview
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Brief Summary
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This was a multicenter, randomized, double-blind, parallel-group, multiple-dose study to evaluate the efficacy and safety of BOTOX in adolescents with urinary incontinence due to overactive bladder (OAB) with inadequate management with anticholinergic therapy. Participants were randomized in a 1:1:1 ratio to receive a single Tx of 25 U, 50 U, or 100 U BOTOX (not to exceed 6 U/kg) on Day 1, were seen after each treatment at Weeks 2, 6, and 12 post-treatment, and thereafter at alternating telephone and clinic visits every 6 weeks until they qualified for further retreatment/exited the study. Participants could receive multiple treatments dependent upon the number and timing of patient requests/qualification for retreatment. At each retreatment the investigator could keep the dose the same or increase it one dose level in a blinded fashion. Participants exited the study once 96 weeks have elapsed since entry on Day 1 and at least 12 weeks follow-up since their last study treatment had occurred.

Official Title
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BOTOX® in the Treatment of Urinary Incontinence Due to Overactive Bladder in Patients 12 to 17 Years of Age

Conditions
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Urinary Incontinence, Urinary Bladder, Overactive

Intervention / Treatment
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* Biological: BOTOX®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of overactive bladder (OAB) (frequency/urgency) with urinary incontinence for at least 6 months OAB symptoms not adequately managed by 1 or more anticholinergic agents Exclusion Criteria OAB caused by a neurological condition Use of anticholinergics or other medications to treat OAB symptoms within 7 days Current use of indwelling catheter or 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: 12 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botox 25 U<br>Participants randomized to receive 25 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment. | Biological: BOTOX®<br>* Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.<br>* Other names: Botulinum Toxin Type A;|
| Experimental: Botox 50 U<br>Participants randomized to receive 50 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment. | Biological: BOTOX®<br>* Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.<br>* Other names: Botulinum Toxin Type A;|
| Experimental: Botox 100 U<br>Participants randomized to receive 100 Units (U) BOTOX (not to exceed 6 U/kg), administered via cystoscopy as 20 intradetrusor injections of 0.5 mL each, sparing the trigone. Posttreatment follow-up clinic visits occurred at Weeks 2, 6, and 12. Participants could request retreatment from Week 12 and 12 weeks after each subsequent treatment for up to 4 cycles. The retreatment dose was determined by the Investigator and could be at the same dose or at the next higher dose compared with the preceding treatment. | Biological: BOTOX®<br>* Each vial of BOTOX (Botulinum Toxin Type A) purified neurotoxin complex, formulation No. 9060X contains 100 U of Clostridium botulinum toxin Type A, 0.5 mg albumin (human), and 0.9 mg sodium chloride in a sterile, vacuum-dried form without a preservative. The study medication was to be reconstituted with 0.9% sodium chloride (preservative-free). The 10 mL of study drug was to be administered as 20 injections each of 0.5 mL. Under direct cystoscopic visualization, injections were to be distributed evenly across the detrusor wall and spaced approximately 1 cm apart. To avoid injecting the trigone, the injections were to be at least 1 cm above the trigone. The injection needle was to be inserted approximately 2 mm into the detrusor for each injection.<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 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 per the respective treatments that participants received in the corresponding treatment cycle. | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition Episodes | Micturition was defined as toilet voids 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 micturition episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | 
| Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency Episodes | Participants recorded daytime urgency episodes 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 urgency episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | 
| Percentage of Participants With Night Time Urinary Incontinence | Urinary incontinence was defined as involuntary loss of urine. Participants recorded night time urinary incontinence episodes in a bladder diary during 2 consecutive days in the week prior to the study visit. Night time is defined as the time between going to bed to sleep for the night and waking up to start the next day. The number of daily night time urinary incontinence episodes were averaged during the 2-day period. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | 
| Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL) | The volume per micturition was derived from the total urine volume voided over 1 daytime period during the 2-day bladder diary collection period divided by the number of voids in the same daytime period. Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. A negative change from Baseline indicates improvement. Data are summarized per the respective treatments that participants received in the corresponding treatment cycle. | From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1 | 
| Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ) | The PinQ is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time) and a total sum score is calculated (from 0 to 80), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | 
| Change From Study Baseline in PinQ Item 'I am Worried That People Might Think my Clothes Smell Like Pee | The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | 
| Change From Study Baseline in PinQ Item 'My Bladder Problem Makes me Feel Bad About Myself | The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | 
| Change From Study Baseline in PinQ Item 'I Miss Out on Being With Friends Because of my Bladder Problems | The Pediatric Urinary Incontinence Quality of (PinQ) is a 20-item questionnaire that asks about the participant's incontinence and its consequences in daily life and relationships. Items are answered on a Likert-type scale of 0 (no) to 4 (all of the time), with higher scores indicating lower health-related quality of life. A negative change from Baseline indicates improvement. | From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1 | 
| Percentage of Participants With a Positive Treatment Response in the Modified Treatment Benefit Scale | The Modified Treatment Benefit Scale (Modified TBS) is a single-item scale designed to assess the change in the participant's overactive bladder (OAB) condition following treatment. The participant's current condition (urinary problems, urinary incontinence) is compared to their condition prior to receipt of any study treatment by selection of greatly improved, improved, not changed or worsened. Participants who selected greatly improved or improved were considered to have a positive treatment response. | At Week 12 in Treatment Cycle 1 | 
| Time to Participant's First Request for Retreatment | The time from the day of BOTOX treatment to the request for the subsequent treatment was estimated using a Kaplan-Meier survival method for each treatment group. Participants who did not request retreatment were treated as censored at the time of their last study visit or study exit. | From the day of BOTOX treatment in Treatment Cycle 1 to the request for subsequent treatment | 
| Time to Participant's Qualification for Retreatment | The time from the day of BOTOX treatment to the qualification for retreatment was estimated using a Kaplan-Meier survival method for each treatment group. Participants who did not qualify for retreatment were treated as censored at the time of their last study visit or study exit. | From the day of BOTOX treatment in Treatment Cycle 1 to the qualification for retreatment |