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

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

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.

Study Overview

• Status: Terminated
• Conditions: Urinary Incontinence; Urinary Bladder; Overactive
• Intervention / Treatment: Biological: BOTOX®

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Sydney Children's Hospital /ID# 237191
    • Sydney, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead /ID# 234337
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Children's Hospital /ID# 234388
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen /ID# 237997
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 237588
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven /ID# 237218
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital /ID# 237510
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Center /ID# 234304
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CHUS - Hopital Fleurimont /ID# 237668
• Czechia
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc /ID# 237577
• France
  • Bordeaux, France, 33076
    • Duplicate_CHU Bordeaux-Hopital Pellegrin /ID# 237392
  • Limoges, France, 87042
    • Hôpital de la Mère et de l'Enfant /ID# 235227
  • Nice, France, 06200
    • Hôpitaux Pédiatriques de Nice CHU-LENVAL /ID# 235278
• Germany
  • Bielefeld, Germany, 33617
    • Evangelisches Krankenhaus Bielefeld /ID# 235234
  • Emmendingen, Germany, 79312
    • Urologische Gemeinschaftspraxis /ID# 234978
  • Luebeck, Germany, 23538
    • Universitaetsklinikum Schleswig-Holstein Campus Luebeck /ID# 234288
• Italy
  • Napoli, Italy, 80138
    • AOU Universita degli Studi della Campania Luigi Vanvitelli /ID# 237308
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Maastricht Universitair Medisch Centrum /ID# 237678
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud Universitair Medisch Centrum /ID# 237043
• Norway
  • Oslo, Norway, 0372
    • Oslo University Hospital /ID# 234434
• Poland
  • Poznan, Poland, 61-512
    • Specjalistyczny Gabinet Lekarski /ID# 235257
  • Warszawa, Poland, 02-798
    • Medical Concierge Centrum Medyczne /ID# 235200
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu /ID# 238166
• South Africa
  • Port Elizabeth, South Africa, 6001
    • St Georges Hospital /ID# 235316
• United Kingdom
  • Aberdeen, United Kingdom, AB15 6RE
    • NHS Grampian /ID# 237379
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's NHS Foundation Trust /ID# 237279
  • Reading, United Kingdom, RG1 5AN
    • Royal Berkshire NHS Foundation Trust /ID# 236915
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children's NHS Foundation Trust /ID# 237854
  • Lancashire
    • Manchester, Lancashire, United Kingdom, M13 9WL
      • Manchester University NHS Foundation Trust /ID# 234380
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 234819
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0XH
      • NHS Greater Glasgow and Clyde /ID# 237430
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99503-3902
      • Alaska Urological Institute /ID# 238189
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital /ID# 237787
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado /ID# 237621
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3206
      • Yale New Haven Hospital - Yale School of Medicine /ID# 238222
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Health-Arnold Palmer Hospital for Children Pediatric Urology /ID# 235283
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Associated Urologist of North Carolina /ID# 235437
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Med. Center /ID# 237539
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital Wisconsin - Milwaukee Campus /ID# 237544

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botox 25 U; 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®; 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.; Other Names: Botulinum Toxin Type A
Experimental: Botox 50 U; 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®; 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.; Other Names: Botulinum Toxin Type A
Experimental: Botox 100 U; 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®; 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.; 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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.	From the first dose of study drug until the last dose, up to 147 weeks

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

Helpful Links

• Additional information on study locations near you may be found at AllerganClinicalTrials.com.,To be considered as a site for current and future Allergan Clinical Trials, please register using the Investigator Databank link.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2014
• Primary Completion (Actual): February 10, 2022
• Study Completion (Actual): February 10, 2022

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Actual): December 28, 2022
• Last Update Submitted That Met QC Criteria: November 23, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Urinary Bladder, Overactive; Urinary Incontinence; Enuresis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 191622-137; 2014-000464-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No