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

Primary Purpose

Urinary Incontinence

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
OnabotulinumtoxinA
Sponsored by
Allergan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urinary Incontinence

Eligibility Criteria

5 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Cedars-Sinai Medical Center
  • Children's Hospital of Orange County
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Riley Hospital for Children
  • William Beaumont Hospital Research Institute
  • Washington University School of Medicine
  • Pediatric Urology Associates, PC
  • McKay Urology Carolinas Medical Center
  • Duke University Health System
  • Cincinnati Children's Hospital Medical Center
  • Oklahoma Childrens Hospital
  • Medical University of South Carolina
  • Children's Hospital of Wisconsin
  • UZ Antwerpen
  • UZ Gent , Urology
  • UZ Leuven
  • McMaster University Medical Centre
  • CHU Sainte-Justine
  • Fakultni nemocnice Hradec Kralove
  • Fakultni nemocnice Olomouc
  • Hopital Pellegrin - Enfants
  • CHU de Limoges - Hopital Mere et l'Enfant
  • Hopital Trousseau
  • Necker Enfants Malades Hospital
  • Seconda Università di Napoli
  • IRCCS Ospedale Pediatrico Bambino Gesu
  • Copernicus Podmiot Leczniczy Sp. z o. o., Kliniczny Oddzial Chirurgii i Urologii Dzieci i Mlodziezy GUMed
  • Specjalistyczny Gabinet Lekarski
  • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
  • Ankara University Medical Faculty Cebeci Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

OnabotulinumtoxinA 50 U

OnabotulinumtoxinA 100 U

OnabotulinumtoxinA 200 U

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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).
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
May 9, 2013
Last Updated
November 13, 2019
Sponsor
Allergan
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1. Study Identification

Unique Protocol Identification Number
NCT01852045
Brief Title
Study of OnabotulinumtoxinA (BOTOX®) for Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Pediatric Patients
Official Title
BOTOX® in the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Patients 5 to 17 Years of Age
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
July 2, 2013 (Actual)
Primary Completion Date
October 11, 2018 (Actual)
Study Completion Date
October 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allergan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Incontinence

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
114 (Actual)

8. Arms, Groups, and Interventions

Arm Title
OnabotulinumtoxinA 50 U
Arm Type
Experimental
Arm Description
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.
Arm Title
OnabotulinumtoxinA 100 U
Arm Type
Experimental
Arm Description
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.
Arm Title
OnabotulinumtoxinA 200 U
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
OnabotulinumtoxinA
Other Intervention Name(s)
BOTOX®, botulinum toxin Type A
Intervention Description
OnabotulinumtoxinA injected into the detrusor wall on Day 1.
Primary Outcome Measure Information:
Title
Change From Baseline in Daily Average Frequency of Daytime Urinary Incontinence Episodes
Description
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.
Time Frame
Baseline (Day -28 to Day -1) to 2 consecutive days prior to Week 6
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Description
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.
Time Frame
First study treatment to 12 weeks after last treatment (Up to 48 weeks after first study injection)
Title
Change From Baseline in Average Urine Volume at First Morning Catheterization
Description
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.
Time Frame
Baseline (Day -28 to Day -1) to 2 consecutive days prior to Week 6
Title
Percentage of Participants With Night Time Urinary Incontinence
Description
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).
Time Frame
Baseline (Day -28 to Day -1), Week 6
Title
Change From Baseline in Maximum Cystometric Capacity (MCC)
Description
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.
Time Frame
Baseline (Day -28 to Day -1) to Week 6
Title
Percentage of Participants With Involuntary Detrusor Contractions (IDC)
Description
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.
Time Frame
Baseline (Day -28 to -1) and Week 6
Title
Change From Baseline in Maximum Detrusor Pressure During the First IDC (PdetMax1stIDC) in Participants With IDC
Description
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.
Time Frame
Baseline (Day-28 to Day-1) to Week 6
Title
Change From Baseline in Maximum Detrusor Pressure (PdetMax) During the Storage Phase
Description
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.
Time Frame
Baseline (Day 1) to Week 6
Title
Change From Baseline in Detrusor Leak Point Pressure (DLPP) During the Storage Phase
Description
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.
Time Frame
Baseline (Day -28 to -1) to Week 6
Title
Time to Participant Request for Retreatment
Description
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.
Time Frame
48 weeks
Title
Time to Participant Qualification for Retreatment
Description
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.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margarita Furmanov
Organizational Affiliation
Allergan
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46032
Country
United States
Facility Name
William Beaumont Hospital Research Institute
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Pediatric Urology Associates, PC
City
Tarrytown
State/Province
New York
ZIP/Postal Code
10591
Country
United States
Facility Name
McKay Urology Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Oklahoma Childrens Hospital
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
UZ Antwerpen
City
Antwerpen
ZIP/Postal Code
2650
Country
Belgium
Facility Name
UZ Gent , Urology
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
McMaster University Medical Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
CHU Sainte-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Králové
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Fakultni nemocnice Olomouc
City
Olomouc
ZIP/Postal Code
77520
Country
Czechia
Facility Name
Hopital Pellegrin - Enfants
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU de Limoges - Hopital Mere et l'Enfant
City
Limoges
ZIP/Postal Code
87000
Country
France
Facility Name
Hopital Trousseau
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Necker Enfants Malades Hospital
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Seconda Università di Napoli
City
Caserta
ZIP/Postal Code
80138
Country
Italy
Facility Name
IRCCS Ospedale Pediatrico Bambino Gesu
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Copernicus Podmiot Leczniczy Sp. z o. o., Kliniczny Oddzial Chirurgii i Urologii Dzieci i Mlodziezy GUMed
City
Gdansk
ZIP/Postal Code
80-803
Country
Poland
Facility Name
Specjalistyczny Gabinet Lekarski
City
Poznan
ZIP/Postal Code
61-512
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
City
Wroclaw
ZIP/Postal Code
50-369
Country
Poland
Facility Name
Ankara University Medical Faculty Cebeci Hospital
City
Ankara
ZIP/Postal Code
6100
Country
Turkey

12. IPD Sharing Statement

Links:
URL
http://www.allerganclinicaltrials.com
Description
Additional information on study locations near you may be found at AllerganClinicalTrials.com. For any study not on AllerganClinicalTrials.com, please contact IR-CTRegistration@Allergan.com for assistance.

Learn more about this trial

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

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