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

Phase 3
Terminated
Conditions
Urinary Incontinence
Urinary Bladder
Overactive
Interventions
Biological: BOTOX®
Registration Number
NCT02097121
Lead Sponsor
Allergan
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
56
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
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Botox 25 UBOTOX®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.
Botox 100 UBOTOX®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.
Botox 50 UBOTOX®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.
Primary Outcome Measures
NameTimeMethod
Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1From Baseline to 2 consecutive days in the week prior to Week 12 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.

Secondary Outcome Measures
NameTimeMethod
Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Micturition EpisodesFrom Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1

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.

Change From Study Baseline in the Daily Average Frequency of Normalized Daytime Urgency EpisodesFrom Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1

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.

Percentage of Participants With Night Time Urinary IncontinenceFrom Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1

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.

Change From Study Baseline in the Daily Average Volume Voided Per Micturition (mL)From Baseline to 2 consecutive days in the week prior to Week 12 in Treatment Cycle 1

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.

Change From Study Baseline in Pediatric Urinary Incontinence Quality of Life Total Score (PinQ)From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1

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.

Change From Study Baseline in PinQ Item 'I am Worried That People Might Think my Clothes Smell Like Pee"From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1

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.

Change From Study Baseline in PinQ Item 'My Bladder Problem Makes me Feel Bad About Myself"From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1

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.

Change From Study Baseline in PinQ Item 'I Miss Out on Being With Friends Because of my Bladder Problems"From Day 1 Prior to Treatment to Week 12 in Treatment Cycle 1

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.

Percentage of Participants With a Positive Treatment Response in the Modified Treatment Benefit ScaleAt Week 12 in Treatment Cycle 1

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.

Time to Participant's First Request for RetreatmentFrom the day of BOTOX treatment in Treatment Cycle 1 to the request for subsequent treatment

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.

Time to Participant's Qualification for RetreatmentFrom the day of BOTOX treatment in Treatment Cycle 1 to the 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.

Trial Locations

Locations (39)

Duplicate_CHU Bordeaux-Hopital Pellegrin /ID# 237392

🇫🇷

Bordeaux, France

Evangelisches Krankenhaus Bielefeld /ID# 235234

🇩🇪

Bielefeld, Germany

Alberta Children's Hospital /ID# 237510

🇨🇦

Calgary, Alberta, Canada

London Health Sciences Center /ID# 234304

🇨🇦

London, Ontario, Canada

Urologische Gemeinschaftspraxis /ID# 234978

🇩🇪

Emmendingen, Germany

Universitaetsklinikum Schleswig-Holstein Campus Luebeck /ID# 234288

🇩🇪

Luebeck, Germany

Universitair Ziekenhuis Antwerpen /ID# 237997

🇧🇪

Edegem, Antwerpen, Belgium

Specjalistyczny Gabinet Lekarski /ID# 235257

🇵🇱

Poznan, Poland

AOU Universita degli Studi della Campania Luigi Vanvitelli /ID# 237308

🇮🇹

Napoli, Italy

NHS Greater Glasgow and Clyde /ID# 237430

🇬🇧

Glasgow, Scotland, United Kingdom

Medical Concierge Centrum Medyczne /ID# 235200

🇵🇱

Warszawa, Poland

Children's Hospital Colorado /ID# 237621

🇺🇸

Aurora, Colorado, United States

Hôpital de la Mère et de l'Enfant /ID# 235227

🇫🇷

Limoges, France

Alaska Urological Institute /ID# 238189

🇺🇸

Anchorage, Alaska, United States

Fakultni nemocnice Olomouc /ID# 237577

🇨🇿

Olomouc, Czechia

Cook Children's Med. Center /ID# 237539

🇺🇸

Fort Worth, Texas, United States

Universitair Ziekenhuis Leuven /ID# 237218

🇧🇪

Leuven, Vlaams-Brabant, Belgium

Associated Urologist of North Carolina /ID# 235437

🇺🇸

Raleigh, North Carolina, United States

Monash Children's Hospital /ID# 234388

🇦🇺

Clayton, Victoria, Australia

UZ Gent /ID# 237588

🇧🇪

Gent, Oost-Vlaanderen, Belgium

Children's Hospital Wisconsin - Milwaukee Campus /ID# 237544

🇺🇸

Milwaukee, Wisconsin, United States

Arkansas Children's Hospital /ID# 237787

🇺🇸

Little Rock, Arkansas, United States

Hôpitaux Pédiatriques de Nice CHU-LENVAL /ID# 235278

🇫🇷

Nice, France

Maastricht Universitair Medisch Centrum /ID# 237678

🇳🇱

Maastricht, Netherlands

Sydney Children's Hospital /ID# 237191

🇦🇺

Randwick, New South Wales, Australia

NHS Grampian /ID# 237379

🇬🇧

Aberdeen, United Kingdom

Royal Berkshire NHS Foundation Trust /ID# 236915

🇬🇧

Reading, United Kingdom

CHUS - Hopital Fleurimont /ID# 237668

🇨🇦

Sherbrooke, Quebec, Canada

Radboud Universitair Medisch Centrum /ID# 237043

🇳🇱

Nijmegen, Gelderland, Netherlands

St Georges Hospital /ID# 235316

🇿🇦

Port Elizabeth, South Africa

Oslo University Hospital /ID# 234434

🇳🇴

Oslo, Norway

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu /ID# 238166

🇵🇱

Wroclaw, Dolnoslaskie, Poland

Manchester University NHS Foundation Trust /ID# 234380

🇬🇧

Manchester, Lancashire, United Kingdom

Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 234819

🇬🇧

Norwich, Norfolk, United Kingdom

Alder Hey Children's NHS Foundation Trust /ID# 237279

🇬🇧

Liverpool, United Kingdom

The Children's Hospital at Westmead /ID# 234337

🇦🇺

Sydney, New South Wales, Australia

Orlando Health-Arnold Palmer Hospital for Children Pediatric Urology /ID# 235283

🇺🇸

Orlando, Florida, United States

Sheffield Children's NHS Foundation Trust /ID# 237854

🇬🇧

Sheffield, United Kingdom

Yale New Haven Hospital - Yale School of Medicine /ID# 238222

🇺🇸

New Haven, Connecticut, United States

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