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NCT01852045

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

Completed Phase 3 Results posted Last updated 21 November 2019
What this trial tests

Phase 3 trial testing OnabotulinumtoxinA in Urinary Incontinence in 114 participants. Completed in 11 October 2018.

Timeline
2 July 2013
Primary endpoint
11 October 2018
11 October 2018

Quick facts

Lead sponsorAllergan
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment114
Start date2 July 2013
Primary completion11 October 2018
Estimated completion11 October 2018
Sites31 locations across France, Italy, Belgium, Poland, Canada, United States, Turkey (Türkiye), Czechia

Drugs / interventions tested

Conditions studied

Sponsor

Allergan — full company profile →

Who can join

Adults 5 to 17, any sex, with Urinary Incontinence. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Daily Average Frequency of Daytime Urinary Incontinence Episodes Primary · Baseline (Day -28 to Day -1) to 2 consecutive days prior to Week 6

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U-1.30± 0.205
OnabotulinumtoxinA 100 U-1.30± 0.189
OnabotulinumtoxinA 200 U-1.34± 0.245
Number of Participants With Treatment Emergent Adverse Events (TEAE) Secondary · First study treatment to 12 weeks after last treatment (Up to 48 weeks after first study injection)

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 t

GroupValue95% CI
OnabotulinumtoxinA 50 U27
OnabotulinumtoxinA 100 U33
OnabotulinumtoxinA 200 U23
Change From Baseline in Average Urine Volume at First Morning Catheterization Secondary · Baseline (Day -28 to Day -1) to 2 consecutive days prior to Week 6

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U21.93± 14.676
OnabotulinumtoxinA 100 U34.90± 13.580
OnabotulinumtoxinA 200 U87.49± 17.808
Percentage of Participants With Night Time Urinary Incontinence Secondary · Baseline (Day -28 to Day -1), Week 6

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).

Baseline (BL): 0 nights of incontinence
GroupValue95% CI
OnabotulinumtoxinA 50 U0.0
OnabotulinumtoxinA 100 U13.3
OnabotulinumtoxinA 200 U3.6
BL: 1 night of incontinence
GroupValue95% CI
OnabotulinumtoxinA 50 U13.2
OnabotulinumtoxinA 100 U2.2
OnabotulinumtoxinA 200 U14.3
BL: 2 nights of incontinence
GroupValue95% CI
OnabotulinumtoxinA 50 U86.8
OnabotulinumtoxinA 100 U84.4
OnabotulinumtoxinA 200 U82.1
Week 6: 0 nights of incontinence
GroupValue95% CI
OnabotulinumtoxinA 50 U30.6
OnabotulinumtoxinA 100 U32.6
OnabotulinumtoxinA 200 U28.6
Week 6: 1 night of incontinence
GroupValue95% CI
OnabotulinumtoxinA 50 U16.7
OnabotulinumtoxinA 100 U16.3
OnabotulinumtoxinA 200 U28.6
Week 6: 2 nights of incontinence
GroupValue95% CI
OnabotulinumtoxinA 50 U52.8
OnabotulinumtoxinA 100 U51.2
OnabotulinumtoxinA 200 U42.9
Change From Baseline in Maximum Cystometric Capacity (MCC) Secondary · Baseline (Day -28 to Day -1) to Week 6

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U62.06± 14.339
OnabotulinumtoxinA 100 U48.57± 13.549
OnabotulinumtoxinA 200 U63.55± 17.363
Percentage of Participants With Involuntary Detrusor Contractions (IDC) Secondary · Baseline (Day -28 to -1) and Week 6

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.

Baseline
GroupValue95% CI
OnabotulinumtoxinA 50 U94.481.34 – 99.32
OnabotulinumtoxinA 100 U88.174.37 – 96.02
OnabotulinumtoxinA 200 U92.675.71 – 99.09
Week 6
GroupValue95% CI
OnabotulinumtoxinA 50 U61.843.56 – 77.83
OnabotulinumtoxinA 100 U44.728.62 – 61.70
OnabotulinumtoxinA 200 U46.427.51 – 66.13
Change From Baseline in Maximum Detrusor Pressure During the First IDC (PdetMax1stIDC) in Participants With IDC Secondary · Baseline (Day-28 to Day-1) to Week 6

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U-7.64± 5.301
OnabotulinumtoxinA 100 U-12.13± 5.573
OnabotulinumtoxinA 200 U-5.46± 8.267
Change From Baseline in Maximum Detrusor Pressure (PdetMax) During the Storage Phase Secondary · Baseline (Day 1) to Week 6

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U-12.88± 3.793
OnabotulinumtoxinA 100 U-20.09± 3.632
OnabotulinumtoxinA 200 U-27.31± 4.557
Change From Baseline in Detrusor Leak Point Pressure (DLPP) During the Storage Phase Secondary · Baseline (Day -28 to -1) to Week 6

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U9.50± 2.121
OnabotulinumtoxinA 100 U-39.00± 0.000
OnabotulinumtoxinA 200 U12.00± 0.000
Time to Participant Request for Retreatment Secondary · 48 weeks

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U30.623.10 – 39.10
OnabotulinumtoxinA 100 U24.118.10 – 27.60
OnabotulinumtoxinA 200 U29.616.30 – 37.30
Time to Participant Qualification for Retreatment Secondary · 48 weeks

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.

GroupValue95% CI
OnabotulinumtoxinA 50 U35.023.10 – 39.10
OnabotulinumtoxinA 100 U25.020.00 – 32.10
OnabotulinumtoxinA 200 U29.616.30 – 38.00

Adverse events — posted to ClinicalTrials.gov

Time frame: First study treatment to 12 weeks after last treatment (Up to 48 weeks after first study injection). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

OnabotulinumtoxinA 50 U
Serious: 4/38 (11%)
Deaths: 0/38
OnabotulinumtoxinA 100 U
Serious: 3/45 (7%)
Deaths: 0/45
OnabotulinumtoxinA 200 U
Serious: 2/30 (7%)
Deaths: 0/30

Serious adverse events (9 terms)

ReactionSystemOnabotulinumtoxinA 50 UOnabotulinumtoxinA 100 UOnabotulinumtoxinA 200 U
Urinary tract infectionInfections and infestations
CystitisInfections and infestations
Postoperative wound infectionInfections and infestations
Encephalitis viralInfections and infestations
EpididymitisInfections and infestations
OrchitisInfections and infestations
Arteriovenous fistula thrombosisInjury, poisoning and procedural complications
HydrocephalusNervous system disorders
HypertensionVascular disorders
Other adverse events (18 terms — click to expand)

ReactionSystemOnabotulinumtoxinA 50 UOnabotulinumtoxinA 100 UOnabotulinumtoxinA 200 U
Urinary tract infectionInfections and infestations
BacteriuriaInfections and infestations
HeadacheNervous system disorders
PyrexiaGeneral disorders
NasopharyngitisInfections and infestations
LeukocyturiaRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
PharyngitisInfections and infestations
GastroenteritisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
Suprapubic painGeneral disorders
SinusitisInfections and infestations
Limb injuryInjury, poisoning and procedural complications
HydronephrosisRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
AcneSkin and subcutaneous tissue disorders

Most-reported serious reactions: Urinary tract infection, Cystitis, Postoperative wound infection, Encephalitis viral, Epididymitis, Orchitis, Arteriovenous fistula thrombosis, Hydrocephalus.

Data from ClinicalTrials.gov NCT01852045 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children.
    Austin PF, Franco I, Dobremez E, Kroll P, et al · · 2021 · cited 23× · PMID 33305474 · DOI 10.1002/nau.24588
  2. Long-term Safety and Tolerability of Repeated Treatments With OnabotulinumtoxinA in Children With Neurogenic Detrusor Overactivity.
    Franco I, Hoebeke PB, Dobremez E, Titanji W, et al · · 2023 · cited 11× · PMID 36655470 · DOI 10.1097/ju.0000000000003157

Verify or expand the search:

Other trials of OnabotulinumtoxinA

Trials testing the same drug.

Other recruiting trials for Urinary Incontinence

Currently open trials in the same condition.

Other Allergan trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01852045.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing