BOTOX® in the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Patients 8 to 17 Years of Age

Phase 1

• Conditions: rinary Incontinence Due to Neurogenic Detrusor Overactivity; MedDRA version: 16.0Level: PTClassification code 10046543Term: Urinary incontinenceSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2012-004877-26-IT
• Lead Sponsor: Allergan Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-06-06
• Study Completion: 2018-10-11
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 114

Inclusion Criteria

1. written informed consent has been obtained from the legally authorized representative and written minor assent has been obtained, in accordance with local laws and institutional review board (IRB)/independent ethics committee (IEC) requirements.

2. written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information (US sites) and written Data Protection consent (European sites).

3. male or female, aged = 8 years to = 17 years of age at the time of informed consent.

4. patient has NDO based on either:
- presence of an IDC during the urodynamic assessment performed in the screening period or on day 1 (prior to randomization), or
- documented presence of an IDC from an historical urodynamic assessment within 12 months of screening

5. patient has NDO due to either:
- spinal dysraphism, which includes spina bifida and all forms of tethered cord (eg, myelomeningocele, meningocele), or
- acquired NDO from a spinal cord injury, with the injury having occurred at least 6 months prior to screening, or
- acquired NDO due to transverse myelitis with diagnosis at least 18 monthsprior to screening

6. spinal lesion/injury must be at thoracic level T1 or below

7. patient must be regularly using CIC to empty the bladder (CIC can be performed by either the patient or the parent/caregiver):
- the CIC schedule must be at least 3 times per day
-CIC must have been initiated at least 3 months prior to screening

8. patient has a total of = 4 daytime urinary incontinence episodes over the 2-day bladder diary completed during the screening period, despite regular CIC(daytime is defined as time between waking up to start the day and going to bed to sleep for the night)

9. patient has not been adequately managed with 1 or more anticholinergic agents for the treatment of NDO in the opinion of the investigator. This includes patients who are still incontinent despite anticholinergic therapy, experiencing intolerable side effects, or are unwilling to continue to take the medication for any reason:
- if continuing to take anticholinergics, patients should be willing to
maintain a stable dose throughout the study (this does not include
intravesical anticholinergics, which are not permitted). The stable dose, as determined by the investigator, should have been established prior to the start of screening.
- if not continuing to take anticholinergics, patients should stop their use for at least 7 days prior to the start of the screening bladder diary.

10. negative urine pregnancy test for females who are postmenarche.

11. patient is able to complete study requirements including completion of bladder diaries and HRQOL questionnaires (these can also be completed by the parent/caregiver), and is likely to attend study visits in the opinion of the investigator
Are the trial subjects under 18? yes
Number of subjects for this age range: 132
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. patient has an uncontrolled systemic disease, previous or current diagnosis of malignancy.

2. patient has had surgery of the spinal cord within 6 months of screening.

3. patient has a history or evidence of any pelvic or urological abnormalities, except NDO, including:
o bladder neck surgery resulting in an open bladder neck, or reconstructive surgery of the lower urinary tract (eg, urostomy, urinary diversion)
o anatomical evidence of bladder outlet obstruction, urethral or urethral valve obstruction/stricture at screening
o surgery of the urinary tract (including minimally invasive surgery) within 6 months of screening (except those listed above which are exclusionary for any time period).
o circumcision within 1 month of screening
4. patient has cerebral palsy
5. patient has uncontrolled epilepsy, defined as:
o more than 1 generalized seizure per month within 3 months prior to screening, or history of prolonged seizures or repetitive seizure activity requiring administration of a rescue benzodiazepine (oral, rectal, etc) more than once a month, seizures lasting more than 10 minutes, status epilepticus, or epilepsy with autonomic involvement within 9 months
prior to screening.

6. patient has history of dysphagia, aspiration pneumonia, or significant lung disease (eg, bronchiectasis)

7. patient has predominance of stress incontinence, in the opinion of the investigator

8. patient currently uses or plans to use a baclofen pump

9. patient currently uses or plans to use an implantable or nonimplantable electrostimulation/neuromodulation device for treatment of NDO. (If a nonimplantable device is used, it must be discontinued at least 7 days prior to the first screening procedure; if a device is implanted, it must be inactive for at least 4 weeks prior to the first screening procedure; neither should be used during the study).

10. patient uses an indwelling catheter for treatment of NDO

11. patient has had previous or current botulinum toxin therapy of any serotype for any urological condition, or treatment with botulinum toxin of any serotype within 3 months of randomization/day 1 for any other condition or use

12. patient has been treated with intravesical capsaicin or resiniferatoxin within 12 months of screening

13. patient has been treated with an intravesical anticholinergic within 4 weeks of screening

14. patient has a known allergy or sensitivity to components of any botulinum toxin preparation (including the
study medication preparation), anesthetics, or antibiotics to be used during the study

15. postmenarche female patients who are pregnant, nursing, or planning to become pregnant during the study
(postmenarche female patients must also either be sexually abstinent or use another acceptable form of
contraception – see Section 4.5.1.1)

16. patient has a condition or is in a situation which in the investigator’s opinion may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient’s participation in the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this study is to evaluate the safety and efficacy of BOTOX for the treatment of urinary incontinence due to Neurogenic Detrusor Overactivity (NDO) in patients 8 to 17 years of age who have not been adequately managed with anticholinergic therapy.;Secondary Objective: Not applicable;Primary end point(s): The primary efficacy measure is the number of daytime urinary incontinence episodes as recorded in the 2-day bladder diary during the week preceding each study visit. ;Timepoint(s) of evaluation of this end point: The primary timepoint is week 6 after treatment.