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: 16.1Level: PTClassification code 10046543Term: Urinary incontinenceSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Not possible to specify

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-13
• Last Update Posted: 10 December 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 132

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 (eg, myelomeningocele, meningocele) and all forms of tethered cord ), 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. neurological 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)
NOTE: If the patient has had a Mitrofanoff procedure, urinary leakage must be via the urethra.

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 and screening urodynamics.

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

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

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

• 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, urinary diversion, urostomy), except for the Mitrofanoff procedure, which is permitted.
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 (eg, bulking agents,
sling), within 6 months of screening (except those listed above which are exclusionary for any time period).
o circumcision within 1 month of screening
• patient has cerebral palsy
• 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.

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

• patient has predominance of stress incontinence, in the opinion of the investigator

• patient currently uses or plans to use a baclofen pump

• 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).

• patient uses an indwelling catheter rather than CIC for treatment of
NDO (NOTE: an indwelling catheter can be used if needed overnight, as long as it is not used during the diary collection periods)

• 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

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

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

• patient has received any other medications or therapies, other than
anticholinergics, to treat the symptoms of NDO within 7 days of the start of the screening period procedures and during the study

• 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

• 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)

• 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