Clinical trial NCT01981954: A Clinical Study to Investigate How Solifenacin Fluid is Taken up, How Long it Stays in the Body and How Effective and Safe it is in Treating Children Aged From 6 Months to Less Than 5 Years With Symptoms of Neurogenic Detrusor Overactivity (NDO)
Official title: A Phase 3, Open-Label, Baseline-controlled, Multi-center, Sequential Dose-Titration Study to Assess the Pharmacokinetics, Long-Term Efficacy and Safety of Solifenacin Succinate Suspension in Children From 6 Months to Less Than 5 Years of Age With Neurogenic Detrusor Overactivity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neurogenic Detrusor Overactivity
Pediatric
Keywords: Solifenacin succinate suspension
Efficacy
Safety
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2013-11-13
Enrollment: 23
Sex: ALL
Minimum age (years): 6
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate long term efficacy and safety of treatment with solifenacin succinate (the study drug) in children with neurogenic detrusor overactivity after multiple dose administration.

Detailed description: In some children with a severe form of spina bifida (which is the consequence of a spinal cord defect), the bladder muscle (detrusor) contracts strongly and without warning (also known as neurogenic detrusor overactivity) and the urethra (the passage connecting the bladder with outside) does not relax. Though these children cannot void, urine leakage can happen when the overactive contractions are strong, and/or the pressure in the bladder is so high that it overcomes the closed urethra (overflow at high filling bladder pressure). This high bladder pressure puts these children at risk for kidney damage and can decrease the quality of the bladder. Therapy was aimed to decrease the high filling bladder pressure and the overactive detrusor contractions.

Eligibility criteria: Inclusion Criteria:

* Myelomeningocoele
* Documented diagnosis of NDO, confirmed by urodynamics
* DSD (detrusor sphincter dyssynergia)
* Practicing clean intermittent catheterization (CIC)

Exclusion Criteria:

* Know genitourinary condition (other than NDO) that may cause incontinence
* Bladder augmentation surgery
* Current faecal impaction
* Electro-stimulation therapy within 2 weeks prior to visit
* Subjects with the following gastro-intestinal problems: partial or complete obstructions, decreased motility like paralytic ileus, subjects at risk of gastric retention
* Reflux grade 3 to 5
* Current urinary tract infection

Primary outcomes:
measure: Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC)
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change From Baseline to Weeks 3, 6, 9, 12 and 52 in MCC
timeFrame: Baseline and Weeks 3, 6, 9, 12, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Compliance
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure at End of Bladder-Filling
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure 5 Minutes After End of Bladder-Filling
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Catheterized Volume 5 Minutes After End of Bladder-Filling
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume Until First Detrusor Contraction (> 15 cmH2O)
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 10 cmH20 Detrusor Pressure
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 20 cmH20 Detrusor Pressure
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 30 cmH20 Detrusor Pressure
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Number of Overactive Detrusor Contractions (> 15 cmH2O) Until Leakage or End of Bladder-Filling
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average Catheterized Volume Per Catheterization
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 36, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Maximum Catheterized Volume (MCV)
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 36, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average First Morning Catheterized Volume
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 36, 52
measure: Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Mean Number of Periods Between the Clean Intermittent Catheterizations (CICs) With Incontinence Per 24 Hours
timeFrame: Baseline and Weeks 3, 6, 9, 12, 24, 36, 52
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day at Baseline
timeFrame: 3 days prior to Baseline visit
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 3
timeFrame: 3 days prior to Week 3 visit
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 6
timeFrame: 3 days prior to Week 6 visit
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 9
timeFrame: 3 days prior to Week 9 visit
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 12
timeFrame: 3 days prior to Week 12 visit
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 24
timeFrame: 3 days prior to Week 24 visit
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 36
timeFrame: 3 days prior to Week 36 visit
measure: Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 52
timeFrame: 3 days prior to Week 52 visit
measure: Percentage of Days With Incontinence for Each Hour of 24 Hour Day at Baseline
timeFrame: 3 days prior to Baseline visit
measure: Percentage of Days With of Incontinence for Each Hour of 24 Hour Day During Week 3
timeFrame: 3 days prior to Week 3 visit
measure: Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 6
timeFrame: 3 days prior to Week 6 visit
measure: Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 9
timeFrame: 3 days prior to Week 9 visit
measure: Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 12
timeFrame: 3 days prior to Week 12 visit
measure: Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 24
timeFrame: 3 days prior to Week 24 visit
measure: Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 36
timeFrame: 3 days prior to Week 36 visit
measure: Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 52
timeFrame: 3 days prior to Week 52 visit
measure: Change From Baseline to Week 24 and 52 in Infant and Toddler Quality of Life Short Form-47 Questionnaire (ITQoL SF-47) - Overall Health Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Physical Abilities Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Growth and Development Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Pain Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Temperament and Moods Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Behaviour Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - General Health Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Change in Health Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Parent-Emotional Impact Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Parent-Time Impact Score
timeFrame: Baseline and Weeks 24, 52
measure: Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Family Cohesion Impact Score
timeFrame: Baseline and Weeks 24, 52
Other outcomes:
Locations:
city: Tarrytown
country: United States
facility: Site US1008 Pediatric Urology Associates, P.C.
state: New York
city: Gent
country: Belgium
facility: Site BE3203 Gent University Hospital
city: Seoul
country: Korea, Republic of
facility: Site KR8207 Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Site KR8201 Severance Hospital
city: Manila
country: Philippines
facility: Site PH6301 Philippines Children's Medical Center
city: Gdansk
country: Poland
facility: Site PL4803 Uniwersyteckie Centrum Kliniczne
city: Warszawa
country: Poland
facility: Site PL4801 Pomnik-Centrum Zdrowia Dziecka
city: Sheffield
country: United Kingdom
facility: Site GB4401 Sheffield Children's Hospital
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Tannenbaum S, den Adel M, Krauwinkel W, Meijer J, Hollestein-Havelaar A, Verheggen F, Newgreen D. Pharmacokinetics of solifenacin in pediatric populations with overactive bladder or neurogenic detrusor overactivity. Pharmacol Res Perspect. 2020 Dec;8(6):e00684. doi: 10.1002/prp2.684.
citation: Franco I, Hoebeke P, Baka-Ostrowska M, Bolong D, Davies LN, Dahler E, Snijder R, Stroosma O, Verheggen F, Newgreen D, Bosman B, Vande Walle J. Long-term efficacy and safety of solifenacin in pediatric patients aged 6 months to 18 years with neurogenic detrusor overactivity: results from two phase 3 prospective open-label studies. J Pediatr Urol. 2020 Apr;16(2):180.e1-180.e8. doi: 10.1016/j.jpurol.2019.12.012. Epub 2019 Dec 27.