Clinical trial NCT01565694: A Study to Assess the Long Term Effect, Safety and Metabolism of a Solifenacin Liquid Suspension in Participants 5 to 18 Years of Age With Neurogenic Detrusor Overactivity
Official title: A Phase 3, Open-Label, Baseline-controlled, Multicenter, Sequential Dose Titration Study to Assess the Long-Term Efficacy and Safety, and the Pharmacokinetics of Solifenacin Succinate Suspension in Patients From 5 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity (NDO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neurogenic Detrusor Overactivity
Keywords: Cognitive Function
Phase 3
Neurogenic Detrusor Overactivity
Pharmacokinetics
Ocular Accommodation
Urodynamics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-03-29
Enrollment: 76
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
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 investigate a medicine for the treatment of symptoms and complications of neurogenic detrusor overactivity (NDO) in children and adolescents.

Detailed description: The NDO often occurs in patients with spina bifida or other spinal cord damage where the bladder muscle contracts more than normal during filling. These patients often have an inability to void, so that catheterization is required to empty the bladder.

The medicine being tested in this study is called solifenacin succinate. Solifenacin tablets are given to adults for the treatment of overactive bladder. A new liquid suspension has been developed to treat children and adolescents in this and other studies.

The efficacy and safety of the solifenacin suspension was investigated. The take-up and length of time that the solifenacin suspension stays in the body was also investigated during this study. Effectiveness was measured by urodynamics (the filling and emptying of the bladder) and the urine volumes during catheterization together with the diary responses relating to the number of incontinence episodes or incontinence free days.

Safety assessments included analysis of the blood and urine, review of the electrocardiogram (ECG), ultrasound of the kidney, simple memory and understanding tests (cognitive function) and the ability to see near and far objects (visual accommodation).

Eligibility criteria: Inclusion Criteria:

* Documented diagnosis of NDO, confirmed by urodynamics
* Practicing clean intermittent catheterization (CIC)
* Currently on treatment with an antimuscarinic drug

Exclusion Criteria:

* Known genitourinary condition (other than NDO) that may cause incontinence
* Bladder augmentation surgery
* Current Faecal impaction
* Electro-stimulation therapy within 2 weeks prior to screening and at any time during the study
* Subjects with the following gastro-intestinal problems: partial or complete obstruction, decreased motility like paralytic ileus, subjects at risk of gastric retention
* Reflux grade 3 or 4
* Current urinary tract infection (UTI)
* Subject has severe renal impairment (glomerular filtration rate \< 30 ml/min)
* Subject has severe hepatic impairment (Child-Pugh score \> 9).
* Subject has received intra-vesical botulinum toxin within 9 months prior to screening

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 Last Possible Titration Step in Maximum Cystometric Capacity
timeFrame: Baseline, Week 9 or Week 12
measure: Change From Baseline in Bladder Compliance
timeFrame: Baseline and Week 24
measure: Change From Baseline in Bladder Volume (mL) Until First Detrusor Contraction > 15 cmH2O as a Percentage of Expected Bladder Capacity (EBC)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Bladder Volume at 30 cmH2O Detrusor Pressure
timeFrame: Baseline and Week 24
measure: Change From Baseline in Bladder Volume at 40 cmH2O Detrusor Pressure
timeFrame: Baseline and Week 24
measure: Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cmH2O) Until End of Bladder Filling
timeFrame: Baseline to Week 24
measure: Change From Baseline in Detrusor Pressure at the End of Bladder Filling
timeFrame: Baseline to Week 24
measure: Change From Baseline in Average Catheterized Volume Per Catheterization
timeFrame: Baseline to Week 24
measure: Change From Baseline in Maximum Catheterized Volume
timeFrame: Baseline to Week 24
measure: Change From Baseline in Average First Morning Catheterized Volume
timeFrame: Baseline to Week 24
measure: Change From Baseline in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline to Week 24
measure: Change From Baseline in Number of Dry (Incontinence-Free) Days Per 7 Days
timeFrame: Baseline to Week 24
measure: Change From Baseline in Number of Dry (Incontinence-Free) Nights Per 7 Days
timeFrame: Baseline to Week 24
measure: Change From Baseline in Quality of Life [QoL] (PinQ Questionnaire Score)
timeFrame: Baseline to Week 24
measure: Number of Participants With Adverse Events
timeFrame: Baseline to End of Study Visit (Week 52)
Other outcomes:
Locations:
city: Tarrytown
country: United States
facility: Site US1008
state: New York
city: Cincinnati
country: United States
facility: Site US1010
state: Ohio
city: Gent
country: Belgium
facility: Site BE3201
city: Sao Jose do Rio Preto
country: Brazil
facility: Site BR5505
state: São Paulo
city: Campinas
country: Brazil
facility: Site BR5507
city: Campinas
country: Brazil
facility: Site BR5504
city: Curitiba
country: Brazil
facility: Site BR5506
city: Porto Alegre
country: Brazil
facility: Site BR5503
city: Aarhus
country: Denmark
facility: Site DK4501
city: Miskolc
country: Hungary
facility: Site HU3602
city: Seoul
country: Korea, Republic of
facility: Site KR8207
city: Seoul
country: Korea, Republic of
facility: Site KR8201
city: Leon
country: Mexico
facility: Site MX5203
city: Mexico City
country: Mexico
facility: Site MX5205
city: Manila
country: Philippines
facility: Site PH6301
city: Quezon City
country: Philippines
facility: Site PH6302
city: Gdansk
country: Poland
facility: Site PL4803
city: Gdansk
country: Poland
facility: Site PL4805
city: Warszawa
country: Poland
facility: Site PL4801
city: Ankara
country: Turkey
facility: Site TR9003
city: Izmir
country: Turkey
facility: Site TR9002
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_CHAIR
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.