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

Neurogenic Detrusor Overactivity Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565694
• Other study ID #: 905-CL-047
• Secondary ID: 2011-000330-11
• Status: Completed
• Phase: Phase 3
• Start date: August 14, 2012
• Est. completion date: April 28, 2016

Study information

• Verified date: February 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: April 28, 2016
• Est. primary completion date: April 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Neurogenic Detrusor Overactivity

Intervention

Drug:
• Solifenacin succinate
Oral suspension administered once a day via syringe.

Locations

Country	Name	City	State
Belgium	Site BE3201	Gent
Brazil	Site BR5504	Campinas
Brazil	Site BR5507	Campinas
Brazil	Site BR5506	Curitiba
Brazil	Site BR5503	Porto Alegre
Brazil	Site BR5505	Sao Jose do Rio Preto	São Paulo
Denmark	Site DK4501	Aarhus
Hungary	Site HU3602	Miskolc
Korea, Republic of	Site KR8201	Seoul
Korea, Republic of	Site KR8207	Seoul
Mexico	Site MX5203	Leon
Mexico	Site MX5205	Mexico City
Philippines	Site PH6301	Manila
Philippines	Site PH6302	Quezon City
Poland	Site PL4803	Gdansk
Poland	Site PL4805	Gdansk
Poland	Site PL4801	Warszawa
Turkey	Site TR9003	Ankara
Turkey	Site TR9002	Izmir
United States	Site US1010	Cincinnati	Ohio
United States	Site US1008	Tarrytown	New York

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Denmark,  Hungary,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC)	During urodynamic assessments, the bladder was filled until voiding/leakage begins, or until it was stopped because either the participant experiences pain or discomfort or 135% of expected bladder capacity for age has been reached. MCC is the maximum bladder capacity reached during filling cystometry before either leakage or pain/discomfort was observed.	Baseline and Week 24
Secondary	Change From Baseline to Last Possible Titration Step in Maximum Cystometric Capacity	During urodynamic assessments, the bladder was filled until voiding/leakage begins, or until it was stopped because either the participant experiences pain or discomfort or 135% of expected bladder capacity for age has been reached. MCC is the maximum bladder capacity reached during filling cystometry before either leakage or pain/discomfort was observed. Based on study requirements, the last possible titration step was Week 9 for participants enrolled under versions 1.0 and 1.1 and Week 12 under later versions.	Baseline, Week 9 or Week 12
Secondary	Change From Baseline in Bladder Compliance	Bladder compliance gives an indication of the elasticity of the bladder wall and was calculated by dividing the change in volume by the change in detrusor pressure during the filling of the bladder.	Baseline and Week 24
Secondary	Change From Baseline in Bladder Volume (mL) Until First Detrusor Contraction > 15 cmH2O as a Percentage of Expected Bladder Capacity (EBC)	Change from baseline in the bladder volume was calculated using urodyanamic assessments. During urodynamic assessments, the bladder is filled until voiding/leakage begins, or until it is stopped because either the subject experiences pain or discomfort or 135% of expected bladder capacity for age has been reached. If no detrusor contraction of at least 15 cmH2O occurs, the bladder volume was imputed with MCC.	Baseline and Week 24
Secondary	Change From Baseline in Bladder Volume at 30 cmH2O Detrusor Pressure	Bladder volumes at 30 cm H2O detrusor pressure was calculated using the urodynamic assessments. During urodynamic assessments, the bladder is filled until voiding/leakage begins, or until it is stopped because either the participants experiences pain or discomfort or 135% of expected bladder capacity for age has been reached.	Baseline and Week 24
Secondary	Change From Baseline in Bladder Volume at 40 cmH2O Detrusor Pressure	Bladder volumes at 40 cm H2O detrusor pressure were calculated using urodynamic assessments. During urodynamic assessments, the bladder is filled until voiding/leakage begins, or until it is stopped because either the subject experiences pain or discomfort or 135% of expected bladder capacity for age has been reached.	Baseline and Week 24
Secondary	Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cmH2O) Until End of Bladder Filling	Change from baseline in number of overactive detrusor contractions until end of bladder filling was measured by urodynamic testing. If leakage occurred, the "Detrusor pressure at leakage" was recorded otherwise the volume of fluid instilled into the bladder was recorded.	Baseline to Week 24
Secondary	Change From Baseline in Detrusor Pressure at the End of Bladder Filling	The bladder was filled until voiding/leakage began or until it was stopped because either the participant experiences pain or discomfort or 135% of expected bladder capacity for age has been reached. Pressure was recorded for an extra 5 minutes after leakage began or the end of bladder-filling, whichever is sooner.	Baseline to Week 24
Secondary	Change From Baseline in Average Catheterized Volume Per Catheterization	The average catheterized volume per catheterization was calculated using all available (non-zero) catheterized volumes recorded over both of the 2 measuring days in the diary, whether or not these 2 days are concurrent.	Baseline to Week 24
Secondary	Change From Baseline in Maximum Catheterized Volume	The maximum catheterized volume per day was calculated using all available (non-zero) catheterized volumes recorded for the 2 measuring days in the diary, whether or not these 2 days were concurrent. The maximum value was calculated separately for each measuring day and the mean of these two values was used.	Baseline to Week 24
Secondary	Change From Baseline in Average First Morning Catheterized Volume	The average first morning catheterized volume was calculated as the average of the available first morning catheterized volumes recorded for the 2 measuring days in the diary, whether or not these 2 days are concurrent.	Baseline to Week 24
Secondary	Change From Baseline in Mean Number of Incontinence Episodes Per 24 Hours	The mean of the number of incontinence episodes per 24h was calculated as the mean over the valid diary days in the 7-day diary.	Baseline to Week 24
Secondary	Change From Baseline in Number of Dry (Incontinence-Free) Days Per 7 Days	The number of incontinence-free days was calculated from the 7-day micturition diary.	Baseline to Week 24
Secondary	Change From Baseline in Number of Dry (Incontinence-Free) Nights Per 7 Days	The number of incontinence-free nights was calculated from the 7-day micturition diary.	Baseline to Week 24
Secondary	Change From Baseline in Quality of Life [QoL] (PinQ Questionnaire Score)	Pediatric Incontinence Questionnaire (PinQ) is a 20-item questionnaire addressing quality of life for participants with bladder disorders. Each question was answered on a scale from 0 (no, never) to 4 (all the time). The total score ranged from 0 to 80, with higher scores indicated more impact on the quality of life.	Baseline to Week 24
Secondary	Number of Participants With Adverse Events	A treatment-emergent adverse event (TEAE) was defined as an adverse event observed after starting administration of the first dose of study medication on Day 1. All adverse events collected within 7 days after taking the last dose of study drug were counted as a TEAE.	Baseline to End of Study Visit (Week 52)

External Links

•   Link to results on the Astellas Clinical Study Results website