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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01565694
Recruitment Status : Completed
First Posted : March 29, 2012
Results First Posted : May 6, 2019
Last Update Posted : May 6, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Tracking Information
First Submitted Date  ICMJE March 27, 2012
First Posted Date  ICMJE March 29, 2012
Results First Submitted Date  ICMJE April 10, 2019
Results First Posted Date  ICMJE May 6, 2019
Last Update Posted Date May 6, 2019
Actual Study Start Date  ICMJE August 14, 2012
Actual Primary Completion Date April 28, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2018)
Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC) [ Time Frame: Baseline and Week 24 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2012)
Change from baseline in maximum cystometric capacity (MCC) [ Time Frame: Baseline and Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2018)
  • Change From Baseline to Last Possible Titration Step in Maximum Cystometric Capacity [ Time Frame: Baseline, Week 9 or Week 12 ]
    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.
  • Change From Baseline in Bladder Compliance [ Time Frame: Baseline and Week 24 ]
    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.
  • Change From Baseline in Bladder Volume (mL) Until First Detrusor Contraction > 15 cmH2O as a Percentage of Expected Bladder Capacity (EBC) [ Time Frame: Baseline and Week 24 ]
    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.
  • Change From Baseline in Bladder Volume at 30 cmH2O Detrusor Pressure [ Time Frame: Baseline and Week 24 ]
    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.
  • Change From Baseline in Bladder Volume at 40 cmH2O Detrusor Pressure [ Time Frame: Baseline and Week 24 ]
    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.
  • Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cmH2O) Until End of Bladder Filling [ Time Frame: Baseline to Week 24 ]
    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.
  • Change From Baseline in Detrusor Pressure at the End of Bladder Filling [ Time Frame: Baseline to Week 24 ]
    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.
  • Change From Baseline in Average Catheterized Volume Per Catheterization [ Time Frame: Baseline to Week 24 ]
    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.
  • Change From Baseline in Maximum Catheterized Volume [ Time Frame: Baseline to Week 24 ]
    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.
  • Change From Baseline in Average First Morning Catheterized Volume [ Time Frame: Baseline to Week 24 ]
    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.
  • Change From Baseline in Mean Number of Incontinence Episodes Per 24 Hours [ Time Frame: Baseline to Week 24 ]
    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.
  • Change From Baseline in Number of Dry (Incontinence-Free) Days Per 7 Days [ Time Frame: Baseline to Week 24 ]
    The number of incontinence-free days was calculated from the 7-day micturition diary.
  • Change From Baseline in Number of Dry (Incontinence-Free) Nights Per 7 Days [ Time Frame: Baseline to Week 24 ]
    The number of incontinence-free nights was calculated from the 7-day micturition diary.
  • Change From Baseline in Quality of Life [QoL] (PinQ Questionnaire Score) [ Time Frame: Baseline to Week 24 ]
    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.
  • Number of Participants With Adverse Events [ Time Frame: Baseline to End of Study Visit (Week 52) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2012)
  • Change in Maximum Cystometric Capacity (MCC) [ Time Frame: Baseline, Week 9, Week 24 and Week 52 ]
  • Change in Urodynamics [ Time Frame: Week 9, Week 24 and Week 52 ]
    Measured by:
    • Bladder compliance (Change in V/ Change in Pdet);
    • Bladder volume until first detrusor contraction (> 15 cmH2O);
    • Bladder volume at 30 cm H2O detrusor pressure;
    • Bladder volume at 40 cm H2O detrusor pressure;
    • Number of uninhibited detrusor contractions (> 15 cmH2O) until leakage or maximum 135% of age-related bladder capacity; Detrusor pressure at leakage or 135% of age-related cystometric capacity
  • Change in Diary Observations [ Time Frame: Baseline, Week 3 to Week 52 ]
    Measured by:
    • Average catheterized volume per catheterization;
    • Maximum catheterized volume per day;
    • Mean number of incontinence episodes per 24 hours;
    • Number of dry (incontinence-free) days/7 days
  • Change in Quality of Life [ Time Frame: Baseline, Week 24 and Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neurogenic Detrusor Overactivity
Intervention  ICMJE Drug: Solifenacin succinate
Oral suspension administered once a day via syringe.
Other Name: YM905
Study Arms  ICMJE Experimental: Solifenacin succinate

Participants aged 5 years to < 18 years received solifenacin orally once a day, with sequential titrated doses for 12 weeks to identify the optimal dose during the dose-titration period. The initial dose was pediatric equivalent dose (PED) 5 mg.

After completing the dose titration period participants entered the fixed-dose period during which solifenacin was taken orally once a day for 40 weeks or until the end of study visit (Week 52).

Intervention: Drug: Solifenacin succinate
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 4, 2018)
76
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2012)
90
Actual Study Completion Date  ICMJE April 28, 2016
Actual Primary Completion Date April 28, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Brazil,   Denmark,   Hungary,   Korea, Republic of,   Mexico,   Philippines,   Poland,   Turkey,   United States
Removed Location Countries Canada,   France,   Germany,   India,   Netherlands,   Russian Federation,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01565694
Other Study ID Numbers  ICMJE 905-CL-047
2011-000330-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/
Responsible Party Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
Study Sponsor  ICMJE Astellas Pharma Europe B.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
PRS Account Astellas Pharma Inc
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP