Neurogenic Detrusor Overactivity
Conditions
Keywords
Cognitive Function, Phase 3, Neurogenic Detrusor Overactivity, Pharmacokinetics, Ocular Accommodation, Urodynamics
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).
Interventions
DRUGSolifenacin succinate
Oral suspension administered once a day via syringe.
Sponsors
Astellas Pharma Europe B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bladder Compliance | 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) | 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 | 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 | 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 | 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 | 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 | 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 to Last Possible Titration Step in Maximum Cystometric Capacity | 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 Average First Morning Catheterized Volume | 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 | 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 | 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 | 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) | 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 | 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. |
| Change From Baseline in Maximum Catheterized Volume | 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. |
Countries
Belgium, Brazil, Denmark, Hungary, Mexico, Philippines, Poland, South Korea, Turkey (Türkiye), United States
Participant flow
Recruitment details
The study population consisted of male and female participants with neurogenic detrusor overactivity (NDO) aged 5 years to \< 18 years old.
Pre-assignment details
After screening and a 14-day washout period, participants were treated with sequential doses of solifenacin oral suspension for 12 weeks (titration period) to determine each participant's optimal dose, after which a fixed dose of solifenacin oral suspension was given for at least 40 weeks (fixed dose assessment period).
Participants by arm
| Arm | Count |
|---|---|
| Solifenacin Succinate Participants aged 5 years to \< 18 years, received solifenacin orally once a day, with sequential titrated doses for 12 weeks to identify optimal dose during the dose-titration period. After the dose titration period participants entered the fixed-dose period and received a fixed dose of solifenacin once a day orally for 40 weeks or until the end of study visit (Week 52). | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Dose-Titration Period | Adverse Event | 4 |
| Dose-Titration Period | Protocol Violation | 10 |
| Fixed-Dose Assessment Period | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Solifenacin Succinate |
|---|---|
| Age, Continuous | 10.8 Years STANDARD_DEVIATION 3.3 |
| Body Mass Index (BMI) | 19.2 (kg/m^2) STANDARD_DEVIATION 4.69 |
| Duration of Neurogenic Detrusor Overactivity (NDO) Disease | 8.24 Years |
| Ethnicity Hispanic or Latino | 11 Participants |
| Ethnicity Not Hispanic or Latino | 65 Participants |
| Height | 138 centimeters (cm) STANDARD_DEVIATION 16.3 |
| Race American Indian/Alaskan Native | 1 Participants |
| Race Asian | 23 Participants |
| Race Black/African American | 2 Participants |
| Race Other | 5 Participants |
| Race White | 45 Participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 37 Participants |
| Weight | 38.1 kilogram (kg) STANDARD_DEVIATION 15.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 76 |
| other Total, other adverse events | 42 / 76 |
| serious Total, serious adverse events | 7 / 76 |
Outcome results
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.
Time frame: Baseline and Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC) | Change from Baseline Week 24 | 57.2 mL | Standard Deviation 107.7 |
| Solifenacin Succinate | Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC) | Change from Baseline Week 24 (LOCF) | 59.3 mL | Standard Deviation 107.5 |
Comparison: Analysis of change from baseline to Week 24.p-value: <0.001t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Average Catheterized Volume Per Catheterization | Change from Baseline Week 24 | 46.23 mL | Standard Deviation 48.32 |
| Solifenacin Succinate | Change From Baseline in Average Catheterized Volume Per Catheterization | Change from Baseline Week 24 (LOCF) | 48.86 mL | Standard Deviation 50.98 |
Comparison: Analysis of change from baseline to Week 24.p-value: <0.001t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Average First Morning Catheterized Volume | Change from Baseline Week 24 | 43.24 mL | Standard Deviation 72.78 |
| Solifenacin Succinate | Change From Baseline in Average First Morning Catheterized Volume | Change from Baseline Week 24 (LOCF) | 44.21 mL | Standard Deviation 73.4 |
Comparison: Analysis of change from baseline to Week 24.p-value: <0.001t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline and Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Bladder Compliance | Change from Baseline Week 24 | 9.1 mL/cmH2O | Standard Deviation 28.6 |
| Solifenacin Succinate | Change From Baseline in Bladder Compliance | Change from Baseline Week 24 (LOCF) | 8.8 mL/cmH2O | Standard Deviation 27.8 |
Comparison: Analysis of change from baseline to Week 24.p-value: 0.029t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: 0.026t-test, 2 sided
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.
Time frame: Baseline and Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized. Only participants who reached 30 cmH20 detrusor pressure were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Bladder Volume at 30 cmH2O Detrusor Pressure | Change from Baseline Week 24 | 61.8 mL | Standard Deviation 80.6 |
| Solifenacin Succinate | Change From Baseline in Bladder Volume at 30 cmH2O Detrusor Pressure | Change from Baseline Week 24 (LOCF) | 71.9 mL | Standard Deviation 88.3 |
Comparison: Analysis of change from baseline to Week 24 in bladder volume at 30 cmH20.p-value: 0.006t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF in bladder volume at 30 cmH20.p-value: 0.001t-test, 2 sided
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.
Time frame: Baseline and Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized. Only participants who reached 40 cmH20 detrusor pressure were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Bladder Volume at 40 cmH2O Detrusor Pressure | Change from Baseline Week 24 | 67.0 mL | Standard Deviation 44.3 |
| Solifenacin Succinate | Change From Baseline in Bladder Volume at 40 cmH2O Detrusor Pressure | Change from Baseline Week 24 (LOCF) | 54.4 mL | Standard Deviation 52.9 |
Comparison: Analysis of change from baseline to week 24 in bladder volume at 40 cmH20.p-value: 0.001t-test, 2 sided
Comparison: Analysis of change from baseline to week 24 LOCF in bladder volume at 40 cmH20.p-value: 0.004t-test, 2 sided
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.
Time frame: Baseline and Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Solifenacin Succinate | Change From Baseline in Bladder Volume (mL) Until First Detrusor Contraction > 15 cmH2O as a Percentage of Expected Bladder Capacity (EBC) | 23.10 Percentage of EBC |
Comparison: Analysis of change from baseline to Week 24.p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Detrusor Pressure at the End of Bladder Filling | Change from Baseline Week 24 | -9.2 cmH2O | Standard Deviation 33.6 |
| Solifenacin Succinate | Change From Baseline in Detrusor Pressure at the End of Bladder Filling | Change from Baseline Week 24 (LOCF) | -8.2 cmH2O | Standard Deviation 32.2 |
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: 0.075t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24.p-value: 0.068t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Maximum Catheterized Volume | Change from Baseline Week 24 | 67.45 mL | Standard Deviation 88.07 |
| Solifenacin Succinate | Change From Baseline in Maximum Catheterized Volume | Change from Baseline Week 24 (LOCF) | 69.63 mL | Standard Deviation 88.84 |
Comparison: Analysis of change from baseline to Week 24.p-value: <0.001t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline Week 24 | -1.60 Incontinence Episodes | Standard Deviation 2.04 |
| Solifenacin Succinate | Change From Baseline in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline Week 24 (LOCF) | -1.62 Incontinence Episodes | Standard Deviation 2.04 |
Comparison: Analysis of change from baseline to Week 24.p-value: <0.001t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Number of Dry (Incontinence-Free) Days Per 7 Days | Change from Baseline Week 24 | 1.06 Days | Standard Deviation 2.83 |
| Solifenacin Succinate | Change From Baseline in Number of Dry (Incontinence-Free) Days Per 7 Days | Change from Baseline Week 24 (LOCF) | 1.19 Days | Standard Deviation 2.86 |
Comparison: Analysis of change from baseline to Week 24.p-value: 0.01t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: 0.004t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Number of Dry (Incontinence-Free) Nights Per 7 Days | Change from Baseline Week 24 | 1.60 Nights | Standard Deviation 3.08 |
| Solifenacin Succinate | Change From Baseline in Number of Dry (Incontinence-Free) Nights Per 7 Days | Change from Baseline Week 24 (LOCF) | 1.64 Nights | Standard Deviation 3.06 |
Comparison: Analysis of change from baseline to Week 24.p-value: <0.001t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cmH2O) Until End of Bladder Filling | Change from Baseline Week 24 | -2.3 Detrusor Contractions | Standard Deviation 5.1 |
| Solifenacin Succinate | Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cmH2O) Until End of Bladder Filling | Change from Baseline Week 24 (LOCF) | -1.8 Detrusor Contractions | Standard Deviation 6 |
Comparison: Analysis of change from baseline to Week 24.p-value: 0.003t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: 0.028t-test, 2 sided
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.
Time frame: Baseline to Week 24
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate | Change From Baseline in Quality of Life [QoL] (PinQ Questionnaire Score) | Change from Baseline Week 24 | -0.7 Units on a Scale | Standard Deviation 8.3 |
| Solifenacin Succinate | Change From Baseline in Quality of Life [QoL] (PinQ Questionnaire Score) | Change from Baseline Week 24 (LOCF) | -0.7 Units on a Scale | Standard Deviation 8.3 |
Comparison: Analysis of change from baseline to Week 24.p-value: 0.568t-test, 2 sided
Comparison: Analysis of change from baseline to Week 24 LOCF.p-value: 0.573t-test, 2 sided
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.
Time frame: Baseline, Week 9 or Week 12
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug. The number of participant analyzed represents participants with a non-missing change from baseline to last possible titration step.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Solifenacin Succinate | Change From Baseline to Last Possible Titration Step in Maximum Cystometric Capacity | 57.4 mL | Standard Deviation 105.5 |
p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline to End of Study Visit (Week 52)
Population: The full analysis set (FAS) consisted of all participants who had a baseline and 1 post baseline measurement for the primary endpoint (MCC) and have received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Solifenacin Succinate | Number of Participants With Adverse Events | TEAEs | 51 Participants |
| Solifenacin Succinate | Number of Participants With Adverse Events | Drug related TEAE | 15 Participants |
| Solifenacin Succinate | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Solifenacin Succinate | Number of Participants With Adverse Events | Serious TEAEs | 7 Participants |
| Solifenacin Succinate | Number of Participants With Adverse Events | Drug related Serious TEAEs | 0 Participants |
| Solifenacin Succinate | Number of Participants With Adverse Events | TEAEs Leading to Discontinuation | 4 Participants |
| Solifenacin Succinate | Number of Participants With Adverse Events | Drug related TEAEs Leading to Discontinuation | 3 Participants |