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)
- Conditions
- Neurogenic Detrusor OveractivityPediatric
- Interventions
- Registration Number
- NCT01981954
- Lead Sponsor
- Astellas Pharma Europe B.V.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
- Myelomeningocoele
- Documented diagnosis of NDO, confirmed by urodynamics
- DSD (detrusor sphincter dyssynergia)
- Practicing clean intermittent catheterization (CIC)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Solifenacin succinate Solifenacin succinate Children aged 6 months to less than 5 years were treated with sequential titrated doses of solifenacin up to 12 weeks in the Titration period after which a fixed dose of solifenacin was given for at least 40 weeks in the Fixed-dose assessment period. Children received solifenacin once daily during these 2 periods.
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC) Baseline and Week 24 MCC was the volume instilled into the bladder prior to leakage or end of bladder-filling (whichever was reached first), as assessed by urodynamics (procedure: the bladder was to be filled until voiding/leakage began, or until it was stopped because either the participant experienced pain or discomfort or 135% of expected bladder capacity \[EBC\] was reached for participants ≥ 2 years or of maximum catheterized volume \[MCV\] for participants aged 6 months to \< 2 years; the participants' bladder was emptied via catheterization).
- Secondary Outcome Measures
Name Time Method Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 10 cmH20 Detrusor Pressure Baseline and Weeks 3, 6, 9, 12, 24, 52 Bladder volume as assessed by urodynamics.
Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 30 cmH20 Detrusor Pressure Baseline and Weeks 3, 6, 9, 12, 24, 52 Bladder volume as assessed by urodynamics.
Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average First Morning Catheterized Volume Baseline and Weeks 3, 6, 9, 12, 24, 36, 52 The first morning catheterized volume was the volume associated with the first morning catheterization. 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.
Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 12 3 days prior to Week 12 visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Change From Baseline to Weeks 3, 6, 9, 12 and 52 in MCC Baseline and Weeks 3, 6, 9, 12, 52 MCC was the volume instilled into the bladder prior to leakage or end of bladder-filling (whichever was reached first) as assessed by urodynamics (procedure: the bladder was to be filled until voiding/leakage began, or until it was stopped because either the participant experienced pain or discomfort or 135% of EBC was reached for participants ≥ 2 years or of MCV for participants aged 6 months to \< 2 years. The participants' bladder was emptied via catheterization).
Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Compliance Baseline and Weeks 3, 6, 9, 12, 24, 52 Bladder compliance gives an indication of the elasticity of the bladder wall. Bladder compliance was calculated by dividing the change in volume during the filling of the bladder by the change in detrusor pressure during that change in bladder volume using urodynamic assessments. The values for bladder volume and detrusor pressure at the beginning and end of filling were taken and used.
Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure at End of Bladder-Filling Baseline and Weeks 3, 6, 9, 12, 24, 52 Detrusor pressure was expressed as bladder pressure minus intra-abdominal pressure as assessed by urodynamics.
Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure 5 Minutes After End of Bladder-Filling Baseline and Weeks 3, 6, 9, 12, 24, 52 Detrusor pressure was expressed as bladder pressure minus intra-abdominal pressure as assessed by urodynamics.
Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Catheterized Volume 5 Minutes After End of Bladder-Filling Baseline and Weeks 3, 6, 9, 12, 24, 52 Catheterized volume was measured when the bladder was emptied via catheterization 5 minutes after the end of bladder-filling.
Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume Until First Detrusor Contraction (> 15 cmH2O) Baseline and Weeks 3, 6, 9, 12, 24, 52 Bladder volume as assessed by urodynamics.
Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 20 cmH20 Detrusor Pressure Baseline and Weeks 3, 6, 9, 12, 24, 52 Bladder volume as assessed by urodynamics.
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 Baseline and Weeks 3, 6, 9, 12, 24, 52 Percentage of Days With Catheterizations for Each Hour of 24 Hour Day at Baseline 3 days prior to Baseline visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 24 3 days prior to Week 24 visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 36 3 days prior to Week 36 visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 52 3 days prior to Week 52 visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all subjects. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 6 3 days prior to Week 6 visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 9 3 days prior to Week 9 visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average Catheterized Volume Per Catheterization Baseline and Weeks 3, 6, 9, 12, 24, 36, 52 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 were concurrent. Catheterized volumes were recorded for 2 days in a participant diary prior to each visit. Four to six catheterizations were performed every day.
Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Maximum Catheterized Volume (MCV) Baseline and Weeks 3, 6, 9, 12, 24, 36, 52 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 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 Baseline and Weeks 3, 6, 9, 12, 24, 36, 52 Participants were required to have 4-6 CICs per day on a schedule fixed for the duration of the study. To calculate the number of periods between CICs with incontinence in a diary day, the diary day was divided into periods between CICs (i.e. inter-CIC periods). The hour period, rather than the exact time, of each CIC and incontinence episode was recorded in the diary. When an incontinence episode and a CIC were marked in the same hour period, the incontinence episode was counted as occurring prior to the CIC (when the bladder had not yet emptied), rather than after it (when the bladder had recently been emptied), i.e. the inter-CIC period ended with the hour in which the CIC was recorded. The mean number of periods between CICs with incontinence per 24 hours was the number of periods between CICs when incontinence occurred, divided by the total number of valid diary days.
Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 3 3 days prior to Week 3 visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 6 3 days prior to Week 6 visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 9 3 days prior to Week 9 visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 12 3 days prior to Week 12 visit For each one hour period of the 24 hour day, the percentage of days with catheterization was assessed as the number of days with catheterization occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Incontinence for Each Hour of 24 Hour Day at Baseline 3 days prior to Baseline visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With of Incontinence for Each Hour of 24 Hour Day During Week 3 3 days prior to Week 3 visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Change in Health Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Parent-Emotional Impact Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Parent-Time Impact Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 24 3 days prior to Week 24 visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
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 Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 36 3 days prior to Week 36 visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 52 3 days prior to Week 52 visit Incontinence was defined as leakage where a diaper is not used, or dampness where a diaper is used. For each one hour period of the 24 hour day, the percentage of days with incontinence was assessed as the number of days with incontinence occurring within the one hour period divided by the number of valid diary days over all participants. Each participant contributed to up to three days of valid diary data for each visit.
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Physical Abilities Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Growth and Development Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Pain Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Temperament and Moods Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Behaviour Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - General Health Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Family Cohesion Impact Score Baseline and Weeks 24, 52 The ITQoL SF-47 consisted of 47 individual items and was filled in by the child's parent. The individual items are based on Likert scales with either 5 responses (coded as 1 through to 5) or 4 responses (coded as 1 through to 4). From subsets of these coded values, 11 scales are derived: overall health, physical activities, development, discomfort, moods and temperaments, perceptions of current past and future health and perception of changes. Each scale score ranges from 0 (worst possible) to 100 (best possible).
Trial Locations
- Locations (8)
Site KR8201 Severance Hospital
🇰🇷Seoul, Korea, Republic of
Site PH6301 Philippines Children's Medical Center
🇵🇭Manila, Philippines
Site US1008 Pediatric Urology Associates, P.C.
🇺🇸Tarrytown, New York, United States
Site GB4401 Sheffield Children's Hospital
🇬🇧Sheffield, United Kingdom
Site BE3203 Gent University Hospital
🇧🇪Gent, Belgium
Site KR8207 Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Site PL4803 Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Site PL4801 Pomnik-Centrum Zdrowia Dziecka
🇵🇱Warszawa, Poland