Clinical Trial Results:
A Phase 3, Openlabel, Baselinecontrolled, Multicenter, Sequential Dosetitration Study to Assess the Pharmacokinetics, Longterm Efficacy and Safety of Solifenacin Succinate
Suspension in Children from 6 Months to less than 5 Years of Age with Neurogenic Detrusor Overactivity
Summary


EudraCT number 
201200317822 
Trial protocol 
GB NL BE DK 
Global end of trial date 
18 Dec 2015

Results information


Results version number 
v3(current) 
This version publication date 
24 Feb 2018

First version publication date 
29 Jun 2016

Other versions 
v1 , v2 
Version creation reason 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
905CL074


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01981954  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Astellas Pharma Europe B.V.


Sponsor organisation address 
Sylviusweg 62, Leiden, Netherlands, 2333 BE


Public contact 
Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com


Scientific contact 
Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
Yes


EMA paediatric investigation plan number(s) 
EMEA000573PIP0213  
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
Yes


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
18 Dec 2015


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
18 Dec 2015


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
To evaluate the longterm efficacy, safety and pharmacokinetics (PK) of solifenacin succinate suspension after multipledose administration.


Protection of trial subjects 
This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines (especially ICH E11), and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki.
Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
25 Sep 2013


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
Yes


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Philippines: 6


Country: Number of subjects enrolled 
Poland: 9


Country: Number of subjects enrolled 
Korea, Republic of: 5


Country: Number of subjects enrolled 
United Kingdom: 1


Country: Number of subjects enrolled 
United States: 1


Country: Number of subjects enrolled 
Belgium: 1


Worldwide total number of subjects 
23


EEA total number of subjects 
11


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
4


Children (211 years) 
19


Adolescents (1217 years) 
0


Adults (1864 years) 
0


From 65 to 84 years 
0


85 years and over 
0



Recruitment


Recruitment details 
Children aged 6 months to < 5 years old with neurogenic detrusor overactivity (NDO) were enrolled from Belgium (1 site), United Kingdom (1 site), Poland (2 sites), United States (1 site), the Philippines (1 site) and South Korea (2 sites).  
Preassignment


Screening details 
Children who met the eligibility criteria were treated with sequential doses of solifenacin up to 12 weeks to determine each participant's optimal dose, after which a fixed dose of solifenacin was given for at least 40 weeks. A washout period was required between screening and baseline if the children were being treated with antimuscarinic agents.  
Period 1


Period 1 title 
Titration Period


Is this the baseline period? 
Yes  
Allocation method 
Nonrandomised  controlled


Blinding used 
Not blinded  
Arms


Arm title

Solifenacin succinate  
Arm description 
Children aged 6 months to < 5 years were treated with sequential titrated doses of solifenacin up to 12 weeks in the Titration period. Children received solifenacin once daily during this period.  
Arm type 
Experimental  
Investigational medicinal product name 
Solifenacin succinate


Investigational medicinal product code 
YM905


Other name 
solifenacin, solifenacin succinate suspension


Pharmaceutical forms 
Oral suspension


Routes of administration 
Oral use


Dosage and administration details 
An initial dose of solifenacin was administered on the baseline visit for children aged 6 months to < 2 years and the day after the baseline visit for children aged 2 years to < 5 years, then once daily for a 12week Titration period, to determine the participant's optimal dose. Doses were calculated per weight determined at the baseline visit of this study and based on a physiologicallybased pharmacokinetic (PK) model, targeting to have equivalent doses of 2.5, 5, 7.5 and 10 mg doses of solifenacin once daily in adults (referred to as PED2.5, PED5, PED7.5 and PED10). During the 12week Titration period, the dose of solifenacin was downtitrated, uptitrated or maintained depending on the study’s titration criteria, which were based on a combination of diary endpoints, urodynamic assessments and adverse event (AE) criteria.




Period 2


Period 2 title 
FixedDose Assessment Period


Is this the baseline period? 
No  
Allocation method 
Nonrandomised  controlled


Blinding used 
Not blinded  
Arms


Arm title

Solifenacin succinate  
Arm description 
Children aged 6 months to < 5 years were treated with a fixed dose of solifenacin for at least 40 weeks in the Fixeddose assessment period. Children received solifenacin once daily during this period.  
Arm type 
Experimental  
Investigational medicinal product name 
Solifenacin succinate


Investigational medicinal product code 
YM905


Other name 
solifenacin, solifenacin succinate suspension


Pharmaceutical forms 
Oral suspension


Routes of administration 
Oral use


Dosage and administration details 
When a fixed and optimal dose of solifenacin was confirmed by Week 12, a participant continued on to receive solifenacin orally once daily until end of the study (Week 52).





Baseline characteristics reporting groups


Reporting group title 
Solifenacin succinate


Reporting group description 
Children aged 6 months to < 5 years were treated with sequential titrated doses of solifenacin up to 12 weeks in the Titration period. Children received solifenacin once daily during this period.  



End points reporting groups


Reporting group title 
Solifenacin succinate


Reporting group description 
Children aged 6 months to < 5 years were treated with sequential titrated doses of solifenacin up to 12 weeks in the Titration period. Children received solifenacin once daily during this period.  
Reporting group title 
Solifenacin succinate


Reporting group description 
Children aged 6 months to < 5 years were treated with a fixed dose of solifenacin for at least 40 weeks in the Fixeddose assessment period. Children received solifenacin once daily during this period. 


End point title 
Change from Baseline to Week 24 in Maximum Cystometric Capacity (MCC) ^{[1]}  
End point description 
MCC was the volume instilled into the bladder prior to leakage or end of bladderfilling (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). The analysis population was the Full Analysis Set (FAS), which consisted of all participants who took at least one dose of study drug and provided both valid baseline and at least one postbaseline value for the primary efficacy endpoint.


End point type 
Primary


End point timeframe 
Baseline and Week 24


Notes [1]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As this is a one treatment arm study, showing statistical analysis is not possible due to system limitations. 



No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12 and 52 in MCC  
End point description 
MCC was the volume instilled into the bladder prior to leakage or end of bladderfilling (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). The analysis population was the FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Compliance  
End point description 
Bladder compliance was calculated by dividing the volume change 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure at End of BladderFilling  
End point description 
Detrusor pressure was expressed as bladder pressure minus intraabdominal pressure as assessed by urodynamics. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure 5 Minutes After End of BladderFilling  
End point description 
Detrusor pressure was expressed as bladder pressure minus intraabdominal pressure as assessed by urodynamics. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Catheterized Volume 5 Minutes After End of BladderFilling  
End point description 
Catheterized volume was measured when the bladder was emptied via catheterization 5 minutes after the end of bladderfilling. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume Until First Detrusor Contraction >15 cmH2O  
End point description 
Bladder volume as assessed by urodynamics. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point and excluding participants who did not have a detrusor contraction.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 10 cmH20 Detrusor Pressure  
End point description 
Bladder volume as assessed by urodynamics. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point and whose pressure reached 10 cmH2O.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 20 cmH20 Detrusor Pressure  
End point description 
Bladder volume as assessed by urodynamics. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point and participants whose pressure reached 20 cmH2O.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 30 cmH20 Detrusor Pressure  
End point description 
Bladder volume as assessed by urodynamics. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point and participants whose pressure reached 30 cmH2O. Since data were only available for one participant, no data has been calculated and is denoted as "99999."


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
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 BladderFilling  
End point description 
The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average Catheterized Volume per Catheterization  
End point description 
The average catheterized volume per catheterization was calculated using all available (nonzero) catheterized volumes recorded over both of the 2 measuring days in the diary, whether or not these 2 days were concurrent. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 36, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Maximum Catheterized Volume (MCV)  
End point description 
The maximum catheterized volume per day was calculated using all available (nonzero) 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 36, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average First Morning Catheterized Volume  
End point description 
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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 36, 52




No statistical analyses for this end point 


End point title 
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  
End point description 
Participants were required to have 46 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. interCIC 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 interCIC 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. FAS population. "N" is the number of participants with available data at baseline and each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 3, 6, 9, 12, 24, 36, 52




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day at Baseline  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 54.


End point type 
Secondary


End point timeframe 
3 days prior to Baseline visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day During Week 3  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 3 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day During Week 6  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 60.


End point type 
Secondary


End point timeframe 
3 days prior to Week 6 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day During Week 9  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 9 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day During Week 12  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 12 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day During Week 24  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 24 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day During Week 36  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 36 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Catheterizations for Each Hour of 24 Hour Day During Week 52  
End point description 
For each one hour period of the 24 hour day, the incidence of 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. The analysis population was FAS. The number of valid diary days was 57.


End point type 
Secondary


End point timeframe 
3 days prior to Week 52 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day at Baseline  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 54.


End point type 
Secondary


End point timeframe 
3 days prior to Baseline visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day During Week 3  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 3 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day During Week 6  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 60.


End point type 
Secondary


End point timeframe 
3 days prior Week 6 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day During Week 9  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 9 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day During Week 12  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 12 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day During Week 24  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 63.


End point type 
Secondary


End point timeframe 
3 days prior to Week 24 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day During Week 36  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 60.


End point type 
Secondary


End point timeframe 
3 days prior to Week 36 visit




No statistical analyses for this end point 


End point title 
Percentage of Days with Incontinence for Each Hour of 24 Hour Day During Week 52  
End point description 
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 incidence of 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. The analysis population was FAS. The number of valid diary days was 57.


End point type 
Secondary


End point timeframe 
3 days prior to Week 52 visit




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in Infant and Toddler Quality of Life Short Form47 questionnaire (ITQoL SF47)  Overall Health Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – Physical Abilities Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – Growth and Development Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – Pain Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – Temperament and Moods Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – Behaviour Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – General Health Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – Change in Health Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – ParentEmotional Impact Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – ParentTime Impact Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 24 and 52 in ITQoL SF47 – Family Cohesion Impact Score  
End point description 
The ITQoL SF47 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). Before calculating a scale, the value of each item is coded so that it ranges from 0 (worst possible) to 100 (best possible). 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. The analysis population was FAS. "N" indicates the number of participants with available data at baseline and at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 24, 52




No statistical analyses for this end point 


Adverse events information


Timeframe for reporting adverse events 
From first dose of study drug to last dose of study drug (up to 54 weeks)


Assessment type 
Systematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
16.0


Reporting groups


Reporting group title 
Solifenacin succinate


Reporting group description 
Children aged 6 months to < 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 Fixeddose assessment period. Children received solifenacin once daily during these 2 periods.  


Frequency threshold for reporting nonserious adverse events: 5%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

24 Jun 2014 
Changes summarized:
● Change in the planned study period: the duration of the study was increased from 4Q2014 to 3Q2015. Recruitment timeframe was extended to include children under the age of 2 years.
● Change in the dosing rationale: the model used to select the drug dose was updated to a PBPK model to account for agerelated physiological changes in clearance and distribution processes.
● Adjustment in the automated dose volume: the volume of medication was adjusted at visit 7 and 8 if any change in weight placed the patient in a new category. The dose volume was adjusted to ensure that patients were being treated effectively as weight in young infants could have increased substantially during the study.
● Added optional unscheduled urodynamic evaluation: new unscheduled urodynamic assessment was permitted 3 weeks after visit 6 (week 12). This evaluation allowed the investigator to confirm that the balance of efficacy and symptoms of intolerability had been established for patients who have had their dose adjusted at visit 6.
● Revised calculation of baseline mean QT interval corrected for heart rate by Bazett’s formula (QTcB): new calculations included the averages of the QTcB mean from visit 1 and 2. Previous calculations used only the QTcB mean from visit 2. This revision was done as statistical analysis of the intrapatient variation in baseline QTcB between visit 1 and visit 2 showed that a more precise estimate of QTcB could be obtained using the measurements from both visits.
● Addition of medical assessment of safety profile of children: New assessment used descriptive statistics rather than formal statistics comparisons given that only a small number of patients under the age of 2 years enrolled.
● Change in the lower age range of patients: the lower age limit was decreased from 2 years to 6 months. The inclusion of children from 6 months of age aligns the study with the approved PIP for solifenacin (EMEA000573PIP0109). 

Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
None reported 