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    Clinical Trial Results:
    A Phase 3, Double-Blind, Randomized, Multi-center, Placebo-Controlled Sequential Dose Titration Study to Assess Efficacy, Safety and Population Pharmacokinetics of Solifenacin Succinate Suspension in Pediatric Subjects from 5 to less than 18 years of Age with Overactive Bladder (OAB)

    Summary
    EudraCT number
    		 2011-002066-20
    Trial protocol
    		 GB   BE   NL   DE   SE   DK   NO  
    Global end of trial date
    02 Jan 2014

    Results information
    Results version number
    		 v1
    This version publication date
    04 May 2016
    First version publication date
    10 Apr 2015
    Other versions
    		 v2 , v3

    Trial information

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    Trial identification
    Sponsor protocol code
    905-CL-076
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01565707
    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 Europe B.V., Astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Europe B.V., Astellas.resultsdisclosure@astellas.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000573-PIP01-09
    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
    02 Jan 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Jan 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jan 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy and safety of solifenacin succinate once daily (o.d.) in children and adolescents with Overactive Bladder (OAB).
    Protection of trial subjects
    This clinical study was written, conducted and reported in accordance with the protocol, ICH GCP Guidelines, 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 and/or regional legislation related to the privacy and protection of personal information.
    Background therapy
    		 Solifenacin succinate as a tablet formulation is already on the market for the treatment of symptoms of overactive bladder in adults. For the use in children and adolescent patients a new formulation of solifenacin has been developed. This study investigated the effect and safety of solifenacin succinate liquid suspension compared to a non-active drug (placebo) over a 12-week period. The 2 weeks prior to the double blind period was a single-blind placebo run-in period in combination with behavioral urotherapy (Non-interventional diary assisted urotherapy consisting of overactive bladder (OAB) information, awareness, instruction, life-style advice and documentation of voiding habits and symptoms for OAB), followed by a 12 week daily treatment period. The study also investigated how well solifenacin succinate suspension is taken-up by the body and how long it stays in the body during this time.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jun 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Norway: 7
    Country: Number of subjects enrolled
    Poland: 22
    Country: Number of subjects enrolled
    Sweden: 9
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Belgium: 38
    Country: Number of subjects enrolled
    Denmark: 22
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    United States: 3
    Country: Number of subjects enrolled
    South Africa: 5
    Country: Number of subjects enrolled
    Serbia: 19
    Country: Number of subjects enrolled
    Ukraine: 11
    Country: Number of subjects enrolled
    Mexico: 10
    Country: Number of subjects enrolled
    Brazil: 12
    Country: Number of subjects enrolled
    Philippines: 4
    Country: Number of subjects enrolled
    Korea, Republic of: 12
    Country: Number of subjects enrolled
    Turkey: 4
    Worldwide total number of subjects
    189
    EEA total number of subjects
    100
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    148
    Adolescents (12-17 years)
    41
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study population consisted of male and female children (5 to 11 years old) and adolescents (12 to 17 years old) with overactive bladder (OAB).

    Pre-assignment
    Screening details
    		 Subjects received 4 weeks of urotherapy (standard first line therapy for pediatric OAB patients). Two weeks after start of urotherapy a single-blind 2-week placebo run-in period began. After run-in period eligible subjects were randomized to 12 weeks of double-blind treatment (solifenacin succinate suspension or placebo) and continued urotherapy.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    In order to ensure blinding, a matching placebo formulation was used during the single-blind 2-week placebo run-in period, and during the double-blind 12 week treatment period. The placebo and corresponding active suspension were indistinguishable with respect to appearance, taste and aroma.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo Children
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Children aged 5 to 11 years received matching placebo liquid suspension once a day orally via syringe for 12 weeks along with non interventional diary assisted urotherapy consisting of overactive bladder (OAB) information, awareness, instruction, life-style advice and documentation of voiding habits and symptoms for OAB. The initial dose started with the equivalent of 5 mg in adults, referred to as pediatric equivalent dose (PED) of 5 mg (PED5), based on body weight for three weeks and was titrated up or down in up to three titration steps of three weeks each to reach the optimal dose. Titration up or down could lead to weight-based doses equivalent to doses in adults of 2.5 mg, 5 mg, 7.5 mg or 10 mg once daily and were referred to as PED2.5, PED5, PED7.5 and PED10. The minimum dose was PED2.5, and the maximum dose was PED10. The decision to titrate up or down was made by the investigator using information from the 7 day patient diary.

    Arm title
    		 Solifenacin Succinate Suspension Children
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Solifenacin Succinate Suspension
    Investigational medicinal product code
    YM905
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Children aged 5 to 11 years received solifenacin succinate liquid suspension once a day orally via syringe for 12 weeks along with non interventional diary assisted urotherapy consisting of overactive bladder (OAB) information, awareness, instruction, life-style advice and documentation of voiding habits and symptoms for OAB. The initial dose started with the equivalent of 5 mg in adults, referred to as pediatric equivalent dose (PED) of 5 mg (PED5), based on body weight for three weeks and was titrated up or down in up to three titration steps of three weeks each to reach the optimal dose. Titration up or down could lead to weight-based doses equivalent to doses in adults of 2.5 mg, 5 mg, 7.5 mg or 10 mg once daily and were referred to as PED2.5, PED5, PED7.5 and PED10. The minimum dose was PED2.5, and the maximum dose was PED10. The decision to titrate up or down was made by the investigator using information from the 7 day patient diary.

    Arm title
    		 Placebo Adolescents
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Adolescents aged 12 to 17 years received matching placebo liquid suspension once a day orally via syringe for 12 weeks along with non interventional diary assisted urotherapy consisting of overactive bladder (OAB) information, awareness, instruction, life-style advice and documentation of voiding habits and symptoms for OAB. The initial dose started with the equivalent of 5 mg in adults, referred to as pediatric equivalent dose (PED) of 5 mg (PED5), based on body weight for three weeks and was titrated up or down in up to three titration steps of three weeks each to reach the optimal dose. Titration up or down could lead to weight-based doses equivalent to doses in adults of 2.5 mg, 5 mg, 7.5 mg or 10 mg once daily and were referred to as PED2.5, PED5, PED7.5 and PED10. The minimum dose was PED2.5, and the maximum dose was PED10. The decision to titrate up or down was made by the investigator using information from the 7 day patient diary.

    Arm title
    		 Solifenacin Succinate Suspension Adolescents
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Solifenacin Succinate Suspension
    Investigational medicinal product code
    YM905
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Adolescents aged 12 to 17 years received solifenacin succinate liquid suspension once a day orally via syringe for 12 weeks along with non interventional diary assisted urotherapy consisting of overactive bladder (OAB) information, awareness, instruction, life-style advice and documentation of voiding habits and symptoms for OAB. The initial dose started with the equivalent of 5 mg in adults, referred to as pediatric equivalent dose (PED) of 5 mg (PED5), based on body weight for three weeks and was titrated up or down in up to three titration steps of three weeks each to reach the optimal dose. Titration up or down could lead to weight-based doses equivalent to doses in adults of 2.5 mg, 5 mg, 7.5 mg or 10 mg once daily and were referred to as PED2.5, PED5, PED7.5 and PED10. The minimum dose was PED2.5, and the maximum dose was PED10. The decision to titrate up or down was made by the investigator using information from the 7 day patient diary.

    Number of subjects in period 1
    		Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Started
    75
    73
    19
    22
    Treated
    73
    73
    19
    22
    Not Completed
    9 [1]
    8 [2]
    3 [3]
    5 [4]
    Completed
    66
    65
    16
    17
    Not completed
    9
    8
    3
    5
         Consent withdrawn by subject
    3
    1
    1
    1
         Adverse event, non-fatal
    1
    6
    2
    1
         Miscellaneous
    1
    1
    -
    2
         Randomized but not evaluable
    2
    -
    -
    -
         Protocol Violation
    1
    -
    -
    1
         Lost to follow-up
    1
    -
    -
    -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The started milestone includes all randomized subjects, treated includes subjects from the Safety Analysis Set (SAF), which consisted of all subjects who received at least 1 dose of double-blind study drug and for whom any safety data were reported after first dose of study drug. The not completed number includes the subjects not included in the SAF and are listed as subject non-completion reasons. If the not completed number is added to the completed number this equals the number started.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Safety Analysis Set (SAF) consisted of all participants who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug. The subject non-completion reasons listed explain and add up to the not completed milestone number. If the not completed number is added to the completed number this equals the number of subjects in the started milestone.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Safety Analysis Set (SAF) consisted of all participants who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug. The subject non-completion reasons listed explain and add up to the not completed milestone number. If the not completed number is added to the completed number this equals the number of subjects in the started milestone.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The Safety Analysis Set (SAF) consisted of all participants who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug. The subject non-completion reasons listed explain and add up to the not completed milestone number. If the not completed number is added to the completed number this equals the number of subjects in the started milestone.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo Children
    Reporting group description
    		 -

    Reporting group title
    Solifenacin Succinate Suspension Children
    Reporting group description
    		 -

    Reporting group title
    Placebo Adolescents
    Reporting group description
    		 -

    Reporting group title
    Solifenacin Succinate Suspension Adolescents
    Reporting group description
    		 -

    Reporting group values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents Total
    Number of subjects
    		 75 73 19 22 189
    Age categorical
    Units: Subjects
    Age continuous
    Age values provided are for the Safety Analysis Set (SAF) population. The SAF consisted of all participants who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug. The number of participants was 73; 73; 19; 22 per treatment arm.
    Units: years
        arithmetic mean (standard deviation)
    		 7.4 ± 1.6 7.6 ± 1.6 14.4 ± 1.9 14.2 ± 1.8 -
    Gender categorical
    Gender values provided are for the Safety Analysis Set (SAF) population. The SAF consisted of all participants who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug. The number of participants was 73; 73; 19; 22 per treatment arm.
    Units: Subjects
        Female
    		 35 44 16 17 112
        Male
    		 38 29 3 5 75
        Not recorded
    		 2 0 0 0 2
    Race
    Race values provided are for the Safety Analysis Set (SAF) population. The SAF consisted of all participants who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug. The number of participants was 73; 73; 19; 22 per treatment arm.
    Units: Subjects
        White
    		 57 62 13 16 148
        Black/African American
    		 3 2 1 2 8
        Asian
    		 6 5 3 4 18
        American Indian/Alaska Native
    		 3 4 2 0 9
        Other
    		 4 0 0 0 4
        Not recorded
    		 2 0 0 0 2
    Ethnicity
    Ethnicity values provided are for the Safety Analysis Set (SAF) population. The SAF consisted of all participants who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug. The number of participants was 73; 73; 19; 22 per treatment arm.
    Units: Subjects
        Hispanic or Latino
    		 8 9 3 2 22
        Not Hispanic or Latino
    		 65 64 16 20 165
        Not recorded
    		 2 0 0 0 2
    Mean Volume Voided (MVV) per Micturition
    Values for this baseline characteristic are based on the Full Analysis Set (FAS). The FAS consisted of all randomized patients that took at least 1 dose of double-blind study medication after randomization and provided a valid baseline and post baseline value for the primary efficacy endpoint. A micturition is any voluntary urination, excluding episodes of incontinence only. Micturitions voided volumes were recorded in a patient diary for any 2 days in the 7 day period prior to the baseline visit (referred to as "measuring days"). The number of participants was 70; 73; 19; 21 per arm.
    Units: mL
        arithmetic mean (standard deviation)
    		 94.06 ± 38.12 96.88 ± 40.98 169.06 ± 63.65 159.55 ± 61.21 -
    Daytime Maximum Volume Voided (DMaxVV)
    FAS population. The mean DMaxVV was determined using the patient diary data recorded during two measuring days (i.e., days when the patient recorded the volume of each micturition) in the 7 days prior to the baseline visit. The DMaxVV is the largest (non-zero) volume recorded over both of the 2 measuring days in the diary. Daytime is defined as the time between waking up in the morning and going to bed later the same day. A micturition is any voluntary urination, excluding episodes of incontinence only. The number of participants was 70; 73; 19; 21 per treatment arm.
    Units: mL
        arithmetic mean (standard deviation)
    		 141.43 ± 52.09 155.51 ± 70.66 278.16 ± 119.21 252.38 ± 108.68 -
    Mean Number of Incontinence Episodes per 24 Hours
    FAS population. The mean of the number of incontinence episodes was determined using diary data recorded by the participant in the 7 days prior to baseline visit. An incontinence episode is defined as an episode with any involuntary loss of urine. The number of participants was 70; 73; 19; 21 per treatment arm.
    Units: incontinence episodes
        arithmetic mean (standard deviation)
    		 2.98 ± 2.63 2.46 ± 2.57 2.81 ± 2.45 1.82 ± 1.66 -
    Mean Number of Daytime Incontinence Episodes per 24 Hours
    FAS population. The mean of the number of incontinence episodes was determined using diary data recorded by the participant in the 7 days prior to baseline visit. Daytime is defined as the time between waking up in the morning and going to bed later the same day. An incontinence episode is defined as an episode with any involuntary loss of urine. The number of participants was 70; 71; 19; 21 per treatment arm.
    Units: incontinence episodes
        arithmetic mean (standard deviation)
    		 2.54 ± 2.75 1.98 ± 3.24 2.03 ± 2.18 1.5 ± 1.44 -
    Mean Number of Nighttime Incontinence Episodes per 24 Hours
    FAS population. The mean of the number of incontinence episodes was determined using diary data recorded by the participant in the 7 days prior to baseline visit. An incontinence episode is defined as an episode with any involuntary loss of urine. Nighttime is defined as the time between going to bed and waking up the following morning. The number of participants was 70; 71; 19; 21 per treatment arm.
    Units: incontinence episodes
        arithmetic mean (standard deviation)
    		 0.59 ± 0.47 0.7 ± 0.82 0.39 ± 0.66 0.33 ± 0.4 -
    Number of Dry (Incontinence-free) Days per 7 Days
    FAS population. The mean of the number of dry days was determined using diary data recorded by the participant in the 7 days prior to baseline visit. The number of participants was 70; 73; 19; 21 per treatment arm.
    Units: dry days
        arithmetic mean (standard deviation)
    		 0.5 ± 0.9 0.9 ± 1.6 1 ± 1 1.5 ± 1.3 -
    Number of Dry (Incontinence-free) Nights per 7 Days
    FAS population. The mean of the number of dry nights was determined using diary data recorded by the participant in the 7 days prior to baseline visit. The number of participants was 70; 73; 19; 21 per treatment arm.
    Units: dry nights
        arithmetic mean (standard deviation)
    		 3.4 ± 3 3.1 ± 3 5.6 ± 2.2 5.4 ± 2.2 -
    Mean Number of Micturitions per 24 Hours
    FAS population. The mean of the number of micturitions was determined using diary data recorded by the participant in the 7 days prior to baseline visit. A micturition is any voluntary urination, excluding episodes of incontinence only. The number of participants was 70; 73; 19; 21 per treatment arm.
    Units: micturitions
        arithmetic mean (standard deviation)
    		 8.26 ± 2.56 8.27 ± 3.01 8.08 ± 3.82 7.52 ± 2.37 -
    Mean Number of Daytime Micturitions per 24 Hours
    FAS population. The mean of the number of micturitions was determined using diary data recorded by the participant in the 7 days prior to baseline visit. A micturition is any voluntary urination, excluding episodes of incontinence only. The number of participants was 70; 71; 19; 21 per treatment arm.
    Units: daytime micturitions
        arithmetic mean (standard deviation)
    		 7.54 ± 3.14 8 ± 3.4 6.79 ± 2.92 6.88 ± 2.14 -
    Mean Number of Nighttime Micturitions per 24 Hours
    FAS population. The mean of the number of micturitions was determined using diary data recorded by the participant in the 7 days prior to baseline visit. A micturition is any voluntary urination, excluding episodes of incontinence only. The number of participants was 70; 71; 19; 21 per treatment arm.
    Units: nightime micturitions
        arithmetic mean (standard deviation)
    		 0.6 ± 0.78 0.56 ± 0.98 0.61 ± 1.09 0.26 ± 0.41 -
    Mean Number of Grade 3 or 4 Urgency Episodes per 24 Hours in Adolescents
    FAS population. Adolescent participants were asked to record the degree of urgency associated with each micturition and incontinence episode according to the Patient Perception of Intensity of Urgency Scale (PPIUS) scale (0 - no urgency, 1 - mild urgency, 2 - moderate urgency, 3 - severe urgency, 4 - urge incontinence). The mean number of grade 3 or 4 urgency episodes was determined using diary data recorded by the participant in the 7 days prior to baseline visit. The number of participants was N/A; N/A; 19; 20 per treatment arm.
    Units: urgency episodes
        arithmetic mean (standard deviation)
    		 0 ± 0 0 ± 0 3.67 ± 4.15 2.42 ± 2.13 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo Children
    Reporting group description
    		 -

    Reporting group title
    Solifenacin Succinate Suspension Children
    Reporting group description
    		 -

    Reporting group title
    Placebo Adolescents
    Reporting group description
    		 -

    Reporting group title
    Solifenacin Succinate Suspension Adolescents
    Reporting group description
    		 -

    Subject analysis set title
    Children PED 5
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic analysis set (PKAS) consisted of the subset of the Safety Analysis Set (SAF) for which plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of last dose prior to sampling was known.

    Subject analysis set title
    Children PED 7.5
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic analysis set (PKAS) consisted of the subset of the Safety Analysis Set (SAF) for which plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of last dose prior to sampling was known.

    Subject analysis set title
    Adolescents PED 7.5
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic analysis set (PKAS) consisted of the subset of the Safety Analysis Set (SAF) for which plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of last dose prior to sampling was known.

    Subject analysis set title
    Children PED 10
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic analysis set (PKAS) consisted of the subset of the Safety Analysis Set (SAF) for which plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of last dose prior to sampling was known.

    Subject analysis set title
    Adolescents PED 10
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic analysis set (PKAS) consisted of the subset of the Safety Analysis Set (SAF) for which plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of last dose prior to sampling was known.

    Primary: Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition

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    End point title
    		 Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition
    End point description
    The mean voided volume was calculated from the patient diary data recorded during two measuring days (i.e., those days when the patient recorded the volume of each micturition) in the 7 days prior to the baseline and end of treatment visits. The MVV is equal to the mean of the non-zero volumes recorded over the 2 measuring days. A micturition is any voluntary urination, excluding episodes of incontinence. Study analysis population for this endpoint consisted of the Full Analysis Set (FAS). The FAS consists of all randomized patients that took at least one dose of double-blind study medication after randomization and provided both valid baseline and post-baseline values for the primary efficacy endpoint. Missing values at End of Treatment (EoT) were imputed using the last observation carried forward (LOCF) method.
    End point type
    Primary
    End point timeframe
    Baseline and Week 12.
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    73
    19
    21
    Units: mL
        least squares mean (standard error)
    13.4 ± 4.8
    25.5 ± 4.8
    6.9 ± 14.6
    2.3 ± 14
    Statistical analysis title
    		 Statistical Analysis Children
    Statistical analysis description
    The following hypotheses were tested at the 2-sided significance level 0.05: • H0: Change from baseline to EoT in mean MVV per micturition is the same for placebo and solifenacin succinate oral suspension • H1: Change from baseline to EoT in mean MVV per micturition is not the same for placebo and solifenacin succinate oral suspension
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.046
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    12.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 24
    Variability estimate
    Standard error of the mean
    Dispersion value
    6
    Notes
    [1] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -4.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.7
         upper limit
    		 27.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    15.7
    Notes
    [2] - From an ANCOVA model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition

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    End point title
    		 Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition
    End point description
    The mean daytime maximum volume voided (DMaxVV) was determined using the patient diary data recorded during two measuring days (i.e., those days when the patient recorded the volume of each micturition) in the 7 days prior to the baseline and end of treatment visits. The daytime maximum volume voided (DMaxVV) is the largest (non-zero) volume recorded over both of the 2 measuring days in the diary. Daytime is defined as the time between waking up in the morning and going to bed later the same day. A micturition is any voluntary urination, excluding episodes of incontinence. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    73
    19
    21
    Units: mL
        least squares mean (standard error)
    11.3 ± 11.2
    43.2 ± 11.1
    -8.4 ± 27
    -25.7 ± 26.3
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 = 0.024
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    31.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.3
         upper limit
    		 59.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    13.9
    Notes
    [3] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -17.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -76.5
         upper limit
    		 41.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    29.1
    Notes
    [4] - From an ANCOVA model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours
    End point description
    An incontinence episode is defined as an episode with any involuntary loss of urine. The mean number of incontinence episodes was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    73
    19
    21
    Units: incontinence episodes
        least squares mean (standard error)
    -1.2 ± 0.2
    -1.1 ± 0.2
    -0.7 ± 0.4
    -0.6 ± 0.4
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 = 0.763 [6]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Notes
    [5] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    [6] - P-value is from a rank ANCOVA analysis stratified by geographic region.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [7] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours
    End point description
    The mean number of incontinence episodes was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    71
    19
    21
    Units: daytime incontinence episodes
        least squares mean (standard error)
    -1.1 ± 0.2
    -1.2 ± 0.2
    -0.2 ± 0.4
    -0.8 ± 0.4
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 other [8]
    P-value
    		 = 0.402 [9]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Notes
    [8] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    [9] - P-value is from a rank ANCOVA analysis stratified by geographic region.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [10]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [10] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours
    End point description
    The mean number of incontinence episodes was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    71
    19
    21
    Units: incontinence episodes
        least squares mean (standard error)
    -0.2 ± 0
    -0.1 ± 0
    -0.2 ± 0.1
    -0.2 ± 0.1
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 other [11]
    P-value
    		 = 0.63 [12]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [11] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    [12] - P-value is from a rank ANCOVA analysis stratified by geographic region.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [13]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [13] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-free) Days Per 7 Days

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-free) Days Per 7 Days
    End point description
    The mean number of dry days was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12.
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    71
    19
    21
    Units: dry days
        least squares mean (standard error)
    1.7 ± 0.3
    1.3 ± 0.3
    1.5 ± 0.8
    1.6 ± 0.7
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 other [14]
    P-value
    		 = 0.563 [15]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Notes
    [14] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    [15] - P-value is from a rank ANCOVA analysis stratified by geographic region.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [16]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.8
    Notes
    [16] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-free) Nighttimes Per 7 Days

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-free) Nighttimes Per 7 Days
    End point description
    The mean number of dry nights was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12.
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    73
    19
    21
    Units: dry nights
        least squares mean (standard error)
    0.7 ± 0.2
    0.4 ± 0.2
    -0.1 ± 0.4
    0.4 ± 0.4
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 other [17]
    P-value
    		 = 0.77 [18]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Notes
    [17] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    [18] - P-value is from a rank ANCOVA analysis stratified by geographic region.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [19]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [19] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours
    End point description
    The mean number of micturitions was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. A micturition is any voluntary urination, excluding episodes of incontinence. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12.
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    73
    19
    21
    Units: micturitions
        least squares mean (standard error)
    -0.8 ± 0.2
    -1.1 ± 0.2
    -0.6 ± 0.5
    -0.4 ± 0.4
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Placebo Children v Solifenacin Succinate Suspension Children
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 other [20]
    P-value
    		 = 0.303
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Notes
    [20] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [21]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [21] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours
    End point description
    The mean number of micturitions was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. A micturition is any voluntary urination, excluding episodes of incontinence. The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12.
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    71
    19
    21
    Units: daytime micturitions
        least squares mean (standard error)
    -1.1 ± 0.2
    -1.2 ± 0.2
    -0.5 ± 0.5
    -0.3 ± 0.5
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Solifenacin Succinate Suspension Children v Placebo Children
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 other [22]
    P-value
    		 = 0.64
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Notes
    [22] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [23]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6
    Notes
    [23] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours
    End point description
    The mean number of micturitions was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. A micturition is any voluntary urination, excluding episodes of incontinence.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12.
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    70
    71
    19
    21
    Units: nighttime micturitions
        least squares mean (standard error)
    0 ± 0.1
    -0.1 ± 0.1
    0.4 ± 0.3
    0.1 ± 0.3
    Statistical analysis title
    		 Statistical Analysis Children
    Comparison groups
    Solifenacin Succinate Suspension Children v Placebo Children
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 other [24]
    P-value
    		 = 0.846 [25]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [24] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.
    [25] - P-value is from a rank ANCOVA analysis stratified by geographic region.
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Solifenacin Succinate Suspension Adolescents v Placebo Adolescents
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other [26]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [26] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Change From Baseline to End of Treatment in Mean Number of Grade 3 or 4 Urgency Episodes Per 24 Hours in Adolescents

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    End point title
    		 Change From Baseline to End of Treatment in Mean Number of Grade 3 or 4 Urgency Episodes Per 24 Hours in Adolescents [27]
    End point description
    Adolescent participants were asked to record the degree of urgency associated with each micturition and incontinence episode according to the Patient Perception of Intensity of Urgency Scale (PPIUS) scale (0 - no urgency, 1 - mild urgency, 2 - moderate urgency, 3 - severe urgency, 4 - urge incontinence). The mean number of grade 3 or 4 urgency episodes was determined using diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. The study analysis population for this endpoint consisted of the FAS population (adolescents only). Missing values at EoT were imputed using the LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12.
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study population for this endpoint consisted of adolescents only.
    End point values
    		 Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    19
    20
    Units: grade 3 or 4 urgency episodes
        least squares mean (standard error)
    -0.7 ± 0.5
    -1 ± 0.5
    Statistical analysis title
    		 Statistical Analysis Adolescents
    Comparison groups
    Placebo Adolescents v Solifenacin Succinate Suspension Adolescents
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other [28]
    Method
    Parameter type
    		 Adjusted Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Notes
    [28] - From an ANCOVA (analysis of covariance) model including treatment and geographic regions as fixed-effect and the baseline value as a covariate.

    Secondary: Maximum Concentration (Cmax) of Solifenacin

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    End point title
    		 Maximum Concentration (Cmax) of Solifenacin
    End point description
    Pharmacokinetic sampling was performed at steady state at the end of treatment. The study analysis population for this endpoint consisted of the Pharmacokinetic Analysis Set (PKAS). The PKAS consisted of the subset of the Safety Analysis Set (SAF) for which plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of last dose prior to sampling was known. Cmax could not be calculated for 2 children and 1 adolescent in the PKAS.
    End point type
    Secondary
    End point timeframe
    Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
    End point values
    		 Children PED 5 Children PED 7.5 Adolescents PED 7.5 Children PED 10 Adolescents PED 10
    Number of subjects analysed
    6
    12
    1 [29]
    46
    16
    Units: ng/mL
        arithmetic mean (standard deviation)
    16.67 ± 4.593
    26.24 ± 6.617
    17.08 ± 0
    33.48 ± 11.93
    42.85 ± 21.44
    Notes
    [29] - Standard deviation is not applicable, only 1 adolescent received PED 7.5 that had Cmax measured.
    No statistical analyses for this end point

    Secondary: Time to Attain Maximum Concentration (Tmax)

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    End point title
    		 Time to Attain Maximum Concentration (Tmax)
    End point description
    Pharmacokinetic sampling was performed at steady state at the end of treatment. The study analysis population for this endpoint consisted of the PKAS. Tmax could not be calculated for 2 children and 1 adolescent in the PKAS
    End point type
    Secondary
    End point timeframe
    Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
    End point values
    		 Children PED 5 Children PED 7.5 Adolescents PED 7.5 Children PED 10 Adolescents PED 10
    Number of subjects analysed
    6
    12
    1 [30]
    46
    16
    Units: ng/mL
        arithmetic mean (standard deviation)
    2.933 ± 0.5354
    3.175 ± 0.561
    2.8 ± 0
    2.874 ± 0.5268
    2.85 ± 0.4733
    Notes
    [30] - Standard deviation is not applicable, only 1 adolescent received PED 7.5 that had Tmax measured.
    No statistical analyses for this end point

    Secondary: Plasma Concentration Before Drug Administration (Ctrough)

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    End point title
    		 Plasma Concentration Before Drug Administration (Ctrough)
    End point description
    Pharmacokinetic sampling was performed at steady state at the end of treatment. The study analysis population for this endpoint consisted of the PKAS. Ctrough could not be calculated for 2 children and 1 adolescent in the PKAS.
    End point type
    Secondary
    End point timeframe
    Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
    End point values
    		 Children PED 5 Children PED 7.5 Adolescents PED 7.5 Children PED 10 Adolescents PED 10
    Number of subjects analysed
    6
    12
    1 [31]
    46
    16
    Units: ng/mL
        arithmetic mean (standard deviation)
    9.534 ± 3.083
    16.1 ± 4.951
    8.828 ± 0
    19.05 ± 8.7
    27.94 ± 16.76
    Notes
    [31] - Standard deviation is not applicable, only 1 adolescent received PED 7.5 that had Ctrough measured.
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau)

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    End point title
    		 Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau)
    End point description
    Pharmacokinetic sampling was performed at steady state at the end of treatment. The study analysis population for this endpoint consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
    End point values
    		 Children PED 5 Children PED 7.5 Adolescents PED 7.5 Children PED 10 Adolescents PED 10
    Number of subjects analysed
    8
    12
    1 [32]
    46
    17
    Units: ng*h/mL
        arithmetic mean (standard deviation)
    298.7 ± 80.35
    452.8 ± 112.6
    269.2 ± 0
    560 ± 216.8
    745.7 ± 411
    Notes
    [32] - Standard deviation is not applicable, only 1 adolescent received PED 7.5 that had AUCtau measured.
    No statistical analyses for this end point

    Secondary: Apparent Terminal Elimination Half-life (t1/2)

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    End point title
    		 Apparent Terminal Elimination Half-life (t1/2)
    End point description
    Pharmacokinetic sampling was performed at steady state at the end of treatment. The study analysis population for this endpoint consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
    End point values
    		 Children PED 5 Children PED 7.5 Adolescents PED 7.5 Children PED 10 Adolescents PED 10
    Number of subjects analysed
    8
    12
    1 [33]
    46
    17
    Units: hours
        arithmetic mean (standard deviation)
    27.3 ± 5.486
    30.98 ± 7.147
    24.84 ± 0
    26.85 ± 7.475
    41.27 ± 17.44
    Notes
    [33] - Standard deviation is not applicable, only 1 adolescent received PED 7.5 that had t1/2 measured.
    No statistical analyses for this end point

    Secondary: Apparent Total Body Clearance (CL/F)

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    End point title
    		 Apparent Total Body Clearance (CL/F)
    End point description
    Pharmacokinetic sampling was performed at steady state at the end of treatment. The study analysis population for this endpoint consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
    End point values
    		 Children PED 5 Children PED 7.5 Adolescents PED 7.5 Children PED 10 Adolescents PED 10
    Number of subjects analysed
    8
    12
    1 [34]
    46
    17
    Units: L/h
        arithmetic mean (standard deviation)
    6.968 ± 2.129
    7.608 ± 1.782
    14.56 ± 0
    8.773 ± 3.763
    11.3 ± 7.294
    Notes
    [34] - Standard deviation is not applicable, only 1 adolescent received PED 7.5 that had CL/F measured.
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (Vz/F)

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    End point title
    		 Apparent Volume of Distribution (Vz/F)
    End point description
    Pharmacokinetic sampling was performed at steady state at the end of treatment. The study analysis population for this endpoint consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
    End point values
    		 Children PED 5 Children PED 7.5 Adolescents PED 7.5 Children PED 10 Adolescents PED 10
    Number of subjects analysed
    8
    12
    1 [35]
    46
    17
    Units: Liters (L)
        arithmetic mean (standard deviation)
    272.4 ± 96.84
    329.5 ± 63.32
    521.9 ± 0
    315.7 ± 96.23
    561.7 ± 181.7
    Notes
    [35] - Standard deviation is not applicable, only 1 adolescent received PED 7.5 that had Vz/F measured.
    No statistical analyses for this end point

    Secondary: Safety as Assessed by Recording Adverse Events, Laboratory Assessments, Vital Signs and electrocardiograms (ECGs)

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    End point title
    		 Safety as Assessed by Recording Adverse Events, Laboratory Assessments, Vital Signs and electrocardiograms (ECGs)
    End point description
    A treatment emergent adverse event (TEAE) was defined as an AE that occurred after the first dose of study drug and within 7 days after last dose of study medication. The study analysis population for this endpoint consisted of the Safety Analysis Set (SAF). The SAF consisted of all patients who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug until 7 days after last dose of study medication (13 weeks).
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    73
    73
    19
    22
    Units: participants
    number (not applicable)
        Any TEAE
    45
    44
    12
    9
        Drug Related TEAEs
    9
    14
    2
    3
        Deaths
    0
    0
    0
    0
        Serious TEAEs
    2
    2
    1
    1
        Drug-related Serious TEAEs
    1
    0
    0
    0
        TEAEs Leading to Discontinuation
    1
    6
    2
    2
        Drug-related TEAEs Leading to Permanent Discont.
    1
    3
    1
    1
    No statistical analyses for this end point

    Secondary: Change From Baseline in Post Void Residual (PVR) Volume

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    End point title
    		 Change From Baseline in Post Void Residual (PVR) Volume
    End point description
    Post Void Residual (PVR) Volume was assessed by ultrasonography or bladder scan. The study analysis population for this endpoint consisted of the SAF.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Number of subjects analysed
    73
    73
    19
    22
    Units: mL
        least squares mean (standard deviation)
    0.07 ± 7.28
    -0.99 ± 6.45
    -3.58 ± 4.72
    0.95 ± 9.85
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    A treatment-emergent adverse event (TEAE) is defined as an adverse event observed after starting administration of the first dose of double-blind study medication on Day 1 and up to 7 days after last dose date (Treatment period was 12 weeks).
    Adverse event reporting additional description
    An adverse event (AE) was defined as any untoward medical occurrence in a patient administered a study drug or who had undergone study procedures and which did not necessarily have a causal relationship with this treatment. SAF population.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.0
    Reporting groups
    Reporting group title
    Placebo Children
    Reporting group description
    		 Children aged 5 to 11 years received matching placebo suspension once a day for 12 weeks.

    Reporting group title
    Solifenacin Succinate Suspension Children
    Reporting group description
    		 Children aged 5 to 11 years received solifenacin succinate suspension once a day for 12 weeks.

    Reporting group title
    Placebo Adolescents
    Reporting group description
    		 Adolescents aged 12 to 17 years received matching placebo suspension once a day for 12 weeks.

    Reporting group title
    Solifenacin Succinate Suspension Adolescents
    Reporting group description
    		 Adolescents aged 12 to 17 years received solifenacin succinate suspension once a day for 12 weeks.

    Serious adverse events
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 73 (2.74%)
    2 / 73 (2.74%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 73 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 73 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Frontal lobe epilepsy
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 73 (1.37%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 73 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 73 (1.37%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Children Solifenacin Succinate Suspension Children Placebo Adolescents Solifenacin Succinate Suspension Adolescents
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 73 (60.27%)
    43 / 73 (58.90%)
    12 / 19 (63.16%)
    9 / 22 (40.91%)
    Investigations
    Electrocardiogram QT prolonged
         subjects affected / exposed
    2 / 73 (2.74%)
    5 / 73 (6.85%)
    1 / 19 (5.26%)
    2 / 22 (9.09%)
         occurrences all number
    2
    5
    1
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Headache
         subjects affected / exposed
    2 / 73 (2.74%)
    5 / 73 (6.85%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    2
    7
    1
    0
    Somnolence
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 73 (1.37%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Constipation
         subjects affected / exposed
    2 / 73 (2.74%)
    4 / 73 (5.48%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    4
    0
    0
    Diarrhoea
         subjects affected / exposed
    4 / 73 (5.48%)
    4 / 73 (5.48%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    4
    4
    0
    2
    Dry mouth
         subjects affected / exposed
    1 / 73 (1.37%)
    2 / 73 (2.74%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    3 / 19 (15.79%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Allergic respiratory symptom
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 73 (1.37%)
    1 / 73 (1.37%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    1
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 73 (2.74%)
    1 / 73 (1.37%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Escherichia urinary tract infection
         subjects affected / exposed
    2 / 73 (2.74%)
    3 / 73 (4.11%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
         occurrences all number
    2
    3
    2
    0
    Influenza
         subjects affected / exposed
    4 / 73 (5.48%)
    0 / 73 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    4
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    7 / 73 (9.59%)
    6 / 73 (8.22%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
         occurrences all number
    8
    6
    2
    0
    Streptobacillus infection
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tooth abscess
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 73 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 73 (2.74%)
    2 / 73 (2.74%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
         occurrences all number
    4
    2
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2012
    Substantial Global Amendment No 1, dated 20 April 2012. Exclusion criteria were updated, the changes to the protocol were implemented prior to the enrollment of participants.
    21 Sep 2013
    Substantial Global Amendment No. 2 dated 21 September 2013. Amendment 2 reduced the planned number of randomized adolescents, due to this and subsequent reduction in statistical power, no conclusions can be drawn for analyses of primary and secondary variables for this age cohort.

    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
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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