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    Clinical Trial Results:
    A Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Adding Mirabegron to Solifenacin in Incontinent OAB Patients who have Received Solifenacin for 4 Weeks and Warrant Additional Relief for their OAB Symptoms

    Summary
    EudraCT number
    2012-005401-41
    Trial protocol
    SK   CZ   GB   SE   IE   BE   PT   NO   AT   FI   GR   HU   ES   SI   NL   DK   PL  
    Global end of trial date
    25 Nov 2014

    Results information
    Results version number
    v3(current)
    This version publication date
    28 Apr 2018
    First version publication date
    21 Jul 2016
    Other versions
    v1 , v2
    Version creation reason

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    905-EC-012
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01908829
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Acronym: BESIDE
    Sponsors
    Sponsor organisation name
    Astellas Pharma Europe Ltd
    Sponsor organisation address
    2000 Hillswood Drive, Chertsey, United Kingdom, KT16 0RS
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Europe Ltd, Astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Europe Ltd, Astellas.resultsdisclosure@astellas.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Nov 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Nov 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of solifenacin 5 mg in combination with mirabegron 50 mg (referred to as combination therapy from here on) vs solifenacin 5 mg monotherapy.
    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, 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
    10 Jul 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Algeria: 15
    Country: Number of subjects enrolled
    Armenia: 52
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Austria: 24
    Country: Number of subjects enrolled
    Belgium: 24
    Country: Number of subjects enrolled
    Canada: 57
    Country: Number of subjects enrolled
    Czech Republic: 129
    Country: Number of subjects enrolled
    Denmark: 39
    Country: Number of subjects enrolled
    Egypt: 11
    Country: Number of subjects enrolled
    Finland: 6
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Georgia: 23
    Country: Number of subjects enrolled
    Germany: 106
    Country: Number of subjects enrolled
    Greece: 53
    Country: Number of subjects enrolled
    Hungary: 53
    Country: Number of subjects enrolled
    Ireland: 8
    Country: Number of subjects enrolled
    Israel: 43
    Country: Number of subjects enrolled
    Italy: 49
    Country: Number of subjects enrolled
    Kazakhstan: 23
    Country: Number of subjects enrolled
    Norway: 9
    Country: Number of subjects enrolled
    Poland: 234
    Country: Number of subjects enrolled
    Portugal: 12
    Country: Number of subjects enrolled
    Romania: 84
    Country: Number of subjects enrolled
    Russian Federation: 241
    Country: Number of subjects enrolled
    Slovakia: 93
    Country: Number of subjects enrolled
    Slovenia: 26
    Country: Number of subjects enrolled
    Spain: 76
    Country: Number of subjects enrolled
    Sweden: 54
    Country: Number of subjects enrolled
    Switzerland: 11
    Country: Number of subjects enrolled
    Turkey: 164
    Country: Number of subjects enrolled
    Ukraine: 28
    Country: Number of subjects enrolled
    United Kingdom: 78
    Country: Number of subjects enrolled
    United States: 320
    Country: Number of subjects enrolled
    Netherlands: 15
    Worldwide total number of subjects
    2174
    EEA total number of subjects
    1183
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1492
    From 65 to 84 years
    671
    85 years and over
    11

    Subject disposition

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    Recruitment
    Recruitment details
    This multicenter study was conducted at 281 centers globally. Randomization was stratified by sex, age group (< 65, ≥ 65 years), 4-week incontinence episode reduction group (< 50%, ≥ 50%) and geographic region.

    Pre-assignment
    Screening details
    Participants who met the screening inclusion/exclusion criteria went through a two week wash-out period and maintained a micturition diary during that the wash-out period. A total of 3815 participants were screened of which 2401 participants received solifenacin 5 mg run-in medication. A total of 2174 participants were randomized.

    Pre-assignment period milestones
    Number of subjects started
    3815 [1]
    Intermediate milestone: Number of subjects
    Received 1 dose, single-blind run-in: 2401
    Number of subjects completed
    2174

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Discontinued before run-in solifenacin 5 mg: 1414
    Reason: Number of subjects
    Exclusion/inclusion criteria not met: 169
    Reason: Number of subjects
    Patient withdrawn: 32
    Reason: Number of subjects
    Adverse event: 16
    Reason: Number of subjects
    Other reasons: 7
    Reason: Number of subjects
    Lost to follow-up: 3
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of participants included in the pre-assignment period were the total number screened. The number of participants included in the worldwide number enrolled were the total number of participants randomized.
    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
    Blinding implementation details
    The study was comprised of a 12 week double-blind treatment period (participants were randomized into the double-blind period if they experienced 1 or more incontinence episodes over the 3-day diary period prior to randomization to double-blind period and warranted additional relief for their OAB symptoms). There was 2 week safety follow up period (placebo administered). The active and placebo tablets were made indistinguishable by using a double-dummy packaging system.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Combination (solifenacin + mirabegron)
    Arm description
    Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
    Arm type
    Experimental

    Investigational medicinal product name
    solifenacin 5 mg
    Investigational medicinal product code
    YM905
    Other name
    Vesicare, Vesitrim, Vesikur, solifenacin succinate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Solifenacin was provided as the marketed formulation in the 5 mg strength. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    solifenacin 10 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    mirabegron 25 mg
    Investigational medicinal product code
    YM178
    Other name
    Betanis, Betmiga, Myrbetriq
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Mirabegron was supplied as the marketed formulation in the 25 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    mirabegron 50 mg
    Investigational medicinal product code
    YM178
    Other name
    Betanis, Betmiga, Myrbetriq
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Mirabegron was supplied as the marketed formulation in the 50 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.

    Arm title
    Solifenacin 5 mg
    Arm description
    Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
    Arm type
    Active comparator

    Investigational medicinal product name
    solifenacin 5 mg
    Investigational medicinal product code
    YM905
    Other name
    Vesicare, Vesitrim, Vesikur, solifenacin succinate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Solifenacin was provided as the marketed formulation in the 5 mg strength. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    solifenacin 10 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    mirabegron 25 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    mirabegron 50 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

    Arm title
    Solifenacin 10 mg
    Arm description
    Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
    Arm type
    Active comparator

    Investigational medicinal product name
    solifenacin 5 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo of solifenacin succinate 5 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    solifenacin 10 mg
    Investigational medicinal product code
    YM905
    Other name
    Vesicare, Vesitrim, Vesikur, solifenacin succinate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Solifenacin was provided as the marketed formulation in the 10 mg strength. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    mirabegron 25 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

    Investigational medicinal product name
    mirabegron 50 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

    Number of subjects in period 1
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Started
    727
    728
    719
    Treated with double-blind drug
    725
    728
    719
    Completed
    678
    679
    680
    Not completed
    49
    49
    39
         Miscellaneous
    -
    2
    -
         Discontinued (no EoT page)
    2
    -
    -
         Randomized no double-blind drug received
    1
    -
    1
         Adverse event
    13
    11
    13
         Lack of efficacy
    1
    3
    2
         Withdrawal by subject
    26
    29
    22
         Protocol Violation
    2
    2
    -
         Lost to follow-up
    4
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Combination (solifenacin + mirabegron)
    Reporting group description
    Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.

    Reporting group title
    Solifenacin 5 mg
    Reporting group description
    Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

    Reporting group title
    Solifenacin 10 mg
    Reporting group description
    Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

    Reporting group values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg Total
    Number of subjects
    727 728 719
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    58.2 ± 13.1 56.9 ± 13.5 57.4 ± 13.2 -
    Gender categorical
    Units:
        Male
    123 124 119 366
        Female
    604 604 600 1808

    End points

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    End points reporting groups
    Reporting group title
    Combination (solifenacin + mirabegron)
    Reporting group description
    Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.

    Reporting group title
    Solifenacin 5 mg
    Reporting group description
    Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

    Reporting group title
    Solifenacin 10 mg
    Reporting group description
    Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

    Primary: Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

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    End point title
    Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours
    End point description
    The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. The analysis population consisted of the Full Analysis Set (FAS) which comprised of all the Randomized Analysis Set's (RAS) participants who met the following criteria: took at least 1 dose of double-blind study drug after randomization, reported at least 1 micturition in the baseline diary & at least 1 micturition postbaseline & reported at least 1 incontinence episode in the baseline diary. For participants who withdrew before EoT (week 12) and have no measurement available for that diary period, the Last Observation Carried Forward (LOCF) value during the double-blind study period was used as EoT value to derive the primary variable.
    End point type
    Primary
    End point timeframe
    Baseline and end of treatment (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    706
    704
    697
    Units: incontinence episodes
        least squares mean (standard error)
    -1.8 ± 0.08
    -1.53 ± 0.08
    -1.67 ± 0.08
    Statistical analysis title
    Adjusted Difference Combination vs Solifenacin 5mg
    Statistical analysis description
    Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1410
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [1]
    Method
    stratified rank ANCOVA
    Parameter type
    Least Squares (LS) Means
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    -0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Notes
    [1] - P values for pairwise comparisons were from the stratified rank ANCOVA model. P < 0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes per 24 Hours

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    End point title
    Change from Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes per 24 Hours
    End point description
    The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. The analysis population consisted of the FAS. N=number of participants with available data (applicable for all secondary endpoints).
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: incontinence episodes
    least squares mean (standard error)
        Week 4 (N= 690, 690, 679)
    -1.24 ± 0.07
    -0.91 ± 0.07
    -1.12 ± 0.07
        Week 8 (N= 661, 674, 673)
    -1.68 ± 0.07
    -1.29 ± 0.07
    -1.49 ± 0.07
        Week 12 (N= 653, 645, 664)
    -1.81 ± 0.08
    -1.57 ± 0.08
    -1.67 ± 0.08
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [2]
    Method
    stratified rank ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.52
         upper limit
    -0.14
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [2] - P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [3]
    Method
    stratified rank ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    -0.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [3] - P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [4]
    Method
    stratified rank ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.46
         upper limit
    -0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Notes
    [4] - P-values for pairwise comparisons are from the stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in Mean Number of Micturitions per 24 Hours

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    End point title
    Change from Baseline in Mean Number of Micturitions per 24 Hours
    End point description
    The average number of micturitions (voluntary urinations (excluding incontinence only episodes)) per 24 hours was derived from number of micturitions recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period (excluding incontinence only episodes). LOCF was used for EoT. The analysis population included the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: micturitions
    least squares mean (standard error)
        Week 4 (N= 690, 690, 679)
    -0.95 ± 0.07
    -0.69 ± 0.07
    -0.79 ± 0.07
        Week 8 (N= 661, 674, 673)
    -1.36 ± 0.08
    -0.94 ± 0.08
    -1.00 ± 0.08
        Week 12 (N= 653, 645, 664)
    -1.63 ± 0.08
    -1.16 ± 0.09
    -1.11 ± 0.08
        EoT (N= 706, 704, 697)
    -1.59 ± 0.08
    -1.14 ± 0.08
    -1.12 ± 0.08
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.01 [5]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    -0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [5] - P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [6]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.65
         upper limit
    -0.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [6] - P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [7]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    -0.23
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [7] - P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [8]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.67
         upper limit
    -0.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [8] - P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Number of Incontinence Episodes Reported During the 3-Day Diary

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    End point title
    Number of Incontinence Episodes Reported During the 3-Day Diary
    End point description
    The number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from total number of incontinence episodes on valid diary days recorded during the 3-day micturition diary period. LOCF was used for EoT. The analysis population included the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: incontinence episodes
    arithmetic mean (standard error)
        Week 4 (N= 690, 690, 679)
    5.81 ± 0.30
    6.68 ± 0.31
    6.41 ± 0.33
        Week 8 (N= 661, 674, 673)
    4.55 ± 0.30
    5.43 ± 0.30
    5.28 ± 0.32
        Week 12 (N= 653, 645, 664)
    4.03 ± 0.29
    4.56 ± 0.28
    4.62 ± 0.31
        EoT (N= 706, 704, 697)
    4.25 ± 0.29
    4.87 ± 0.28
    4.72 ± 0.31
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 4
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of incontinence episodes during EoT 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005 [9]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.79
         upper limit
    0.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [9] - p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 8
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of incontinence episodes during EoT 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [10]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    0.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [10] - p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 12
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of incontinence episodes during EoT 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.021 [11]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    0.97
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [11] - p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin EoT
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of incontinence episodes during EoT 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014 [12]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.71
         upper limit
    0.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [12] - p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.

    Secondary: Change from Baseline in Mean Volume Voided (MVV) per Micturition

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    End point title
    Change from Baseline in Mean Volume Voided (MVV) per Micturition
    End point description
    MVV per micturition was defined as MVV (mL) per micturition during last 3 days of the 3-day micturition diary period. MVV per micturition was calculated as the sum of each volume voided for each record with volume voided > 0 on valid diary days divided by the total number of records with a volume voided > 0 on valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: mL
    least squares mean (standard error)
        Week 4 (N= 665, 669, 664)
    15.06 ± 1.55
    11.20 ± 1.55
    14.99 ± 1.55
        Week 8 (N= 638, 648, 655)
    25.21 ± 1.89
    14.02 ± 1.87
    21.08 ± 1.86
        Week 12 (N= 627, 617, 642)
    29.54 ± 2.06
    17.16 ± 2.08
    20.99 ± 2.04
        EoT (N= 680, 682, 682)
    28.05 ± 1.97
    16.52 ± 1.97
    20.30 ± 1.97
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.078 [13]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    3.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.43
         upper limit
    8.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.19
    Notes
    [13] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [14]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    11.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.98
         upper limit
    16.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.66
    Notes
    [14] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [15]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    12.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.65
         upper limit
    18.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.92
    Notes
    [15] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [16]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    11.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.06
         upper limit
    16.99
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.79
    Notes
    [16] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline to EoT in Corrected Micturition Frequency (CMF)

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    End point title
    Change from Baseline to EoT in Corrected Micturition Frequency (CMF)
    End point description
    CMF was defined as the mean number of micturitions per 24 hours that participants would have at EoT if their fluid intake had remained unchanged since baseline. This was calculated by the MVV per Micturition at baseline multiplied by the mean number of micturitions per 24 hours at baseline divided by the MVV per micturition at EoT. LOCF was used. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    706
    704
    697
    Units: micturitions
        least squares mean (standard error)
    -0.96 ± 0.10
    -0.52 ± 0.10
    -0.71 ± 0.10
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1410
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [17]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.73
         upper limit
    -0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [17] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in Mean Number of Urgency Incontinence (UI) Episodes per 24 Hours

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    End point title
    Change from Baseline in Mean Number of Urgency Incontinence (UI) Episodes per 24 Hours
    End point description
    UI was defined as the complaint of involuntary urine leakage accompanied by or immediately preceded by urgency. UI was measured using the Patient Perception of Intensity of Urgency Scale (PPIUS), a patient reported outcome validated 5-point categorical scale rating the degree of associated urinary urgency severity (0=No urgency, I felt no need to empty my bladder, but did so for other reasons. 1=Mild, I could postpone voiding as long as necessary, without fear of wetting myself. 2= Moderate, I could postpone voiding for a short while, without fear of wetting myself. 3=Severe, I could not postpone voiding, but had to rush to the toilet in order not to wet myself. 4=Urgency incontinence, I leaked before arriving to the toilet). One urgency incontinence episode was counted for each record of the diary in which the following occurred: incontinence episode or ‘both’ was recorded & severity of urinary urgency recorded was 3 or 4. LOCF was used for EoT. FAS population.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: UI episodes
    least squares mean (standard error)
        Week 4 (N= 676, 670, 650)
    -1.26 ± 0.07
    -0.91 ± 0.07
    -1.14 ± 0.07
        Week 8 (N= 649, 654, 645)
    -1.70 ± 0.07
    -1.25 ± 0.07
    -1.45 ± 0.07
        Week 12 (N= 643, 627, 635)
    -1.84 ± 0.07
    -1.58 ± 0.07
    -1.62 ± 0.07
        EoT (N= 691, 683, 666)
    -1.82 ± 0.07
    -1.54 ± 0.07
    -1.63 ± 0.07
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [18]
    P-value
    < 0.001 [19]
    Method
    stratified rank ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.54
         upper limit
    -0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Notes
    [18] - Only participants with at least one UI episode reported in baseline diary were included.
    [19] - P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [20]
    P-value
    < 0.001 [21]
    Method
    stratified rank ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.65
         upper limit
    -0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [20] - Only participants with at least one UI episode reported in baseline diary were included.
    [21] - P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [22]
    P-value
    = 0.004 [23]
    Method
    stratified rank ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    -0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Notes
    [22] - Only participants with at least one UI episode reported in baseline diary were included.
    [23] - P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [24]
    P-value
    = 0.003 [25]
    Method
    stratified rank ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    -0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [24] - Only participants with at least one UI episode reported in baseline diary were included.
    [25] - P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Number of UI Episodes Reported During the 3-Day Diary

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    End point title
    Number of UI Episodes Reported During the 3-Day Diary
    End point description
    Number of UI episodes was calculated using the number of UI episodes recorded on valid diary days during the 3-day micturition diary period. NOTE: Only urgency incontinence episodes recorded on a valid diary day were counted. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: UI episodes
    arithmetic mean (standard error)
        Week 4 (N= 676, 670, 650)
    4.96 ± 0.27
    5.86 ± 0.29
    5.50 ± 0.30
        Week 8 (N= 649, 654, 645)
    3.55 ± 0.25
    4.76 ± 0.27
    4.50 ± 0.30
        Week 12 (N= 643, 627, 635)
    3.10 ± 0.24
    3.78 ± 0.25
    3.91 ± 0.30
        EoT (N= 691, 683, 666)
    3.33 ± 0.24
    4.00 ± 0.25
    3.96 ± 0.29
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 4
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of UI episodes during EoT 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [26]
    P-value
    = 0.003 [27]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.76
         upper limit
    0.94
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [26] - Only participants with at least one UI episode reported in baseline diary were included.
    [27] - p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 8
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of UI episodes during EoT 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [28]
    P-value
    < 0.001 [29]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.74
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.63
         upper limit
    0.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [28] - Only participants with at least one UI episode reported in baseline diary were included.
    [29] - p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 12
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of UI episodes during EoT 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [30]
    P-value
    = 0.038 [31]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.83
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    0.99
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Notes
    [30] - Only participants with at least one UI episode reported in baseline diary were included.
    [31] - p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin EoT
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of UI episodes during EoT 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [32]
    P-value
    = 0.022 [33]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    0.97
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Notes
    [32] - Only participants with at least one UI episode reported in baseline diary were included.
    [33] - p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.

    Secondary: Change from Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) per 24 Hours

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    End point title
    Change from Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) per 24 Hours
    End point description
    An urgency episode was defined as the complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes (severity of 3 or 4) per 24 hours was defined as the average number of times a participant recorded an urgency episode (severity of 3 or 4) with or without incontinence per day during the 3-day micturition diary period. Measured using the PPIUS scale. This was calculated using the sum of each record with an urgency episode (severity of 3 or 4) recorded on a valid diary day divided by the number of valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: urgency episodes
    least squares mean (standard error)
        Week 4 (N= 684, 681, 663)
    -1.84 ± 0.09
    -1.39 ± 0.09
    -1.74 ± 0.10
        Week 8 (N= 654, 665, 659)
    -2.64 ± 0.10
    -2.00 ± 0.10
    -2.29 ± 0.10
        Week 12 (N= 647, 638, 648)
    -2.97 ± 0.11
    -2.44 ± 0.11
    -2.55 ± 0.11
        EoT (N= 699, 694, 680)
    -2.95 ± 0.10
    -2.41 ± 0.10
    -2.54 ± 0.11
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [34]
    P-value
    = 0.001 [35]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.72
         upper limit
    -0.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Notes
    [34] - Only participants with at least one urgency episode reported in baseline diary were included.
    [35] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [36]
    P-value
    < 0.001 [37]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.93
         upper limit
    -0.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [36] - Only participants with at least one urgency episode reported in baseline diary were included.
    [37] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [38]
    P-value
    = 0.001 [39]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.82
         upper limit
    -0.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [38] - Only participants with at least one urgency episode reported in baseline diary were included.
    [39] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [40]
    P-value
    < 0.001 [41]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.83
         upper limit
    -0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [40] - Only participants with at least one urgency episode reported in baseline diary were included.
    [41] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in Mean Number of Pads per 24 hours

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    End point title
    Change from Baseline in Mean Number of Pads per 24 hours
    End point description
    The mean number of pads per 24 hours was defined as the average number of times a participant recorded a new pad used per day during the 3-day micturition diary period. This was calculated using the number of new pads used during valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: pads
    least squares mean (standard error)
        Week 4 (N= 497, 467, 474)
    -1.12 ± 0.07
    -0.86 ± 0.07
    -1.04 ± 0.07
        Week 8 (N= 482, 459, 469)
    -1.50 ± 0.07
    -1.17 ± 0.08
    -1.36 ± 0.08
        Week 12 (N= 477, 440, 468)
    -1.65 ± 0.07
    -1.38 ± 0.07
    -1.43 ± 0.07
        EoT (N= 510, 476, 487)
    -1.66 ± 0.07
    -1.35 ± 0.07
    -1.43 ± 0.07
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [42]
    P-value
    = 0.008 [43]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.46
         upper limit
    -0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [42] - Only participants with reported use of at least one pad reported in baseline diary were included.
    [43] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [44]
    P-value
    = 0.002 [45]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.55
         upper limit
    -0.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Notes
    [44] - Only participants with reported use of at least one pad reported in baseline diary were included.
    [45] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [46]
    P-value
    = 0.006 [47]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    -0.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [46] - Only participants with reported use of at least one pad reported in baseline diary were included.
    [47] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [48]
    P-value
    = 0.002 [49]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.51
         upper limit
    -0.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [48] - Only participants with reported use of at least one pad reported in baseline diary were included.
    [49] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Number of Pads Used During the 3-Day Diary

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    End point title
    Number of Pads Used During the 3-Day Diary
    End point description
    The number of pads used was defined as the number of times a participant recorded a new pad used during the 3-day micturition diary period. This was calculated using the sum of each record with new pad checked. Only records with new pad checked on a valid diary day were counted. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: pads
    arithmetic mean (standard error)
        Week 4 (N= 497, 467, 474)
    4.80 ± 0.28
    5.69 ± 0.36
    5.41 ± 0.29
        Week 8 (N= 482, 459, 469)
    3.64 ± 0.24
    4.71 ± 0.37
    4.50 ± 0.29
        Week 12 (N= 477, 440, 468)
    3.23 ± 0.22
    4.13 ± 0.28
    4.07 ± 0.28
        EoT (N= 510, 476, 487)
    3.29 ± 0.22
    4.27 ± 0.28
    4.17 ± 0.29
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 4
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [50]
    P-value
    = 0.545 [51]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.87
         upper limit
    1.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.06
    Notes
    [50] - Only participants who reported use of at least one pad in baseline diary were included.
    [51] - p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 8
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [52]
    P-value
    = 0.01 [53]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    0.95
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [52] - Only participants who reported use of at least one pad in baseline diary were included.
    [53] - p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 12
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [54]
    P-value
    = 0.007 [55]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.79
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.67
         upper limit
    0.94
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Notes
    [54] - Only participants who reported use of at least one pad in baseline diary were included.
    [55] - p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin EoT
    Statistical analysis description
    Rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [56]
    P-value
    = 0.003 [57]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    0.92
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [56] - Only participants who reported use of at least one pad in baseline diary were included.
    [57] - p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.

    Secondary: Change from Baseline in Mean Number of Nocturia Episodes

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    End point title
    Change from Baseline in Mean Number of Nocturia Episodes
    End point description
    Mean number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) while sleeping during the 3-day diary period, divided by the number of valid diary days during the diary period. Night time episode of incontinence only was not considered a nocturia episode. Nocturia episodes were counted for each micturition record which occurred between the date/time of going to bed with intention to sleep and the date/time of getting up with intention to stay awake on a valid diary day & which was accompanied by a sleep interruption. Nocturia only determined for those who were not night-shift workers. LOCF used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: nocturia episodes
    least squares mean (standard error)
        Week 4 (N= 526, 514, 517)
    -0.28 ± 0.03
    -0.27 ± 0.03
    -0.29 ± 0.03
        Week 8 (N= 500, 501, 514)
    -0.37 ± 0.03
    -0.35 ± 0.03
    -0.37 ± 0.03
        Week 12 (N= 492, 480, 510)
    -0.46 ± 0.03
    -0.38 ± 0.03
    -0.41 ± 0.03
        EoT (N= 537, 523, 531)
    -0.43 ± 0.03
    -0.37 ± 0.03
    -0.41 ± 0.03
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [58]
    P-value
    = 0.836 [59]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.1
         upper limit
    0.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [58] - Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS.
    [59] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [60]
    P-value
    = 0.617 [61]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.12
         upper limit
    0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [60] - Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS.
    [61] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [62]
    P-value
    = 0.134 [63]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.17
         upper limit
    0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [62] - Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS.
    [63] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [64]
    P-value
    = 0.174 [65]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.16
         upper limit
    0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [64] - Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS.
    [65] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.

    Secondary: Number of Nocturia Episodes Reported Over 3-Day Diary

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    End point title
    Number of Nocturia Episodes Reported Over 3-Day Diary
    End point description
    The number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) during sleeping time during the 3-day micturition diary period. This was calculated using the sum of each nocturia episode recorded on valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: nocturia episodes
    arithmetic mean (standard error)
        Week 4 (N= 526, 514, 517)
    3.63 ± 0.12
    3.59 ± 0.12
    3.58 ± 0.12
        Week 8 (N= 500, 501, 514)
    3.33 ± 0.12
    3.35 ± 0.12
    3.32 ± 0.12
        Week 12 (N= 492, 480, 510)
    3.12 ± 0.13
    3.26 ± 0.12
    3.23 ± 0.12
        EoT (N= 537, 523, 531)
    3.16 ± 0.12
    3.28 ± 0.11
    3.19 ± 0.12
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 4
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of nocturia episodes during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [66]
    P-value
    = 0.993 [67]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.93
         upper limit
    1.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04
    Notes
    [66] - Only participants with at least one nocturia episode reported in baseline diary were included.
    [67] - p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 8
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of nocturia episodes during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [68]
    P-value
    = 0.736 [69]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.9
         upper limit
    1.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04
    Notes
    [68] - Only participants with at least one nocturia episode reported in baseline diary were included.
    [69] - p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin Week 12
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of nocturia episodes during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [70]
    P-value
    = 0.121 [71]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.85
         upper limit
    1.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [70] - Only participants with at least one nocturia episode reported in baseline diary were included.
    [71] - p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.
    Statistical analysis title
    Rate Ratio Combination vs 5 mg Solifenacin EoT
    Statistical analysis description
    Rate ratio, 95% CIs, & p-value for number of nocturia episodes during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [72]
    P-value
    = 0.172 [73]
    Method
    Mixed Effects Poisson
    Parameter type
    Rate Ratio
    Point estimate
    0.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.86
         upper limit
    1.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04
    Notes
    [72] - Only participants with at least one nocturia episode reported in baseline diary were included.
    [73] - p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.

    Secondary: Number of Participants with Change from Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility

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    End point title
    Number of Participants with Change from Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility
    End point description
    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: participants
    number (not applicable)
        No problems -> no problems
    409
    370
    374
        No problems -> slight problems
    33
    35
    36
        No problems -> moderate problems
    14
    11
    11
        No problems -> severe problems
    0
    7
    4
        No problems -> extreme problems
    0
    1
    0
        No problems -> no data
    2
    4
    5
        Slight problems -> no problems
    52
    58
    60
        Slight problems -> slight problems
    43
    46
    40
        Slight problems -> moderate problems
    15
    28
    16
        Slight problems -> severe problems
    1
    3
    3
        Slight problems -> extreme problems
    0
    0
    0
        Slight problems -> no data
    2
    0
    0
        Moderate problems -> no problems
    24
    36
    25
        Moderate problems -> slight problems
    25
    18
    23
        Moderate problems -> moderate problems
    28
    28
    40
        Moderate problems -> severe problems
    2
    3
    7
        Moderate problems -> extreme problems
    0
    1
    0
        Moderate problems -> no data
    1
    0
    0
        Severe problems -> no problems
    7
    8
    2
        Severe problems -> slight problems
    6
    7
    7
        Severe problems -> moderate problems
    17
    11
    11
        Severe problems -> severe problems
    12
    10
    14
        Severe problems -> extreme problems
    0
    0
    0
        Severe problems -> no data
    1
    1
    0
        Extreme problems -> no problems
    3
    2
    2
        Extreme problems -> slight problems
    1
    0
    0
        Extreme problems -> moderate problems
    1
    1
    1
        Extreme problems -> severe problems
    1
    0
    0
        Extreme problems -> extreme problems
    0
    0
    0
        Extreme problems -> no data
    0
    0
    0
        No data -> no problems
    4
    9
    13
        No data -> slight problems
    2
    4
    1
        No data -> moderate problems
    0
    3
    3
        No data -> severe problems
    0
    0
    0
        No data -> extreme problems
    0
    0
    0
        No data -> no data
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Self-care

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    End point title
    Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Self-care
    End point description
    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: participants
    number (not applicable)
        No problems -> no problems
    548
    541
    548
        No problems -> slight problems
    28
    26
    25
        No problems -> moderate problems
    0
    14
    7
        No problems -> severe problems
    3
    0
    2
        No problems -> extreme problems
    0
    0
    0
        No problems -> no data
    6
    5
    4
        Slight problems -> no problems
    37
    25
    32
        Slight problems -> slight problems
    23
    24
    22
        Slight problems -> moderate problems
    9
    7
    9
        Slight problems -> severe problems
    1
    0
    0
        Slight problems -> extreme problems
    0
    0
    0
        Slight problems -> no data
    0
    0
    1
        Moderate problems -> no problems
    12
    16
    7
        Moderate problems -> slight problems
    9
    9
    5
        Moderate problems -> moderate problems
    11
    7
    12
        Moderate problems -> severe problems
    0
    2
    2
        Moderate problems -> extreme problems
    0
    0
    0
        Moderate problems -> no data
    0
    0
    0
        Severe problems -> no problems
    7
    5
    0
        Severe problems -> slight problems
    2
    2
    2
        Severe problems -> moderate problems
    2
    1
    2
        Severe problems -> severe problems
    1
    4
    1
        Severe problems -> extreme problems
    0
    0
    0
        Severe problems -> no data
    0
    0
    0
        Extreme problems -> no problems
    0
    0
    0
        Extreme problems -> slight problems
    0
    1
    0
        Extreme problems -> moderate problems
    0
    0
    0
        Extreme problems -> severe problems
    1
    0
    0
        Extreme problems -> extreme problems
    0
    0
    0
        Extreme problems -> no data
    0
    0
    0
        No data -> no problems
    6
    14
    17
        No data -> slight problems
    0
    2
    0
        No data -> moderate problems
    0
    0
    0
        No data -> severe problems
    0
    0
    0
        No data -> extreme problems
    0
    0
    0
        No data -> no data
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Usual Activities

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    End point title
    Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Usual Activities
    End point description
    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: participants
    number (not applicable)
        No problems -> no problems
    397
    384
    379
        No problems -> slight problems
    38
    30
    42
        No problems -> moderate problems
    12
    19
    11
        No problems -> severe problems
    1
    4
    1
        No problems -> extreme problems
    0
    0
    1
        No problems -> no data
    4
    3
    3
        Slight problems -> no problems
    75
    81
    78
        Slight problems -> slight problems
    46
    45
    37
        Slight problems -> moderate problems
    12
    16
    15
        Slight problems -> severe problems
    1
    1
    3
        Slight problems -> extreme problems
    0
    1
    0
        Slight problems -> no data
    0
    1
    2
        Moderate problems -> no problems
    29
    35
    25
        Moderate problems -> slight problems
    22
    20
    28
        Moderate problems -> moderate problems
    22
    18
    21
        Moderate problems -> severe problems
    3
    3
    4
        Moderate problems -> extreme problems
    1
    0
    0
        Moderate problems -> no data
    2
    1
    0
        Severe problems -> no problems
    9
    8
    12
        Severe problems -> slight problems
    7
    5
    1
        Severe problems -> moderate problems
    7
    6
    9
        Severe problems -> severe problems
    5
    7
    9
        Severe problems -> extreme problems
    0
    0
    0
        Severe problems -> no data
    0
    0
    0
        Extreme problems -> no problems
    2
    0
    0
        Extreme problems -> slight problems
    1
    0
    0
        Extreme problems -> moderate problems
    3
    1
    0
        Extreme problems -> severe problems
    1
    0
    0
        Extreme problems -> extreme problems
    0
    0
    0
        Extreme problems -> no data
    0
    0
    0
        No data -> no problems
    5
    11
    15
        No data -> slight problems
    1
    4
    1
        No data -> moderate problems
    0
    1
    1
        No data -> severe problems
    0
    0
    0
        No data -> extreme problems
    0
    0
    0
        No data -> no data
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort

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    End point title
    Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort
    End point description
    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: participants
    number (not applicable)
        No pain -> no pain
    299
    290
    283
        No pain -> slight pain
    45
    62
    51
        No pain -> moderate pain
    12
    14
    17
        No pain -> severe pain
    3
    9
    2
        No pain -> extreme pain
    0
    0
    1
        No pain -> no data
    4
    4
    3
        Slight pain -> no pain
    79
    82
    81
        Slight pain -> slight pain
    58
    64
    55
        Slight pain -> moderate pain
    28
    17
    31
        Slight pain -> severe pain
    0
    2
    5
        Slight pain -> extreme pain
    1
    2
    0
        Slight pain -> no data
    0
    0
    2
        Moderate pain -> no pain
    39
    36
    21
        Moderate pain -> slight pain
    37
    36
    39
        Moderate pain -> moderate pain
    34
    30
    39
        Moderate pain -> severe pain
    7
    4
    8
        Moderate pain -> extreme pain
    0
    1
    0
        Moderate pain -> no data
    2
    1
    0
        Severe pain -> no pain
    7
    4
    10
        Severe pain -> slight pain
    12
    7
    4
        Severe pain -> moderate pain
    11
    16
    16
        Severe pain -> severe pain
    10
    4
    9
        Severe pain -> extreme pain
    0
    1
    1
        Severe pain -> no data
    0
    0
    0
        Extreme pain -> no pain
    4
    1
    0
        Extreme pain -> slight pain
    0
    1
    1
        Extreme pain -> moderate pain
    1
    0
    1
        Extreme pain -> severe pain
    6
    1
    1
        Extreme pain -> extreme pain
    1
    0
    0
        Extreme pain -> no data
    0
    0
    0
        No data -> no pain
    4
    8
    11
        No data -> slight pain
    1
    3
    4
        No data -> moderate pain
    1
    5
    2
        No data -> severe pain
    0
    0
    0
        No data -> extreme pain
    0
    0
    0
        No data -> no data
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression

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    End point title
    Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression
    End point description
    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: participants
    number (not applicable)
        Not anxious -> not anxious
    322
    300
    307
        Not anxious -> slightly anxious
    43
    39
    43
        Not anxious -> moderately anxious
    11
    17
    15
        Not anxious -> severely anxious
    2
    2
    3
        Not anxious-> extremely anxious
    0
    0
    0
        Not anxious -> no data
    4
    3
    3
        Slightly anxious -> not anxious
    107
    99
    90
        Slightly anxious -> slightly anxious
    56
    60
    69
        Slightly anxious -> moderately anxious
    13
    11
    23
        Slightly anxious -> severely anxious
    1
    2
    2
        Slightly anxious -> extremely anxious
    0
    0
    0
        Slightly anxious -> no data
    1
    2
    2
        Moderately anxious -> not anxious
    36
    38
    34
        Moderately anxious -> slightly anxious
    36
    40
    33
        Moderately anxious -> moderately anxious
    22
    26
    17
        Moderately anxious -> severely anxious
    3
    7
    1
        Moderately anxious -> extremely anxious
    0
    3
    1
        Moderately anxious -> no data
    0
    0
    0
        Severely anxious -> not anxious
    10
    8
    8
        Severely anxious -> slightly anxious
    9
    5
    5
        Severely anxious -> moderately anxious
    6
    6
    11
        Severely anxious -> severely anxious
    5
    8
    7
        Severely anxious -> extremely anxious
    0
    3
    0
        Severely anxious -> no data
    0
    0
    0
        Extremely anxious -> not anxious
    1
    4
    1
        Extremely anxious -> slightly anxious
    2
    1
    1
        Extremely anxious -> moderately anxious
    4
    2
    3
        Extremely anxious -> severely anxious
    4
    1
    1
        Extremely anxious -> extremely anxious
    1
    2
    1
        Extremely anxious -> no data
    1
    0
    0
        No data -> not anxious
    5
    13
    11
        No data -> slightly anxious
    0
    2
    5
        No data -> moderately anxious
    1
    1
    1
        No data -> severely anxious
    0
    0
    0
        No data -> extremely anxious
    0
    0
    0
        No data -> no data
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score

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    End point title
    Change from Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score
    End point description
    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 682, 677, 669)
    -16.68 ± 0.65
    -13.79 ± 0.65
    -15.82 ± 0.65
        Week 8 (N= 670, 660, 658)
    -22.86 ± 0.68
    -18.36 ± 0.69
    -19.34 ± 0.69
        Week 12 (N= 644, 641, 647)
    -27.90 ± 0.71
    -22.31 ± 0.71
    -24.09 ± 0.71
        EoT (N= 694, 683, 676)
    -26.89 ± 0.69
    -21.93 ± 0.70
    -23.59 ± 0.70
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002 [74]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -2.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.68
         upper limit
    -1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.91
    Notes
    [74] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [75]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -4.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.4
         upper limit
    -2.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.97
    Notes
    [75] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [76]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -5.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.56
         upper limit
    -3.62
    Variability estimate
    Standard error of the mean
    Dispersion value
    1
    Notes
    [76] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [77]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -4.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.88
         upper limit
    -3.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.98
    Notes
    [77] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score

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    End point title
    Change from Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score
    End point description
    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 682, 677, 669)
    12.95 ± 0.59
    11.03 ± 0.59
    12.44 ± 0.59
        Week 8 (N= 670, 660, 658)
    17.58 ± 0.63
    15.26 ± 0.63
    14.60 ± 0.64
        Week 12 (N= 644, 641, 647)
    21.40 ± 0.66
    17.91 ± 0.67
    17.72 ± 0.66
        EoT (N= 694, 683, 676)
    20.78 ± 0.65
    17.63 ± 0.65
    17.40 ± 0.65
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.021
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    1.92
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.29
         upper limit
    3.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.01 [78]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    2.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.56
         upper limit
    4.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.89
    Notes
    [78] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [79]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    3.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.65
         upper limit
    5.33
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.94
    Notes
    [79] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [80]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    3.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.35
         upper limit
    4.95
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.92
    Notes
    [80] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Coping

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    End point title
    Change from Baseline in OAB-q HRQL Subscale Score: Coping
    End point description
    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 682, 677, 669)
    15.17 ± 0.68
    12.27 ± 0.68
    14.25 ± 0.68
        Week 8 (N= 670, 660, 658)
    20.82 ± 0.74
    17.47 ± 0.74
    16.87 ± 0.74
        Week 12 (N= 644, 641, 647)
    25.16 ± 0.78
    20.45 ± 0.78
    20.20 ± 0.78
        EoT (N= 694, 683, 676)
    24.48 ± 0.75
    20.19 ± 0.76
    19.90 ± 0.76
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [81]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    2.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.02
         upper limit
    4.78
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.96
    Notes
    [81] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [82]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    3.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.29
         upper limit
    5.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.05
    Notes
    [82] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [83]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    4.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.55
         upper limit
    6.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.1
    Notes
    [83] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [84]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    4.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.2
         upper limit
    6.39
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.07
    Notes
    [84] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Concern

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    End point title
    Change from Baseline in OAB-q HRQL Subscale Score: Concern
    End point description
    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 682, 677, 669)
    13.79 ± 0.68
    11.85 ± 0.68
    13.82 ± 0.69
        Week 8 (N= 670, 660, 658)
    18.87 ± 0.70
    16.36 ± 0.71
    15.88 ± 0.71
        Week 12 (N= 644, 641, 647)
    22.85 ± 0.74
    19.24 ± 0.75
    19.67 ± 0.74
        Week EoT (N= 694, 683, 676)
    22.28 ± 0.72
    19.00 ± 0.73
    19.28 ± 0.73
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.044 [85]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    1.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.05
         upper limit
    3.83
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.96
    Notes
    [85] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012 [86]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    2.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    4.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    1
    Notes
    [86] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [87]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    3.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.54
         upper limit
    5.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.05
    Notes
    [87] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [88]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    3.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.27
         upper limit
    5.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.03
    Notes
    [88] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Sleep

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    End point title
    Change from Baseline in OAB-q HRQL Subscale Score: Sleep
    End point description
    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 682, 677, 669)
    11.58 ± 0.68
    11.04 ± 0.68
    11.16 ± 0.69
        Week 8 (N= 670, 660, 658)
    16.18 ± 0.71
    14.57 ± 0.71
    13.72 ± 0.71
        Week 12 (N= 644, 641, 647)
    20.00 ± 0.74
    17.74 ± 0.74
    16.84 ± 0.74
        Week EoT (N= 694, 683, 676)
    19.16 ± 0.72
    17.30 ± 0.73
    16.55 ± 0.73
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.575 [89]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    0.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.35
         upper limit
    2.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.96
    Notes
    [89] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.109 [90]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    1.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.36
         upper limit
    3.58
    Variability estimate
    Standard error of the mean
    Dispersion value
    1
    Notes
    [90] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.032 [91]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    2.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.2
         upper limit
    4.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.05
    Notes
    [91] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.069 [92]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    1.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.15
         upper limit
    3.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.02
    Notes
    [92] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Social Interaction

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    End point title
    Change from Baseline in OAB-q HRQL Subscale Score: Social Interaction
    End point description
    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 682, 677, 669)
    9.58 ± 0.59
    7.85 ± 0.59
    8.95 ± 0.59
        Week 8 (N= 670, 660, 658)
    11.93 ± 0.60
    10.84 ± 0.60
    10.16 ± 0.60
        Week 12 (N= 644, 641, 647)
    14.70 ± 0.61
    12.08 ± 0.61
    11.98 ± 0.61
        Week EoT (N= 694, 683, 676)
    14.39 ± 0.60
    11.91 ± 0.60
    11.72 ± 0.61
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.037 [93]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    1.73
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.1
         upper limit
    3.36
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Notes
    [93] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.199 [94]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    1.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.57
         upper limit
    2.76
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.85
    Notes
    [94] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [95]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    2.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.92
         upper limit
    4.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.87
    Notes
    [95] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004 [96]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    2.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.81
         upper limit
    4.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.85
    Notes
    [96] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score

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    End point title
    Change from Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score
    End point description
    The TS-VAS rated participant satisfaction with treatment on a scale from 0 (No, not at all) to 10 (Yes, completely). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 680, 677, 668)
    1.2 ± 0.1
    0.8 ± 0.1
    1.1 ± 0.1
        Week 8 (N= 668, 660, 656)
    1.5 ± 0.1
    1.2 ± 0.1
    1.3 ± 0.1
        Week 12 (N= 644, 641, 646)
    1.9 ± 0.1
    1.4 ± 0.1
    1.6 ± 0.1
        EoT (N= 693, 683, 675)
    1.8 ± 0.1
    1.4 ± 0.1
    1.6 ± 0.1
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [97]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.2
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [97] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.019 [98]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [98] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [99]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.3
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [99] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [100]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.2
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [100] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Change from Baseline in Patient Perception Bladder Control (PPBC) Score

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    End point title
    Change from Baseline in Patient Perception Bladder Control (PPBC) Score
    End point description
    The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. PPBC score: 1-no problem, 2- some very minor problems, 3-some minor problems, 4-moderate problems, 5-severe problems, 6-many severe problems. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: units on a scale
    least squares mean (standard error)
        Week 4 (N= 687, 685, 677)
    -0.9 ± 0.0
    -0.6 ± 0.0
    -0.7 ± 0.0
        Week 8 (N= 673, 667, 669)
    -1.2 ± 0.0
    -1.0 ± 0.0
    -1.0 ± 0.0
        Week 12 (N= 647, 648, 655)
    -1.5 ± 0.0
    -1.2 ± 0.0
    -1.3 ± 0.0
        EoT (N= 697, 688, 683)
    -1.5 ± 0.0
    -1.2 ± 0.0
    -1.3 ± 0.0
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [101]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [101] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [102]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [102] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [103]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [103] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
    Statistical analysis title
    Adj. Diff. Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [104]
    Method
    ANCOVA
    Parameter type
    LS Means
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Notes
    [104] - P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.

    Secondary: Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)

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    End point title
    Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)
    End point description
    The PGIC was a 2-part questionnaire, assessing both the change in the participant’s overall condition (Patient Impression in General Health (PIBS)) and change in bladder condition since the start of the study (Patient Impression in General Health (PIGH)) (from very much worse to very much improved). The CGIC was a single questionnaire assessing the participant’s change in bladder condition since the beginning of the study (Clinician Impression in Bladder Symptoms (CIBS)). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    End of treatment (up to 12 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: participants
    number (not applicable)
        PIBS Very Much Improved
    227
    152
    171
        PIBS Much Improved
    257
    264
    284
        PIBS Minimally Improved
    135
    170
    152
        PIBS No Change
    25
    55
    56
        PIBS Minimally Worse
    7
    11
    4
        PIBS Much Worse
    4
    4
    6
        PIBS Very Much Worse
    0
    1
    1
        PIGH Very Much Improved
    144
    104
    108
        PIGH Much Improved
    239
    236
    244
        PIGH Minimally Improved
    143
    147
    146
        PIGH No Change
    113
    142
    160
        PIGH Minimally Worse
    14
    23
    10
        PIGH Much Worse
    1
    4
    4
        PIGH Very Much Worse
    1
    1
    2
        CIBS Very Much Improved
    184
    118
    141
        CIBS Much Improved
    311
    316
    329
        CIBS Minimally Improved
    141
    164
    155
        CIBS No Change
    23
    56
    40
        CIBS Minimally Worse
    4
    8
    5
        CIBS Much Worse
    4
    3
    5
        CIBS Very Much Worse
    3
    3
    4
    No statistical analyses for this end point

    Secondary: Percentage of Participants with at Least a 50% Decrease from Baseline in Mean Number of Incontinence Episodes per 24 Hours

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    End point title
    Percentage of Participants with at Least a 50% Decrease from Baseline in Mean Number of Incontinence Episodes per 24 Hours
    End point description
    Incontinence was defined as any involuntary leakage of urine. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: percentage of participants
    number (not applicable)
        Week 4 (N= 690, 690, 679)
    52.5
    43.3
    49.0
        Week 8 (N= 661, 674, 673)
    66.9
    57.6
    61.8
        Week 12 (N= 653, 645, 664)
    72.4
    64.0
    66.9
        EoT (N= 706, 704, 697)
    71.2
    63.1
    66.6
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [105]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.19
         upper limit
    1.84
    Notes
    [105] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [106]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.25
         upper limit
    1.98
    Notes
    [106] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [107]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.21
         upper limit
    1.95
    Notes
    [107] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [108]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.2
         upper limit
    1.9
    Notes
    [108] - p<0.05 indicated superiority in favor of treatment group with highest response.

    Secondary: Percentage of Participants with Zero Incontinence Episodes Postbaseline

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    End point title
    Percentage of Participants with Zero Incontinence Episodes Postbaseline
    End point description
    Incontinence was defined as any involuntary leakage of urine. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: percentage of participants
    number (not applicable)
        Week 4 (N= 690, 690, 679)
    23.5
    20.0
    22.1
        Week 8 (N= 661, 674, 673)
    40.4
    31.6
    34.3
        Week 12 (N= 653, 645, 664)
    47.3
    39.5
    40.7
        EoT (N= 706, 704, 697)
    46.0
    37.9
    40.2
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.119 [109]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.95
         upper limit
    1.63
    Notes
    [109] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [110]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.23
         upper limit
    1.98
    Notes
    [110] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002 [111]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.14
         upper limit
    1.82
    Notes
    [111] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [112]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.17
         upper limit
    1.84
    Notes
    [112] - p<0.05 indicated superiority in favor of treatment group with highest response.

    Secondary: Percentage of Participants with a Mean of at Least 8 Micturitions per 24 Hours at Baseline and Less than 8 Micturitions per 24 Hours Postbaseline

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    End point title
    Percentage of Participants with a Mean of at Least 8 Micturitions per 24 Hours at Baseline and Less than 8 Micturitions per 24 Hours Postbaseline
    End point description
    Micturitions were defined as voluntary urinations (excluding incontinence only episodes). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: percentage of participants
    number (not applicable)
        Week 4 (N= 690, 690, 679)
    21.0
    18.7
    20.2
        Week 8 (N= 661 674, 673)
    28.1
    22.4
    26.3
        Week 12 (N= 653, 645, 664)
    31.4
    24.8
    28.0
        EoT (N= 706, 704, 697)
    30.2
    25.0
    27.7
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.305 [113]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.88
         upper limit
    1.5
    Notes
    [113] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014 [114]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.06
         upper limit
    1.76
    Notes
    [114] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012 [115]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.07
         upper limit
    1.76
    Notes
    [115] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.036 [116]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.02
         upper limit
    1.64
    Notes
    [116] - p<0.05 indicated superiority in favor of treatment group with highest response.

    Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in OAB-q Symptom Bother Score

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    End point title
    Percentage of Participants with at Least a 10-Point Improvement from Baseline in OAB-q Symptom Bother Score
    End point description
    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: percentage of participants
    number (not applicable)
        Week 4 (N= 682, 677, 669)
    67.9
    58.2
    61.9
        Week 8 (N= 670, 660, 658)
    77.2
    66.4
    69.1
        Week 12 (N= 644, 641, 647)
    83.5
    72.1
    75.4
        EoT (N= 694, 683, 676)
    81.7
    71.7
    74.6
    Statistical analysis title
    OAB-q Odds Ratio Comb. vs Solifenacin 5mg Week 4
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [117]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.18
         upper limit
    1.88
    Notes
    [117] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    OAB-q Odds Ratio Comb. vs Solifenacin 5mg Week 8
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [118]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.31
         upper limit
    2.18
    Notes
    [118] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    OAB-q Odds Ratio Comb. vs Solifenacin 5mg Week 12
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [119]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.47
         upper limit
    2.61
    Notes
    [119] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    OAB-q Odds Ratio Comb. vs Solifenacin 5mg EoT
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [120]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.34
         upper limit
    2.3
    Notes
    [120] - p<0.05 indicated superiority in favor of treatment group with highest response.

    Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in HRQL Total Score

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    End point title
    Percentage of Participants with at Least a 10-Point Improvement from Baseline in HRQL Total Score
    End point description
    HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: percentage of participants
    number (not applicable)
        Week 4 (N= 682, 677, 669)
    52.6
    44.5
    48.1
        Week 8 (N= 670, 660, 658)
    63.6
    54.8
    53.8
        Week 12 (N= 644, 641, 647)
    70.5
    60.8
    60.4
        EoT (N= 694, 683, 676)
    68.6
    60.6
    60.1
    Statistical analysis title
    HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 4
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [121]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.14
         upper limit
    1.82
    Notes
    [121] - p<0.05 indicates superiority in favor of treatment group with highest response.
    Statistical analysis title
    HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 8
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [122]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.18
         upper limit
    1.93
    Notes
    [122] - p<0.05 indicates superiority in favor of treatment group with highest response.
    Statistical analysis title
    HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 12
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [123]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.27
         upper limit
    2.13
    Notes
    [123] - p<0.05 indicates superiority in favor of treatment group with highest response.
    Statistical analysis title
    HRQL Odds Ratio Comb. vs Solifenacin 5mg EoT
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001 [124]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.17
         upper limit
    1.91
    Notes
    [124] - p<0.05 indicates superiority in favor of treatment group with highest response.

    Secondary: Percentage of Participants with at Least a 1-Point Improvement from Baseline in PPBC

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    End point title
    Percentage of Participants with at Least a 1-Point Improvement from Baseline in PPBC
    End point description
    The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: percentage of participants
    number (not applicable)
        Week 4 (N= 687, 685, 677)
    61.1
    52.1
    56.3
        Week 8 (N= 673, 667, 669)
    70.1
    62.1
    64.6
        Week 12 (N= 647, 648, 655)
    77.9
    70.4
    72.7
        EoT (N= 697, 688, 683)
    76.5
    69.5
    71.9
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [125]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.13
         upper limit
    1.79
    Notes
    [125] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004 [126]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.12
         upper limit
    1.84
    Notes
    [126] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [127]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.15
         upper limit
    1.96
    Notes
    [127] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006 [128]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.11
         upper limit
    1.84
    Notes
    [128] - p<0.05 indicated superiority in favor of treatment group with highest response.

    Secondary: Percentage of Participants with Major (at Least 2-Point) Improvement from Baseline in PPBC

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    End point title
    Percentage of Participants with Major (at Least 2-Point) Improvement from Baseline in PPBC
    End point description
    The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. LOCF was used for EoT. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8 and 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    707
    705
    698
    Units: percentage of participants
    number (not applicable)
        Week 4 (N= 687, 685, 677)
    26.6
    21.6
    21.6
        Week 8 (N= 673, 667, 669)
    39.5
    31.5
    31.8
        Week 12 (N= 647, 648, 655)
    51.8
    39.8
    43.8
        EoT (N= 697, 688, 683)
    49.8
    39.1
    43.2
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 4
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.065 [129]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.99
         upper limit
    1.66
    Notes
    [129] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 8
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004 [130]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.11
         upper limit
    1.79
    Notes
    [130] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg Week 12
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [131]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.3
         upper limit
    2.07
    Notes
    [131] - p<0.05 indicated superiority in favor of treatment group with highest response.
    Statistical analysis title
    Odds Ratio Combination vs Solifenacin 5mg EoT
    Statistical analysis description
    Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.
    Comparison groups
    Combination (solifenacin + mirabegron) v Solifenacin 5 mg
    Number of subjects included in analysis
    1412
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [132]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.55
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.24
         upper limit
    1.94
    Notes
    [132] - p<0.05 indicated superiority in favor of treatment group with highest response.

    Secondary: Number of Participants with Adverse Events (AEs)

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    End point title
    Number of Participants with Adverse Events (AEs)
    End point description
    AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures & which does not necessarily have a causal relationship with this treatment. Treatment-Emergent Adverse Event (TEAE) referred to an adverse event which started or worsened in the period from first double-blind medication intake until 30 days after the last double-blind medication intake. The analysis population consisted of the Safety Analysis Set, the SAF comprised all randomized participants who received at least 1 dose of double-blind treatment.
    End point type
    Secondary
    End point timeframe
    From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    725
    728
    719
    Units: participants
        AEs
    260
    241
    283
        Drug-related AEs
    141
    125
    161
        Serious Adverse Events (SAEs)
    13
    10
    15
        Drug-related SAEs
    1
    0
    3
        AEs Leading to Perm. Disc. of Study Drug
    11
    11
    11
        Drug-related AEs Leading to Perm. Disc. of Drug
    9
    10
    9
        Deaths
    0
    0
    0
    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
    PVR Volume was assessed by bladder scan. The analysis population consisted of the SAF with data available at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 8 & 12
    End point values
    Combination (solifenacin + mirabegron) Solifenacin 5 mg Solifenacin 10 mg
    Number of subjects analysed
    725
    728
    719
    Units: mL
    arithmetic mean (standard deviation)
        Week 4 (N= 705, 712, 704)
    1.545 ± 40.313
    2.821 ± 38.588
    7.308 ± 72.122
        Week 8 (N= 683, 694, 690)
    2.245 ± 38.347
    1.117 ± 36.470
    7.232 ± 60.096
        Week 12 (N= 669, 680, 681)
    6.356 ± 51.067
    2.337 ± 42.147
    6.552 ± 48.505
        EoT (N= 706, 713, 707)
    5.478 ± 51.595
    3.046 ± 43.499
    7.354 ± 54.121
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)
    Adverse event reporting additional description
    Population consisted of the SAF. An AE was defined as any untoward medical occurrence in a participant administered a study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Combination (solifenacin + mirabegron)
    Reporting group description
    Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.

    Reporting group title
    Solifenacin 10 mg
    Reporting group description
    Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

    Reporting group title
    Solifenacin 5 mg
    Reporting group description
    Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

    Serious adverse events
    Combination (solifenacin + mirabegron) Solifenacin 10 mg Solifenacin 5 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 725 (1.79%)
    15 / 719 (2.09%)
    10 / 728 (1.37%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders