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    Clinical Trial Results:
    A Randomized, Double-blind, Parallel-group, Placebo- and Active-controlled, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Combinations of Solifenacin Succinate and Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in the Treatment of Overactive Bladder

    Summary
    EudraCT number
    2012-005735-91
    Trial protocol
    GB   BE   DE   NL   CZ   HU   LV   SE   IT   EE   FI   SK   SI   DK   ES   LT   PL   GR   BG  
    Global end of trial date
    22 Oct 2015

    Results information
    Results version number
    v2(current)
    This version publication date
    19 Jul 2018
    First version publication date
    04 Nov 2016
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    178-CL-101
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01972841
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Astellas Pharma Europe B.V.
    Sponsor organisation address
    Sylviusweg 62, Leiden, Netherlands, 2333 BE
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Europe B.V., astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Europe B.V., astellas.resultsdisclosure@astellas.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    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
    22 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Oct 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of 2 dose combinations of solifenacin and mirabegron (5 + 25 mg and 5 + 50 mg) compared to solifenacin (5 mg) and mirabegron (25 mg and 50 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
    05 Nov 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 5
    Country: Number of subjects enrolled
    Australia: 56
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Bulgaria: 116
    Country: Number of subjects enrolled
    Canada: 133
    Country: Number of subjects enrolled
    China: 118
    Country: Number of subjects enrolled
    Czech Republic: 184
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    Estonia: 12
    Country: Number of subjects enrolled
    Finland: 6
    Country: Number of subjects enrolled
    France: 18
    Country: Number of subjects enrolled
    Germany: 159
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Hong Kong: 4
    Country: Number of subjects enrolled
    Hungary: 114
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Latvia: 29
    Country: Number of subjects enrolled
    Lithuania: 55
    Country: Number of subjects enrolled
    Malaysia: 8
    Country: Number of subjects enrolled
    Mexico: 19
    Country: Number of subjects enrolled
    New Zealand: 16
    Country: Number of subjects enrolled
    Norway: 40
    Country: Number of subjects enrolled
    Peru: 14
    Country: Number of subjects enrolled
    Philippines: 20
    Country: Number of subjects enrolled
    Poland: 317
    Country: Number of subjects enrolled
    Romania: 68
    Country: Number of subjects enrolled
    Russian Federation: 108
    Country: Number of subjects enrolled
    Singapore: 17
    Country: Number of subjects enrolled
    Slovakia: 158
    Country: Number of subjects enrolled
    Slovenia: 6
    Country: Number of subjects enrolled
    South Africa: 36
    Country: Number of subjects enrolled
    Korea, Republic of: 211
    Country: Number of subjects enrolled
    Spain: 48
    Country: Number of subjects enrolled
    Sweden: 79
    Country: Number of subjects enrolled
    Taiwan: 8
    Country: Number of subjects enrolled
    Thailand: 50
    Country: Number of subjects enrolled
    Turkey: 5
    Country: Number of subjects enrolled
    Ukraine: 325
    Country: Number of subjects enrolled
    United Kingdom: 23
    Country: Number of subjects enrolled
    United States: 873
    Country: Number of subjects enrolled
    Netherlands: 31
    Worldwide total number of subjects
    3527
    EEA total number of subjects
    1501
    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)
    2383
    From 65 to 84 years
    1134
    85 years and over
    10

    Subject disposition

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    Recruitment
    Recruitment details
    Participants who had symptoms of “wet” overactive bladder (OAB) (urgency, urinary frequency and urgency incontinence) for ≥ 3 months were enrolled in 435 centers in 42 countries. Eligible participants went into a single-blind, 4-week placebo run-in period and completed a micturition diary 7 days prior to each study visit.

    Pre-assignment
    Screening details
    A total of 6991 participants were screened, 6275 participants received placebo run-in treatment and 3527 participants were randomized into 1 of 6 treatment arms in a 1:1:1:1:2:2 ratio in the 12-week double-blind treatment period. A total of 953 participants were also enrolled in an ambulatory blood pressure monitoring (ABPM) substudy.

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Participants who received matching placebo once a day for 12 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo to mirabegron
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received placebo to match mirabegron 25 mg or 50 mg orally once a day at the same time each day.

    Investigational medicinal product name
    Placebo to solifenacin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received placebo to match solifenacin 5 mg orally once a day at the same time each day.

    Arm title
    Mirabegron 25 mg
    Arm description
    Participants who received mirabegron 25 mg once a day for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Mirabegron
    Investigational medicinal product code
    YM178
    Other name
    Myrbetriq, Myrbetric, Betanis, Betmiga
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received mirabegron 25 mg orally once a day at the same time each day.

    Arm title
    Mirabegron 50 mg
    Arm description
    Participants who received mirabegron 50 mg once a day for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Mirabegron
    Investigational medicinal product code
    YM178
    Other name
    Myrbetriq, Myrbetric, Betanis, Betmiga
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received mirabegron 50 mg orally once a day at the same time each day.

    Arm title
    Solifenacin 5 mg
    Arm description
    Participants who received solifenacin 5 mg once a day for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Solifenacin succinate
    Investigational medicinal product code
    YM905
    Other name
    Solifenacin, Vesicare, Vesikur, Vesitrim
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received solifenacin succinate 5 mg orally once a day at the same time each day.

    Arm title
    Solifenacin 5 mg + mirabegron 25 mg
    Arm description
    Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Solifenacin succinate
    Investigational medicinal product code
    YM905
    Other name
    Solifenacin, Vesicare, Vesikur, Vesitrim
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received solifenacin succinate 5 mg orally once a day at the same time each day.

    Investigational medicinal product name
    Mirabegron
    Investigational medicinal product code
    YM178
    Other name
    Myrbetriq, Myrbetric, Betanis, Betmiga
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received mirabegron 25 mg orally once a day at the same time each day.

    Arm title
    Solifenacin 5 mg + mirabegron 50 mg
    Arm description
    Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Solifenacin succinate
    Investigational medicinal product code
    YM905
    Other name
    Solifenacin, Vesicare, Vesikur, Vesitrim
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received solifenacin succinate 5 mg orally once a day at the same time each day.

    Investigational medicinal product name
    Mirabegron
    Investigational medicinal product code
    YM178
    Other name
    Myrbetriq, Myrbetric, Betanis, Betmiga
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received mirabegron 50 mg orally once a day at the same time each day.

    Number of subjects in period 1
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Started
    447
    441
    437
    434
    885
    883
    Treated
    444
    436
    433
    432
    878
    871
    Completed
    404
    397
    387
    397
    802
    798
    Not completed
    43
    44
    50
    37
    83
    85
         Did not have a treatment page
    -
    -
    -
    -
    1
    -
         Miscellaneous
    -
    -
    4
    1
    -
    4
         Randomized but never received treatment
    2
    5
    4
    2
    6
    13
         Protocol violation
    2
    2
    3
    5
    9
    4
         Adverse event
    13
    8
    12
    9
    21
    26
         Lack of efficacy
    1
    -
    -
    2
    4
    1
         Withdrawal by participant
    21
    27
    23
    16
    33
    34
         Lost to follow-up
    4
    2
    4
    2
    9
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants who received matching placebo once a day for 12 weeks.

    Reporting group title
    Mirabegron 25 mg
    Reporting group description
    Participants who received mirabegron 25 mg once a day for 12 weeks.

    Reporting group title
    Mirabegron 50 mg
    Reporting group description
    Participants who received mirabegron 50 mg once a day for 12 weeks.

    Reporting group title
    Solifenacin 5 mg
    Reporting group description
    Participants who received solifenacin 5 mg once a day for 12 weeks.

    Reporting group title
    Solifenacin 5 mg + mirabegron 25 mg
    Reporting group description
    Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.

    Reporting group title
    Solifenacin 5 mg + mirabegron 50 mg
    Reporting group description
    Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.

    Reporting group values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg Total
    Number of subjects
    447 441 437 434 885 883
    Age categorical
    Units: Subjects
    Age continuous
    Randomized analysis set (RAS), comprised of all randomized participants.
    Units: years
        arithmetic mean (standard deviation)
    57.46 ± 13.2 56.77 ± 13.46 56.69 ± 13.28 57.88 ± 12.92 56.94 ± 13.78 57.3 ± 13.46 -
    Gender categorical
    RAS
    Units:
        Male
    102 98 99 92 199 199 789
        Female
    345 343 338 342 686 684 2738
    Mean Number of Incontinence Episodes per 24 Hours
    RAS; data only available for 3490 participants [444, 434, 433, 432, 877, 870].
    Units: incontinence episodes
        arithmetic mean (standard deviation)
    3.32 ± 3.32 3.33 ± 3.36 3.16 ± 3.44 3.56 ± 3.51 3.15 ± 3.15 3.11 ± 3.05 -
    Mean Number of Micturitions per 24 Hours
    RAS; data only available for 3490 participants [444, 434, 433, 432, 877, 870].
    Units: micturitions
        arithmetic mean (standard deviation)
    10.9 ± 2.81 10.79 ± 2.61 11.14 ± 3.22 10.77 ± 2.64 10.72 ± 2.85 10.74 ± 2.35 -
    Mean Volume Voided per Micturition
    RAS; data only available for 3475 participants [440, 433, 431, 430, 873, 868].
    Units: mL
        arithmetic mean (standard deviation)
    157.53 ± 58.53 151.79 ± 60.39 155.36 ± 59.7 152.09 ± 59.57 159.47 ± 58.15 153.74 ± 59.38 -
    Number of Incontinence Episodes per Week
    RAS; data only available for 3490 participants [444, 434, 433, 432, 877, 870].
    Units: incontinence episodes
        arithmetic mean (standard deviation)
    22.99 ± 23.2 22.85 ± 23.31 21.58 ± 23.53 24.64 ± 24.46 21.57 ± 21.6 21.41 ± 21.1 -
    Mean Number of Urgency Incontinence Episodes per 24 Hours
    RAS; data only available for 3469 participants [441, 432, 427, 431, 872, 866]. Only participants with ≥ 1 urgency incontinence episode at baseline were included.
    Units: urgency incontinence episodes
        arithmetic mean (standard deviation)
    3.07 ± 3.18 2.92 ± 3.05 2.88 ± 3.28 3.21 ± 3.32 2.79 ± 2.8 2.76 ± 2.63 -
    Number of Urgency Incontinence Episodes per Week
    RAS; data only available for 3469 participants [441, 432, 427, 431, 872, 866]. Only participants with ≥ 1 urgency incontinence episode at baseline were included.
    Units: urgency incontinence episodes
        arithmetic mean (standard deviation)
    21.25 ± 22.2 20.03 ± 21.09 19.73 ± 22.43 22.23 ± 23.19 19.15 ± 19.26 18.99 ± 18.11 -
    Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours
    RAS; data only available for 3488 participants [442, 434, 433, 432, 876, 870]. Only participants with ≥ 1 urgency episode at baseline were included.
    Units: urgency episodes
        arithmetic mean (standard deviation)
    6.66 ± 4.02 6.35 ± 3.88 6.58 ± 4.83 6.6 ± 3.87 6.34 ± 3.72 6.33 ± 3.59 -
    Mean Number of Nocturia Episodes per 24 Hours
    RAS; data only available for 3002 participants [393, 366, 377, 367, 754, 745]. Only participants with ≥ 1 nocturia episode at baseline were included.
    Units: nocturia episodes
        arithmetic mean (standard deviation)
    1.57 ± 1.04 1.53 ± 1.01 1.59 ± 1.08 1.61 ± 0.95 1.57 ± 1.06 1.54 ± 0.97 -
    Number of Nocturia Episodes per Week
    RAS; data only available for 3002 participants [393, 366, 377, 367, 754, 745]. Only participants with ≥ 1 nocturia episode at baseline were included.
    Units: nocturia episodes
        arithmetic mean (standard deviation)
    10.83 ± 7.26 10.57 ± 7.06 10.98 ± 7.52 11.13 ± 6.6 10.82 ± 7.38 10.62 ± 6.74 -
    Mean Number of Pads Used per 24 Hours
    RAS; data only available for 2203 participants [281, 272, 270, 278, 554, 548]. Only participants with ≥ 1 pad used at baseline were included.
    Units: pads
        arithmetic mean (standard deviation)
    2.79 ± 2.91 2.74 ± 2.63 2.56 ± 3.11 2.84 ± 3.08 2.44 ± 2.56 2.55 ± 2.37 -
    Number of Pads Used per Week
    RAS; data only available for 2203 participants [281, 272, 270, 278, 554, 548]. Only participants with ≥ 1 pad used at baseline were included.
    Units: pads
        arithmetic mean (standard deviation)
    19.29 ± 20.38 18.78 ± 18.21 17.5 ± 21.17 19.62 ± 21.39 16.72 ± 17.58 17.5 ± 16.34 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants who received matching placebo once a day for 12 weeks.

    Reporting group title
    Mirabegron 25 mg
    Reporting group description
    Participants who received mirabegron 25 mg once a day for 12 weeks.

    Reporting group title
    Mirabegron 50 mg
    Reporting group description
    Participants who received mirabegron 50 mg once a day for 12 weeks.

    Reporting group title
    Solifenacin 5 mg
    Reporting group description
    Participants who received solifenacin 5 mg once a day for 12 weeks.

    Reporting group title
    Solifenacin 5 mg + mirabegron 25 mg
    Reporting group description
    Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.

    Reporting group title
    Solifenacin 5 mg + mirabegron 50 mg
    Reporting group description
    Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.

    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
    An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period. The analysis population was the Full Analysis Set (FAS), which was comprised of all randomized participants who took ≥ 1 dose of double-blind treatment, reported ≥ 1 micturition in the baseline diary and ≥ 1 micturition postbaseline, reported ≥ 1 incontinence episode in the baseline diary and excluded participants from one site. Last observation carried forward (LOCF) was used for EoT.
    End point type
    Primary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    412
    409
    406
    413
    823
    816
    Units: incontinence episodes
        least squares mean (standard error)
    -1.34 ± 0.10
    -1.70 ± 0.10
    -1.76 ± 0.10
    -1.79 ± 0.10
    -2.04 ± 0.07
    -1.98 ± 0.07
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1236
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.072 [2]
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.49
         upper limit
    -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [1] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [2] - Nominal p-value
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1229
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.033
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.44
         upper limit
    0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [3] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    Statistical analysis title
    Difference vs. Mirabegron 25 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1232
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    = 0.001 [5]
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.58
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [4] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [5] - Nominal p-value
    Statistical analysis title
    Difference vs. Mirabegron 50 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    superiority [6]
    P-value
    = 0.052
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [6] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.

    Primary: Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours

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    End point title
    Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours
    End point description
    A micturition was defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period. The analysis population was the FAS. LOCF was used for EoT.
    End point type
    Primary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    412
    409
    406
    413
    823
    816
    Units: micturitions
        least squares mean (standard error)
    -1.64 ± 0.12
    -2.00 ± 0.12
    -2.03 ± 0.12
    -2.20 ± 0.12
    -2.49 ± 0.08
    -2.59 ± 0.08
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1236
    Analysis specification
    Pre-specified
    Analysis type
    superiority [7]
    P-value
    = 0.04 [8]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.57
         upper limit
    -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [7] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [8] - Nominal p-value
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1229
    Analysis specification
    Pre-specified
    Analysis type
    superiority [9]
    P-value
    = 0.006 [10]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.67
         upper limit
    -0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [9] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [10] - Nominal p-value
    Statistical analysis title
    Difference vs. Mirabegron 25 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1232
    Analysis specification
    Pre-specified
    Analysis type
    superiority [11]
    P-value
    = 0.001 [12]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.76
         upper limit
    -0.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [11] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [12] - Nominal p-value
    Statistical analysis title
    Difference vs. Mirabegron 50 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    superiority [13]
    P-value
    < 0.001 [14]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.84
         upper limit
    -0.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [13] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [14] - Nominal p-value

    Secondary: Change from Baseline to EoT in Mean Volume Voided per Micturition

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    End point title
    Change from Baseline to EoT in Mean Volume Voided per Micturition
    End point description
    The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period. The analysis population was the FAS. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    413
    407
    408
    411
    821
    821
    Units: mL
        least squares mean (standard error)
    8.44 ± 2.55
    13.32 ± 2.57
    21.99 ± 2.57
    30.99 ± 2.56
    34.84 ± 1.81
    39.73 ± 1.81
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1232
    Analysis specification
    Pre-specified
    Analysis type
    superiority [15]
    P-value
    = 0.219 [16]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    3.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.29
         upper limit
    10
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.13
    Notes
    [15] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [16] - Nominal p-value
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1232
    Analysis specification
    Pre-specified
    Analysis type
    superiority [17]
    P-value
    = 0.005 [18]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    8.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.61
         upper limit
    14.89
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.13
    Notes
    [17] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [18] - Nominal p-value
    Statistical analysis title
    Difference vs. Mirabegron 25 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1228
    Analysis specification
    Pre-specified
    Analysis type
    superiority [19]
    P-value
    < 0.001 [20]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    21.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.35
         upper limit
    27.68
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.14
    Notes
    [19] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [20] - Nominal p-value
    Statistical analysis title
    Difference vs. Mirabegron 50 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1229
    Analysis specification
    Pre-specified
    Analysis type
    superiority [21]
    P-value
    < 0.001 [22]
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    17.74
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.58
         upper limit
    23.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.14
    Notes
    [21] - Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
    [22] - Nominal p-value

    Secondary: Change from Baseline to EoT in OAB Questionnaire (OAB-q) Symptom Bother Score

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    End point title
    Change from Baseline to EoT in OAB Questionnaire (OAB-q) Symptom Bother Score
    End point description
    The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consisted of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement. The analysis population was the FAS. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    400
    392
    398
    399
    800
    795
    Units: units on a scale
        least squares mean (standard error)
    -19.45 ± 0.98
    -23.93 ± 0.99
    -26.14 ± 0.98
    -26.44 ± 0.98
    -31.06 ± 0.69
    -32.24 ± 0.70
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1199
    Analysis specification
    Pre-specified
    Analysis type
    superiority [23]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -4.63
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.98
         upper limit
    -2.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2
    Notes
    [23] - No adjustment for multiplicity was made for this comparison.
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1194
    Analysis specification
    Pre-specified
    Analysis type
    superiority [24]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -5.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.17
         upper limit
    -3.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.21
    Notes
    [24] - No adjustment for multiplicity was made for this comparison.
    Statistical analysis title
    Difference vs. Mirabegron 25 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1192
    Analysis specification
    Pre-specified
    Analysis type
    superiority [25]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -7.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.5
         upper limit
    -4.76
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.21
    Notes
    [25] - No adjustment for multiplicity was made for this comparison.
    Statistical analysis title
    Difference vs. Mirabegron 50 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1193
    Analysis specification
    Pre-specified
    Analysis type
    superiority [26]
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -6.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.46
         upper limit
    -3.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2
    Notes
    [26] - No adjustment for multiplicity was made for this comparison.

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

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    End point title
    Change from Baseline to EoT in Treatment Satisfaction-Visual Analogue Scale (TS-VAS)
    End point description
    The TS-VAS was a visual analogue scale which asked participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement. The analysis population was the FAS. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    399
    391
    398
    399
    798
    794
    Units: units on a scale
        least squares mean (standard error)
    1.42 ± 0.11
    2.16 ± 0.11
    2.18 ± 0.11
    2.28 ± 0.11
    2.53 ± 0.08
    2.55 ± 0.08
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1197
    Analysis specification
    Pre-specified
    Analysis type
    superiority [27]
    P-value
    = 0.077
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.03
         upper limit
    0.52
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [27] - No adjustment for multiplicity was made for this comparison.
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1193
    Analysis specification
    Pre-specified
    Analysis type
    superiority [28]
    P-value
    = 0.05
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    0.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [28] - No adjustment for multiplicity was made for this comparison.
    Statistical analysis title
    Difference vs. Mirabegron 25 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1189
    Analysis specification
    Pre-specified
    Analysis type
    superiority [29]
    P-value
    = 0.008
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.1
         upper limit
    0.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [29] - No adjustment for multiplicity was made for this comparison.
    Statistical analysis title
    Difference vs. Mirabegron 50 mg
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1192
    Analysis specification
    Pre-specified
    Analysis type
    superiority [30]
    P-value
    = 0.007
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.1
         upper limit
    0.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Notes
    [30] - No adjustment for multiplicity was made for this comparison.

    Secondary: Number of Incontinence Episodes at Weeks 4, 8, 12 and EoT

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    End point title
    Number of Incontinence Episodes at Weeks 4, 8, 12 and EoT
    End point description
    The number of incontinence episodes was calculated as the total number of incontinence episodes on valid diary days recorded during the 7-day micturition diary period. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EOT.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: incontinence episodes
    least squares mean (standard error)
        Week 4 [N=406, 406, 402, 402, 817, 810]
    18.09 ± 1.17
    15.65 ± 1.08
    12.90 ± 1.06
    15.31 ± 1.11
    12.51 ± 0.67
    11.44 ± 0.70
        Week 8 [N=397, 385, 386, 386, 784, 769]
    14.45 ± 1.12
    12.84 ± 1.05
    11.31 ± 1.09
    12.19 ± 1.06
    9.70 ± 0.65
    9.33 ± 0.68
        Week 12 [N=374, 369, 369, 379, 754, 750]
    14.06 ± 1.17
    10.60 ± 0.98
    9.50 ± 0.98
    11.25 ± 1.03
    7.62 ± 0.57
    8.21 ± 0.68
        Eot [N=412, 409, 406, 413, 823, 816]
    13.70 ± 1.08
    11.19 ± 0.95
    9.79 ± 0.94
    11.21 ± 0.98
    8.02 ± 0.55
    8.18 ± 0.64
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.135
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.72
         upper limit
    1.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.282
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.75
         upper limit
    1.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    Rate ratio vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.59
         upper limit
    0.85
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    Rate ratio vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.172
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.73
         upper limit
    1.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Incontinence Episodes

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Incontinence Episodes
    End point description
    The number of incontinence episodes was calculated as the total number of incontinence episodes on valid diary days recorded during the 7-day micturition diary period. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    823
    816
    Units: incontinence episodes
    least squares mean (standard error)
        Week 4 [N=406, 406, 402, 402, 817, 810]
    -5.23 ± 0.66
    -7.59 ± 0.66
    -8.99 ± 0.67
    -8.92 ± 0.67
    -9.62 ± 0.47
    -10.51 ± 0.47
        Week 8 [N=397, 385, 386, 386, 784, 769]
    -8.79 ± 0.71
    -10.57 ± 0.72
    -10.97 ± 0.72
    -11.89 ± 0.72
    -12.53 ± 0.50
    -12.78 ± 0.51
        Week 12 [N=374, 369, 369, 379, 754, 750]
    -9.05 ± 0.72
    -12.33 ± 0.72
    -12.58 ± 0.72
    -12.75 ± 0.71
    -14.50 ± 0.51
    -13.94 ± 0.51
        EoT [N=412, 409, 406, 413, 823, 816]
    -9.42 ± 0.68
    -11.93 ± 0.68
    -12.39 ± 0.68
    -12.65 ± 0.68
    -14.29 ± 0.48
    -13.98 ± 0.48
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.074
    Method
    Stratified rank ANCOVA
    Parameter type
    least squares mean difference
    Point estimate
    -1.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.27
         upper limit
    -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1231
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.025
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.96
         upper limit
    0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1233
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Stratified rank ANCOVA
    Parameter type
    least square mean difference
    Point estimate
    -2.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4
         upper limit
    -0.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1227
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.024
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.23
         upper limit
    0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.84

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

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    End point title
    Change from Baseline to Weeks 4, 8 and 12 in Mean Number of Incontinence Episodes per 24 Hours
    End point description
    The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: incontinence episodes
    least squares mean (standard error)
        Week 4 [N=406, 406, 402, 402, 817, 810]
    -0.74 ± 0.10
    -1.07 ± 0.10
    -1.24 ± 0.10
    -1.24 ± 0.10
    -1.38 ± 0.07
    -1.50 ± 0.07
        Week 8 [N=397, 385, 386, 386, 784, 769]
    -1.20 ± 0.10
    -1.51 ± 0.10
    -1.57 ± 0.10
    -1.66 ± 0.10
    -1.79 ± 0.07
    -1.84 ± 0.07
        Week 12 [N=374, 369, 369, 379, 754, 750]
    -1.30 ± 0.11
    -1.76 ± 0.11
    -1.81 ± 0.11
    -1.80 ± 0.10
    -2.08 ± 0.07
    -1.98 ± 0.07
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 4, 8 and 12 in Mean Number of Micturitions per 24 Hours

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    End point title
    Change from Baseline to Weeks 4, 8 and 12 in Mean Number of Micturitions per 24 Hours
    End point description
    The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: micturitions
    least squares mean (standard error)
        Week 4 [N=406, 406, 402, 402, 817, 810]
    -1.02 ± 0.11
    -1.46 ± 0.11
    -1.44 ± 0.11
    -1.39 ± 0.11
    -1.67 ± 0.08
    -1.91 ± 0.08
        Week 8 [N=397, 385, 386, 386, 784, 769]
    -1.43 ± 0.11
    -1.95 ± 0.12
    -1.89 ± 0.12
    -1.84 ± 0.12
    -2.23 ± 0.08
    -2.42 ± 0.08
        Week 12 [N=374, 369, 369, 379, 754, 750]
    -1.51 ± 0.12
    -2.01 ± 0.12
    -2.03 ± 0.12
    -2.22 ± 0.12
    -2.47 ± 0.08
    -2.60 ± 0.08
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 4, 8 and 12 in Mean Volume Voided per Micturition

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    End point title
    Change from Baseline to Weeks 4, 8 and 12 in Mean Volume Voided per Micturition
    End point description
    The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: mL
    least squares mean (standard error)
        Week 4 [N=403, 398, 399, 395, 798, 802]
    6.95 ± 2.13
    10.08 ± 2.14
    15.52 ± 2.14
    24.23 ± 2.15
    25.54 ± 1.51
    28.99 ± 1.51
        Week 8 [N=395, 382, 380, 387, 770, 771]
    9.00 ± 2.48
    10.96 ± 2.52
    17.73 ± 2.53
    27.55 ± 2.50
    32.94 ± 1.78
    36.51 ± 1.77
        Week 12 [N=373, 362, 364, 378, 750, 750]
    8.70 ± 2.70
    12.88 ± 2.74
    22.40 ± 2.73
    31.89 ± 2.68
    35.52 ± 1.90
    41.28 ± 1.90
    No statistical analyses for this end point

    Secondary: Change from Baseline to EoT in Corrected Micturition Frequency

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    End point title
    Change from Baseline to EoT in Corrected Micturition Frequency
    End point description
    Corrected micturition frequency was defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline. The analysis population was the FAS. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    412
    409
    406
    413
    823
    816
    Units: micturitions
        least squares mean (standard error)
    0.15 ± 0.24
    -0.17 ± 0.24
    -0.97 ± 0.24
    -1.28 ± 0.24
    -1.10 ± 0.17
    -1.52 ± 0.17
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1236
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.52
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    0.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.39
         upper limit
    0.76
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.29
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1229
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.413
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.82
         upper limit
    0.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.29
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1232
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.92
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    -0.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.29
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.06
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.13
         upper limit
    0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3

    Secondary: Number of Urgency Incontinence Episodes at Weeks 4, 8, 12 and EOT

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    End point title
    Number of Urgency Incontinence Episodes at Weeks 4, 8, 12 and EOT
    End point description
    An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was number of times a participant recorded an urgency incontinence episode during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EOT.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: urgency incontinence episodes
    least squares mean (standard error)
        Week 4 [N=403, 404, 396, 401, 813, 806]
    15.76 ± 1.10
    13.36 ± 0.99
    11.46 ± 1.00
    13.19 ± 1.06
    10.22 ± 0.58
    9.33 ± 0.58
        Week 8 [N=394, 383, 380, 385, 780, 765]
    12.77 ± 1.07
    10.65 ± 0.94
    10.09 ± 1.02
    10.41 ± 1.00
    7.58 ± 0.53
    7.31 ± 0.54
        Week 12 [N=371, 367, 363, 378, 750, 746]
    12.00 ± 1.09
    8.84 ± 0.89
    8.32 ± 0.94
    9.29 ± 0.96
    5.86 ± 0.46
    6.27 ± 0.49
        EOT [N=409, 407, 400, 412, 819, 812]
    11.69 ± 1.00
    9.37 ± 0.86
    8.63 ± 0.89
    9.29 ± 0.91
    6.25 ± 0.45
    6.15 ± 0.47
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.11
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    1.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.288
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.73
         upper limit
    1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Rate ratio vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.53
         upper limit
    0.79
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Rate ratio vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.084
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.68
         upper limit
    1.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Urgency Incontinence Episodes

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Urgency Incontinence Episodes
    End point description
    The number of urgency incontinence episodes was number of times a participant recorded an urgency incontinence episode during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: urgency incontinence episodes
    least squares mean (standard error)
        Week 4 [N=403, 404, 396, 401, 813, 806]
    -5.49 ± 0.63
    -7.07 ± 0.63
    -8.39 ± 0.63
    -8.53 ± 0.63
    -9.44 ± 0.44
    -10.23 ± 0.44
        Week 8 [N=394, 383, 380, 385, 780, 765]
    -8.30 ± 0.66
    -9.93 ± 0.67
    -10.07 ± 0.67
    -11.10 ± 0.67
    -12.18 ± 0.47
    -12.38 ± 0.47
        Week 12 [N=371, 367, 363, 378, 750, 746]
    -8.96 ± 0.65
    -11.39 ± 0.66
    -11.66 ± 0.66
    -12.10 ± 0.65
    -13.87 ± 0.46
    -13.53 ± 0.46
        EoT [N=409, 407, 400, 412, 819, 812]
    -9.26 ± 0.62
    -11.03 ± 0.62
    -11.44 ± 0.62
    -12.03 ± 0.62
    -13.64 ± 0.44
    -13.64 ± 0.44
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.114
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.09
         upper limit
    -0.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.034
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.1
         upper limit
    -0.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -2.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.09
         upper limit
    -1.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -2.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.7
         upper limit
    -0.71
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76

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

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours
    End point description
    The mean number of urgency incontinence episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: urgency incontinence episodes
    least squares mean (standard error)
        Week 4 [N=403, 404, 396, 401, 813, 806]
    -0.78 ± 0.09
    -1.00 ± 0.09
    -1.15 ± 0.09
    -1.19 ± 0.09
    -1.35 ± 0.06
    -1.47 ± 0.06
        Week 8 [N=394, 383, 380, 385, 780, 765]
    -1.15 ± 0.10
    -1.43 ± 0.10
    -1.44 ± 0.10
    -1.56 ± 0.10
    -1.74 ± 0.07
    -1.79 ± 0.07
        Week 12 [N=371, 367, 363, 378, 750, 746]
    -1.29 ± 0.10
    -1.63 ± 0.10
    -1.67 ± 0.10
    -1.72 ± 0.10
    -1.99 ± 0.07
    -1.93 ± 0.07
        EoT [N=409, 407, 400, 412, 819, 812]
    -1.33 ± 0.09
    -1.58 ± 0.09
    -1.62 ± 0.09
    -1.71 ± 0.09
    -1.95 ± 0.06
    -1.94 ± 0.06
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.134
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.46
         upper limit
    -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.043
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.45
         upper limit
    -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.59
         upper limit
    -0.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.019
    Method
    Stratified rank ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.54
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours
    End point description
    An urgency episode was a complaint of a sudden, compelling desire to pass urine, which was difficult to defer; it was recorded when a micturition or incontinence episode was recorded and the severity of urinary urgency recorded was 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS). The mean number of urgency episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency episode at baseline were included in the analysis. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: urgency episodes
    least squares mean (standard error)
        Week 4 [N=405, 406, 402, 402, 817, 810]
    -1.34 ± 0.15
    -1.95 ± 0.14
    -1.91 ± 0.15
    -2.14 ± 0.15
    -2.42 ± 0.10
    -2.66 ± 0.10
        Week 8 [N=396, 385, 386, 386, 784, 769]
    -1.85 ± 0.15
    -2.54 ± 0.15
    -2.43 ± 0.15
    -2.90 ± 0.15
    -3.13 ± 0.11
    -3.28 ± 0.11
        Week 12 [N=373, 369, 369, 379, 754, 750]
    -2.05 ± 0.16
    -2.85 ± 0.16
    -2.70 ± 0.16
    -3.11 ± 0.16
    -3.45 ± 0.11
    -3.50 ± 0.11
        EoT [N=411, 409, 406, 413, 823, 816]
    -2.06 ± 0.15
    -2.74 ± 0.15
    -2.63 ± 0.15
    -3.05 ± 0.15
    -3.38 ± 0.11
    -3.51 ± 0.11
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.074
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.69
         upper limit
    0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.82
         upper limit
    -0.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.01
         upper limit
    -0.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.24
         upper limit
    0.51
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.19

    Secondary: Number of Nocturia Episodes at Weeks 4, 8, 12 and EoT

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    End point title
    Number of Nocturia Episodes at Weeks 4, 8, 12 and EoT
    End point description
    A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EOT.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: nocturia episodes
    least squares mean (standard error)
        Week 4 [N=359, 341, 349, 341, 705, 693]
    9.62 ± 0.43
    8.46 ± 0.36
    9.11 ± 0.47
    9.22 ± 0.42
    8.40 ± 0.25
    8.09 ± 0.25
        Week 8 [N=349, 327, 336, 329, 676, 655]
    8.99 ± 0.44
    8.07 ± 0.34
    8.61 ± 0.45
    8.37 ± 0.38
    7.63 ± 0.25
    7.11 ± 0.24
        Week 12 [N=336, 312, 321, 320, 652, 641]
    8.91 ± 0.43
    7.99 ± 0.37
    8.34 ± 0.48
    8.17 ± 0.39
    7.26 ± 0.24
    6.67 ± 0.23
        EoT [N=363, 344, 353, 350, 708, 697]
    8.83 ± 0.42
    7.79 ± 0.35
    8.14 ± 0.45
    8.12 ± 0.37
    7.33 ± 0.24
    6.67 ± 0.22
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.81
         upper limit
    0.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.81
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.74
         upper limit
    0.88
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Statistical analysis title
    Rate ratio vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.049
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.91
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Statistical analysis title
    Rate ratio vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.79
         upper limit
    0.94
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Nocturia Episodes

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Nocturia Episodes
    End point description
    The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: nocturia episodes
    least squares mean (standard error)
        Week 4 [N=359, 341, 349, 341, 705, 693]
    -1.27 ± 0.27
    -2.25 ± 0.28
    -1.80 ± 0.27
    -1.79 ± 0.28
    -2.39 ± 0.19
    -2.50 ± 0.19
        Week 8 [N=349, 327, 336, 329, 676, 655]
    -1.94 ± 0.27
    -2.70 ± 0.28
    -2.41 ± 0.28
    -2.60 ± 0.28
    -3.13 ± 0.20
    -3.48 ± 0.20
        Week 12 [N=336, 312, 321, 320, 652, 641]
    -1.95 ± 0.29
    -2.77 ± 0.30
    -2.73 ± 0.29
    -2.89 ± 0.29
    -3.49 ± 0.21
    -3.96 ± 0.21
        EoT [N=363, 344, 353, 350, 708, 697]
    -2.05 ± 0.27
    -2.91 ± 0.28
    -2.75 ± 0.28
    -2.81 ± 0.28
    -3.42 ± 0.20
    -3.96 ± 0.20
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.073
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.28
         upper limit
    0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.83
         upper limit
    -0.48
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.14
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.18
         upper limit
    0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.88
         upper limit
    -0.54
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours
    End point description
    The mean number of nocturia episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: nocturia episodes
    least squares mean (standard error)
        Week 4 [N=359, 341, 349, 341, 705, 693]
    -0.17 ± 0.04
    -0.31 ± 0.04
    -0.25 ± 0.04
    -0.24 ± 0.04
    -0.33 ± 0.03
    -0.35 ± 0.03
        Week 8 [N=349, 327, 336, 329, 676, 655]
    -0.27 ± 0.04
    -0.37 ± 0.04
    -0.35 ± 0.04
    -0.36 ± 0.04
    -0.44 ± 0.03
    -0.50 ± 0.03
        Week 12 [N=336, 312, 321, 320, 652, 641]
    -0.26 ± 0.04
    -0.38 ± 0.04
    -0.39 ± 0.04
    -0.41 ± 0.04
    -0.49 ± 0.03
    -0.56 ± 0.03
        EoT [N=363, 344, 353, 350, 708, 697]
    -0.27 ± 0.04
    -0.40 ± 0.04
    -0.39 ± 0.04
    -0.39 ± 0.04
    -0.48 ± 0.03
    -0.56 ± 0.03
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.065
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.19
         upper limit
    0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    -0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.18
         upper limit
    0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    -0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05

    Secondary: Number of Pads Used at Weeks 4, 8, 12 and EoT

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    End point title
    Number of Pads Used at Weeks 4, 8, 12 and EoT
    End point description
    The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 pad used at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EOT.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: pads
    least squares mean (standard error)
        Week 4 [N=248, 250, 247, 257, 506, 499]
    15.62 ± 1.33
    13.46 ± 1.24
    10.05 ± 1.21
    11.41 ± 1.23
    9.71 ± 0.70
    9.34 ± 0.68
        Week 8 [N=239, 237, 240, 243, 485, 472]
    12.75 ± 1.22
    10.79 ± 1.05
    9.53 ± 1.39
    8.45 ± 1.03
    8.07 ± 0.65
    7.58 ± 0.62
        Week 12 [N=226, 225, 229, 241, 468, 461]
    12.62 ± 1.21
    9.65 ± 1.00
    8.44 ± 1.26
    8.21 ± 0.95
    6.60 ± 0.58
    6.64 ± 0.61
        EoT [N=252, 252, 249, 262, 510, 502]
    12.29 ± 1.11
    10.15 ± 0.97
    8.16 ± 1.17
    8.53 ± 0.94
    7.04 ± 0.56
    6.80 ± 0.59
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.938
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    1.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8
         upper limit
    1.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Statistical analysis title
    Rate ratio vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.967
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.79
         upper limit
    1.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Statistical analysis title
    Rate ratio vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.008
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.73
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.58
         upper limit
    0.92
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Statistical analysis title
    Rate ratio vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.069
    Method
    Negative binomial regression
    Parameter type
    Rate ratio
    Point estimate
    0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.64
         upper limit
    1.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Pads Used

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Pads Used
    End point description
    The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 pad used at baseline were included in the analysis. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: pads
    least squares mean (standard error)
        Week 4 [N=248, 250, 247, 257, 506, 499]
    -3.69 ± 0.71
    -5.68 ± 0.71
    -7.83 ± 0.71
    -8.23 ± 0.70
    -7.61 ± 0.50
    -8.58 ± 0.50
        Week 8 [N=239, 237, 240, 243, 485, 472]
    -6.24 ± 0.77
    -8.44 ± 0.77
    -8.43 ± 0.76
    -10.67 ± 0.76
    -9.49 ± 0.54
    -10.59 ± 0.54
        Week 12 [N=226, 225, 229, 241, 468, 461]
    -6.29 ± 0.75
    -9.06 ± 0.75
    -9.41 ± 0.75
    -10.80 ± 0.73
    -10.66 ± 0.52
    -11.23 ± 0.53
        EoT [N=252, 252, 249, 262, 510, 502]
    -6.60 ± 0.71
    -8.76 ± 0.71
    -9.80 ± 0.72
    -10.63 ± 0.70
    -10.67 ± 0.50
    -11.21 ± 0.50
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.958
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.73
         upper limit
    1.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.27
         upper limit
    1.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.028
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.91
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.62
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.87
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.108
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.13
         upper limit
    0.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.88

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Pads Used per 24 Hours

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Pads Used per 24 Hours
    End point description
    The mean number of pads used was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 pads used at baseline were included in the analysis. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: pads
    least squares mean (standard error)
        Week 4 [N=248, 250, 247, 257, 506, 499]
    -0.52 ± 0.10
    -0.81 ± 0.10
    -1.12 ± 0.10
    -1.19 ± 0.10
    -1.09 ± 0.07
    -1.23 ± 0.07
        Week 8 [N=239, 237, 240, 243, 485, 472]
    -0.82 ± 0.11
    -1.20 ± 0.11
    -1.24 ± 0.11
    -1.53 ± 0.11
    -1.36 ± 0.08
    -1.51 ± 0.08
        Week 12 [N=226, 225, 229, 241, 468, 461]
    -0.92 ± 0.11
    -1.30 ± 0.11
    -1.37 ± 0.11
    -1.56 ± 0.11
    -1.54 ± 0.08
    -1.59 ± 0.08
        EoT [N=252, 252, 249, 262, 510, 502]
    -0.94 ± 0.10
    -1.26 ± 0.10
    -1.41 ± 0.10
    -1.53 ± 0.10
    -1.53 ± 0.07
    -1.58 ± 0.07
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.993
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.25
         upper limit
    0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.65
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    0.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.035
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.52
         upper limit
    -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.169
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.43
         upper limit
    0.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13

    Secondary: Number of Incontinence-Free Days at Weeks 4, 8, 12 and EoT

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    End point title
    Number of Incontinence-Free Days at Weeks 4, 8, 12 and EoT
    End point description
    The number of incontinence-free days was the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EOT.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: incontinence-free days
    arithmetic mean (standard error)
        Week 4 [N=406, 406, 402, 402, 817, 810]
    2.25 ± 0.13
    2.48 ± 0.13
    2.98 ± 0.13
    2.74 ± 0.14
    3.08 ± 0.10
    3.37 ± 0.10
        Week 8 [N=397, 385, 386, 386, 784, 769]
    2.92 ± 0.14
    3.17 ± 0.14
    3.63 ± 0.15
    3.31 ± 0.14
    3.88 ± 0.10
    4.01 ± 0.10
        Week 12 [N=374, 369, 369, 379, 754, 750]
    3.19 ± 0.15
    3.69 ± 0.15
    3.96 ± 0.15
    3.68 ± 0.14
    4.33 ± 0.10
    4.25 ± 0.10
        EoT [N=412, 409, 406, 413, 823, 816]
    3.16 ± 0.14
    3.51 ± 0.14
    3.89 ± 0.14
    3.61 ± 0.14
    4.20 ± 0.10
    4.23 ± 0.10
    Statistical analysis title
    Odds ratio vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of mean number of incontinence episodes per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.11
         upper limit
    1.68
    Statistical analysis title
    Odds ratio vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of mean number of incontinence episodes per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.11
         upper limit
    1.68
    Statistical analysis title
    Odds ratio vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of mean number of incontinence episodes per 24 hours as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.29
         upper limit
    1.95
    Statistical analysis title
    Odds ratio vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of mean number of incontinence episodes per 24 hours as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.1
         upper limit
    1.68

    Secondary: Number of Days with < 8 Micturitions at Weeks 4, 8, 12 and EoT

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    End point title
    Number of Days with < 8 Micturitions at Weeks 4, 8, 12 and EoT
    End point description
    The number of days with < 8 micturitions was the number of valid diary days during the 7-day micturition diary period with less than 8 micturitions per day. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EOT.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: days
    arithmetic mean (standard error)
        Week 4 [N=406, 406, 402, 402, 817, 810]
    1.49 ± 0.10
    1.74 ± 0.10
    1.55 ± 0.10
    1.86 ± 0.11
    2.07 ± 0.08
    2.11 ± 0.08
        Week 8 [N=397, 385, 386, 386, 784, 769]
    1.69 ± 0.10
    2.08 ± 0.12
    1.99 ± 0.11
    2.22 ± 0.12
    2.59 ± 0.09
    2.70 ± 0.09
        Week 12 [N=374, 369, 369, 379, 754, 750]
    1.76 ± 0.11
    2.31 ± 0.13
    2.25 ± 0.12
    2.49 ± 0.13
    2.87 ± 0.09
    2.95 ± 0.10
        EoT [N=412, 409, 406, 413, 823, 816]
    1.80 ± 0.11
    2.28 ± 0.12
    2.22 ± 0.12
    2.49 ± 0.12
    2.84 ± 0.09
    2.92 ± 0.09
    Statistical analysis title
    Odds ratio vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.039
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.01
         upper limit
    1.5
    Statistical analysis title
    Odds ratio vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.009
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.07
         upper limit
    1.59
    Statistical analysis title
    Odds ratio vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.19
         upper limit
    1.77
    Statistical analysis title
    Odds ratio vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.23
         upper limit
    1.84

    Secondary: Number of Incontinence-Free Days with < 8 Micturitions per Day at Weeks 4, 8, 12 and EoT

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    End point title
    Number of Incontinence-Free Days with < 8 Micturitions per Day at Weeks 4, 8, 12 and EoT
    End point description
    The number of incontinence-free days with < 8 micturitions per day was the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded and with < 8 micturitions per day. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EOT.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: days
    arithmetic mean (standard error)
        Week 4 [N=406, 406, 402, 402, 817, 810]
    0.64 ± 0.07
    0.84 ± 0.08
    0.87 ± 0.08
    0.91 ± 0.08
    1.21 ± 0.07
    1.32 ± 0.07
        Week 8 [N=397, 385, 386, 386, 784, 769]
    0.85 ± 0.08
    1.20 ± 0.10
    1.23 ± 0.10
    1.31 ± 0.10
    1.75 ± 0.08
    1.89 ± 0.08
        Week 12 [N=374, 369, 369, 379, 754, 750]
    0.98 ± 0.09
    1.47 ± 0.11
    1.50 ± 0.11
    1.60 ± 0.11
    2.12 ± 0.09
    2.15 ± 0.09
        EoT [N=412, 409, 406, 413, 823, 816]
    1.01 ± 0.08
    1.40 ± 0.10
    1.47 ± 0.10
    1.59 ± 0.10
    2.04 ± 0.08
    2.12 ± 0.09
    Statistical analysis title
    Odds ratio vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.07
         upper limit
    1.64
    Statistical analysis title
    Odds ratio vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.14
         upper limit
    1.75
    Statistical analysis title
    Odds ratio vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.32
         upper limit
    2.06
    Statistical analysis title
    Odds ratio vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Overdispersed binomial regression
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.33
         upper limit
    2.07

    Secondary: Change from Baseline in Patient Perception of Bladder Condition Questionnaire (PPBC) at Weeks 4, 8, 12 and EoT

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    End point title
    Change from Baseline in Patient Perception of Bladder Condition Questionnaire (PPBC) at Weeks 4, 8, 12 and EoT
    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. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. The analysis population is FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=397, 388, 393, 394, 791, 791]
    -0.54 ± 0.06
    -0.72 ± 0.06
    -0.83 ± 0.06
    -0.81 ± 0.06
    -0.99 ± 0.04
    -1.07 ± 0.04
        Week 8 [N=381, 372, 380, 385, 758, 761]]
    -0.80 ± 0.06
    -1.07 ± 0.06
    -1.12 ± 0.06
    -1.18 ± 0.06
    -1.32 ± 0.04
    -1.48 ± 0.04
        Week 12 [N=371, 362, 366, 375, 739, 735]
    -0.95 ± 0.06
    -1.23 ± 0.06
    -1.34 ± 0.06
    -1.32 ± 0.06
    -1.57 ± 0.04
    -1.72 ± 0.04
        EoT [N=400, 393, 398, 399, 801, 795]
    -0.91 ± 0.06
    -1.18 ± 0.06
    -1.31 ± 0.06
    -1.27 ± 0.06
    -1.53 ± 0.04
    -1.66 ± 0.04
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.41
         upper limit
    -0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.54
         upper limit
    -0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    -0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07

    Secondary: Change from Baseline to Weeks 4, 8 and 12 in the OAB-q Symptom Bother Score

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    End point title
    Change from Baseline to Weeks 4, 8 and 12 in the OAB-q Symptom Bother Score
    End point description
    The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion (seen in this endpoint) consisted of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=397, 388, 392, 394, 790, 789]
    -13.84 ± 0.92
    -17.05 ± 0.93
    -18.98 ± 0.93
    -19.53 ± 0.93
    -23.46 ± 0.65
    -25.19 ± 0.65
        Week 8 [N=381, 370, 380, 385, 757, 761]
    -17.35 ± 0.98
    -22.79 ± 0.99
    -23.54 ± 0.98
    -24.69 ± 0.97
    -29.10 ± 0.69
    -30.04 ± 0.69
        Week 12 [N=371, 362, 366, 374, 738, 734]
    -19.94 ± 1.01
    -24.44 ± 1.02
    -26.80 ± 1.02
    -26.72 ± 1.01
    -31.70 ± 0.72
    -33.15 ± 0.72
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQL) Total Score

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQL) Total Score
    End point description
    The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion (seen in this endpoint) consisted of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1 -6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=397, 388, 392, 394, 790, 789]
    10.16 ± 0.83
    13.54 ± 0.83
    15.28 ± 0.83
    14.78 ± 0.83
    17.46 ± 0.58
    17.95 ± 0.59
        Week 8 [N=381, 370, 380, 385, 757, 761]
    14.51 ± 0.88
    17.95 ± 0.89
    18.54 ± 0.88
    18.57 ± 0.88
    22.30 ± 0.62
    22.45 ± 0.62
        Week 12 [N=371, 362, 366, 374, 738, 734]
    15.76 ± 0.92
    19.59 ± 0.93
    21.48 ± 0.92
    20.54 ± 0.91
    24.63 ± 0.65
    24.93 ± 0.65
        EoT [N=400, 392, 398, 399, 800, 795]
    15.37 ± 0.88
    18.94 ± 0.89
    21.00 ± 0.89
    20.15 ± 0.89
    23.96 ± 0.63
    24.30 ± 0.63
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    3.81
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.69
         upper limit
    5.94
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.08
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.03
         upper limit
    6.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.09
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    5.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.88
         upper limit
    7.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.09
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    3.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.17
         upper limit
    5.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.09

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Coping

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Coping
    End point description
    The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. The Coping score was calculated by adding 8 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=397, 388, 392, 394, 790, 789]
    11.74 ± 0.99
    14.87 ± 1.00
    17.68 ± 1.00
    16.52 ± 1.00
    19.31 ± 0.70
    20.36 ± 0.70
        Week 8 [N=381, 370, 380, 385, 757, 761]
    16.13 ± 1.04
    20.64 ± 1.05
    21.52 ± 1.04
    21.69 ± 1.03
    25.49 ± 0.74
    25.85 ± 0.73
        Week 12 [N=371, 362, 366, 374, 738, 734]
    18.17 ± 1.09
    22.04 ± 1.10
    24.94 ± 1.10
    23.67 ± 1.09
    28.32 ± 0.77
    29.03 ± 0.78
        EoT [N=400, 392, 398, 399, 800, 795]
    17.73 ± 1.05
    21.28 ± 1.06
    24.32 ± 1.05
    23.25 ± 1.05
    27.37 ± 0.74
    28.12 ± 0.75
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.6
         upper limit
    6.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.29
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Lest squares mean difference
    Point estimate
    4.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.34
         upper limit
    7.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.29
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    6.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.55
         upper limit
    8.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.3
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    3.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.27
         upper limit
    6.33
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.29

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Concern

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Concern
    End point description
    The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. The Concern score was calculated by adding 7 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=397, 388, 392, 394, 790, 789]
    11.24 ± 0.95
    15.89 ± 0.96
    17.39 ± 0.95
    17.18 ± 0.95
    20.48 ± 0.67
    21.09 ± 0.67
        Week 8 [N=381, 370, 380, 385, 757, 761]
    16.10 ± 0.99
    20.63 ± 1.01
    20.55 ± 1.00
    20.96 ± 0.99
    25.26 ± 0.71
    25.65 ± 0.70
        Week 12 [N=371, 362, 366, 374, 738, 734]
    17.53 ± 1.03
    22.37 ± 1.04
    23.62 ± 1.04
    23.19 ± 1.03
    27.53 ± 0.73
    28.24 ± 0.73
        EoT [N=400, 392, 398, 399, 800, 795]
    16.98 ± 1.00
    21.55 ± 1.01
    23.07 ± 1.00
    22.65 ± 1.00
    26.89 ± 0.71
    27.47 ± 0.71
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.84
         upper limit
    6.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.22
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.42
         upper limit
    7.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.22
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    5.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.93
         upper limit
    7.75
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.23
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.01
         upper limit
    6.81
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.22

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Sleep

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Sleep
    End point description
    The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consisted of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. The Sleep score was calculated by adding 5 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=397, 388, 392, 394, 790, 789]
    9.28 ± 0.95
    12.70 ± 0.96
    13.80 ± 0.96
    13.08 ± 0.96
    15.97 ± 0.68
    16.66 ± 0.68
        Week 8 [N=381, 370, 380, 385, 757, 761]
    13.58 ± 1.03
    16.39 ± 1.05
    17.33 ± 1.03
    16.43 ± 1.03
    20.29 ± 0.73
    20.49 ± 0.73
        Week 12 [N=371, 362, 366, 374, 738, 734]
    14.40 ± 1.05
    18.04 ± 1.06
    19.16 ± 1.06
    18.35 ± 1.05
    22.97 ± 0.74
    22.76 ± 0.75
        EoT [N=400, 392, 398, 399, 800, 795]
    14.17 ± 1.01
    17.51 ± 1.02
    19.11 ± 1.02
    17.97 ± 1.01
    22.39 ± 0.72
    22.39 ± 0.72
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.98
         upper limit
    6.85
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.24
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.98
         upper limit
    6.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.24
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    4.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.42
         upper limit
    7.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.25
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.008
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    3.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    5.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.24

    Secondary: Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Social

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    End point title
    Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Social
    End point description
    The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consisted of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. The Social score was calculated by adding 5 response scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=397, 388, 392, 394, 790, 789]
    7.07 ± 0.78
    9.04 ± 0.79
    10.19 ± 0.78
    9.89 ± 0.78
    11.55 ± 0.55
    11.25 ± 0.55
        Week 8 [N=381, 370, 380, 385, 757, 761]
    10.65 ± 0.82
    11.50 ± 0.83
    12.34 ± 0.82
    12.02 ± 0.81
    14.89 ± 0.58
    14.73 ± 0.58
        Week 12 [N=371, 362, 366, 374, 738, 734]
    10.84 ± 0.83
    13.43 ± 0.84
    15.35 ± 0.84
    13.74 ± 0.83
    16.16 ± 0.59
    16.08 ± 0.59
        EoT [N=400, 392, 398, 399, 800, 795]
    10.56 ± 0.81
    13.04 ± 0.81
    14.87 ± 0.81
    13.57 ± 0.81
    15.84 ± 0.57
    15.82 ± 0.57
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (1) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.022
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    2.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.33
         upper limit
    4.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.99
    Statistical analysis title
    Difference vs. Solifenacin 5 mg (2) (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1242
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.023
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    2.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.31
         upper limit
    4.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.99
    Statistical analysis title
    Difference vs. Mirabegron 25 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg
    Number of subjects included in analysis
    1237
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    2.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.85
         upper limit
    4.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.99
    Statistical analysis title
    Difference vs. Mirabegron 50 mg (EoT)
    Statistical analysis description
    Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects included in analysis
    1238
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.337
    Method
    ANCOVA
    Parameter type
    Least squares mean difference
    Point estimate
    0.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.99
         upper limit
    2.89
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.99

    Secondary: Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Week 12 and EoT

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    End point title
    Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Week 12 and EoT
    End point description
    The PGIC was a 2-part questionnaire, assessing both the change in the participant’s overall condition and change in bladder condition since the start of the study (from very much worse to very much improved). The analysis population was the FAS. The number of participants analyzed includes participants with data available. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Week 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: percentage of participants
    number (not applicable)
        Week 12: Very much improved
    8.4
    13.9
    15.1
    13.5
    19.8
    27.1
        Week 12: Much improved
    29.7
    32.9
    34.8
    40.5
    39.8
    34.0
        Week 12: Minimally improved
    29.7
    26.8
    26.5
    25.8
    22.2
    20.7
        Week 12: No change
    17.5
    12.9
    9.7
    8.9
    7.7
    7.3
        Week 12: Minimally worse
    4.1
    1.5
    2.2
    1.7
    0.8
    0.8
        Week 12: Much worse
    1.0
    1.0
    1.2
    0.5
    0.2
    0
        Week 12: Very much worse
    0.5
    0.5
    0.7
    0.5
    0.2
    0.5
        EoT: Very much improved
    8.4
    13.9
    15.1
    13.5
    20.0
    27.1
        EoT: Much improved
    30.4
    33.2
    34.8
    41.0
    40.0
    34.6
        EoT: Minimally improved
    29.9
    26.8
    27.0
    26.3
    22.6
    21.3
        EoT: No change
    18.2
    13.4
    10.2
    9.6
    7.9
    7.4
        EoT: Minimally worse
    4.1
    1.5
    2.2
    1.7
    0.8
    0.8
        EoT: Much worse
    1.0
    1.0
    1.2
    0.7
    0.4
    0
        EoT: Very much worse
    0.5
    0.5
    0.7
    0.5
    0.2
    0.6
    No statistical analyses for this end point

    Secondary: PGIC Scale: Impression in General Health at Week 12 and EoT

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    End point title
    PGIC Scale: Impression in General Health at Week 12 and EoT
    End point description
    The PGIC was a 2-part questionnaire, assessing both the change in the participant’s overall condition and change in bladder condition since the start of the study (from very much worse to very much improved). The analysis population was the FAS. The number of participants analyzed includes participants with data available. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Week 12 and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: percentage of participants
    number (not applicable)
        Week 12: Very much improved
    4.8
    8.0
    7.3
    7.7
    10.3
    14.6
        Week 12: Much improved
    23.9
    28.0
    29.2
    31.8
    33.4
    30.2
        Week 12: Minimally improved
    23.9
    21.5
    22.4
    24.1
    20.1
    20.9
        Week 12: No change
    31.8
    27.8
    27.5
    25.3
    23.9
    21.6
        Week 12: Minimally worse
    4.3
    2.9
    2.2
    1.4
    2.5
    2.2
        Week 12: Much worse
    1.7
    0.7
    1.2
    0.5
    0.5
    0.1
        Week 12: Very much worse
    0.2
    0.5
    0.5
    0.5
    0.2
    0.6
        EoT: Very much improved
    4.8
    8.0
    7.3
    7.7
    10.3
    14.6
        EoT: Much improved
    24.2
    28.0
    29.2
    31.8
    33.6
    30.4
        EoT: Minimally improved
    24.4
    21.5
    22.9
    24.1
    20.2
    21.3
        EoT: No change
    32.3
    28.3
    27.7
    26.5
    24.3
    21.9
        EoT: Minimally worse
    4.3
    2.9
    2.4
    1.9
    2.8
    2.7
        EoT: Much worse
    1.9
    0.7
    1.2
    0.5
    0.5
    0.2
        EoT: Very much worse
    0.5
    0.7
    0.5
    0.7
    0.2
    0.7
    No statistical analyses for this end point

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

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    End point title
    Change from Baseline to EoT in European Quality of Life in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility
    End point description
    The EQ-5D questionnaire was an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension had 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The analysis population was the FAS. LOCF was used for EoT.
    End point type
    Secondary
    End point timeframe
    Baseline and EoT (up to 12 weeks)
    End point values
    Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + mirabegron 25 mg Solifenacin 5 mg + mirabegron 50 mg
    Number of subjects analysed
    418
    410
    411
    415
    827
    827
    Units: participants
    number (not applicable)
        No problems -> no problems
    204
    239
    225
    227
    449
    452
        No problems -> slight problems
    16
    20
    25
    22
    41
    38
        No problems -> moderate problems
    11
    12
    9
    8
    20
    10
        No problems -> severe problems
    1
    3
    3
    1
    1
    2
        No problems -> unable to walk about
    0
    1
    0
    0
    0
    1
        No problems -> no data
    2
    4
    5
    4
    6
    9
        Slight problems -> no problems
    33
    35
    35
    30
    76
    60
        Slight problems -> slight problems
    27
    20
    24
    19
    40
    49
        Slight problems -> moderate problems
    11
    6
    4
    6
    19
    9
        Slight problems -> severe problems
    5
    0
    3
    1
    2
    2
        Slight problems -> unable to walk about
    0
    0
    0
    0
    0
    0
        Slight problems -> no data
    2
    3
    0
    0
    0
    2
        Moderate problems -> no problems
    17
    7
    25
    18
    31
    46
        Moderate problems -> slight problems
    18
    10
    10
    22
    24
    25
        Moderate problems -> moderate problems
    21
    12
    10
    13
    33
    35
        Moderate problems -> severe problems
    10
    5
    4
    2
    8
    10
        Moderate problems -> unable to walk about
    0
    0
    0
    1
    1
    1
        Moderate problems -> no data
    1
    1
    0
    1
    0
    2
        Severe problems -> no problems
    3
    5
    9
    7
    12
    17
        Severe problems -> slight problems
    6
    7