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    Clinical Trial Results:
    A Phase 4, Double-Blind, Randomized, Placebo-controlled, Multi-Center Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Men with Overactive Bladder (OAB) Symptoms While Taking the Alpha Blocker Tamsulosin Hydrochloride for Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH)

    Summary
    EudraCT number
    2015-004036-36
    Trial protocol
    CZ   DE   PL   ES   GB   IT  
    Global end of trial date
    11 Sep 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    18 Jun 2020
    First version publication date
    30 Aug 2019
    Other versions
    v1
    Version creation reason

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    178-MA-1008
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02757768
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Acronym: PLUS
    Sponsors
    Sponsor organisation name
    Astellas Pharma Global Development, Inc.
    Sponsor organisation address
    1 Astellas Way, Northbrook, IL, United States, 60062
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    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
    11 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Sep 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to study the efficacy of mirabegron versus placebo in men with OAB symptoms while taking tamsulosin for LUTS due to BPH.
    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
    13 Jun 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 28
    Country: Number of subjects enrolled
    Czech Republic: 105
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 91
    Country: Number of subjects enrolled
    Italy: 92
    Country: Number of subjects enrolled
    Poland: 150
    Country: Number of subjects enrolled
    Spain: 49
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    United States: 173
    Worldwide total number of subjects
    715
    EEA total number of subjects
    514
    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)
    312
    From 65 to 84 years
    402
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    The study enrolled male participants with overactive bladder (OAB) symptoms who were taking the alpha-blocker tamsulosin for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).

    Pre-assignment
    Screening details
    Eligible participants who met inclusion criteria and none of the exclusion criteria were enrolled. Participants entered a 4-week open label tamsulosin hydrochloride 0.4 mg once daily (QD) run-in period prior to being randomized in a 1:1 ratio into the 12-week double-blind treatment period of either mirabegron or placebo once daily.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Mirabegron
    Arm description
    Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.
    Arm type
    Experimental

    Investigational medicinal product name
    Mirabegron
    Investigational medicinal product code
    YM178
    Other name
    Myrbetriq, Betmiga
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks.

    Investigational medicinal product name
    Tamsulosin Hydrochloride
    Investigational medicinal product code
    Other name
    Flomax, Omnic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received once daily treatment with tamsulosin hydrochloride 0.4 mg throughout the study.

    Arm title
    Placebo
    Arm description
    Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received initial dose of 25 mg of matching placebo which was increased to 50 mg after 4 weeks.

    Investigational medicinal product name
    Tamsulosin Hydrochloride
    Investigational medicinal product code
    Other name
    Flomax, Omnic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received once daily treatment with tamsulosin hydrochloride 0.4 mg throughout the study.

    Number of subjects in period 1
    Mirabegron Placebo
    Started
    356
    359
    Treated
    352
    354
    Completed
    323
    331
    Not completed
    33
    28
         Protocol Deviation
    2
    9
         Miscellaneous
    4
    2
         Randomized Never Received Study Drug
    3
    4
         Lack of efficacy
    2
    1
         Adverse event, non-fatal
    5
    3
         Consent withdrawn by subject
    16
    9
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Mirabegron
    Reporting group description
    Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.

    Reporting group title
    Placebo
    Reporting group description
    Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.

    Reporting group values
    Mirabegron Placebo Total
    Number of subjects
    356 359
    Age categorical
    Units: Subjects
    Age continuous
    The analysis population was the all randomized (RAS), which consisted of participants who received initial does of 25 mg of mirabegron or matching placebo which was increased after 4 weeks to 50 mg.
    Units: years
        arithmetic mean (standard deviation)
    65 ± 8.3 65 ± 9.5 -
    Gender categorical
    Units: Subjects
        M
    356 359 715
    Race/Ethnicity, Customized
    Units: Subjects
        WHITE
    332 325 657
        BLACK OR AFRICAN AMERICAN
    16 27 43
        ASIAN
    4 4 8
        OTHER
    2 2 4
        MISSING/UNKNOWN
    2 1 3
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    10 12 22
        Not Hispanic or Latino
    339 336 675
        Unknown or Not Reported
    7 11 18
    Geographic Region
    Units: Subjects
        Europe
    257 257 514
        North America
    99 102 201
    Micturition Episodes per 24 Hours
    This baseline measure is based on the full analysis set (FAS), the FAS was defined as all randomized participants who took at least one dose of double-blind treatment after randomization, reported at least one micturition in the baseline diary and at least one micturition post-baseline.
    Units: micturitions in 24 hours (M24MIC)
        log mean (standard deviation)
    10.7 ± 2.5 10.7 ± 2.6 -

    End points

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    End points reporting groups
    Reporting group title
    Mirabegron
    Reporting group description
    Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.

    Reporting group title
    Placebo
    Reporting group description
    Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.

    Primary: Change From Baseline to End of Treatment (EoT) in Mean Number of Micturitions Per Day

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    End point title
    Change From Baseline to End of Treatment (EoT) in Mean Number of Micturitions Per Day
    End point description
    Participants recorded micturitions in the e-diary during three days. The mean number of micturitions was calculated as the average number of times a participant recorded a micturition per day during the 3-day period. Only voluntary micturitions were counted and the episodes of incontinence were not included. The analysis population was the full analysis set (FAS), which consisted of all randomized participants who took at least 1 dose of double-blind study drug, reported at least 1 baseline micturition recorded in the 3-day e-diary and at least 1 postbaseline micturition. Last observation carried forward (LOCF) was used for missing values in the EoT.
    End point type
    Primary
    End point timeframe
    Baseline and Week 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: micturitions
    least squares mean (standard error)
        micturitions
    -2.00 ± 0.13
    -1.62 ± 0.15
    Statistical analysis title
    Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.039
    Method
    ANCOVA
    Parameter type
    Least Squares (LS) Mean of Difference
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.76
         upper limit
    -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.19

    Secondary: Change From Baseline to Week 4, Week 8, and Week 12 in Mean Number of Micturitions Per Day

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    End point title
    Change From Baseline to Week 4, Week 8, and Week 12 in Mean Number of Micturitions Per Day
    End point description
    Participants recorded micturitions in the e-diary during three days. The mean number of micturitions was calculated as the average number of times a participant recorded a micturition per day during the 3-day period. Only voluntary micturitions were counted and the episodes of incontinence were not included. The analysis population was the FAS. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: micturitions
    least squares mean (standard error)
        Week 4 [N=334, 334]
    -1.42 ± 0.13
    -1.32 ± 0.13
        Week 8 [N=328, 326]
    -1.89 ± 0.13
    -1.38 ± 0.13
        Week 12 [N=317, 319]
    -1.95 ± 0.13
    -1.56 ± 0.13
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.558
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.46
         upper limit
    0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.007 [1]
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.89
         upper limit
    -0.14
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.19
    Notes
    [1] - P-value indicates statistical significance at the 0.05 level.
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.041 [2]
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.76
         upper limit
    -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.19
    Notes
    [2] - P-value indicates statistical significance at the 0.05 level.

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Volume Voided Per Micturition

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Volume Voided Per Micturition
    End point description
    The mean volume voided per micturition collected in the micturition diary during the 3-day period. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: mL
    least squares mean (standard error)
        Week 4 [N=334, 333]
    17.74 ± 1.98
    13.87 ± 1.98
        Week 8 [N=328, 325]
    22.56 ± 2.31
    16.28 ± 2.32
        Week 12 [N=317, 319]
    26.31 ± 2.53
    17.32 ± 2.52
        EoT [N=337, 339]
    25.57 ± 2.42
    16.32 ± 2.42
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.167
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    3.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.63
         upper limit
    9.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.8
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.056
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    6.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.15
         upper limit
    12.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.28
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    8.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.97
         upper limit
    16.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.58
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.007
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    9.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.53
         upper limit
    15.98
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.43

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Incontinence Episodes Per Day

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Incontinence Episodes Per Day
    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 as the average number of times a participant recorded an incontinence episode per day during the 3-day micturition diary period. The analysis population was the full analysis set - incontinence (FAS-I), which consisted of all randomized participants who took at least 1 dose of double-blind study drug and reported 1 micturition at baseline and postbaseline in the 3-day e-diary. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    132
    129
    Units: incontinence episodes
    least squares mean (standard error)
        Week 4 [N=131, 129]
    -0.97 ± 0.18
    -0.84 ± 0.18
        Week 8 [N=130, 121]
    -1.29 ± 0.22
    -1.20 ± 0.23
        Week 12 [N=125, 119]
    -1.48 ± 0.22
    -1.23 ± 0.23
        EoT [N=132, 129]
    -1.45 ± 0.21
    -1.15 ± 0.22
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.747
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.63
         upper limit
    0.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.26
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.393
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.72
         upper limit
    0.54
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.672
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.87
         upper limit
    0.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.64
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per Day

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per Day
    End point description
    Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode with a severity of grade 3 or 4, assessed by participants based on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The mean number of urgency episodes (grade 3 and/or 4) per day was calculated as the average number of times a participant recorded an urgency episode (grade 3 and/or 4) with or without incontinence per day during the 3-day micturition diary period. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: urgency episodes
    least squares mean (standard error)
        Week 4 [N=334, 334]
    -1.79 ± 0.15
    -1.53 ± 0.15
        Week 8 [N=328, 326]
    -2.68 ± 0.17
    -1.97 ± 0.17
        Week 12 [N=317, 319]
    -2.86 ± 0.17
    -2.21 ± 0.17
        EoT [N=337, 339]
    -2.90 ± 0.17
    -2.24 ± 0.17
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.222
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.68
         upper limit
    0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [3]
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.18
         upper limit
    -0.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.24
    Notes
    [3] - P-value indicates statistical significance at the 0.05 level.
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.008 [4]
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.13
         upper limit
    -0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.24
    Notes
    [4] - P-value indicates statistical significance at the 0.05 level.
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004 [5]
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.13
         upper limit
    -0.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.23
    Notes
    [5] - P-value indicates statistical significance at the 0.05 level.

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in International Prostate Symptom Score (IPSS) Total Score

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in International Prostate Symptom Score (IPSS) Total Score
    End point description
    The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=335, 330]
    -3.9 ± 0.3
    -4.0 ± 0.3
        Week 8 [N=327, 331]
    -5.0 ± 0.3
    -5.2 ± 0.3
        Week 12 [N=318, 323]
    -5.9 ± 0.3
    -5.5 ± 0.3
        EoT [N=336, 335]
    -5.7 ± 0.3
    -5.6 ± 0.3
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.723
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.812
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Voiding Score

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Voiding Score
    End point description
    The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=335, 330]
    -1.7 ± 0.2
    -2.1 ± 0.2
        Week 8 [N=327, 331]
    -2.2 ± 0.2
    -2.5 ± 0.2
        Week 12 [N=318, 323]
    -2.5 ± 0.2
    -2.5 ± 0.2
        EoT [N=336, 335]
    -2.5 ± 0.2
    -2.6 ± 0.2
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.121
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.1
         upper limit
    0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.241
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.2
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.843
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.679
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3

    Secondary: Change From Baseline to Week 4, Week 8, Week 12, and EoT in IPSS Subscale Storage Score

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12, and EoT in IPSS Subscale Storage Score
    End point description
    The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=335, 330]
    -2.2 ± 0.1
    -1.9 ± 0.1
        Week 8 [N=327, 331]
    -2.8 ± 0.2
    -2.6 ± 0.1
        Week 12 [N=318, 323]
    -3.3 ± 0.2
    -3.0 ± 0.2
        EoT [N=336, 335]
    -3.3 ± 0.2
    -3.0 ± 0.2
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.175
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.43
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.141
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.288
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Quality of Life (QoL) Score

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Quality of Life (QoL) Score
    End point description
    The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=335, 330]
    -0.9 ± 0.1
    -0.7 ± 0.1
        Week 8 [N=327, 331]
    -1.3 ± 0.1
    -1.1 ± 0.1
        Week 12 [N=318, 323]
    -1.5 ± 0.1
    -1.3 ± 0.1
        EoT [N=336, 335]
    -1.4 ± 0.1
    -1.3 ± 0.1
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.128
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.054
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.079
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.148
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Incontinence Episodes Per Day

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Incontinence Episodes Per Day
    End point description
    Urgency Incontinence was defined as the complaint of involuntary leakage accompanied by or immediately proceeded by urgency. The mean number of urgency incontinence episodes was calculated as the average number of times a participant recorded an urgency incontinence episode per day during the 3-day micturition diary period. The analysis population was the FAS-I. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8 and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    132
    129
    Units: urgency incontinence episodes
    least squares mean (standard error)
        Week 4 [N=131, 129]
    -0.97 ± 0.18
    -0.85 ± 0.18
        Week 8 [N=130, 121]
    -1.29 ± 0.22
    -1.19 ± 0.23
        Week 12 [N=125, 119]
    -1.52 ± 0.22
    -1.24 ± 0.22
        EoT [N=132, 129]
    -1.49 ± 0.21
    -1.16 ± 0.21
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.66
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.61
         upper limit
    0.39
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.767
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.72
         upper limit
    0.53
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.372
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.89
         upper limit
    0.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.272
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.92
         upper limit
    0.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Symptom Bother Score

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Symptom Bother Score
    End point description
    Overactive bladder symptoms were assessed using the Symptom Bother Scale of the Overactive Bladder questionnaire (OAB-q). The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 questions, 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). Lower scores on OAB-q symptom bother indicate a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=330, 325]
    -13.73 ± 0.91
    -11.98 ± 0.92
        Week 8 [N=323, 325]
    -18.72 ± 1.00
    -14.88 ± 0.99
        Week 12 [N=314, 318]
    -20.93 ± 1.07
    -18.03 ± 1.06
        EoT [N=332, 330]
    -20.18 ± 1.04
    -18.07 ± 1.05
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.179
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -1.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.29
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.3
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -3.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.6
         upper limit
    -1.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.41
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.055
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -2.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.86
         upper limit
    0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.51
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.154
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -2.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.02
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.48

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Health Related Quality of Life (HRQL) Score

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Health Related Quality of Life (HRQL) Score
    End point description
    The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was 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 higher score on OAB-q HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=330, 325]
    9.08 ± 0.80
    10.43 ± 0.80
        Week 8 [N=323, 325]
    13.06 ± 0.85
    13.53 ± 0.85
        Week 12 [N=314, 318]
    15.90 ± 0.91
    15.00 ± 0.90
        EoT [N=332, 330]
    15.07 ± 0.89
    15.12 ± 0.89
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.233
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -1.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.57
         upper limit
    0.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.13
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.698
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.89
         upper limit
    2.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Week 12 Difference vs. Mirabegron: Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.486
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.62
         upper limit
    3.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.28
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.968
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.52
         upper limit
    2.42
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.26

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

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Coping Score
    End point description
    The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=330, 325]
    10.58 ± 0.96
    12.47 ± 0.97
        Week 8 [N=323, 325]
    16.01 ± 1.00
    15.25 ± 1.00
        Week 12 [N=314, 318]
    18.93 ± 1.09
    18.03 ± 1.08
        EoT [N=332, 330]
    18.05 ± 1.07
    18.02 ± 1.07
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.165
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -1.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.56
         upper limit
    0.78
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.36
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.592
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.02
         upper limit
    3.54
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.41
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.559
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.12
         upper limit
    3.92
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.54
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.985
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.94
         upper limit
    3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.51

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

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Concern Score
    End point description
    The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=330, 325]
    9.06 ± 0.91
    10.87 ± 0.92
        Week 8 [N=323, 325]
    13.34 ± 0.98
    12.99 ± 0.98
        Week 12 [N=314, 318]
    15.64 ± 1.00
    14.47 ± 1.00
        EoT [N=332, 330]
    14.81 ± 0.98
    14.67 ± 0.99
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron:
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.161
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -1.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.35
         upper limit
    0.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.29
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.798
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.36
         upper limit
    3.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.38
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.408
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    1.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.61
         upper limit
    3.95
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.42
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.919
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.6
         upper limit
    2.88
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.39

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

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Sleep Score
    End point description
    The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8 and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=330, 325]
    10.43 ± 1.05
    10.45 ± 1.06
        Week 8 [N=323, 325]
    15.32 ± 1.10
    14.41 ± 1.09
        Week 12 [N=314, 318]
    17.94 ± 1.15
    16.41 ± 1.15
        EoT [N=332, 330]
    16.87 ± 1.13
    16.62 ± 1.13
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.99
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.94
         upper limit
    2.91
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.49
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.554
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.92
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.12
         upper limit
    3.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.55
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.348
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    1.53
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.67
         upper limit
    4.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.63
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.876
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.89
         upper limit
    3.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.6

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Social Interaction Score

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Social Interaction Score
    End point description
    The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. A higher score on OAB-q HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=330, 325]
    5.55 ± 0.74
    6.65 ± 0.74
        Week 8 [N=323, 325]
    8.03 ± 0.79
    8.35 ± 0.79
        Week 12 [N=314, 318]
    9.48 ± 0.79
    9.57 ± 0.79
        EoT [N=332, 330]
    8.96 ± 0.77
    9.67 ± 0.78
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.293
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.16
         upper limit
    0.95
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.05
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.773
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.52
         upper limit
    1.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.12
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.94
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.28
         upper limit
    2.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.12
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.516
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.86
         upper limit
    1.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.1

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in European Quality of Life in 5 Dimensions and 5 Levels (EQ-5D-5L Questionnaire) Utilities

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in European Quality of Life in 5 Dimensions and 5 Levels (EQ-5D-5L Questionnaire) Utilities
    End point description
    The EQ-5D-5L is an international standardized non-disease specific generic instrument for describing and valuing health status. It has a multidimensional measure of health-related QoL, capable of being expressed as a single index value and specifically designed to complement other health status measures. The EQ-5D-5L has five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels (e.g., 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems/unable to perform the activity). Health-state utility (HSU) data are estimates of the preference for a given state of health on a cardinal numeric scale, where a value of 1.0 represents full health, 0.0 represents dead, and negative values represent states worse than death. The analysis population was the FAS. Missing EoT values were imputed using LOCF method.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    arithmetic mean (standard error)
        Week 4 [N=328, 320]
    0.011 ± 0.009
    0.019 ± 0.008
        Week 8 [N=321, 321]
    0.019 ± 0.009
    0.030 ± 0.009
        Week 12 [N=313, 313]
    0.028 ± 0.009
    0.032 ± 0.008
        EoT [N=331, 326]
    0.026 ± 0.009
    0.034 ± 0.008
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4591 [6]
    Method
    t-test, 2 sided
    Confidence interval
    Notes
    [6] - Statistical comparisons were be made using 2-sided tests at α = 0.05 significance level.
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4073 [7]
    Method
    t-test, 2 sided
    Confidence interval
    Notes
    [7] - Statistical comparisons were be made using 2-sided tests at α = 0.05 significance level.
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.774 [8]
    Method
    t-test, 2 sided
    Confidence interval
    Notes
    [8] - Statistical comparisons were be made using 2-sided tests at α = 0.05 significance level.
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5121 [9]
    Method
    t-test, 2 sided
    Confidence interval
    Notes
    [9] - Statistical comparisons were be made using 2-sided tests at α = 0.05 significance level.

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Patient Perception of Bladder Condition (PPBC)

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Patient Perception of Bladder Condition (PPBC)
    End point description
    The PPBC is a validated, global assessment tool using a 6-point Likert scale that asks participants to rate 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. A higher score indicated a worse perception of bladder condition. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=330, 325]
    -0.6 ± 0.1
    -0.5 ± 0.1
        Week 8 [N=323, 325]
    -0.8 ± 0.1
    -0.7 ± 0.1
        Week 12 [N=314, 318]
    -1.0 ± 0.1
    -0.9 ± 0.1
        EoT [N=332, 330]
    -0.9 ± 0.1
    -0.9 ± 0.1
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.223
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.2
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.598
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.2
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.312
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Placebo v Mirabegron
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.525
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.2
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Urgency and Frequency Score (TUFS)

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Urgency and Frequency Score (TUFS)
    End point description
    The TUFS was calculated by adding the PPIUS scores of every void in a participant’s 3-day diary, and dividing this by the number of days recorded in the diary. The analysis population was the FAS. Due to a programming failure in the e-diary data for the number of pads used was not collected. Data not calculable is denoted as "99999" as applicable.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8 and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        units on a scale
    99999 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours
    End point description
    A nocturia episode was defined as waking at night one or more time to void (i.e., any voiding associated with sleep disturbance between the date/time the participant goes to bed with the intention to sleep until the date/time the participant gets up in the morning with the intention to stay awake). A night time episode of incontinence is not considered a nocturia episode. The mean number of nocturia episodes per day (24 hours) was calculated as the average number of times a participant recorded a nocturia episode per day during the 3-day micturition diary period. The analysis population was the full analysis set - nocturia (FAS-N), which consisted of all randomized participants who took at least 1 dose of double-blind study drug and reported 1 micturition at baseline and postbaseline in the 3-day e-diary. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    142
    124
    Units: nocturia episodes
    least squares mean (standard error)
        Week 4 [N=141, 123]
    -0.32 ± 0.07
    -0.45 ± 0.08
        Week 8 [N=135, 118]
    -0.48 ± 0.07
    -0.55 ± 0.08
        Week 12 [N=130, 114]
    -0.51 ± 0.08
    -0.52 ± 0.08
        EoT [N=142, 124]
    -0.49 ± 0.07
    -0.52 ± 0.08
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    266
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.226
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.08
         upper limit
    0.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    266
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.501
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.14
         upper limit
    0.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    266
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.984
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.22
         upper limit
    0.23
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    266
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.78
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.18
         upper limit
    0.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11

    Secondary: Change From Baseline to Week 4, Week 8, Week 12 and EoT in Treatment Satisfaction Visual Analog Scale (TS-VAS)

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    End point title
    Change From Baseline to Week 4, Week 8, Week 12 and EoT in Treatment Satisfaction Visual Analog Scale (TS-VAS)
    End point description
    The TS-VAS is a visual analog scale that asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) to 100 (Yes, completely). The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, and 12
    End point values
    Mirabegron Placebo
    Number of subjects analysed
    337
    339
    Units: units on a scale
    least squares mean (standard error)
        Week 4 [N=328, 324]
    15.6 ± 1.3
    12.5 ± 1.4
        Week 8 [N=321, 325]
    18.6 ± 1.4
    16.1 ± 1.4
        Week 12 [N=313, 317]
    19.1 ± 1.5
    16.9 ± 1.5
        EoT [N=331, 330]
    18.4 ± 1.5
    16.9 ± 1.5
    Statistical analysis title
    Week 4 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.107
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    3.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    6.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.9
    Statistical analysis title
    Week 8 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.19
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    2.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    6.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.9
    Statistical analysis title
    Week 12 Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.297
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    2.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    6.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.1
    Statistical analysis title
    EoT Placebo vs. Mirabegron
    Statistical analysis description
    Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.
    Comparison groups
    Mirabegron v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.493
    Method
    ANCOVA
    Parameter type
    LS Mean of Difference
    Point estimate
    1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    5.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.1

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first double-blind medication intake until 30 days after last double-blind medication intake; 16 weeks
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Mirabegron
    Reporting group description
    Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.

    Reporting group title
    Placebo
    Reporting group description
    Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.

    Serious adverse events
    Mirabegron Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 352 (2.84%)
    8 / 354 (2.26%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Knee arthroplasty
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Glioblastoma
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronotropic incompetence
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Peripheral swelling
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 352 (0.00%)
    1 / 354 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Neuroborreliosis
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 352 (0.28%)
    0 / 354 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    Mirabegron Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 352 (3.41%)
    19 / 354 (5.37%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 352 (1.70%)
    11 / 354 (3.11%)
         occurrences all number
    6
    12
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 352 (1.70%)
    8 / 354 (2.26%)
         occurrences all number
    6
    9

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 May 2016
    The changes include: ● Updated mode of administration of tamsulosin to include capsules in the US and tablets in the EU and Canada. Nonsubstantial changes were as follows: ● Added study name PLUS to protocol title ● Updated patient e-diary – micturition and incontinence section ● Made minor administrative type corrections
    10 May 2017
    The changes include: ● Updated acceptable PSA range to ≥ 4 ng/mL but < 10 ng/mL if a negative biopsy was obtained within the last year Nonsubstantial changes were minor administrative type corrections.
    24 Oct 2017
    The changes include: ● Updated the sample size by reducing the power from 90% to 80%, where approximately 640 patients would be randomized 1:1; with 320 to mirabegron and 320 to placebo ● Updated acceptable PSA range if negative biopsy was obtained within the past 2 years Nonsubstantial changes were implemented in addition to the substantial changes mentioned above.
    22 Jan 2018
    The changes include: ● Updated reference safety information from the US package insert, Canadian monograph and SmPC to the company core data sheet for mirabegron

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The analysis of the EQ-5D endpoint was completed by an external vendor outside of the main study report. Astellas had previously anticipated to post the results in April 2020.
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