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This Was a Multinational Study Comparing the Efficacy and Safety of Two Medicines , Solifenacin Succinate and Mirabegron Taken Together, or Separately, or a Mock Treatment (Placebo) in Subjects With Symptoms of Overactive Bladder (SYNERGY)

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ClinicalTrials.gov Identifier: NCT01972841
Recruitment Status : Completed
First Posted : October 31, 2013
Results First Posted : June 12, 2018
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Urinary Bladder Overactive
Urinary Bladder Diseases\Urologic Diseases
Overactive Bladder
Urgency Incontinence
Interventions Drug: Solifenacin succinate
Drug: Mirabegron
Drug: Placebo to match solifenacin succinate
Drug: Placebo to match mirabegron
Enrollment 3527
Recruitment Details Patients who had symptoms of “wet” overactive bladder (OAB) (urgency, urinary frequency and urgency incontinence) for ≥ 3 months were enrolled at 435 centers in 42 countries. Eligible participants went into a single-blind, 4-week placebo run-in period and completed a micturition diary the last 7 days prior to each study visit.
Pre-assignment Details A total of 6991 participants were screened, 6275 participants received placebo run-in treatment and 3527 participants were randomized into 1 of 6 treatment arms in a 1:1:1:1:2:2 ratio in the 12-week double-blind treatment period. A total of 953 participants were also enrolled in an ambulatory blood pressure monitoring (ABPM) substudy.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description Participants who received matching placebo once a day for 12 weeks. Participants who received mirabegron 25 mg once a day for 12 weeks. Participants who received mirabegron 50 mg once a day for 12 weeks. Participants who received solifenacin 5 mg once a day for 12 weeks. Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks. Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Period Title: Overall Study
Started 447 441 437 434 885 883
Completed 404 397 387 397 802 798
Not Completed 43 44 50 37 83 85
Reason Not Completed
Randomized but Never Received Treatment             2             5             4             2             6             13
Adverse Event             13             8             12             9             21             26
Lack of Efficacy             1             0             0             2             4             1
Lost to Follow-up             4             2             4             2             9             3
Protocol Violation             2             2             3             5             9             4
Withdrawal by participants             21             27             23             16             33             34
Miscellaneous             0             0             4             1             0             4
Did not have end of treatment page             0             0             0             0             1             0
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg Total
Hide Arm/Group Description Participants who received matching placebo once a day for 12 weeks. Participants who received mirabegron 25 mg once a day for 12 weeks. Participants who received mirabegron 50 mg once a day for 12 weeks. Participants who received solifenacin 5 mg once a day for 12 weeks. Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks. Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 447 441 437 434 885 883 3527
Hide Baseline Analysis Population Description
Randomized analysis set (RAS), comprised all randomized patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Year
Number Analyzed 447 participants 441 participants 437 participants 434 participants 885 participants 883 participants 3527 participants
57.46  (13.2) 56.77  (13.46) 56.69  (13.28) 57.88  (12.92) 56.94  (13.78) 57.3  (13.46) 57.16  (13.42)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 447 participants 441 participants 437 participants 434 participants 885 participants 883 participants 3527 participants
Female
345
  77.2%
343
  77.8%
338
  77.3%
342
  78.8%
686
  77.5%
684
  77.5%
2738
  77.6%
Male
102
  22.8%
98
  22.2%
99
  22.7%
92
  21.2%
199
  22.5%
199
  22.5%
789
  22.4%
Mean number of incontinence episodes/24 h   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Incontinence episodes
Number Analyzed 418 participants 409 participants 411 participants 415 participants 827 participants 826 participants 3306 participants
3.41  (3.37) 3.42  (3.40) 3.18  (3.47) 3.58  (3.51) 3.22  (3.17) 3.16  (3.08) 3.29  (3.29)
[1]
Measure Description: An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period.
[2]
Measure Analysis Population Description: Full analysis set (FAS) comprised all RAS patients who took ≥ 1 dose of double-blind treatment after randomization, reported ≥ 1 micturition in the baseline diary and ≥ 1 micturition postbaseline, reported ≥ 1 incontinence episode in the baseline diary and excluded participants from one site. Participants with available data were included.
Mean number of micturitions/24 h   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Micturitions
Number Analyzed 418 participants 409 participants 411 participants 415 participants 827 participants 826 participants 3306 participants
10.97  (2.86) 10.81  (2.63) 11.19  (3.27) 10.76  (2.47) 10.73  (2.88) 10.74  (2.36) 10.84  (2.73)
[1]
Measure Description: A micturition was defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Mean volume voided per micturition   [1] [2] 
Least Squares Mean (Standard Deviation)
Unit of measure:  mL
Number Analyzed 414 participants 407 participants 409 participants 413 participants 823 participants 824 participants 3290 participants
157.94  (58.78) 152.46  (60.96) 155.31  (60.78) 151.94  (59.29) 159.32  (58.29) 153.57  (59.67) 155.43  (59.49)
[1]
Measure Description: The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Number of incontinence episodes/week   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Incontinence episodes
Number Analyzed 418 participants 409 participants 411 participants 415 participants 827 participants 826 participants 3306 participants
23.6  (23.6) 23.5  (23.6) 21.7  (23.8) 24.8  (24.5) 22.1  (21.7) 21.7  (21.3) 22.7  (22.7)
[1]
Measure Description: The number of incontinence episodes was calculated from total number of incontinence episodes recorded by the participant per day on valid diary days during the 7-day micturition diary period.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Mean number of urgency incontinence episodes/24 h   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Urgency incontinence episodes
Number Analyzed 415 participants 407 participants 405 participants 414 participants 823 participants 822 participants 3286 participants
3.14  (3.23) 3.00  (3.09) 2.89  (3.31) 3.23  (3.34) 2.85  (2.81) 2.80  (2.64) 2.94  (3.00)
[1]
Measure Description: An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes per 24 hours was calculated from number of times a participant recorded an urgency incontinence episode per day on valid diary days during the 7-day micturition diary period prior to each visit.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Number of urgency incontinence episodes/week   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Urgency incontinence episodes
Number Analyzed 415 participants 407 participants 405 participants 414 participants 823 participants 822 participants 3286 participants
21.7  (22.6) 20.6  (21.4) 19.8  (22.7) 22.4  (23.3) 19.5  (19.3) 19.2  (18.2) 20.3  (20.7)
[1]
Measure Description: The number of urgency incontinence episodes was number of times a participant recorded an urgency incontinence episode on valid diary days during the 7-day micturition diary period prior to each visit.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Mean number of urgency episodes (Grade 3 or 4)/24 h   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Urgency episodes
Number Analyzed 417 participants 409 participants 411 participants 415 participants 827 participants 826 participants 3305 participants
6.52  (4.05) 6.22  (3.89) 6.46  (4.88) 6.48  (3.88) 6.22  (3.70) 6.22  (3.56) 6.32  (3.92)
[1]
Measure Description: An urgency episode (Grade 3 or 4) was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer; it was recorded when a micturition or incontinence episode was recorded and the severity of urinary urgency recorded was 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS). The mean number of urgency episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Mean number of nocturia episodes/24 h   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Nocturia episodes
Number Analyzed 368 participants 344 participants 356 participants 352 participants 710 participants 704 participants 2834 participants
1.57  (1.06) 1.53  (1.02) 1.59  (1.09) 1.59  (0.96) 1.56  (1.07) 1.52  (0.97) 1.56  (1.03)
[1]
Measure Description: A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the patients gets up in the morning with the intention to stay awake). The mean number of nocturia episodes per 24hr was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Number of nocturia episodes/week   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Nocturia episode
Number Analyzed 368 participants 344 participants 356 participants 352 participants 710 participants 704 participants 2834 participants
10.9  (7.4) 10.6  (7.1) 11.0  (7.6) 11.0  (6.6) 10.8  (7.4) 10.5  (6.7) 10.8  (7.2)
[1]
Measure Description: The number of nocturia episodes was calculated from sun of each nocturia episodes recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Mean number of pads used/24 h   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Pads
Number Analyzed 256 participants 252 participants 251 participants 262 participants 513 participants 511 participants 2045 participants
2.87  (2.99) 2.86  (2.70) 2.62  (3.18) 2.87  (3.14) 2.50  (2.58) 2.58  (2.39) 2.67  (2.76)
[1]
Measure Description: The mean number of pads used per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
Number of pads used/week   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Pads
Number Analyzed 256 participants 252 participants 251 participants 262 participants 513 participants 511 participants 2045 participants
19.8  (20.9) 19.6  (18.7) 17.9  (21.7) 19.9  (21.8) 17.1  (17.7) 17.7  (16.4) 19.3  (19.0)
[1]
Measure Description: The number of pads used was calculated from sum of each record with a new pad checked on valid diary days during the 7-day micturition diary period prior to each visit.
[2]
Measure Analysis Population Description: FAS participants with available data were included in the analysis.
1.Primary Outcome
Title Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours
Hide Description An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all RAS patients who took ≥ 1 dose of double-blind treatment after randomization, reported ≥ 1 micturition in the baseline diary and ≥ 1 micturition postbaseline, reported ≥ 1 incontinence episode in the baseline diary and excluded participants from one site. Last observation carried forward (LOCF) was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 412 409 406 413 823 816
Least Squares Mean (Standard Error)
Unit of Measure: incontinence episodes
-1.34  (0.10) -1.70  (0.10) -1.76  (0.10) -1.79  (0.10) -2.04  (0.07) -1.98  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments Nominal p-value
Method Stratified rank ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.49 to -0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments Nominal p-value
Method Stratified rank ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.44 to 0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.58 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.47 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
2.Primary Outcome
Title Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours
Hide Description A micturition was defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 412 409 406 413 823 816
Least Squares Mean (Standard Error)
Unit of Measure: micturitions
-1.64  (0.12) -2.00  (0.12) -2.03  (0.12) -2.20  (0.12) -2.49  (0.08) -2.59  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.57 to -0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.67 to -0.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.76 to -0.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-0.84 to -0.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
3.Secondary Outcome
Title Change From Baseline to EoT in Mean Volume Voided Per Micturition
Hide Description The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 413 407 408 411 821 821
Least Squares Mean (Standard Error)
Unit of Measure: mL
8.44  (2.55) 13.32  (2.57) 21.99  (2.57) 30.99  (2.56) 34.84  (1.81) 39.73  (1.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.219
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 3.85
Confidence Interval (2-Sided) 95%
-2.29 to 10.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.13
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 8.75
Confidence Interval (2-Sided) 95%
2.61 to 14.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.13
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 21.52
Confidence Interval (2-Sided) 95%
15.35 to 27.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.14
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value
Method ANCOVA
Comments No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 17.74
Confidence Interval (2-Sided) 95%
11.58 to 23.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.14
Estimation Comments Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferroni-based testing procedure.
4.Secondary Outcome
Title Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score
Hide Description The OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consisted of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicates an improvement.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 400 392 398 399 800 795
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-19.45  (0.98) -23.93  (0.99) -26.14  (0.98) -26.44  (0.98) -31.06  (0.69) -32.24  (0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -4.63
Confidence Interval (2-Sided) 95%
-6.98 to -2.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.20
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -5.80
Confidence Interval (2-Sided) 95%
-8.17 to -3.44
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -7.13
Confidence Interval (2-Sided) 95%
-9.50 to -4.76
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -6.10
Confidence Interval (2-Sided) 95%
-8.46 to -3.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.20
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to EoT in Treatment Satisfaction-Visual Analogue Scale (TS-VAS)
Hide Description The TS-VAS was a visual analogue scale which asked participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 399 391 398 399 798 794
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.42  (0.11) 2.16  (0.11) 2.18  (0.11) 2.28  (0.11) 2.53  (0.08) 2.55  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.03 to 0.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
0.00 to 0.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.10 to 0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method ANCOVA
Comments No adjustment for multiplicity was made for this comparison.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.10 to 0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Incontinence Episodes at Weeks 4, 8, 12 and EoT
Hide Description The number of incontinence episodes was calculated as the total number of incontinence episodes on valid diary days recorded during the 7-day micturition diary period.
Time Frame Weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Mean (Standard Error)
Unit of Measure: incontinence episodes
Week 4 Number Analyzed 406 participants 406 participants 402 participants 402 participants 817 participants 810 participants
18.09  (1.17) 15.65  (1.08) 12.90  (1.06) 15.31  (1.11) 12.51  (0.67) 11.44  (0.70)
Week 8 Number Analyzed 397 participants 385 participants 386 participants 386 participants 784 participants 769 participants
14.45  (1.12) 12.84  (1.05) 11.31  (1.09) 12.19  (1.06) 9.70  (0.65) 9.33  (0.68)
Week 12 Number Analyzed 374 participants 369 participants 369 participants 379 participants 754 participants 750 participants
14.06  (1.17) 10.60  (0.98) 9.50  (0.98) 11.25  (1.03) 7.62  (0.57) 8.21  (0.68)
End of treatment Number Analyzed 412 participants 409 participants 406 participants 413 participants 823 participants 816 participants
13.70  (1.08) 11.19  (0.95) 9.79  (0.94) 11.21  (0.98) 8.02  (0.55) 8.18  (0.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.72 to 1.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.282
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.75 to 1.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.59 to 0.85
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.172
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.73 to 1.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Incontinence Episodes
Hide Description [Not Specified]
Time Frame Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: incontinence episodes
Week 4 Number Analyzed 406 participants 406 participants 402 participants 402 participants 817 participants 810 participants
-5.23  (0.66) -7.59  (0.66) -8.99  (0.67) -8.92  (0.67) -9.62  (0.47) -10.51  (0.47)
Week 8 Number Analyzed 397 participants 385 participants 386 participants 386 participants 784 participants 769 participants
-8.79  (0.71) -10.57  (0.72) -10.97  (0.72) -11.89  (0.72) -12.53  (0.50) -12.78  (0.51)
Week 12 Number Analyzed 374 participants 369 participants 369 participants 379 participants 754 participants 750 participants
-9.05  (0.72) -12.33  (0.72) -12.58  (0.72) -12.75  (0.71) -14.50  (0.51) -13.94  (0.51)
End of treatment Number Analyzed 412 participants 409 participants 406 participants 413 participants 823 participants 816 participants
-9.42  (0.68) -11.93  (0.68) -12.39  (0.68) -12.65  (0.68) -14.29  (0.48) -13.98  (0.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean difference
Estimated Value -1.64
Confidence Interval (2-Sided) 95%
-3.27 to -0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.83
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.33
Confidence Interval (2-Sided) 95%
-2.96 to 0.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.83
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least square mean difference
Estimated Value -2.36
Confidence Interval (2-Sided) 95%
-4.00 to -0.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.83
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.59
Confidence Interval (2-Sided) 95%
-3.23 to 0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.84
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline to Weeks 4, 8 and 12 in Mean Number of Incontinence Episodes Per 24 Hours
Hide Description [Not Specified]
Time Frame Baseline and weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: incontinence episodes
Week 4 Number Analyzed 406 participants 406 participants 402 participants 402 participants 817 participants 810 participants
-0.74  (0.10) -1.07  (0.10) -1.24  (0.10) -1.24  (0.10) -1.38  (0.07) -1.50  (0.07)
Week 8 Number Analyzed 397 participants 385 participants 386 participants 386 participants 784 participants 769 participants
-1.20  (0.10) -1.51  (0.10) -1.57  (0.10) -1.66  (0.10) -1.79  (0.07) -1.84  (0.07)
Week 12 Number Analyzed 374 participants 369 participants 369 participants 379 participants 754 participants 750 participants
-1.30  (0.11) -1.76  (0.11) -1.81  (0.11) -1.80  (0.10) -2.08  (0.07) -1.98  (0.07)
9.Secondary Outcome
Title Change From Baseline to Weeks 4, 8 and 12 in Mean Number of Micturitions Per 24 Hours
Hide Description [Not Specified]
Time Frame Baseline and weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point data were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: micturitions
Week 4 Number Analyzed 406 participants 406 participants 402 participants 402 participants 817 participants 810 participants
-1.02  (0.11) -1.46  (0.11) -1.44  (0.11) -1.39  (0.11) -1.67  (0.08) -1.91  (0.08)
Week 8 Number Analyzed 397 participants 385 participants 386 participants 386 participants 784 participants 769 participants
-1.43  (0.11) -1.95  (0.12) -1.89  (0.12) -1.84  (0.12) -2.23  (0.08) -2.42  (0.08)
Week 12 Number Analyzed 374 participants 369 participants 369 participants 379 participants 754 participants 750 participants
-1.51  (0.12) -2.01  (0.12) -2.03  (0.12) -2.22  (0.12) -2.47  (0.08) -2.60  (0.08)
10.Secondary Outcome
Title Change From Baseline to Weeks 4, 8 and 12 in Mean Volume Voided Per Micturition
Hide Description [Not Specified]
Time Frame Baseline and weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: mL
Week 4 Number Analyzed 403 participants 398 participants 399 participants 395 participants 798 participants 802 participants
6.95  (2.13) 10.08  (2.14) 15.52  (2.14) 24.23  (2.15) 25.54  (1.51) 28.99  (1.51)
Week 8 Number Analyzed 395 participants 382 participants 380 participants 387 participants 770 participants 771 participants
9.00  (2.48) 10.96  (2.52) 17.73  (2.53) 27.55  (2.50) 32.94  (1.78) 36.51  (1.77)
Week 12 Number Analyzed 373 participants 362 participants 364 participants 378 participants 750 participants 750 participants
8.70  (2.70) 12.88  (2.74) 22.40  (2.73) 31.89  (2.68) 35.52  (1.90) 41.28  (1.90)
11.Secondary Outcome
Title Change From Baseline to EoT in Corrected Micturition Frequency
Hide Description Corrected micturition frequency was defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 412 409 406 413 823 816
Least Squares Mean (Standard Error)
Unit of Measure: micturitions
0.15  (0.24) -0.17  (0.24) -0.97  (0.24) -1.28  (0.24) -1.10  (0.17) -1.52  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.520
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.39 to 0.76
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.413
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.82 to 0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-1.50 to -0.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.060
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean diffrence
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-1.13 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.30
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Number of Urgency Incontinence Episodes at Weeks 4, 8, 12 and EoT
Hide Description An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was the number of times a participant recorded an urgency incontinence episode on valid diary days during the 7-day micturition diary period prior to each visit.
Time Frame Weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Mean (Standard Error)
Unit of Measure: urgency incontinence episodes
Week 4 Number Analyzed 403 participants 404 participants 396 participants 401 participants 813 participants 806 participants
15.76  (1.10) 13.36  (0.99) 11.46  (1.00) 13.19  (1.06) 10.22  (0.58) 9.33  (0.58)
Week 8 Number Analyzed 394 participants 383 participants 380 participants 385 participants 780 participants 765 participants
12.77  (1.07) 10.65  (0.94) 10.09  (1.02) 10.41  (1.00) 7.58  (0.53) 7.31  (0.54)
Week 12 Number Analyzed 371 participants 367 participants 363 participants 378 participants 750 participants 746 participants
12.00  (1.09) 8.84  (0.89) 8.32  (0.94) 9.29  (0.96) 5.86  (0.46) 6.27  (0.49)
End of treatment Number Analyzed 409 participants 407 participants 400 participants 412 participants 819 participants 812 participants
11.69  (1.00) 9.37  (0.86) 8.63  (0.89) 9.29  (0.91) 6.25  (0.45) 6.15  (0.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.110
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.70 to 1.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.288
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.73 to 1.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.53 to 0.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of urgency incontinence episodes during the 7-day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.084
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.68 to 1.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Urgency Incontinence Episodes
Hide Description [Not Specified]
Time Frame Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: urgency incontinence episodes
Week 4 Number Analyzed 403 participants 404 participants 396 participants 401 participants 813 participants 806 participants
-5.49  (0.63) -7.07  (0.63) -8.39  (0.63) -8.53  (0.63) -9.44  (0.44) -10.23  (0.44)
Week 8 Number Analyzed 394 participants 383 participants 380 participants 385 participants 780 participants 765 participants
-8.30  (0.66) -9.93  (0.67) -10.07  (0.67) -11.10  (0.67) -12.18  (0.47) -12.18  (0.47)
Week 12 Number Analyzed 371 participants 367 participants 363 participants 378 participants 750 participants 746 participants
-8.96  (0.65) -11.39  (0.66) -11.66  (0.66) -12.10  (0.65) -13.87  (0.46) -13.53  (0.46)
End of treatment Number Analyzed 409 participants 407 participants 400 participants 412 participants 819 participants 812 participants
-9.26  (0.62) -11.03  (0.62) -11.44  (0.62) -12.03  (0.62) -13.64  (0.44) -13.64  (0.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.114
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.61
Confidence Interval (2-Sided) 95%
-3.09 to -0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.62
Confidence Interval (2-Sided) 95%
-3.10 to -0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -2.61
Confidence Interval (2-Sided) 95%
-4.09 to -1.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -2.21
Confidence Interval (2-Sided) 95%
-3.70 to -0.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.76
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours
Hide Description The mean number of urgency incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
Time Frame Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: urgency incontinence episodes
Week 4 Number Analyzed 403 participants 404 participants 396 participants 401 participants 813 participants 806 participants
-0.78  (0.09) -1.00  (0.09) -1.15  (0.09) -1.19  (0.09) -1.35  (0.06) -1.47  (0.06)
Week 8 Number Analyzed 394 participants 383 participants 380 participants 385 participants 780 participants 765 participants
-1.15  (0.10) -1.43  (0.10) -1.44  (0.10) -1.56  (0.10) -1.74  (0.07) -1.79  (0.07)
Week 12 Number Analyzed 371 participants 367 participants 363 participants 378 participants 750 participants 746 participants
-1.29  (0.10) -1.63  (0.10) -1.67  (0.10) -1.72  (0.10) -1.99  (0.07) -1.93  (0.07)
End of treatment Number Analyzed 409 participants 407 participants 400 participants 412 participants 819 participants 812 participants
-1.33  (0.09) -1.58  (0.09) -1.62  (0.09) -1.71  (0.09) -1.95  (0.06) -1.94  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.46 to -0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.45 to -0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean diffeence
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.59 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50mg ) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Standard Error of the Mean
Estimated Value -0.32
Confidence Interval (2-Sided) 05%
-0.54 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours
Hide Description An urgency episode was a complaint of a sudden, compelling desire to pass urine, which was difficult to defer; it was recorded when a micturition or incontinence episode was recorded and the severity of urinary urgency recorded was 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS). The mean number of urgency episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
Time Frame Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 urgency episode at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: urgency episodes
Week 4 Number Analyzed 405 participants 406 participants 402 participants 402 participants 817 participants 810 participants
-1.34  (0.15) -1.95  (0.14) -1.91  (0.15) -2.14  (0.15) -2.42  (0.10) -2.66  (0.10)
Week 8 Number Analyzed 396 participants 385 participants 386 participants 386 participants 784 participants 769 participants
-1.85  (0.15) -2.54  (0.15) -2.43  (0.15) -2.90  (0.15) -3.13  (0.11) -3.28  (0.11)
Week 12 Number Analyzed 373 participants 369 participants 369 participants 379 participants 754 participants 750 participants
-2.05  (0.16) -2.85  (0.16) -2.70  (0.16) -3.11  (0.16) -3.45  (0.11) -3.50  (0.11)
End of treatment Number Analyzed 411 participants 409 participants 406 participants 413 participants 823 participants 816 participants
-2.06  (0.15) -2.74  (0.15) -2.63  (0.15) -3.05  (0.15) -3.38  (0.11) -3.51  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.69 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.82 to -0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-1.01 to -0.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-1.24 to 0.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.19
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Number of Nocturia Episodes at Weeks 4, 8, 12 and EoT
Hide Description A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant went to bed with the intention to sleep until the time the patients got up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode on valid diary days during the 7-day micturition diary period prior to each visit.
Time Frame Weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Mean (Standard Error)
Unit of Measure: nocturia episodes
Week 4 Number Analyzed 359 participants 341 participants 349 participants 341 participants 705 participants 693 participants
9.62  (0.43) 8.46  (0.36) 9.11  (0.47) 9.22  (0.42) 8.40  (0.25) 8.09  (0.25)
Week 8 Number Analyzed 349 participants 327 participants 336 participants 329 participants 676 participants 655 participants
8.99  (0.44) 8.07  (0.34) 8.61  (0.45) 8.37  (0.38) 7.63  (0.25) 7.11  (0.24)
Week 12 Number Analyzed 336 participants 312 participants 321 participants 320 participants 652 participants 641 participants
8.91  (0.43) 7.99  (0.37) 8.34  (0.48) 8.17  (0.39) 7.26  (0.24) 6.67  (0.23)
End of treatment Number Analyzed 363 participants 344 participants 353 participants 350 participants 708 participants 697 participants
8.83  (0.42) 7.79  (0.35) 8.14  (0.45) 8.12  (0.37) 7.33  (0.24) 6.67  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.81 to 0.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.74 to 0.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.049
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.84 to 1.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.79 to 0.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Nocturia Episodes
Hide Description [Not Specified]
Time Frame Baseline and weeks 4, 8, 12, and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: nocturia episodes
Week 4 Number Analyzed 359 participants 341 participants 349 participants 341 participants 705 participants 693 participants
-1.27  (0.27) -2.25  (0.28) -1.80  (0.27) -1.79  (0.28) -2.39  (0.19) -2.50  (0.19)
Week 8 Number Analyzed 349 participants 327 participants 336 participants 329 participants 676 participants 655 participants
-1.94  (0.27) -2.70  (0.28) -2.41  (0.28) -2.60  (0.28) -3.13  (0.20) -3.48  (0.20)
Week 12 Number Analyzed 336 participants 312 participants 321 participants 320 participants 652 participants 641 participants
-1.95  (0.29) -2.77  (0.30) -2.73  (0.29) -2.89  (0.29) -3.49  (0.21) -3.96  (0.21)
End of treatment Number Analyzed 363 participants 344 participants 353 participants 350 participants 708 participants 697 participants
-2.05  (0.27) -2.91  (0.28) -2.75  (0.28) -2.81  (0.28) -3.42  (0.20) -3.96  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.61
Confidence Interval (2-Sided) 95%
-1.28 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.16
Confidence Interval (2-Sided) 95%
-1.83 to -0.48
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-1.18 to 0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.21
Confidence Interval (2-Sided) 95%
-1.88 to -0.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours
Hide Description The mean number of nocturia episodes per 24hr was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
Time Frame Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: nocturia episodes
Week 4 Number Analyzed 359 participants 341 participants 349 participants 341 participants 705 participants 693 participants
-0.17  (0.04) -0.31  (0.04) -0.25  (0.04) -0.24  (0.04) -0.33  (0.03) -0.35  (0.03)
Week 8 Number Analyzed 349 participants 327 participants 336 participants 329 participants 676 participants 655 participants
-0.27  (0.04) -0.37  (0.04) -0.35  (0.04) -0.36  (0.04) -0.44  (0.03) -0.50  (0.03)
Week 12 Number Analyzed 336 participants 312 participants 321 participants 320 participants 652 participants 641 participants
-0.26  (0.04) -0.38  (0.04) -0.39  (0.04) -0.41  (0.04) -0.49  (0.03) -0.56  (0.03)
End of treatmemt Number Analyzed 363 participants 344 participants 353 participants 350 participants 708 participants 697 participants
-0.27  (0.04) -0.40  (0.04) -0.39  (0.04) -0.39  (0.04) -0.48  (0.03) -0.56  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.19 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.26 to -0.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.100
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.18 to 0.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.26 to -0.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Number of Pads Used at Weeks 4, 8, 12 and EoT
Hide Description The number of pads used was the number of times a participant recorded a new pad used on valid diary days during the 7-day micturition diary period prior to each visit.
Time Frame Weeks 4, 8 and 12 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 pad used at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Mean (Standard Error)
Unit of Measure: pads
Week 4 Number Analyzed 248 participants 250 participants 247 participants 257 participants 506 participants 499 participants
15.62  (1.33) 13.46  (1.24) 10.05  (1.21) 11.41  (1.23) 9.71  (0.70) 9.34  (0.68)
Week 8 Number Analyzed 239 participants 237 participants 240 participants 243 participants 485 participants 472 participants
12.75  (1.22) 10.79  (1.05) 9.53  (1.39) 8.45  (1.03) 8.07  (0.65) 7.58  (0.62)
Week 12 Number Analyzed 226 participants 225 participants 229 participants 241 participants 468 participants 461 participants
12.62  (1.21) 9.65  (1.00) 8.44  (1.26) 8.21  (0.95) 6.60  (0.58) 6.64  (0.61)
End of treatment Number Analyzed 252 participants 252 participants 249 participants 262 participants 510 participants 502 participants
12.29  (1.11) 10.15  (0.97) 8.16  (1.17) 8.53  (0.94) 7.04  (0.56) 6.80  (0.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.938
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.80 to 1.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.79 to 1.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Standard Error of the Mean
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.58 to 0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Rate ratio of number of incontinence episodes during the 7-day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments [Not Specified]
Method Negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.64 to 1.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Pads Used
Hide Description [Not Specified]
Time Frame Baseline and weeks 4, 8, 12 and EOT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 pad used at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: pads
Week 4 Number Analyzed 248 participants 250 participants 247 participants 257 participants 506 participants 499 participants
-3.69  (0.71) -5.68  (0.71) -7.83  (0.71) -8.23  (0.70) -7.61  (0.50) -8.58  (0.50)
Week 8 Number Analyzed 239 participants 237 participants 240 participants 243 participants 485 participants 472 participants
-6.24  (0.77) -8.44  (0.77) -8.43  (0.76) -10.67  (0.76) -9.49  (0.54) -10.59  (0.54)
Week 12 Number Analyzed 226 participants 225 participants 229 participants 241 participants 468 participants 461 participants
-6.29  (0.75) -9.06  (0.75) -9.41  (0.75) -10.80  (0.73) -10.66  (0.52) -11.23  (0.53)
End of treatment Number Analyzed 252 participants 252 participants 249 participants 262 participants 510 participants 502 participants
-6.60  (0.71) -8.76  (0.71) -9.80  (0.72) -10.63  (0.70) -10.67  (0.50) -11.21  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.958
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-1.73 to 1.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.86
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.500
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-2.27 to 1.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.86
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Mirabegron 25 mg, Solifenacin 5 mg + Mirabegron 25 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.91
Confidence Interval (2-Sided) 95%
-3.62 to -0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.87
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
Comments Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.108
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.41
Confidence Interval (2-Sided) 95%
-3.13 to 0.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.88
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Pads Used Per 24 Hours
Hide Description The mean number of pads used per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.
Time Frame Baseline and weeks 4, 8 and 12 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS participants with available data at each time point were included in the analysis. LOCF was used for EoT. Only participants with ≥ 1 pad used at baseline were included in the analysis.
Arm/Group Title Placebo Mirabegron 25 mg Mirabegron 50 mg Solifenacin 5 mg Solifenacin 5 mg + Mirabegron 25 mg Solifenacin 5 mg + Mirabegron 50 mg
Hide Arm/Group Description:
Participants who received matching placebo once a day for 12 weeks.
Participants who received mirabegron 25 mg once a day for 12 weeks.
Participants who received mirabegron 50 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Overall Number of Participants Analyzed 418 410 411 415 827 827
Least Squares Mean (Standard Error)
Unit of Measure: pads
Week 4 Number Analyzed 248 participants 250 participants 247 participants 257 participants 506 participants 499 participants