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A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin) (BESIDE)

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ClinicalTrials.gov Identifier: NCT01908829
Recruitment Status : Completed
First Posted : July 26, 2013
Results First Posted : October 9, 2017
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Urinary Bladder Diseases
Urinary Bladder Overactive
Urologic Diseases
Interventions Drug: mirabegron 25 mg
Drug: mirabegron 50 mg
Drug: solifenacin 5 mg
Drug: solifenacin 10 mg
Drug: mirabegron 25 mg matching placebo
Drug: mirabegron 50 mg matching placebo
Drug: solifenacin 5 mg matching placebo
Drug: solifenacin 10 mg matching placebo
Enrollment 2174
Recruitment Details This multicenter study was conducted at 281 centers globally. Randomization was stratified by sex, age group (< 65, ≥ 65 years), 4-week incontinence episode reduction group (< 50%, ≥ 50%) and geographic region.
Pre-assignment Details Participants who met the screening inclusion/exclusion criteria went through a two week wash-out period and maintained a micturition diary during that the wash-out period. A total of 3815 participants were screened of which 2401 participants received solifenacin 5 mg run-in medication. A total of 2174 participants were randomized.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Period Title: Overall Study
Started 727 728 719
Treated With Double-blind Drug 725 728 719
Completed 678 679 680
Not Completed 49 49 39
Reason Not Completed
Adverse Event             13             11             13
Lost to Follow-up             4             2             1
Randomized no double-blind drug received             1             0             1
Discontinued (no EoT page)             2             0             0
Miscellaneous             0             2             0
Protocol Violation             2             2             0
Lack of Efficacy             1             3             2
Withdrawal by Subject             26             29             22
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg Total
Hide Arm/Group Description Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period. Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period. Total of all reporting groups
Overall Number of Baseline Participants 727 728 719 2174
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Year
Number Analyzed 727 participants 728 participants 719 participants 2174 participants
58.2  (13.1) 56.9  (13.5) 57.4  (13.2) 57.5  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 727 participants 728 participants 719 participants 2174 participants
Female
604
  83.1%
604
  83.0%
600
  83.4%
1808
  83.2%
Male
123
  16.9%
124
  17.0%
119
  16.6%
366
  16.8%
1.Primary Outcome
Title Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours
Hide Description The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. The analysis population consisted of the Full Analysis Set (FAS) which comprised of all the Randomized Analysis Set's (RAS) participants who met the following criteria: took at least 1 dose of double-blind study drug after randomization, reported at least 1 micturition in the baseline diary & at least 1 micturition postbaseline & reported at least 1 incontinence episode in the baseline diary. For participants who withdrew before EoT (week 12) and have no measurement available for that diary period, the Last Observation Carried Forward (LOCF) value during the double-blind study period was used as EoT value to derive the primary variable.
Time Frame Baseline and end of treatment (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of the FAS. LOCF was used for EoT.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 706 704 697
Least Squares Mean (Standard Error)
Unit of Measure: incontinence episodes
-1.8  (0.08) -1.53  (0.08) -1.67  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P values for pairwise comparisons were from the stratified rank ANCOVA model. P < 0.05 indicated superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Means
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.47 to -0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes Per 24 Hours
Hide Description The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period.
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: incontinence episodes
Week 4 Number Analyzed 690 participants 690 participants 679 participants
-1.24  (0.07) -0.91  (0.07) -1.12  (0.07)
Week 8 Number Analyzed 661 participants 674 participants 673 participants
-1.68  (0.07) -1.29  (0.07) -1.49  (0.07)
Week 12 Number Analyzed 653 participants 645 participants 664 participants
-1.81  (0.08) -1.57  (0.08) -1.67  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% CIs are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.52 to -0.14
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% CIs are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.60 to -0.18
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95% CIs are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4-week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P-values for pairwise comparisons are from the stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.46 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Number of Micturitions Per 24 Hours
Hide Description The average number of micturitions (voluntary urinations (excluding incontinence only episodes)) per 24 hours was derived from number of micturitions recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period (excluding incontinence only episodes).
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: micturitions
Week 4 Number Analyzed 690 participants 690 participants 679 participants
-0.95  (0.07) -0.69  (0.07) -0.79  (0.07)
Week 8 Number Analyzed 661 participants 674 participants 673 participants
-1.36  (0.08) -0.94  (0.08) -1.00  (0.08)
Week 12 Number Analyzed 653 participants 645 participants 664 participants
-1.63  (0.08) -1.16  (0.09) -1.11  (0.08)
EoT Number Analyzed 706 participants 704 participants 697 participants
-1.59  (0.08) -1.14  (0.08) -1.12  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.010
Comments P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.47 to -0.06
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.65 to -0.19
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.70 to -0.23
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.67 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.12
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Incontinence Episodes Reported During the 3-Day Diary
Hide Description The number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from total number of incontinence episodes on valid diary days recorded during the 3-day micturition diary period.
Time Frame Weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Mean (Standard Error)
Unit of Measure: incontinence episodes
Week 4 Number Analyzed 690 participants 690 participants 679 participants
5.81  (0.30) 6.68  (0.31) 6.41  (0.33)
Week 8 Number Analyzed 661 participants 674 participants 673 participants
4.55  (0.30) 5.43  (0.30) 5.28  (0.32)
Week 12 Number Analyzed 653 participants 645 participants 664 participants
4.03  (0.29) 4.56  (0.28) 4.62  (0.31)
EoT Number Analyzed 706 participants 704 participants 697 participants
4.25  (0.29) 4.87  (0.28) 4.72  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during Week 4 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.005
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.79 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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during Week 8 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.66 to 0.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during Week 12 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.021
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.70 to 0.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT rate ratio, 95% CIs, & p-value for number of incontinence episodes (IEs) during EoT 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week IE reduction group as factors, log of (number of IEs/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.014
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.71 to 0.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Mean Volume Voided (MVV) Per Micturition
Hide Description MVV per micturition was defined as MVV (mL) per micturition during last 3 days of the 3-day micturition diary period. MVV per micturition was calculated as the sum of each volume voided for each record with volume voided > 0 on valid diary days divided by the total number of records with a volume voided > 0 on valid diary days during the 3-day micturition diary period.
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: mL
Week 4 Number Analyzed 665 participants 669 participants 664 participants
15.06  (1.55) 11.20  (1.55) 14.99  (1.55)
Week 8 Number Analyzed 638 participants 648 participants 655 participants
25.21  (1.89) 14.02  (1.87) 21.08  (1.86)
Week 12 Number Analyzed 627 participants 617 participants 642 participants
29.54  (2.06) 17.16  (2.08) 20.99  (2.04)
EoT Number Analyzed 680 participants 682 participants 682 participants
28.05  (1.97) 16.52  (1.97) 20.30  (1.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.078
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 3.86
Confidence Interval (2-Sided) 95%
-0.43 to 8.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 11.19
Confidence Interval (2-Sided) 95%
5.98 to 16.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.66
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 12.38
Confidence Interval (2-Sided) 95%
6.65 to 18.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.92
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 11.52
Confidence Interval (2-Sided) 95%
6.06 to 16.99
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.79
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to EoT in Corrected Micturition Frequency (CMF)
Hide Description CMF was defined as the mean number of micturitions per 24 hours that participants would have at EoT if their fluid intake had remained unchanged since baseline. This was calculated by the MVV per Micturition at baseline multiplied by the mean number of micturitions per 24 hours at baseline divided by the MVV per micturition at EoT.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used. The analysis population consisted of the FAS.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 706 704 697
Least Squares Mean (Standard Error)
Unit of Measure: micturitions
-0.96  (0.10) -0.52  (0.10) -0.71  (0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.003
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-0.73 to -0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Mean Number of Urgency Incontinence (UI) Episodes Per 24 Hours
Hide Description UI was defined as the complaint of involuntary urine leakage accompanied by or immediately preceded by urgency. UI was measured using the Patient Perception of Intensity of Urgency Scale (PPIUS), a patient reported outcome validated 5-point categorical scale rating the degree of associated urinary urgency severity (0=No urgency, I felt no need to empty my bladder, but did so for other reasons. 1=Mild, I could postpone voiding as long as necessary, without fear of wetting myself. 2= Moderate, I could postpone voiding for a short while, without fear of wetting myself. 3=Severe, I could not postpone voiding, but had to rush to the toilet in order not to wet myself. 4=Urgency incontinence, I leaked before arriving to the toilet). One urgency incontinence episode was counted for each record of the diary in which the following occurred: incontinence episode or ‘both’ was recorded & severity of urinary urgency recorded was 3 or 4.
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one UI episode reported in baseline diary were included.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: UI episodes
Week 4 Number Analyzed 676 participants 670 participants 650 participants
-1.26  (0.07) -0.91  (0.07) -1.14  (0.07)
Week 8 Number Analyzed 649 participants 654 participants 645 participants
-1.70  (0.07) -1.25  (0.07) -1.45  (0.07)
Week 12 Number Analyzed 643 participants 627 participants 635 participants
-1.84  (0.07) -1.58  (0.07) -1.62  (0.07)
EoT Number Analyzed 707 participants 705 participants 698 participants
-1.82  (0.07) -1.54  (0.07) -1.63  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.54 to -0.17
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 djusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.65 to -0.25
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.004
Comments P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.47 to -0.05
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.003
Comments P-values for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method stratified rank ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.47 to -0.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of UI Episodes Reported During the 3-Day Diary
Hide Description Number of UI episodes was calculated using the number of UI episodes recorded on valid diary days during the 3-day micturition diary period. NOTE: Only urgency incontinence episodes recorded on a valid diary day were counted.
Time Frame Weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one UI episode reported in baseline diary were included.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Mean (Standard Error)
Unit of Measure: UI episodes
Week 4 Number Analyzed 676 participants 670 participants 650 participants
4.96  (0.27) 5.86  (0.29) 5.50  (0.30)
Week 8 Number Analyzed 649 participants 654 participants 645 participants
3.55  (0.25) 4.76  (0.27) 4.50  (0.30)
Week 12 Number Analyzed 643 participants 627 participants 635 participants
3.10  (0.24) 3.78  (0.25) 3.91  (0.30)
EoT Number Analyzed 691 participants 683 participants 666 participants
3.33  (0.24) 4.00  (0.25) 3.96  (0.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 rate ratio, 95% CIs, and p-value for number of UI episodes during Week 4 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.003
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.76 to 0.94
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 rate ratio, 95% CIs, and p-value for number of UI episodes during Week 8 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.63 to 0.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 rate ratio, 95% CIs, and p-value for number of UI episodes during Week 12 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.038
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.69 to 0.99
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT rate ratio, 95% CIs, and p-value for number of UI episodes during EoT 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.022
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.69 to 0.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours
Hide Description An urgency episode was defined as the complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes (severity of 3 or 4) per 24 hours was defined as the average number of times a participant recorded an urgency episode (severity of 3 or 4) with or without incontinence per day during the 3-day micturition diary period. Measured using the PPIUS scale. This was calculated using the sum of each record with an urgency episode (severity of 3 or 4) recorded on a valid diary day divided by the number of valid diary days during the 3-day micturition diary period.
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one urgency episode reported in baseline diary were included.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: urgency episodes
Week 4 Number Analyzed 684 participants 681 participants 663 participants
-1.84  (0.09) -1.39  (0.09) -1.74  (0.10)
Week 8 Number Analyzed 654 participants 665 participants 659 participants
-2.64  (0.10) -2.00  (0.10) -2.29  (0.10)
Week 12 Number Analyzed 647 participants 638 participants 648 participants
-2.97  (0.11) -2.44  (0.11) -2.55  (0.11)
EoT Number Analyzed 699 participants 694 participants 680 participants
-2.95  (0.10) -2.41  (0.10) -2.54  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.72 to -0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-0.93 to -0.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.82 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.83 to -0.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Mean Number of Pads Per 24 Hours
Hide Description The mean number of pads per 24 hours was defined as the average number of times a participant recorded a new pad used per day during the 3-day micturition diary period. This was calculated using the number of new pads used during valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period.
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with reported use of at least one pad reported in baseline diary were included.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: pads
Week 4 Number Analyzed 497 participants 467 participants 474 participants
-1.12  (0.07) -0.86  (0.07) -1.04  (0.07)
Week 8 Number Analyzed 482 participants 459 participants 469 participants
-1.50  (0.07) -1.17  (0.08) -1.36  (0.08)
Week 12 Number Analyzed 477 participants 440 participants 468 participants
-1.65  (0.07) -1.38  (0.07) -1.43  (0.07)
EoT Number Analyzed 510 participants 476 participants 487 participants
-1.66  (0.07) -1.35  (0.07) -1.43  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.008
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.46 to -0.07
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.002
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.55 to -0.13
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.006
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.47 to -0.08
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.002
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.51 to -0.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Pads Used During the 3-Day Diary
Hide Description The number of pads used was defined as the number of times a participant recorded a new pad used during the 3-day micturition diary period. This was calculated using the sum of each record with new pad checked. Only records with new pad checked on a valid diary day were counted.
Time Frame Weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants who reported use of at least one pad in baseline diary were included.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Mean (Standard Error)
Unit of Measure: pads
Week 4 Number Analyzed 497 participants 467 participants 474 participants
4.80  (0.28) 5.69  (0.36) 5.41  (0.29)
Week 8 Number Analyzed 482 participants 459 participants 469 participants
3.64  (0.24) 4.71  (0.37) 4.50  (0.29)
Week 12 Number Analyzed 477 participants 440 participants 468 participants
3.23  (0.22) 4.13  (0.28) 4.07  (0.28)
EoT Number Analyzed 510 participants 476 participants 487 participants
3.29  (0.22) 4.27  (0.28) 4.17  (0.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.545
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.87 to 1.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.010
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.70 to 0.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.007
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.67 to 0.94
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.003
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.66 to 0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Mean Number of Nocturia Episodes
Hide Description Mean number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) while sleeping during the 3-day diary period, divided by the number of valid diary days during the diary period. Night time episode of incontinence only was not considered a nocturia episode. Nocturia episodes were counted for each micturition record which occurred between the date/time of going to bed with intention to sleep and the date/time of getting up with intention to stay awake on a valid diary day & which was accompanied by a sleep interruption. Nocturia only determined for those who were not night-shift workers.
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one nocturia episode reported in baseline diary were included.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: nocturia episodes
Week 4 Number Analyzed 526 participants 514 participants 517 participants
-0.28  (0.03) -0.27  (0.03) -0.29  (0.03)
Week 8 Number Analyzed 500 participants 501 participants 514 participants
-0.37  (0.03) -0.35  (0.03) -0.37  (0.03)
Week 12 Number Analyzed 492 participants 480 participants 510 participants
-0.46  (0.03) -0.38  (0.03) -0.41  (0.03)
EoT Number Analyzed 537 participants 523 participants 531 participants
-0.43  (0.03) -0.37  (0.03) -0.41  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.836
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.10 to 0.08
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.617
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.12 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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.134
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.17 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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EOT adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.174
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.16 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Nocturia Episodes Reported Over 3-Day Diary
Hide Description The number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) during sleeping time during the 3-day micturition diary period. This was calculated using the sum of each nocturia episode recorded on valid diary days during the 3-day micturition diary period.
Time Frame Weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point. Only participants with at least one nocturia episode reported in baseline diary were included.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Mean (Standard Error)
Unit of Measure: nocturia episodes
Week 4 Number Analyzed 526 participants 514 participants 517 participants
3.63  (0.12) 3.59  (0.12) 3.58  (0.12)
Week 8 Number Analyzed 500 participants 501 participants 514 participants
3.33  (0.12) 3.35  (0.12) 3.32  (0.12)
Week 12 Number Analyzed 492 participants 480 participants 510 participants
3.12  (0.13) 3.26  (0.12) 3.23  (0.12)
EoT Number Analyzed 537 participants 523 participants 531 participants
3.16  (0.12) 3.28  (0.11) 3.19  (0.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.993
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.93 to 1.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.736
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.90 to 1.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.121
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.85 to 1.02
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT rate ratio, 95% CIs, & p-value for number of nocturia episodes during 3-day diary between combination & solifenacin treatment calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.172
Comments p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes.
Method Mixed Effects Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.86 to 1.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Change From Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility
Hide Description The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Measure Type: Number
Unit of Measure: participants
No problems -> no problems 409 370 374
No problems -> slight problems 33 35 36
No problems -> moderate problems 14 11 11
No problems -> severe problems 0 7 4
No problems -> extreme problems 0 1 0
No problems -> no data 2 4 5
Slight problems -> no problems 52 58 60
Slight problems -> slight problems 43 46 40
Slight problems -> moderate problems 15 28 16
Slight problems -> severe problems 1 3 3
Slight problems -> extreme problems 0 0 0
Slight problems -> no data 2 0 0
Moderate problems -> no problems 24 36 25
Moderate problems -> slight problems 25 18 23
Moderate problems -> moderate problems 28 28 40
Moderate problems -> severe problems 2 3 7
Moderate problems -> extreme problems 0 1 0
Moderate problems -> no data 1 0 0
Severe problems -> no problems 7 8 2
Severe problems -> slight problems 6 7 7
Severe problems -> moderate problems 17 11 11
Severe problems -> severe problems 12 10 14
Severe problems -> extreme problems 0 0 0
Severe problems -> no data 1 1 0
Extreme problems -> no problems 3 2 2
Extreme problems -> slight problems 1 0 0
Extreme problems -> moderate problems 1 1 1
Extreme problems -> severe problems 1 0 0
Extreme problems -> extreme problems 0 0 0
Extreme problems -> no data 0 0 0
No data -> no problems 4 9 13
No data -> slight problems 2 4 1
No data -> moderate problems 0 3 3
No data -> severe problems 0 0 0
No data -> extreme problems 0 0 0
No data -> no data 1 0 0
15.Secondary Outcome
Title Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Self-care
Hide Description The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Measure Type: Number
Unit of Measure: participants
No problems -> no problems 548 541 548
No problems -> slight problems 28 26 25
No problems -> moderate problems 0 14 7
No problems -> severe problems 3 0 2
No problems -> extreme problems 0 0 0
No problems -> no data 6 5 4
Slight problems -> no problems 37 25 32
Slight problems -> slight problems 23 24 22
Slight problems -> moderate problems 9 7 9
Slight problems -> severe problems 1 0 0
Slight problems -> extreme problems 0 0 0
Slight problems -> no data 0 0 1
Moderate problems -> no problems 12 16 7
Moderate problems -> slight problems 9 9 5
Moderate problems -> moderate problems 11 7 12
Moderate problems -> severe problems 0 2 2
Moderate problems -> extreme problems 0 0 0
Moderate problems -> no data 0 0 0
Severe problems -> no problems 7 5 0
Severe problems -> slight problems 2 2 2
Severe problems -> moderate problems 2 1 2
Severe problems -> severe problems 1 4 1
Severe problems -> extreme problems 0 0 0
Severe problems -> no data 0 0 0
Extreme problems -> no problems 0 0 0
Extreme problems -> slight problems 0 1 0
Extreme problems -> moderate problems 0 0 0
Extreme problems -> severe problems 1 0 0
Extreme problems -> extreme problems 0 0 0
Extreme problems -> no data 0 0 0
No data -> no problems 6 14 17
No data -> slight problems 0 2 0
No data -> moderate problems 0 0 0
No data -> severe problems 0 0 0
No data -> extreme problems 0 0 0
No data -> no data 1 0 0
16.Secondary Outcome
Title Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Usual Activities
Hide Description The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Measure Type: Number
Unit of Measure: participants
No problems -> no problems 397 384 379
No problems -> slight problems 38 30 42
No problems -> moderate problems 12 19 11
No problems -> severe problems 1 4 1
No problems -> extreme problems 0 0 1
No problems -> no data 4 3 3
Slight problems -> no problems 75 81 78
Slight problems -> slight problems 46 45 37
Slight problems -> moderate problems 12 16 15
Slight problems -> severe problems 1 1 3
Slight problems -> extreme problems 0 1 0
Slight problems -> no data 0 1 2
Moderate problems -> no problems 29 35 25
Moderate problems -> slight problems 22 20 28
Moderate problems -> moderate problems 22 18 21
Moderate problems -> severe problems 3 3 4
Moderate problems -> extreme problems 1 0 0
Moderate problems -> no data 2 1 0
Severe problems -> no problems 9 8 12
Severe problems -> slight problems 7 5 1
Severe problems -> moderate problems 7 6 9
Severe problems -> severe problems 5 7 9
Severe problems -> extreme problems 0 0 0
Severe problems -> no data 0 0 0
Extreme problems -> no problems 2 0 0
Extreme problems -> slight problems 1 0 0
Extreme problems -> moderate problems 3 1 0
Extreme problems -> severe problems 1 0 0
Extreme problems -> extreme problems 0 0 0
Extreme problems -> no data 0 0 0
No data -> no problems 5 11 15
No data -> slight problems 1 4 1
No data -> moderate problems 0 1 1
No data -> severe problems 0 0 0
No data -> extreme problems 0 0 0
No data -> no data 1 0 0
17.Secondary Outcome
Title Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort
Hide Description The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Measure Type: Number
Unit of Measure: participants
No pain -> no pain 299 290 283
No pain -> slight pain 45 62 51
No pain -> moderate pain 12 14 17
No pain -> severe pain 3 9 2
No pain -> extreme pain 0 0 1
No pain -> no data 4 4 3
Slight pain -> no pain 79 82 81
Slight pain -> slight pain 58 64 55
Slight pain -> moderate pain 28 17 31
Slight pain -> severe pain 0 2 5
Slight pain -> extreme pain 1 2 0
Slight pain -> no data 0 0 2
Moderate pain -> no pain 39 36 21
Moderate pain -> slight pain 37 36 39
Moderate pain -> moderate pain 34 30 39
Moderate pain -> severe pain 7 4 8
Moderate pain -> extreme pain 0 1 0
Moderate pain -> no data 2 1 0
Severe pain -> no pain 7 4 10
Severe pain -> slight pain 12 7 4
Severe pain -> moderate pain 11 16 16
Severe pain -> severe pain 10 4 9
Severe pain -> extreme pain 0 1 1
Severe pain -> no data 0 0 0
Extreme pain -> no pain 4 1 0
Extreme pain -> slight pain 0 1 1
Extreme pain -> moderate pain 1 0 1
Extreme pain -> severe pain 6 1 1
Extreme pain -> extreme pain 1 0 0
Extreme pain -> no data 0 0 0
No data -> no pain 4 8 11
No data -> slight pain 1 3 4
No data -> moderate pain 1 5 2
No data -> severe pain 0 0 0
No data -> extreme pain 0 0 0
No data -> no data 1 0 0
18.Secondary Outcome
Title Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression
Hide Description The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.
Time Frame Baseline and EoT (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Measure Type: Number
Unit of Measure: participants
Not anxious -> not anxious 322 300 307
Not anxious -> slightly anxious 43 39 43
Not anxious -> moderately anxious 11 17 15
Not anxious -> severely anxious 2 2 3
Not anxious-> extremely anxious 0 0 0
Not anxious -> no data 4 3 3
Slightly anxious -> not anxious 107 99 90
Slightly anxious -> slightly anxious 56 60 69
Slightly anxious -> moderately anxious 13 11 23
Slightly anxious -> severely anxious 1 2 2
Slightly anxious -> extremely anxious 0 0 0
Slightly anxious -> no data 1 2 2
Moderately anxious -> not anxious 36 38 34
Moderately anxious -> slightly anxious 36 40 33
Moderately anxious -> moderately anxious 22 26 17
Moderately anxious -> severely anxious 3 7 1
Moderately anxious -> extremely anxious 0 3 1
Moderately anxious -> no data 0 0 0
Severely anxious -> not anxious 10 8 8
Severely anxious -> slightly anxious 9 5 5
Severely anxious -> moderately anxious 6 6 11
Severely anxious -> severely anxious 5 8 7
Severely anxious -> extremely anxious 0 3 0
Severely anxious -> no data 0 0 0
Extremely anxious -> not anxious 1 4 1
Extremely anxious -> slightly anxious 2 1 1
Extremely anxious -> moderately anxious 4 2 3
Extremely anxious -> severely anxious 4 1 1
Extremely anxious -> extremely anxious 1 2 1
Extremely anxious -> no data 1 0 0
No data -> not anxious 5 13 11
No data -> slightly anxious 0 2 5
No data -> moderately anxious 1 1 1
No data -> severely anxious 0 0 0
No data -> extremely anxious 0 0 0
No data -> no data 1 0 0
19.Secondary Outcome
Title Change From Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score
Hide Description The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity).
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 682 participants 677 participants 669 participants
-16.68  (0.65) -13.79  (0.65) -15.82  (0.65)
Week 8 Number Analyzed 670 participants 660 participants 658 participants
-22.86  (0.68) -18.36  (0.69) -19.34  (0.69)
Week 12 Number Analyzed 644 participants 641 participants 647 participants
-27.90  (0.71) -22.31  (0.71) -24.09  (0.71)
EoT Number Analyzed 694 participants 683 participants 676 participants
-26.89  (0.69) -21.93  (0.70) -23.59  (0.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.002
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -2.89
Confidence Interval (2-Sided) 95%
-4.68 to -1.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.91
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -4.50
Confidence Interval (2-Sided) 95%
-6.40 to -2.60
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.97
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -5.59
Confidence Interval (2-Sided) 95%
-7.56 to -3.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value -4.96
Confidence Interval (2-Sided) 95%
-6.88 to -3.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.98
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score
Hide Description The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 682 participants 677 participants 669 participants
12.95  (0.59) 11.03  (0.59) 12.44  (0.59)
Week 8 Number Analyzed 670 participants 660 participants 658 participants
17.58  (0.63) 15.26  (0.63) 14.60  (0.64)
Week 12 Number Analyzed 644 participants 641 participants 647 participants
21.40  (0.66) 17.91  (0.67) 17.72  (0.66)
EoT Number Analyzed 694 participants 683 participants 676 participants
20.78  (0.65) 17.63  (0.65) 17.40  (0.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.021
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 1.92
Confidence Interval (2-Sided) 95%
0.29 to 3.55
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.010
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 2.31
Confidence Interval (2-Sided) 95%
0.56 to 4.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.89
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 3.49
Confidence Interval (2-Sided) 95%
1.65 to 5.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.94
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 3.15
Confidence Interval (2-Sided) 95%
1.35 to 4.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.92
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in OAB-q HRQL Subscale Score: Coping
Hide Description The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 682 participants 677 participants 669 participants
15.17  (0.68) 12.27  (0.68) 14.25  (0.68)
Week 8 Number Analyzed 670 participants 660 participants 658 participants
20.82  (0.74) 17.47  (0.74) 16.87  (0.74)
Week 12 Number Analyzed 644 participants 641 participants 647 participants
25.16  (0.78) 20.45  (0.78) 20.20  (0.78)
EoT Number Analyzed 694 participants 683 participants 676 participants
24.48  (0.75) 20.19  (0.76) 19.90  (0.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.003
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 2.90
Confidence Interval (2-Sided) 95%
1.02 to 4.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.96
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 3.35
Confidence Interval (2-Sided) 95%
1.29 to 5.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 4.71
Confidence Interval (2-Sided) 95%
2.55 to 6.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.10
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 4.29
Confidence Interval (2-Sided) 95%
2.20 to 6.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.07
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in OAB-q HRQL Subscale Score: Concern
Hide Description The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 682 participants 677 participants 669 participants
13.79  (0.68) 11.85  (0.68) 13.82  (0.69)
Week 8 Number Analyzed 670 participants 660 participants 658 participants
18.87  (0.70) 16.36  (0.71) 15.88  (0.71)
Week 12 Number Analyzed 644 participants 641 participants 647 participants
22.85  (0.74) 19.24  (0.75) 19.67  (0.74)
Week EoT Number Analyzed 694 participants 683 participants 676 participants
22.28  (0.72) 19.00  (0.73) 19.28  (0.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.044
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 1.94
Confidence Interval (2-Sided) 95%
0.05 to 3.83
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.96
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.012
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 2.50
Confidence Interval (2-Sided) 95%
0.55 to 4.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 3.61
Confidence Interval (2-Sided) 95%
1.54 to 5.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.001
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 3.28
Confidence Interval (2-Sided) 95%
1.27 to 5.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.03
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in OAB-q HRQL Subscale Score: Sleep
Hide Description The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 682 participants 677 participants 669 participants
11.58  (0.68) 11.04  (0.68) 11.16  (0.69)
Week 8 Number Analyzed 670 participants 660 participants 658 participants
16.18  (0.71) 14.57  (0.71) 13.72  (0.71)
Week 12 Number Analyzed 644 participants 641 participants 647 participants
20.00  (0.74) 17.74  (0.74) 16.84  (0.74)
Week EoT Number Analyzed 694 participants 683 participants 676 participants
19.16  (0.72) 17.30  (0.73) 16.55  (0.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.575
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
-1.35 to 2.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.96
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.109
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
-0.36 to 3.58
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.00
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.032
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 2.26
Confidence Interval (2-Sided) 95%
0.20 to 4.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments EoT adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.069
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
-0.15 to 3.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.02
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Change From Baseline in OAB-q HRQL Subscale Score: Social Interaction
Hide Description The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).
Time Frame Baseline and weeks 4, 8 & 12
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF was used for EoT. The analysis population consisted of the FAS with data available at each time point.
Arm/Group Title Combination (Solifenacin + Mirabegron) Solifenacin 5 mg Solifenacin 10 mg
Hide Arm/Group Description:
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Overall Number of Participants Analyzed 707 705 698
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 4 Number Analyzed 682 participants 677 participants 669 participants
9.58  (0.59) 7.85  (0.59) 8.95  (0.59)
Week 8 Number Analyzed 670 participants 660 participants 658 participants
11.93  (0.60) 10.84  (0.60) 10.16  (0.60)
Week 12 Number Analyzed 644 participants 641 participants 647 participants
14.70  (0.61) 12.08  (0.61) 11.98  (0.61)
EoT Number Analyzed 694 participants 683 participants 676 participants
14.39  (0.60) 11.91  (0.60) 11.72  (0.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 4 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.037
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 1.73
Confidence Interval (2-Sided) 95%
0.10 to 3.36
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 Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 8 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.199
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
-0.57 to 2.76
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.85
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Combination (Solifenacin + Mirabegron), Solifenacin 5 mg
Comments Week 12 adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.003
Comments P-values for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
0.92 to 4.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.87
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
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