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


EudraCT number 
201200540141 
Trial protocol 
SK CZ GB SE IE BE PT NO AT FI GR HU ES SI NL DK PL 
Global end of trial date 
25 Nov 2014

Results information


Results version number 
v3(current) 
This version publication date 
28 Apr 2018

First version publication date 
21 Jul 2016

Other versions 
v1 , v2 
Version creation reason 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
905EC012


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01908829  
WHO universal trial number (UTN) 
  
Other trial identifiers 
Acronym: BESIDE  
Sponsors


Sponsor organisation name 
Astellas Pharma Europe Ltd


Sponsor organisation address 
2000 Hillswood Drive, Chertsey, United Kingdom, KT16 0RS


Public contact 
Clinical Trial Disclosure, Astellas Pharma Europe Ltd, Astellas.resultsdisclosure@astellas.com


Scientific contact 
Clinical Trial Disclosure, Astellas Pharma Europe Ltd, Astellas.resultsdisclosure@astellas.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
25 Nov 2014


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
25 Nov 2014


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
The primary objective of this study was to evaluate the efficacy of solifenacin 5 mg in combination with mirabegron 50 mg (referred to as combination therapy from here on) vs solifenacin 5 mg monotherapy.


Protection of trial subjects 
This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
10 Jul 2013


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Algeria: 15


Country: Number of subjects enrolled 
Armenia: 52


Country: Number of subjects enrolled 
Australia: 3


Country: Number of subjects enrolled 
Austria: 24


Country: Number of subjects enrolled 
Belgium: 24


Country: Number of subjects enrolled 
Canada: 57


Country: Number of subjects enrolled 
Czech Republic: 129


Country: Number of subjects enrolled 
Denmark: 39


Country: Number of subjects enrolled 
Egypt: 11


Country: Number of subjects enrolled 
Finland: 6


Country: Number of subjects enrolled 
France: 11


Country: Number of subjects enrolled 
Georgia: 23


Country: Number of subjects enrolled 
Germany: 106


Country: Number of subjects enrolled 
Greece: 53


Country: Number of subjects enrolled 
Hungary: 53


Country: Number of subjects enrolled 
Ireland: 8


Country: Number of subjects enrolled 
Israel: 43


Country: Number of subjects enrolled 
Italy: 49


Country: Number of subjects enrolled 
Kazakhstan: 23


Country: Number of subjects enrolled 
Norway: 9


Country: Number of subjects enrolled 
Poland: 234


Country: Number of subjects enrolled 
Portugal: 12


Country: Number of subjects enrolled 
Romania: 84


Country: Number of subjects enrolled 
Russian Federation: 241


Country: Number of subjects enrolled 
Slovakia: 93


Country: Number of subjects enrolled 
Slovenia: 26


Country: Number of subjects enrolled 
Spain: 76


Country: Number of subjects enrolled 
Sweden: 54


Country: Number of subjects enrolled 
Switzerland: 11


Country: Number of subjects enrolled 
Turkey: 164


Country: Number of subjects enrolled 
Ukraine: 28


Country: Number of subjects enrolled 
United Kingdom: 78


Country: Number of subjects enrolled 
United States: 320


Country: Number of subjects enrolled 
Netherlands: 15


Worldwide total number of subjects 
2174


EEA total number of subjects 
1183


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
1492


From 65 to 84 years 
671


85 years and over 
11



Recruitment


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


Screening details 
Participants who met the screening inclusion/exclusion criteria went through a two week washout period and maintained a micturition diary during that the washout period. A total of 3815 participants were screened of which 2401 participants received solifenacin 5 mg runin medication. A total of 2174 participants were randomized.  
Preassignment period milestones


Number of subjects started 
3815 ^{[1]}  
Intermediate milestone: Number of subjects 
Received 1 dose, singleblind runin: 2401


Number of subjects completed 
2174  
Preassignment subject noncompletion reasons


Reason: Number of subjects 
Discontinued before runin solifenacin 5 mg: 1414  
Reason: Number of subjects 
Exclusion/inclusion criteria not met: 169  
Reason: Number of subjects 
Patient withdrawn: 32  
Reason: Number of subjects 
Adverse event: 16  
Reason: Number of subjects 
Other reasons: 7  
Reason: Number of subjects 
Lost to followup: 3  
Notes [1]  The number of subjects reported to have started the preassignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The number of participants included in the preassignment period were the total number screened. The number of participants included in the worldwide number enrolled were the total number of participants randomized. 

Period 1


Period 1 title 
Overall Study (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Blinding implementation details 
The study was comprised of a 12 week doubleblind treatment period (participants were randomized into the doubleblind period if they experienced 1 or more incontinence episodes over the 3day diary period prior to randomization to doubleblind period and warranted additional relief for their OAB symptoms). There was 2 week safety follow up period (placebo administered). The active and placebo tablets were made indistinguishable by using a doubledummy packaging system.


Arms


Are arms mutually exclusive 
Yes


Arm title

Combination (solifenacin + mirabegron)  
Arm description 
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of doubleblind period. For the last 8 weeks of the doubleblind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week singleblind safety followup period.  
Arm type 
Experimental  
Investigational medicinal product name 
solifenacin 5 mg


Investigational medicinal product code 
YM905


Other name 
Vesicare, Vesitrim, Vesikur, solifenacin succinate


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Solifenacin was provided as the marketed formulation in the 5 mg strength. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
solifenacin 10 mg matching placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
mirabegron 25 mg


Investigational medicinal product code 
YM178


Other name 
Betanis, Betmiga, Myrbetriq


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Mirabegron was supplied as the marketed formulation in the 25 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
mirabegron 50 mg


Investigational medicinal product code 
YM178


Other name 
Betanis, Betmiga, Myrbetriq


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Mirabegron was supplied as the marketed formulation in the 50 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.


Arm title

Solifenacin 5 mg  
Arm description 
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period.  
Arm type 
Active comparator  
Investigational medicinal product name 
solifenacin 5 mg


Investigational medicinal product code 
YM905


Other name 
Vesicare, Vesitrim, Vesikur, solifenacin succinate


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Solifenacin was provided as the marketed formulation in the 5 mg strength. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
solifenacin 10 mg matching placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
mirabegron 25 mg matching placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
mirabegron 50 mg matching placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.


Arm title

Solifenacin 10 mg  
Arm description 
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period.  
Arm type 
Active comparator  
Investigational medicinal product name 
solifenacin 5 mg matching placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Matching placebo of solifenacin succinate 5 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
solifenacin 10 mg


Investigational medicinal product code 
YM905


Other name 
Vesicare, Vesitrim, Vesikur, solifenacin succinate


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Solifenacin was provided as the marketed formulation in the 10 mg strength. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
mirabegron 25 mg matching placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.


Investigational medicinal product name 
mirabegron 50 mg matching placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.





Baseline characteristics reporting groups


Reporting group title 
Combination (solifenacin + mirabegron)


Reporting group description 
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of doubleblind period. For the last 8 weeks of the doubleblind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week singleblind safety followup period.  
Reporting group title 
Solifenacin 5 mg


Reporting group description 
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period.  
Reporting group title 
Solifenacin 10 mg


Reporting group description 
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period.  



End points reporting groups


Reporting group title 
Combination (solifenacin + mirabegron)


Reporting group description 
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of doubleblind period. For the last 8 weeks of the doubleblind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week singleblind safety followup period.  
Reporting group title 
Solifenacin 5 mg


Reporting group description 
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period.  
Reporting group title 
Solifenacin 10 mg


Reporting group description 
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period. 


End point title 
Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours  
End point description 
The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3day micturition diary period divided by the number of valid diary days during the 3day 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 doubleblind 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 doubleblind study period was used as EoT value to derive the primary variable.


End point type 
Primary


End point timeframe 
Baseline and end of treatment (up to 12 weeks)




Statistical analysis title 
Adjusted Difference Combination vs Solifenacin 5mg  
Statistical analysis description 
Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy
groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95%
Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1410


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[1]}  
Method 
stratified rank ANCOVA  
Parameter type 
Least Squares (LS) Means  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.05  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [1]  P values for pairwise comparisons were from the stratified rank ANCOVA model. P < 0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes per 24 Hours  
End point description 
The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3day micturition diary period divided by the number of valid diary days during the 3day micturition diary period. The analysis population consisted of the FAS. N=number of participants with available data (applicable for all secondary endpoints).


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy
groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95%
Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[2]}  
Method 
stratified rank ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.52  
upper limit 
0.14  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [2]  P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy
groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95%
Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[3]}  
Method 
stratified rank ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.18  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [3]  P values for pairwise comparisons are from the stratified rank ANCOVA model. P < 0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy
groups from adjusted mean of combination group based on ANCOVA model. Means (LS means) and 95%
Confidence Intervals (CIs) are from an ANCOVA model with sex, age group (< 65, ≥ 65 years), geographic region, and 4week incontinence episode reduction group as fixed factors and mean number of incontinence episodes per 24 hours at baseline as a covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[4]}  
Method 
stratified rank ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.46  
upper limit 
0.03  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [4]  Pvalues for pairwise comparisons are from the stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in Mean Number of Micturitions per 24 Hours  
End point description 
The average number of micturitions (voluntary urinations (excluding incontinence only episodes)) per 24 hours was derived from number of micturitions recorded on valid diary days during the 3day micturition diary period divided by the number of valid diary days during the 3day micturition diary period (excluding incontinence only episodes). LOCF was used for EoT. The analysis population included the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.01 ^{[5]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.06  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [5]  Pvalues for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[6]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.65  
upper limit 
0.19  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [6]  Pvalues for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[7]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.23  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [7]  Pvalues for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[8]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.67  
upper limit 
0.22  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [8]  Pvalues for pairwise comparisons are from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Number of Incontinence Episodes Reported During the 3Day Diary  
End point description 
The number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from total number of incontinence episodes on valid diary days recorded during the 3day micturition diary period. LOCF was used for EoT. The analysis population included the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 4  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of incontinence episodes during EoT 3day 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 & 4week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005 ^{[9]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
0.96  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Notes [9]  p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 8  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of incontinence episodes during EoT 3day 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 & 4week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[10]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
0.86  
Variability estimate 
Standard error of the mean


Dispersion value 
0.07


Notes [10]  p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 12  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of incontinence episodes during EoT 3day 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 & 4week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.021 ^{[11]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.97  
Variability estimate 
Standard error of the mean


Dispersion value 
0.08


Notes [11]  p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin EoT  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of incontinence episodes during EoT 3day 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 & 4week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014 ^{[12]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.71  
upper limit 
0.96  
Variability estimate 
Standard error of the mean


Dispersion value 
0.08


Notes [12]  p<0.05 indicates superiority in favor of treatment group with lowest rate of incontinence episodes. 


End point title 
Change from Baseline in Mean Volume Voided (MVV) per Micturition  
End point description 
MVV per micturition was defined as MVV (mL) per micturition during last 3 days of the 3day 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 3day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.078 ^{[13]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
3.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
8.16  
Variability estimate 
Standard error of the mean


Dispersion value 
2.19


Notes [13]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[14]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
11.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.98  
upper limit 
16.4  
Variability estimate 
Standard error of the mean


Dispersion value 
2.66


Notes [14]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[15]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
12.38


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.65  
upper limit 
18.12  
Variability estimate 
Standard error of the mean


Dispersion value 
2.92


Notes [15]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[16]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
11.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.06  
upper limit 
16.99  
Variability estimate 
Standard error of the mean


Dispersion value 
2.79


Notes [16]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline to EoT in Corrected Micturition Frequency (CMF)  
End point description 
CMF was defined as the mean number of micturitions per 24 hours that participants would have at EoT if their fluid intake had remained unchanged since baseline. This was calculated by the MVV per Micturition at baseline multiplied by the mean number of micturitions per 24 hours at baseline divided by the MVV per micturition at EoT. LOCF was used. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and EoT (up to 12 weeks)




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1410


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[17]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
0.16  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [17]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in Mean Number of Urgency Incontinence (UI) Episodes per 24 Hours  
End point description 
UI was defined as the complaint of involuntary urine leakage accompanied by or immediately preceded by urgency. UI was measured using the Patient Perception of Intensity of Urgency Scale (PPIUS), a patient reported outcome validated 5point categorical scale rating the degree of associated urinary urgency severity (0=No urgency, I felt no need to empty my bladder, but did so for other reasons. 1=Mild, I could postpone voiding as long as necessary, without fear of wetting myself. 2= Moderate, I could postpone voiding for a short while, without fear of wetting myself. 3=Severe, I could not postpone voiding, but had to rush to the toilet in order not to wet myself. 4=Urgency incontinence, I leaked before arriving to the toilet). One urgency incontinence episode was counted for each record of the diary in which the following occurred: incontinence episode or ‘both’ was recorded & severity of urinary urgency recorded was 3 or 4. LOCF was used for EoT. FAS population.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[18]}  
Pvalue 
< 0.001 ^{[19]}  
Method 
stratified rank ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
0.17  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Notes [18]  Only participants with at least one UI episode reported in baseline diary were included. [19]  Pvalues for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[20]}  
Pvalue 
< 0.001 ^{[21]}  
Method 
stratified rank ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.65  
upper limit 
0.25  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [20]  Only participants with at least one UI episode reported in baseline diary were included. [21]  Pvalues for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[22]}  
Pvalue 
= 0.004 ^{[23]}  
Method 
stratified rank ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.05  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [22]  Only participants with at least one UI episode reported in baseline diary were included. [23]  Pvalues for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[24]}  
Pvalue 
= 0.003 ^{[25]}  
Method 
stratified rank ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.07  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [24]  Only participants with at least one UI episode reported in baseline diary were included. [25]  Pvalues for pairwise comparisons were from stratified rank ANCOVA model. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Number of UI Episodes Reported During the 3Day Diary  
End point description 
Number of UI episodes was calculated using the number of UI episodes recorded on valid diary days during the 3day micturition diary period. NOTE: Only urgency incontinence episodes recorded on a valid diary day were counted. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 4  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of UI episodes during EoT 3day 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 4week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[26]}  
Pvalue 
= 0.003 ^{[27]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.85


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.94  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Notes [26]  Only participants with at least one UI episode reported in baseline diary were included. [27]  p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 8  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of UI episodes during EoT 3day 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 4week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[28]}  
Pvalue 
< 0.001 ^{[29]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.74


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.63  
upper limit 
0.86  
Variability estimate 
Standard error of the mean


Dispersion value 
0.08


Notes [28]  Only participants with at least one UI episode reported in baseline diary were included. [29]  p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 12  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of UI episodes during EoT 3day 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 4week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[30]}  
Pvalue 
= 0.038 ^{[31]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.83


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
0.99  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Notes [30]  Only participants with at least one UI episode reported in baseline diary were included. [31]  p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin EoT  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of UI episodes during EoT 3day 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 4week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[32]}  
Pvalue 
= 0.022 ^{[33]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
0.97  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Notes [32]  Only participants with at least one UI episode reported in baseline diary were included. [33]  p<0.05 indicates superiority in favor of treatment group with lowest rate of UI episodes. 


End point title 
Change from Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) per 24 Hours  
End point description 
An urgency episode was defined as the complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes (severity of 3 or 4) per 24 hours was defined as the average number of times a participant recorded an urgency episode (severity of 3 or 4) with or without incontinence per day during the 3day 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 3day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[34]}  
Pvalue 
= 0.001 ^{[35]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
0.19  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Notes [34]  Only participants with at least one urgency episode reported in baseline diary were included. [35]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[36]}  
Pvalue 
< 0.001 ^{[37]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.64


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.93  
upper limit 
0.35  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [36]  Only participants with at least one urgency episode reported in baseline diary were included. [37]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[38]}  
Pvalue 
= 0.001 ^{[39]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
0.22  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [38]  Only participants with at least one urgency episode reported in baseline diary were included. [39]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[40]}  
Pvalue 
< 0.001 ^{[41]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.54


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.83  
upper limit 
0.25  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [40]  Only participants with at least one urgency episode reported in baseline diary were included. [41]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in Mean Number of Pads per 24 hours  
End point description 
The mean number of pads per 24 hours was defined as the average number of times a participant recorded a new pad used per day during the 3day micturition diary period. This was calculated using the number of new pads used during valid diary days during the 3day micturition diary period divided by the number of valid diary days during the 3day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[42]}  
Pvalue 
= 0.008 ^{[43]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.46  
upper limit 
0.07  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [42]  Only participants with reported use of at least one pad reported in baseline diary were included. [43]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[44]}  
Pvalue 
= 0.002 ^{[45]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.55  
upper limit 
0.13  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [44]  Only participants with reported use of at least one pad reported in baseline diary were included. [45]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[46]}  
Pvalue 
= 0.006 ^{[47]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.08  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [46]  Only participants with reported use of at least one pad reported in baseline diary were included. [47]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group & geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[48]}  
Pvalue 
= 0.002 ^{[49]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.51  
upper limit 
0.12  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [48]  Only participants with reported use of at least one pad reported in baseline diary were included. [49]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Number of Pads Used During the 3Day Diary  
End point description 
The number of pads used was defined as the number of times a participant recorded a new pad used during the 3day micturition diary period. This was calculated using the sum of each record with new pad checked. Only records with new pad checked on a valid diary day were counted. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 4  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of pads used during the 3day 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 4week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[50]}  
Pvalue 
= 0.545 ^{[51]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.97


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
1.08  
Variability estimate 
Standard error of the mean


Dispersion value 
0.06


Notes [50]  Only participants who reported use of at least one pad in baseline diary were included. [51]  p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 8  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of pads used during the 3day 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 4week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[52]}  
Pvalue 
= 0.01 ^{[53]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.95  
Variability estimate 
Standard error of the mean


Dispersion value 
0.08


Notes [52]  Only participants who reported use of at least one pad in baseline diary were included. [53]  p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 12  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of pads used during the 3day 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 4week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[54]}  
Pvalue 
= 0.007 ^{[55]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.67  
upper limit 
0.94  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Notes [54]  Only participants who reported use of at least one pad in baseline diary were included. [55]  p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin EoT  
Statistical analysis description 
Rate ratio, 95% CIs, and pvalue for number of pads used during the 3day 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 4week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[56]}  
Pvalue 
= 0.003 ^{[57]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.66  
upper limit 
0.92  
Variability estimate 
Standard error of the mean


Dispersion value 
0.08


Notes [56]  Only participants who reported use of at least one pad in baseline diary were included. [57]  p<0.05 indicates superiority in favor of treatment group with lowest rate of pads used. 


End point title 
Change from Baseline in Mean Number of Nocturia Episodes  
End point description 
Mean number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) while sleeping during the 3day 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 nightshift workers. LOCF used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[58]}  
Pvalue 
= 0.836 ^{[59]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.08  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Notes [58]  Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS. [59]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[60]}  
Pvalue 
= 0.617 ^{[61]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.12  
upper limit 
0.07  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Notes [60]  Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS. [61]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[62]}  
Pvalue 
= 0.134 ^{[63]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.17  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Notes [62]  Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS. [63]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[64]}  
Pvalue 
= 0.174 ^{[65]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.16  
upper limit 
0.03  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Notes [64]  Only participants with at least one nocturia episode reported in baseline diary were included. The analysis population consisted of the FAS. [65]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicates superiority in favor of treatment group with the largest improvement. 


End point title 
Number of Nocturia Episodes Reported Over 3Day Diary  
End point description 
The number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) during sleeping time during the 3day micturition diary period. This was calculated using the sum of each nocturia episode recorded on valid diary days during the 3day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 4  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of nocturia episodes during the 3day 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 & 4week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[66]}  
Pvalue 
= 0.993 ^{[67]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.93  
upper limit 
1.08  
Variability estimate 
Standard error of the mean


Dispersion value 
0.04


Notes [66]  Only participants with at least one nocturia episode reported in baseline diary were included. [67]  p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 8  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of nocturia episodes during the 3day 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 & 4week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[68]}  
Pvalue 
= 0.736 ^{[69]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.99


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.07  
Variability estimate 
Standard error of the mean


Dispersion value 
0.04


Notes [68]  Only participants with at least one nocturia episode reported in baseline diary were included. [69]  p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin Week 12  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of nocturia episodes during the 3day 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 & 4week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[70]}  
Pvalue 
= 0.121 ^{[71]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
1.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Notes [70]  Only participants with at least one nocturia episode reported in baseline diary were included. [71]  p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. 

Statistical analysis title 
Rate Ratio Combination vs 5 mg Solifenacin EoT  
Statistical analysis description 
Rate ratio, 95% CIs, & pvalue for number of nocturia episodes during the 3day 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 & 4week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority ^{[72]}  
Pvalue 
= 0.172 ^{[73]}  
Method 
Mixed Effects Poisson  
Parameter type 
Rate Ratio  
Point estimate 
0.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.86  
upper limit 
1.03  
Variability estimate 
Standard error of the mean


Dispersion value 
0.04


Notes [72]  Only participants with at least one nocturia episode reported in baseline diary were included. [73]  p<0.05 indicates superiority in favor of treatment group with lowest rate of nocturia episodes. 


End point title 
Number of Participants with Change from Baseline to EoT in Euroqol European Quality of Life5 Dimensions (EQ5D) Subscale Score: Mobility  
End point description 
The EQ5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and EoT (up to 12 weeks)




No statistical analyses for this end point 


End point title 
Number of Participants with Change from Baseline to EoT in EQ5D Subscale Score: Selfcare  
End point description 
The EQ5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and EoT (up to 12 weeks)




No statistical analyses for this end point 


End point title 
Number of Participants with Change from Baseline to EoT in EQ5D Subscale Score: Usual Activities  
End point description 
The EQ5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and EoT (up to 12 weeks)




No statistical analyses for this end point 


End point title 
Number of Participants with Change from Baseline to EoT in EQ5D Subscale Score: Pain/Discomfort  
End point description 
The EQ5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and EoT (up to 12 weeks)




No statistical analyses for this end point 


End point title 
Number of Participants with Change from Baseline to EoT in EQ5D Subscale Score: Anxiety/Depression  
End point description 
The EQ5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and EoT (up to 12 weeks)




No statistical analyses for this end point 


End point title 
Change from Baseline in Overactive Bladder Symptom (OABq) Symptom Bother Score  
End point description 
The OABq was a selfreported questionnaire comprising 33items each rated on a 6point Likert scale. The questionnaire consisted of an 8item symptom bother scale and 25 healthrelated QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002 ^{[74]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
2.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.68  
upper limit 
1.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.91


Notes [74]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[75]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
4.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.4  
upper limit 
2.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.97


Notes [75]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[76]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
5.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.56  
upper limit 
3.62  
Variability estimate 
Standard error of the mean


Dispersion value 
1


Notes [76]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[77]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
4.96


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.88  
upper limit 
3.04  
Variability estimate 
Standard error of the mean


Dispersion value 
0.98


Notes [77]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in OABq HealthRelated Quality of Life (HRQL) Total Score  
End point description 
The OABq was a selfreported questionnaire comprising 33items each rated on a 6point Likert scale. The questionnaire consisted of an 8item symptom bother scale and 25 healthrelated QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.021  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
1.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.29  
upper limit 
3.55  
Variability estimate 
Standard error of the mean


Dispersion value 
0.83


Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.01 ^{[78]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
2.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.56  
upper limit 
4.06  
Variability estimate 
Standard error of the mean


Dispersion value 
0.89


Notes [78]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[79]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
3.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.65  
upper limit 
5.33  
Variability estimate 
Standard error of the mean


Dispersion value 
0.94


Notes [79]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[80]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
3.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.35  
upper limit 
4.95  
Variability estimate 
Standard error of the mean


Dispersion value 
0.92


Notes [80]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in OABq HRQL Subscale Score: Coping  
End point description 
The OABq was a selfreported questionnaire comprising 33items each rated on a 6point Likert scale. The questionnaire consisted of an 8item symptom bother scale and 25 healthrelated QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[81]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
2.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.02  
upper limit 
4.78  
Variability estimate 
Standard error of the mean


Dispersion value 
0.96


Notes [81]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[82]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
3.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.29  
upper limit 
5.4  
Variability estimate 
Standard error of the mean


Dispersion value 
1.05


Notes [82]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[83]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
4.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.55  
upper limit 
6.87  
Variability estimate 
Standard error of the mean


Dispersion value 
1.1


Notes [83]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[84]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
4.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
6.39  
Variability estimate 
Standard error of the mean


Dispersion value 
1.07


Notes [84]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in OABq HRQL Subscale Score: Concern  
End point description 
The OABq was a selfreported questionnaire comprising 33items each rated on a 6point Likert scale. The questionnaire consisted of an 8item symptom bother scale and 25 healthrelated QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.044 ^{[85]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
1.94


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.05  
upper limit 
3.83  
Variability estimate 
Standard error of the mean


Dispersion value 
0.96


Notes [85]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012 ^{[86]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
2.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.55  
upper limit 
4.46  
Variability estimate 
Standard error of the mean


Dispersion value 
1


Notes [86]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[87]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
3.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.54  
upper limit 
5.67  
Variability estimate 
Standard error of the mean


Dispersion value 
1.05


Notes [87]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[88]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
3.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.27  
upper limit 
5.29  
Variability estimate 
Standard error of the mean


Dispersion value 
1.03


Notes [88]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in OABq HRQL Subscale Score: Sleep  
End point description 
The OABq was a selfreported questionnaire comprising 33items each rated on a 6point Likert scale. The questionnaire consisted of an 8item symptom bother scale and 25 healthrelated QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.575 ^{[89]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.54


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.35  
upper limit 
2.43  
Variability estimate 
Standard error of the mean


Dispersion value 
0.96


Notes [89]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.109 ^{[90]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
1.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.36  
upper limit 
3.58  
Variability estimate 
Standard error of the mean


Dispersion value 
1


Notes [90]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.032 ^{[91]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
2.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
4.32  
Variability estimate 
Standard error of the mean


Dispersion value 
1.05


Notes [91]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.069 ^{[92]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
1.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.15  
upper limit 
3.87  
Variability estimate 
Standard error of the mean


Dispersion value 
1.02


Notes [92]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in OABq HRQL Subscale Score: Social Interaction  
End point description 
The OABq was a selfreported questionnaire comprising 33items each rated on a 6point Likert scale. The questionnaire consisted of an 8item symptom bother scale and 25 healthrelated QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.037 ^{[93]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
1.73


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
3.36  
Variability estimate 
Standard error of the mean


Dispersion value 
0.83


Notes [93]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.199 ^{[94]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
1.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.57  
upper limit 
2.76  
Variability estimate 
Standard error of the mean


Dispersion value 
0.85


Notes [94]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[95]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
2.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
4.31  
Variability estimate 
Standard error of the mean


Dispersion value 
0.87


Notes [95]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as 95% CIs & pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[96]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
2.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
4.15  
Variability estimate 
Standard error of the mean


Dispersion value 
0.85


Notes [96]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in Treatment Satisfaction  Visual Analogue Scale (TSVAS) Score  
End point description 
The TSVAS rated participant satisfaction with treatment on a scale from 0 (No, not at all) to 10 (Yes, completely). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[97]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [97]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.019 ^{[98]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [98]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[99]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [99]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[100]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [100]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Change from Baseline in Patient Perception Bladder Control (PPBC) Score  
End point description 
The PPBC was a validated, global assessment tool using a 6point Likert scale on which participants rated their subjective impression of their current bladder condition. PPBC score: 1no problem, 2 some very minor problems, 3some minor problems, 4moderate problems, 5severe problems, 6many severe problems. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[101]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [101]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[102]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [102]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[103]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [103]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 

Statistical analysis title 
Adj. Diff. Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Adjusted change from baseline values as well as the 95% CIs and pvalue were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[104]}  
Method 
ANCOVA  
Parameter type 
LS Means  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Notes [104]  Pvalues for pairwise comparisons were from the ANCOVA model described above. p<0.05 indicated superiority in favor of treatment group with the largest improvement. 


End point title 
Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)  
End point description 
The PGIC was a 2part questionnaire, assessing both the change in the participant’s overall condition (Patient Impression in General Health (PIBS)) and change in bladder condition since the start of the study (Patient Impression in General Health (PIGH)) (from very much worse to very much improved). The CGIC was a single questionnaire assessing the participant’s change in bladder condition since the beginning of the study (Clinician Impression in Bladder Symptoms (CIBS)). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
End of treatment (up to 12 weeks)




No statistical analyses for this end point 


End point title 
Percentage of Participants with at Least a 50% Decrease from Baseline in Mean Number of Incontinence Episodes per 24 Hours  
End point description 
Incontinence was defined as any involuntary leakage of urine. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[105]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.19  
upper limit 
1.84  
Notes [105]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[106]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.57


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.25  
upper limit 
1.98  
Notes [106]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[107]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.54


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.21  
upper limit 
1.95  
Notes [107]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[108]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
1.9  
Notes [108]  p<0.05 indicated superiority in favor of treatment group with highest response. 


End point title 
Percentage of Participants with Zero Incontinence Episodes Postbaseline  
End point description 
Incontinence was defined as any involuntary leakage of urine. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.119 ^{[109]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.95  
upper limit 
1.63  
Notes [109]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[110]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.23  
upper limit 
1.98  
Notes [110]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002 ^{[111]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
1.82  
Notes [111]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[112]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.47


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.17  
upper limit 
1.84  
Notes [112]  p<0.05 indicated superiority in favor of treatment group with highest response. 


End point title 
Percentage of Participants with a Mean of at Least 8 Micturitions per 24 Hours at Baseline and Less than 8 Micturitions per 24 Hours Postbaseline  
End point description 
Micturitions were defined as voluntary urinations (excluding incontinence only episodes). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.305 ^{[113]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.88  
upper limit 
1.5  
Notes [113]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014 ^{[114]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.06  
upper limit 
1.76  
Notes [114]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012 ^{[115]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.07  
upper limit 
1.76  
Notes [115]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.036 ^{[116]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.02  
upper limit 
1.64  
Notes [116]  p<0.05 indicated superiority in favor of treatment group with highest response. 


End point title 
Percentage of Participants with at Least a 10Point Improvement from Baseline in OABq Symptom Bother Score  
End point description 
The OABq was a selfreported questionnaire comprising 33items each rated on a 6point Likert scale. The questionnaire consisted of an 8item symptom bother scale and 25 healthrelated QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
OABq Odds Ratio Comb. vs Solifenacin 5mg Week 4  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[117]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.49


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.18  
upper limit 
1.88  
Notes [117]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
OABq Odds Ratio Comb. vs Solifenacin 5mg Week 8  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[118]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.31  
upper limit 
2.18  
Notes [118]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
OABq Odds Ratio Comb. vs Solifenacin 5mg Week 12  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[119]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.96


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.47  
upper limit 
2.61  
Notes [119]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
OABq Odds Ratio Comb. vs Solifenacin 5mg EoT  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[120]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.34  
upper limit 
2.3  
Notes [120]  p<0.05 indicated superiority in favor of treatment group with highest response. 


End point title 
Percentage of Participants with at Least a 10Point Improvement from Baseline in HRQL Total Score  
End point description 
HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 4  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[121]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
1.82  
Notes [121]  p<0.05 indicates superiority in favor of treatment group with highest response. 

Statistical analysis title 
HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 8  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[122]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.18  
upper limit 
1.93  
Notes [122]  p<0.05 indicates superiority in favor of treatment group with highest response. 

Statistical analysis title 
HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 12  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[123]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.64


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.27  
upper limit 
2.13  
Notes [123]  p<0.05 indicates superiority in favor of treatment group with highest response. 

Statistical analysis title 
HRQL Odds Ratio Comb. vs Solifenacin 5mg EoT  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001 ^{[124]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.17  
upper limit 
1.91  
Notes [124]  p<0.05 indicates superiority in favor of treatment group with highest response. 


End point title 
Percentage of Participants with at Least a 1Point Improvement from Baseline in PPBC  
End point description 
The PPBC was a validated, global assessment tool using a 6point Likert scale on which participants rated their subjective impression of their current bladder condition. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[125]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.13  
upper limit 
1.79  
Notes [125]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[126]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.12  
upper limit 
1.84  
Notes [126]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[127]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.15  
upper limit 
1.96  
Notes [127]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006 ^{[128]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.43


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.11  
upper limit 
1.84  
Notes [128]  p<0.05 indicated superiority in favor of treatment group with highest response. 


End point title 
Percentage of Participants with Major (at Least 2Point) Improvement from Baseline in PPBC  
End point description 
The PPBC was a validated, global assessment tool using a 6point Likert scale on which participants rated their subjective impression of their current bladder condition. LOCF was used for EoT. The analysis population consisted of the FAS.


End point type 
Secondary


End point timeframe 
Weeks 4, 8 and 12




Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 4  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.065 ^{[129]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.99  
upper limit 
1.66  
Notes [129]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 8  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[130]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.11  
upper limit 
1.79  
Notes [130]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg Week 12  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[131]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.64


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
2.07  
Notes [131]  p<0.05 indicated superiority in favor of treatment group with highest response. 

Statistical analysis title 
Odds Ratio Combination vs Solifenacin 5mg EoT  
Statistical analysis description 
Odds ratios, 95% Two sided CIs for Odds ratios and pvalues were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4week incontinence episode reduction group, geographic region as factors and baseline value as covariate.


Comparison groups 
Combination (solifenacin + mirabegron) v Solifenacin 5 mg


Number of subjects included in analysis 
1412


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[132]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.24  
upper limit 
1.94  
Notes [132]  p<0.05 indicated superiority in favor of treatment group with highest response. 


End point title 
Number of Participants with Adverse Events (AEs)  
End point description 
AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures & which does not necessarily have a causal relationship with this treatment. TreatmentEmergent Adverse Event (TEAE) referred to an adverse event which started or worsened in the period from first doubleblind medication intake until 30 days after the last doubleblind medication intake. The analysis population consisted of the Safety Analysis Set, the SAF comprised all randomized participants who received at least 1 dose of doubleblind treatment.


End point type 
Secondary


End point timeframe 
From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)




No statistical analyses for this end point 


End point title 
Change From Baseline in Post Void Residual (PVR) Volume  
End point description 
PVR Volume was assessed by bladder scan. The analysis population consisted of the SAF with data available at each time point.


End point type 
Secondary


End point timeframe 
Baseline and weeks 4, 8 & 12




No statistical analyses for this end point 


Adverse events information


Timeframe for reporting adverse events 
From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)


Adverse event reporting additional description 
Population consisted of the SAF. An AE was defined as any untoward medical occurrence in a participant administered a study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment.


Assessment type 
Systematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
16.0


Reporting groups


Reporting group title 
Combination (solifenacin + mirabegron)


Reporting group description 
Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of doubleblind period. For the last 8 weeks of the doubleblind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week singleblind safety followup period.  
Reporting group title 
Solifenacin 10 mg


Reporting group description 
Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period.  
Reporting group title 
Solifenacin 5 mg


Reporting group description 
Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the doubleblind 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 singleblind safety followup period.  
