Clinical Trial Results:
A Randomized, Doubleblind, Parallelgroup, Activecontrolled, Multicenter Study to Evaluate the Longterm Safety and Efficacy of Combination of Solifenacin Succinate with Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in Patients with Overactive Bladder
Summary


EudraCT number 
201200573629 
Trial protocol 
NL BE HU IT FI GB EE SE SK CZ LV DK SI PL ES LT BG GR 
Global end of trial date 
08 Sep 2016

Results information


Results version number 
v2(current) 
This version publication date 
19 Jul 2018

First version publication date 
17 Aug 2017

Other versions 
v1 
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 
178CL102


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT02045862  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Astellas Pharma Europe B.V.


Sponsor organisation address 
Sylviusweg 62, Leiden, Netherlands, 2333 BE


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


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


Paediatric regulatory details


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


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


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


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
08 Sep 2016


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
08 Sep 2016


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 safety and tolerability of longterm combination treatment with solifenacin (5 mg) and mirabegron (50 mg) compared to solifenacin and mirabegron monotherapy. The study comprised a singleblind, 2week placebo runin period followed by a randomized, doubleblind, activecontrolled, 12month treatment period and then by a 2week followup period.


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 
17 Mar 2014


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 
Slovakia: 108


Country: Number of subjects enrolled 
Slovenia: 2


Country: Number of subjects enrolled 
South Africa: 26


Country: Number of subjects enrolled 
Spain: 27


Country: Number of subjects enrolled 
Sweden: 13


Country: Number of subjects enrolled 
Thailand: 4


Country: Number of subjects enrolled 
Ukraine: 154


Country: Number of subjects enrolled 
United Kingdom: 7


Country: Number of subjects enrolled 
United States: 311


Country: Number of subjects enrolled 
Australia: 30


Country: Number of subjects enrolled 
Belgium: 6


Country: Number of subjects enrolled 
Bulgaria: 61


Country: Number of subjects enrolled 
Canada: 71


Country: Number of subjects enrolled 
Czech Republic: 142


Country: Number of subjects enrolled 
Denmark: 4


Country: Number of subjects enrolled 
Estonia: 6


Country: Number of subjects enrolled 
Finland: 1


Country: Number of subjects enrolled 
Germany: 94


Country: Number of subjects enrolled 
Hungary: 75


Country: Number of subjects enrolled 
Italy: 29


Country: Number of subjects enrolled 
Korea, Republic of: 122


Country: Number of subjects enrolled 
Latvia: 24


Country: Number of subjects enrolled 
Lithuania: 39


Country: Number of subjects enrolled 
Malaysia: 3


Country: Number of subjects enrolled 
Mexico: 8


Country: Number of subjects enrolled 
Netherlands: 14


Country: Number of subjects enrolled 
New Zealand: 12


Country: Number of subjects enrolled 
Norway: 32


Country: Number of subjects enrolled 
Poland: 278


Country: Number of subjects enrolled 
Romania: 32


Country: Number of subjects enrolled 
Russian Federation: 86


Country: Number of subjects enrolled 
Singapore: 8


Worldwide total number of subjects 
1829


EEA total number of subjects 
994


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) 
1201


From 65 to 84 years 
622


85 years and over 
6



Recruitment


Recruitment details 
Participants who had symptoms of “wet” overactive bladder (OAB) (urgency, urinary frequency and urgency incontinence) for ≥ 3 months were enrolled in 251 centers globally. A majority of the participants were recruited from participants who enrolled and completed studies 178CL101 or 905EC012.  
Preassignment


Screening details 
A total of 2084 participants were screened, 2063 participants received placebo runin treatment and 1829 participants were randomized into 1 of 3 treatment arms in a 1:1:4 ratio in the 52week doubleblind treatment period. Randomization was stratified by sex, age group (< 65 years, ≥ 65 years) and geographic region.  
Period 1


Period 1 title 
Overall period


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Arms


Are arms mutually exclusive 
Yes


Arm title

Mirabegron 50 mg  
Arm description 
Participants received mirabegron 50 mg once a day for 52 weeks.  
Arm type 
Active comparator  
Investigational medicinal product name 
Mirabegron


Investigational medicinal product code 
YM178


Other name 
Myrbetriq, Myrbetric, Betanis, Betmiga


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received mirabegron 50 mg orally once a day at the same time each day.


Investigational medicinal product name 
Placebo to solifenacin


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received placebo to match solifenacin 5 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.


Arm title

Solifenacin 5 mg  
Arm description 
Participants received solifenacin 5 mg once a day for 52 weeks.  
Arm type 
Active comparator  
Investigational medicinal product name 
Solifenacin succinate


Investigational medicinal product code 
YM905


Other name 
Solifenacin, Vesicare, Vesikur, Vesitrim


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received solifenacin 5 mg orally once a day at the same time each day.


Investigational medicinal product name 
Placebo to mirabegron


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received placebo to match mirabegron 50 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.


Arm title

Solifenacin 5 mg + mirabegron 50 mg  
Arm description 
Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.  
Arm type 
Experimental  
Investigational medicinal product name 
Mirabegron


Investigational medicinal product code 
YM178


Other name 
Myrbetriq, Myrbetric, Betanis, Betmiga


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received mirabegron 50 mg orally once a day at the same time each day.


Investigational medicinal product name 
Solifenacin succinate


Investigational medicinal product code 
YM905


Other name 
Solifenacin, Vesicare, Vesikur, Vesitrim


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received solifenacin 5 mg orally once a day at the same time each day.





Baseline characteristics reporting groups


Reporting group title 
Mirabegron 50 mg


Reporting group description 
Participants received mirabegron 50 mg once a day for 52 weeks.  
Reporting group title 
Solifenacin 5 mg


Reporting group description 
Participants received solifenacin 5 mg once a day for 52 weeks.  
Reporting group title 
Solifenacin 5 mg + mirabegron 50 mg


Reporting group description 
Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.  



End points reporting groups


Reporting group title 
Mirabegron 50 mg


Reporting group description 
Participants received mirabegron 50 mg once a day for 52 weeks.  
Reporting group title 
Solifenacin 5 mg


Reporting group description 
Participants received solifenacin 5 mg once a day for 52 weeks.  
Reporting group title 
Solifenacin 5 mg + mirabegron 50 mg


Reporting group description 
Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks. 


End point title 
Number of Participants with TreatmentEmergent Adverse Events (TEAEs) ^{[1]}  
End point description 
A TEAE is defined as an adverse event (AE) observed after taking the first dose of doubleblind treatment until 14 days after taking the last dose of doubleblind treatment for nonserious AEs and until 30 days after taking the last dose of doubleblind treatment for serious adverse events (SAEs). This includes abnormal laboratory tests, vital signs or electrocardiogram data that were defined as AEs if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant in the investigator's opinion. The severity of an AE was measured by: Mild (No disruption of normal daily activities); Moderate (Affected normal daily activities) and Severe (Inability to perform daily activities). The analysis population was the Safety Analysis Set (SAF), which consisted of all participants who received ≥ 1 dose of doubleblind study drug and excluded participants from one site due to protocol noncompliance.


End point type 
Primary


End point timeframe 
From first dose of doubleblind study drug up to 30 days after last dose of doubleblind study drug (up to 56 weeks)


Notes [1]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There were no predetermined hypothesis or comparative statistical analyses performed on the primary safety endpoint. However, hypothesis testing was performed for the primary and secondary efficacy endpoints. 



No statistical analyses for this end point 


End point title 
Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes per 24 Hours  
End point description 
An incontinence episode is defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and week 52 clinic visits. The analysis population was the Full Analysis Set (FAS), which was comprised of all randomized participants who took ≥ 1 dose of doubleblind treatment, reported ≥ 1 micturition in the baseline diary and ≥ 1 micturition postbaseline, reported ≥ 1 incontinence episode in the baseline diary and excluded participants from 2 sites due to protocol noncompliance and data integrity issues. Last observation carried forward (LOCF) was used for EoT.


End point type 
Primary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg + mirabegron 50 mg v Mirabegron 50 mg


Number of subjects included in analysis 
1485


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[2]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
0.21  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [2]  The 2sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the stratified rank ANCOVA. 

Statistical analysis title 
Difference vs. Solifenacin 5 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1481


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002 ^{[3]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.37  
upper limit 
0.11  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [3]  The 2sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the stratified rank ANCOVA. 


End point title 
Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours  
End point description 
A micturition is defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7days before the baseline and week 52 clinic visits. The analysis population was the FAS. LOCF was used for EoT.


End point type 
Primary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1485


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[4]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [4]  The 2sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the ANCOVA model. 

Statistical analysis title 
Difference vs. Solifenacin 5 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1481


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[5]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.71  
upper limit 
0.13  
Variability estimate 
Standard error of the mean


Dispersion value 
0.15


Notes [5]  The 2sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the ANCOVA model. 


End point title 
Change from Baseline to EoT in Mean Volume Voided per Micturition  
End point description 
The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7day micturition diary period. The analysis population was the FAS, with baseline and at least one postbaseline measurement. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Difference vs. Solifenacin 5 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1455


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
12.77


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.98  
upper limit 
19.57  
Variability estimate 
Standard error of the mean


Dispersion value 
3.47


Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1451


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
15.84


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.99  
upper limit 
22.69  
Variability estimate 
Standard error of the mean


Dispersion value 
3.49



End point title 
Change from Baseline to EoT in OAB Questionnaire (OABq) Symptom Bother Score  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicates an improvement. The analysis population was the FAS, with baseline and at least one postbaseline measurement. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1453


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
7.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
10.05  
upper limit 
5.05  
Variability estimate 
Standard error of the mean


Dispersion value 
1.27


Statistical analysis title 
Difference vs. Solifenacin 5 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1457


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.09  
upper limit 
2.12  
Variability estimate 
Standard error of the mean


Dispersion value 
1.27



End point title 
Change from Baseline to EoT in the Patient's Assessment of Treatment SatisfactionVisual Analogue Scale (TSVAS)  
End point description 
The TSVAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement. The analysis population was the FAS, with baseline and at least one postbaseline measurement. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Week 52




Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1452


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.28  
upper limit 
0.82  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Statistical analysis title 
Difference vs. Solifenacin 5 mg  
Statistical analysis description 
Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1457


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.32  
upper limit 
0.86  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14



End point title 
Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes per 24 Hours  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




No statistical analyses for this end point 


End point title 
Number of Incontinence Episodes Reported During the 7Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant recorded an incontinence episode during the 7day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the EoT 7day diary between the combination therapy group and the mirabegron monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of incontinence episodes divided by number of valid diary days) at baseline included as a covariate and number of valid diary day at EoT as the offset variable.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Mixed Effects Poissonnegative binomial  
Parameter type 
Rate ratio  
Point estimate 
0.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
0.84  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the EoT 7day diary between the combination therapy group and the solifenacin monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of incontinence episodes divided by number of valid diary days) at baseline included as a covariate and number of valid diary day at EoT as the offset variable.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.029  
Method 
Mixed Effects Poissonnegative binomial  
Parameter type 
Rate ratio  
Point estimate 
0.77


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.97  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant recorded an incontinence episode during the 7day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.76  
upper limit 
1.49  
Variability estimate 
Standard error of the mean


Dispersion value 
0.83


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.57  
upper limit 
0.72  
Variability estimate 
Standard error of the mean


Dispersion value 
0.84



End point title 
Number of IncontinenceFree Days Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
The number of incontinencefree days was the number of valid diary days during the 7day micturition diary period with no incontinence episodes recorded. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.26  
upper limit 
2.01  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.009  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.38


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.08  
upper limit 
1.75 


End point title 
Number of IncontinenceFree Days with < 8 Micturitions per Day Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
The number of incontinencefree days with < 8 micturitions per day was the number of valid diary days during the 7day micturition diary period with no incontinence episodes recorded and with < 8 micturitions per day. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours and baseline mean number of micturitions per 24 hours as a covariates.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
1.85  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours and baseline mean number of micturitions per 24 hours as a covariates.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.26  
upper limit 
2.05 


End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours  
End point description 
An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1489


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[6]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.43


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.65  
upper limit 
0.21  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [6]  The twosided pvalue is for pairwise comparisons between the combination therapy group and the solifenacin monotherapy group from stratified rank ANCOVA. 

Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1484


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.009 ^{[7]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.36  
upper limit 
0.09  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Notes [7]  The twosided pvalue is for pairwise comparisons between the combination therapy group and the solifenacin monotherapy group from stratified rank ANCOVA. 


End point title 
Number of Urgency Incontinence Episodes Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the EoT 7day diary between the combination therapy group and the mirabegron monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥65 years), geographic region and previous study history as factors, log(number of urgency incontinence episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary days at EoT as the offset variable.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1489


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.48  
upper limit 
0.79  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the EoT 7day diary between the combination therapy group and the solifenacin monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of urgency incontinence episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary day at EoT as the offset variable


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1484


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.023  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.58  
upper limit 
0.96  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001 ^{[8]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.98


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.51  
upper limit 
1.46  
Variability estimate 
Standard error of the mean


Dispersion value 
0.78


Notes [8]  The 2sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the stratified rank ANCOVA. 

Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006 ^{[9]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.93


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.47  
upper limit 
0.61  
Variability estimate 
Standard error of the mean


Dispersion value 
0.78


Notes [9]  The 2sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the stratified rank ANCOVA. 


End point title 
Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions per 24 Hours  
End point description 
A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7days before the baseline and prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




No statistical analyses for this end point 


End point title 
Number of Days with < 8 Micturitions per Day Reported During the 7Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)  
End point description 
The number of days with < 8 micturitions was the number of valid diary days during the 7day micturition diary period with with less than 8 micturitions per day. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.007  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.09  
upper limit 
1.73  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
1.8 


End point title 
Change from Baseline to EoT in Corrected Micturition Frequency  
End point description 
Corrected micturition frequency was defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline. Corrected micturition frequency was calculated as the baseline mean volume voided per micturition multiplied by the baseline mean number of micturitions per 24 hours divided by the mean volume voided per micturition at EoT. The analysis population was the FAS. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Month 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1485


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.16  
upper limit 
0.41  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1481


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.037  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19



End point title 
Change from Baseline to Months 3, 6 and 12 in Mean Volume Voided per Micturition  
End point description 
The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Months 3, 6, 12




No statistical analyses for this end point 


End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours  
End point description 
Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode recorded by the participant in the micturition diary for 7 days prior to each visit as 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency episode at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.73


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
0.37  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.036  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.03  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours  
End point description 
A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The mean number of nocturia episodes was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1279


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.068  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.19  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1289


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.059  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.19  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05



End point title 
Number of Nocturia Episodes Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of nocturia episodes during the EoT 7day diary between the combination therapy group and the mirabegron monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of nocturia episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary days as the offset variable.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1289


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.067  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
1.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.06


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Rate ratio of number of nocturia episodes during the EoT 7day diary between the combination therapy group and the solifenacin monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of nocturia episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary day as the offset variable.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1279


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.131  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
1.03  
Variability estimate 
Standard error of the mean


Dispersion value 
0.06



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1289


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.055  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.34  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.35


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1279


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.048  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.39  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.35



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used per 24 Hours  
End point description 
The mean number of pads used per 24 hours was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 pads used at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
972


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
0.16  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
964


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.039  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.55  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14



End point title 
Number of Pads Used Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
The number of pads used was the number of times a participant recorded a new pad used during the 7day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 pad used at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of pads during the EoT 7day diary between the combination therapy group and the mirabegron monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of pads divided by number of valid diary days) included as a covariate and post baseline number of valid diary days as the offset variable.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
972


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.45  
upper limit 
0.76  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Rate ratio of number of pads during the EoT 7day diary between the combination therapy group and the solifenacin monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of pads divided by number of valid diary days) included as a covariate and post baseline number of valid diary days as the offset variable.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
964


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.044  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.76


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.58  
upper limit 
0.99  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used Reported During the 7Day Micturition Diary Period Prior to Each Visit  
End point description 
The number of pads used was the number of times a participant recorded a new pad used during the 7day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 pad used at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
972


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.98


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.78  
upper limit 
1.18  
Variability estimate 
Standard error of the mean


Dispersion value 
0.92


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
964


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.072  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.68


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.52  
upper limit 
0.15  
Variability estimate 
Standard error of the mean


Dispersion value 
0.93



End point title 
Change from Baseline to Months 1, 3, 6, 9 and 12 in the OABq Symptom Bother Score  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




No statistical analyses for this end point 


End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in HealthRelated Quality of Life Questionnaire (HRQL): Total score  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.76


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.56  
upper limit 
6.96  
Variability estimate 
Standard error of the mean


Dispersion value 
1.12


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.01  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.68  
upper limit 
5.04  
Variability estimate 
Standard error of the mean


Dispersion value 
1.11



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in HealthRelated Quality of Life (HRQL) Subscale Score: Coping  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
5.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.99  
upper limit 
8.2  
Variability estimate 
Standard error of the mean


Dispersion value 
1.33


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.022  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
5.6  
Variability estimate 
Standard error of the mean


Dispersion value 
1.32



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in HealthRelated Quality of Life (HRQL) Subscale Score: Concern  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
5.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.65  
upper limit 
7.38  
Variability estimate 
Standard error of the mean


Dispersion value 
1.21


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.78


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.43  
upper limit 
6.13  
Variability estimate 
Standard error of the mean


Dispersion value 
1.2



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in HealthRelated Quality of Life (HRQL) Subscale Score: Sleep  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consisted of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each time was scored 16. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
5.15


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.47  
upper limit 
7.83  
Variability estimate 
Standard error of the mean


Dispersion value 
1.36


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.016  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.62  
upper limit 
5.93  
Variability estimate 
Standard error of the mean


Dispersion value 
1.35



End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in HealthRelated Quality of Life (HRQL) Subscale Score: Social  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.68


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.77  
upper limit 
4.59  
Variability estimate 
Standard error of the mean


Dispersion value 
0.98


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.287  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
2.93  
Variability estimate 
Standard error of the mean


Dispersion value 
0.97



End point title 
Change from Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of Treatment SatisfactionVisual Analogue Scale (TSVAS)  
End point description 
The TSVAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




No statistical analyses for this end point 


End point title 
Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition Questionnaire (PPBC)  
End point description 
The PPBC is a validated, global assessment tool using a 6point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. The analysis population is FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.16  
Variability estimate 
Standard error of the mean


Dispersion value 
0.08


Statistical analysis title 
Difference vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.011  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.36  
upper limit 
0.05  
Variability estimate 
Standard error of the mean


Dispersion value 
0.08



End point title 
Percentage of Participants in Each Category of Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT  
End point description 
The PGIC is a 2part questionnaire, assessing both the change in the participant’s overall condition and change in bladder condition since the start of the study (from very much worse to very much improved). The analysis population was the FAS. The number of participants analyzed includes participants with data available. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Month 12




No statistical analyses for this end point 


End point title 
Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT  
End point description 
The PGIC is a 2part questionnaire, assessing both the change in the participant’s overall condition and change in bladder condition since the start of the study (from very much worse to very much improved). The analysis population was the FAS. The number of participants analyzed includes participants with data available. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Month 12




No statistical analyses for this end point 


End point title 
Number of Participants With Change from Baseline to EoT in European Quality of Life in 5 Dimensions (EQ5D) Questionnaire Subscale Score: Mobility  
End point description 
The EQ5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The analysis population was the FAS. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Month 12




No statistical analyses for this end point 


End point title 
Number of Participants With Change from Baseline to EoT in EQ5D Questionnaire Subscale Score: Selfcare  
End point description 
The EQ5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The analysis population was the FAS. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Month 12




No statistical analyses for this end point 


End point title 
Number of Participants With Change from Baseline to EoT in EQ5D Questionnaire Subscale Score: Usual Activities  
End point description 
The EQ5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The analysis population was the FAS. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Month 12




No statistical analyses for this end point 


End point title 
Number of Participants With Change from Baseline to EoT in EQ5D Questionnaire Subscale Score: Pain/Discomfort  
End point description 
The EQ5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The analysis population was the FAS. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Month 12




No statistical analyses for this end point 


End point title 
Number of Participants With Change from Baseline to EoT in EQ5D Questionnaire Subscale Score: Anxiety/Depression  
End point description 
The EQ5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The analysis population was the FAS. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Month 12




No statistical analyses for this end point 


End point title 
Change from Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed  
End point description 
The WPAI:SHP is a selfadministered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicates improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with both baseline and postbaseline values are included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 6,12




No statistical analyses for this end point 


End point title 
Change from Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working  
End point description 
The WPAI:SHP is a selfadministered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicates improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with both baseline and postbaseline values and who were employed during the study are included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 6,12




No statistical analyses for this end point 


End point title 
Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment  
End point description 
The WPAI:SHP is a selfadministered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement. N is the number of participants analyzed with data available at each time point. Only participants with both baseline and postbaseline values and who were employed during the study are included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 6, 12




No statistical analyses for this end point 


End point title 
Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment  
End point description 
The WPAI:SHP is a selfadministered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement. N is the number of participants analyzed with data available at each time point. Only participants with both baseline and postbaseline values during the study are included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 6, 12




No statistical analyses for this end point 


End point title 
Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the last 3 days of the 7day micturition diary is reported. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours during the last 3 days as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.26  
upper limit 
2.15  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours during the last 3 days as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.08  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.97  
upper limit 
1.67 


End point title 
Percentage of Participants with ≥ 10 Points Improvement from Baseline in the OABq Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OABq subscale as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.37  
upper limit 
2.57  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OABq subscale as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
2.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.49  
upper limit 
2.78 


End point title 
Percentage of Participants with ≥ 10 Points Improvement from Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT  
End point description 
The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OABq subscale as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.08  
upper limit 
1.92  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OABq subscale as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.36  
upper limit 
2.43 


End point title 
Percentage of Participants with 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours at Months 1, 3, 6, 9, 12 and EoT  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.34  
upper limit 
2.41  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.019  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.44


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.06  
upper limit 
1.95 


End point title 
Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the 7day micturition diary is reported. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.133  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.94  
upper limit 
1.62  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.26  
upper limit 
2.19 


End point title 
Percentage of Participants with Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT  
End point description 
The percentage of participants with micturition frequency normalization was defined as any participant who had ≥ 8 micturitions/24 hours at baseline and < 8 micturitions/24 h postbaseline at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Participants with less < 8 micturitions per 24 hours at baseline were not included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.55


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.18  
upper limit 
2.03  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.12  
upper limit 
1.95 


End point title 
Percentage of Participants with ≥ 1 Point Improvement from Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT  
End point description 
The PPBC is a validated, global assessment tool using a 6point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.68


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.24  
upper limit 
2.29  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.109  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.94  
upper limit 
1.77 


End point title 
Percentage of Participants with Major (≥ 2 points) Improvement from Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT  
End point description 
The PPBC is a validated, global assessment tool using a 6point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.26  
upper limit 
2.25  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.22  
upper limit 
2.16 


End point title 
Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 10 Points Improvement on OABq Symptom Bother Scale) at Months 1, 3, 6, 9, 12 and EoT  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12




Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline OABq symptom bother scale as covariates.


Comparison groups 
Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1495


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.99


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
2.62  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (EoT)  
Statistical analysis description 
Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline OABq symptom bother scale as covariates.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg


Number of subjects included in analysis 
1492


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Logistic regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.79


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.35  
upper limit 
2.36 


End point title 
Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 10 Points Improvement on OABq HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT  
End point description 
An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OABq is a selfreported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Months 1, 3, 6, 9, 12


