Clinical Trial Results:
A Randomized, Doubleblind, Parallelgroup, Placebo and Activecontrolled, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Combinations of Solifenacin Succinate and Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in the Treatment of Overactive Bladder
Summary


EudraCT number 
201200573591 
Trial protocol 
GB BE DE NL CZ HU LV SE IT EE FI SK SI DK ES LT PL GR BG 
Global end of trial date 
22 Oct 2015

Results information


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

First version publication date 
04 Nov 2016

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 
178CL101


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01972841  
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 
22 Oct 2015


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
22 Oct 2015


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
To evaluate the efficacy of 2 dose combinations of solifenacin and mirabegron
(5 + 25 mg and 5 + 50 mg) compared to solifenacin (5 mg) and mirabegron (25 mg and
50 mg) monotherapy.


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


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
05 Nov 2013


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
Yes


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Slovakia: 158


Country: Number of subjects enrolled 
Slovenia: 6


Country: Number of subjects enrolled 
South Africa: 36


Country: Number of subjects enrolled 
Spain: 48


Country: Number of subjects enrolled 
Sweden: 79


Country: Number of subjects enrolled 
Taiwan: 8


Country: Number of subjects enrolled 
Thailand: 50


Country: Number of subjects enrolled 
Turkey: 5


Country: Number of subjects enrolled 
Ukraine: 325


Country: Number of subjects enrolled 
United Kingdom: 23


Country: Number of subjects enrolled 
United States: 873


Country: Number of subjects enrolled 
Argentina: 5


Country: Number of subjects enrolled 
Australia: 56


Country: Number of subjects enrolled 
Belgium: 5


Country: Number of subjects enrolled 
Bulgaria: 116


Country: Number of subjects enrolled 
Canada: 133


Country: Number of subjects enrolled 
China: 118


Country: Number of subjects enrolled 
Czech Republic: 184


Country: Number of subjects enrolled 
Denmark: 7


Country: Number of subjects enrolled 
Estonia: 12


Country: Number of subjects enrolled 
Finland: 6


Country: Number of subjects enrolled 
France: 18


Country: Number of subjects enrolled 
Germany: 159


Country: Number of subjects enrolled 
Greece: 1


Country: Number of subjects enrolled 
Hong Kong: 4


Country: Number of subjects enrolled 
Hungary: 114


Country: Number of subjects enrolled 
Italy: 25


Country: Number of subjects enrolled 
Korea, Republic of: 211


Country: Number of subjects enrolled 
Latvia: 29


Country: Number of subjects enrolled 
Lithuania: 55


Country: Number of subjects enrolled 
Malaysia: 8


Country: Number of subjects enrolled 
Mexico: 19


Country: Number of subjects enrolled 
Netherlands: 31


Country: Number of subjects enrolled 
New Zealand: 16


Country: Number of subjects enrolled 
Norway: 40


Country: Number of subjects enrolled 
Peru: 14


Country: Number of subjects enrolled 
Philippines: 20


Country: Number of subjects enrolled 
Poland: 317


Country: Number of subjects enrolled 
Romania: 68


Country: Number of subjects enrolled 
Russian Federation: 108


Country: Number of subjects enrolled 
Singapore: 17


Worldwide total number of subjects 
3527


EEA total number of subjects 
1501


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) 
2383


From 65 to 84 years 
1134


85 years and over 
10



Recruitment


Recruitment details 
Participants who had symptoms of “wet” overactive bladder (OAB) (urgency, urinary frequency and urgency incontinence) for ≥ 3 months were enrolled in 435 centers in 42 countries. Eligible participants went into a singleblind, 4week placebo runin period and completed a micturition diary 7 days prior to each study visit.  
Preassignment


Screening details 
A total of 6991 participants were screened, 6275 participants received placebo runin treatment and 3527 participants were randomized into 1 of 6 treatment arms in a 1:1:1:1:2:2 ratio in the 12week doubleblind treatment period. A total of 953 participants were also enrolled in an ambulatory blood pressure monitoring (ABPM) substudy.  
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

Placebo  
Arm description 
Participants who received matching placebo once a day for 12 weeks.  
Arm type 
Placebo  
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 25 mg or 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.


Arm title

Mirabegron 25 mg  
Arm description 
Participants who received mirabegron 25 mg once a day for 12 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 25 mg orally once a day at the same time each day.


Arm title

Mirabegron 50 mg  
Arm description 
Participants who received mirabegron 50 mg once a day for 12 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.


Arm title

Solifenacin 5 mg  
Arm description 
Participants who received solifenacin 5 mg once a day for 12 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 succinate 5 mg orally once a day at the same time each day.


Arm title

Solifenacin 5 mg + mirabegron 25 mg  
Arm description 
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.  
Arm type 
Experimental  
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 succinate 5 mg orally once a day at the same time each day.


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 25 mg orally once a day at the same time each day.


Arm title

Solifenacin 5 mg + mirabegron 50 mg  
Arm description 
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.  
Arm type 
Experimental  
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 succinate 5 mg orally once a day at the same time each day.


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.





Baseline characteristics reporting groups


Reporting group title 
Placebo


Reporting group description 
Participants who received matching placebo once a day for 12 weeks.  
Reporting group title 
Mirabegron 25 mg


Reporting group description 
Participants who received mirabegron 25 mg once a day for 12 weeks.  
Reporting group title 
Mirabegron 50 mg


Reporting group description 
Participants who received mirabegron 50 mg once a day for 12 weeks.  
Reporting group title 
Solifenacin 5 mg


Reporting group description 
Participants who received solifenacin 5 mg once a day for 12 weeks.  
Reporting group title 
Solifenacin 5 mg + mirabegron 25 mg


Reporting group description 
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.  
Reporting group title 
Solifenacin 5 mg + mirabegron 50 mg


Reporting group description 
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.  



End points reporting groups


Reporting group title 
Placebo


Reporting group description 
Participants who received matching placebo once a day for 12 weeks.  
Reporting group title 
Mirabegron 25 mg


Reporting group description 
Participants who received mirabegron 25 mg once a day for 12 weeks.  
Reporting group title 
Mirabegron 50 mg


Reporting group description 
Participants who received mirabegron 50 mg once a day for 12 weeks.  
Reporting group title 
Solifenacin 5 mg


Reporting group description 
Participants who received solifenacin 5 mg once a day for 12 weeks.  
Reporting group title 
Solifenacin 5 mg + mirabegron 25 mg


Reporting group description 
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.  
Reporting group title 
Solifenacin 5 mg + mirabegron 50 mg


Reporting group description 
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks. 


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 was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7day micturition diary period. 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 one site. Last observation carried forward (LOCF) was used for EoT.


End point type 
Primary


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




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1236


Analysis specification 
Prespecified


Analysis type 
superiority ^{[1]}  
Pvalue 
= 0.072 ^{[2]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.49  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [1]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [2]  Nominal pvalue 

Statistical analysis title 
Difference vs. Solifenacin 5 mg (2)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1229


Analysis specification 
Prespecified


Analysis type 
superiority ^{[3]}  
Pvalue 
= 0.033  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.44  
upper limit 
0.04  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [3]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. 

Statistical analysis title 
Difference vs. Mirabegron 25 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1232


Analysis specification 
Prespecified


Analysis type 
superiority ^{[4]}  
Pvalue 
= 0.001 ^{[5]}  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.58  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [4]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [5]  Nominal pvalue 

Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1222


Analysis specification 
Prespecified


Analysis type 
superiority ^{[6]}  
Pvalue 
= 0.052  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.47  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Notes [6]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. 


End point title 
Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours  
End point description 
A micturition was defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7day micturition diary period. The analysis population was the FAS. LOCF was used for EoT.


End point type 
Primary


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




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1236


Analysis specification 
Prespecified


Analysis type 
superiority ^{[7]}  
Pvalue 
= 0.04 ^{[8]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.57  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [7]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [8]  Nominal pvalue 

Statistical analysis title 
Difference vs. Solifenacin 5 mg (2)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1229


Analysis specification 
Prespecified


Analysis type 
superiority ^{[9]}  
Pvalue 
= 0.006 ^{[10]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.67  
upper limit 
0.11  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [9]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [10]  Nominal pvalue 

Statistical analysis title 
Difference vs. Mirabegron 25 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1232


Analysis specification 
Prespecified


Analysis type 
superiority ^{[11]}  
Pvalue 
= 0.001 ^{[12]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.48


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.21  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [11]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [12]  Nominal pvalue 

Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1222


Analysis specification 
Prespecified


Analysis type 
superiority ^{[13]}  
Pvalue 
< 0.001 ^{[14]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
0.28  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [13]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [14]  Nominal pvalue 


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. LOCF was used for EoT.


End point type 
Secondary


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




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1232


Analysis specification 
Prespecified


Analysis type 
superiority ^{[15]}  
Pvalue 
= 0.219 ^{[16]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.85


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.29  
upper limit 
10  
Variability estimate 
Standard error of the mean


Dispersion value 
3.13


Notes [15]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [16]  Nominal pvalue 

Statistical analysis title 
Difference vs. Solifenacin 5 mg (2)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1232


Analysis specification 
Prespecified


Analysis type 
superiority ^{[17]}  
Pvalue 
= 0.005 ^{[18]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
8.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.61  
upper limit 
14.89  
Variability estimate 
Standard error of the mean


Dispersion value 
3.13


Notes [17]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [18]  Nominal pvalue 

Statistical analysis title 
Difference vs. Mirabegron 25 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1228


Analysis specification 
Prespecified


Analysis type 
superiority ^{[19]}  
Pvalue 
< 0.001 ^{[20]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
21.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
15.35  
upper limit 
27.68  
Variability estimate 
Standard error of the mean


Dispersion value 
3.14


Notes [19]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [20]  Nominal pvalue 

Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1229


Analysis specification 
Prespecified


Analysis type 
superiority ^{[21]}  
Pvalue 
< 0.001 ^{[22]}  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
17.74


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.58  
upper limit 
23.9  
Variability estimate 
Standard error of the mean


Dispersion value 
3.14


Notes [21]  Adjustment for multiplicity across primary and the first secondary endpoint as well as across the 2 combination doses was made using a sequential Bonferronibased testing procedure. No adjustment for multiplicity was needed for testing combination therapy vs. its 2 monotherapy components. [22]  Nominal pvalue 


End point title 
Change from Baseline to EoT in OAB Questionnaire (OABq) Symptom Bother Score  
End point description 
The OABq was a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The symptom bother portion consisted 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. LOCF was used for EoT.


End point type 
Secondary


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




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1199


Analysis specification 
Prespecified


Analysis type 
superiority ^{[23]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.63


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.98  
upper limit 
2.27  
Variability estimate 
Standard error of the mean


Dispersion value 
1.2


Notes [23]  No adjustment for multiplicity was made for this comparison. 

Statistical analysis title 
Difference vs. Solifenacin 5 mg (2)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1194


Analysis specification 
Prespecified


Analysis type 
superiority ^{[24]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
5.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.17  
upper limit 
3.44  
Variability estimate 
Standard error of the mean


Dispersion value 
1.21


Notes [24]  No adjustment for multiplicity was made for this comparison. 

Statistical analysis title 
Difference vs. Mirabegron 25 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1192


Analysis specification 
Prespecified


Analysis type 
superiority ^{[25]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
7.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.5  
upper limit 
4.76  
Variability estimate 
Standard error of the mean


Dispersion value 
1.21


Notes [25]  No adjustment for multiplicity was made for this comparison. 

Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1193


Analysis specification 
Prespecified


Analysis type 
superiority ^{[26]}  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
6.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.46  
upper limit 
3.74  
Variability estimate 
Standard error of the mean


Dispersion value 
1.2


Notes [26]  No adjustment for multiplicity was made for this comparison. 


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


End point type 
Secondary


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




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1197


Analysis specification 
Prespecified


Analysis type 
superiority ^{[27]}  
Pvalue 
= 0.077  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.03  
upper limit 
0.52  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [27]  No adjustment for multiplicity was made for this comparison. 

Statistical analysis title 
Difference vs. Solifenacin 5 mg (2)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1193


Analysis specification 
Prespecified


Analysis type 
superiority ^{[28]}  
Pvalue 
= 0.05  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.55  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [28]  No adjustment for multiplicity was made for this comparison. 

Statistical analysis title 
Difference vs. Mirabegron 25 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1189


Analysis specification 
Prespecified


Analysis type 
superiority ^{[29]}  
Pvalue 
= 0.008  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.65  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [29]  No adjustment for multiplicity was made for this comparison. 

Statistical analysis title 
Difference vs. Mirabegron 50 mg  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous overactive bladder medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1192


Analysis specification 
Prespecified


Analysis type 
superiority ^{[30]}  
Pvalue 
= 0.007  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.65  
Variability estimate 
Standard error of the mean


Dispersion value 
0.14


Notes [30]  No adjustment for multiplicity was made for this comparison. 


End point title 
Number of Incontinence Episodes at Weeks 4, 8, 12 and EoT  
End point description 
The number of incontinence episodes was calculated as the total number of incontinence episodes on valid diary days recorded during the 7day micturition diary period. 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 
Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.135  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
1.04  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.282  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.75  
upper limit 
1.09  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Statistical analysis title 
Rate ratio vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
0.85  
Variability estimate 
Standard error of the mean


Dispersion value 
0.09


Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, ≥65 years), geographic region and previous OAB medication (yes, no) as factors, log(number of incontinence episodes used divided by number of valid diary days) at baseline included as a covariate and number of valid diary days at EoT as the offset variable.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.172  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
1.06  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Incontinence Episodes  
End point description 
The number of incontinence episodes was calculated as the total number of incontinence episodes on valid diary days recorded during the 7day micturition diary period. 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.074  
Method 
Stratified rank ANCOVA  
Parameter type 
least squares mean difference  
Point estimate 
1.64


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.27  
upper limit 
0.01  
Variability estimate 
Standard error of the mean


Dispersion value 
0.83


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the solifenacin 5 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1231


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.025  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.96  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.83


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 25 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1233


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Stratified rank ANCOVA  
Parameter type 
least square mean difference  
Point estimate 
2.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4  
upper limit 
0.73  
Variability estimate 
Standard error of the mean


Dispersion value 
0.83


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the mirabegron 50 mg monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1227


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.024  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.23  
upper limit 
0.05  
Variability estimate 
Standard error of the mean


Dispersion value 
0.84



End point title 
Change from Baseline to Weeks 4, 8 and 12 in Mean Number of Incontinence Episodes per 24 Hours  
End point description 
The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7day micturition diary period. 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 Weeks 4, 8, 12




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 4, 8 and 12 in Mean Number of Micturitions per 24 Hours  
End point description 
The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7day micturition diary period. 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 Weeks 4, 8, 12




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 4, 8 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. 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 Weeks 4, 8, 12




No statistical analyses for this end point 


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. The analysis population was the FAS. LOCF was used for EoT.


End point type 
Secondary


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




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1236


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.52  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.19


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.39  
upper limit 
0.76  
Variability estimate 
Standard error of the mean


Dispersion value 
0.29


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline 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 
1229


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.413  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
0.34  
Variability estimate 
Standard error of the mean


Dispersion value 
0.29


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1232


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.34  
Variability estimate 
Standard error of the mean


Dispersion value 
0.29


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline 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 
1222


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.06  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.56


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.13  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3



End point title 
Number of Urgency Incontinence Episodes at Weeks 4, 8, 12 and EOT  
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 number of times a participant recorded an urgency incontinence episode 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 
Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Rate ratio of number of urgency incontinence episodes during the 7day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.11  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.85


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
1.04  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Rate ratio of number of urgency incontinence episodes during the 7day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.288  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.73  
upper limit 
1.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
Rate ratio vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Rate ratio of number of urgency incontinence episodes during the 7day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.53  
upper limit 
0.79  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of urgency incontinence episodes during the 7day diary bet. the given combination group & the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65,≥ 65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of urgency incontinence episodes used divided by number of valid diary days) included as a covariate & postbaseline number of valid diary days as offset variable.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.084  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.84


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.68  
upper limit 
1.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Urgency Incontinence Episodes  
End point description 
The number of urgency incontinence episodes was number of times a participant recorded an urgency 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. 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.114  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.09  
upper limit 
0.13  
Variability estimate 
Standard error of the mean


Dispersion value 
0.76


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.034  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.62


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.1  
upper limit 
0.13  
Variability estimate 
Standard error of the mean


Dispersion value 
0.76


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.09  
upper limit 
1.12  
Variability estimate 
Standard error of the mean


Dispersion value 
0.76


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.7  
upper limit 
0.71  
Variability estimate 
Standard error of the mean


Dispersion value 
0.76



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours  
End point description 
The mean number of urgency incontinence episodes was calculated from data recorded by the participant per day on valid diary days 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.134  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.46  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.043  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.45  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Statistical analysis title 
Difference vs. Mirabegron 25 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.59  
upper limit 
0.15  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Statistical analysis title 
Difference vs. Mirabegron 25 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.019  
Method 
Stratified rank ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours  
End point description 
An urgency episode was a complaint of a sudden, compelling desire to pass urine, which was difficult to defer; it was recorded when a micturition or incontinence episode was recorded and the severity of urinary urgency recorded was 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS). The mean number of urgency episodes was calculated from data recorded by the participant per day on valid diary days 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 episode at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.074  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.69  
upper limit 
0.03  
Variability estimate 
Standard error of the mean


Dispersion value 
0.18


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.82  
upper limit 
0.09  
Variability estimate 
Standard error of the mean


Dispersion value 
0.18


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.01  
upper limit 
0.28  
Variability estimate 
Standard error of the mean


Dispersion value 
0.18


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.24  
upper limit 
0.51  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19



End point title 
Number of Nocturia Episodes at Weeks 4, 8, 12 and EoT  
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 
Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.88


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.81  
upper limit 
0.96  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.81


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.74  
upper limit 
0.88  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Statistical analysis title 
Rate ratio vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.049  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of nocturia episodes used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.86


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
0.94  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Nocturia Episodes  
End point description 
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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.073  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.61


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.28  
upper limit 
0.06  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.83  
upper limit 
0.48  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.14  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.18  
upper limit 
0.17  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.21


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.88  
upper limit 
0.54  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours  
End point description 
The mean number of nocturia episodes was calculated from data recorded by the participant per day on valid diary days 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.065  
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. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.26  
upper limit 
0.07  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
0.02  
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 calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.26  
upper limit 
0.07  
Variability estimate 
Standard error of the mean


Dispersion value 
0.05



End point title 
Number of Pads Used at Weeks 4, 8, 12 and EoT  
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 
Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.938  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
1.01


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1.27  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Statistical analysis title 
Rate ratio vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.967  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.79  
upper limit 
1.25  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Statistical analysis title 
Rate ratio vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.008  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.73


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.58  
upper limit 
0.92  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Statistical analysis title 
Rate ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Rate ratio of number of incontinence episodes during the 7day diary between the given combination group and the given monotherapy group calculated from a negative binomial regression model incl. treatment group, sex, age group (<65, >=65 years), geographic region and previous OAB medication (yes, no) as factors, baseline log(number of pads used divided by number of valid diary days) included as a covariate and postbaseline number of valid diary days as offset variable.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.069  
Method 
Negative binomial regression  
Parameter type 
Rate ratio  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.64  
upper limit 
1.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Number of Pads Used  
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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.958  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.73  
upper limit 
1.64  
Variability estimate 
Standard error of the mean


Dispersion value 
0.86


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.27  
upper limit 
1.11  
Variability estimate 
Standard error of the mean


Dispersion value 
0.86


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.028  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.91


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.62  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.87


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.108  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.13  
upper limit 
0.31  
Variability estimate 
Standard error of the mean


Dispersion value 
0.88



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Pads Used per 24 Hours  
End point description 
The mean number of pads used was calculated from data recorded by the participant per day on valid diary days 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 pads used at baseline were included in the analysis. LOCF was used for EoT.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.993  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


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


Dispersion value 
0.13


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.65  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.19  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.035  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.52  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.169  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.18


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.43  
upper limit 
0.08  
Variability estimate 
Standard error of the mean


Dispersion value 
0.13



End point title 
Number of IncontinenceFree Days at Weeks 4, 8, 12 and EoT  
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 
Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.11  
upper limit 
1.68  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of 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 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.11  
upper limit 
1.68  
Statistical analysis title 
Odds ratio vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of mean number of incontinence episodes per 24 hours as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.59


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.29  
upper limit 
1.95  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline logarithm of 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 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.36


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
1.68 


End point title 
Number of Days with < 8 Micturitions at Weeks 4, 8, 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 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 
Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) 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 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.039  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.23


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.01  
upper limit 
1.5  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) 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 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.009  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.07  
upper limit 
1.59  
Statistical analysis title 
Odds ratio vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.45


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.19  
upper limit 
1.77  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) 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 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.23  
upper limit 
1.84 


End point title 
Number of IncontinenceFree Days with < 8 Micturitions per Day at Weeks 4, 8, 12 and EoT  
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 
Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) 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 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.011  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.07  
upper limit 
1.64  
Statistical analysis title 
Odds ratio vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) 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 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.14  
upper limit 
1.75  
Statistical analysis title 
Odds ratio vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


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


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.32  
upper limit 
2.06  
Statistical analysis title 
Odds ratio vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Odds ratio from a overdispersed binomial regression model (Williams' method) including treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) 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 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
Overdispersed binomial regression  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.66


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.33  
upper limit 
2.07 


End point title 
Change from Baseline in Patient Perception of Bladder Condition Questionnaire (PPBC) at Weeks 4, 8, 12 and EoT  
End point description 
The PPBC was a validated, global assessment tool using a 6point Likert scale on which participants rated their subjective impression of their current bladder condition. 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.41  
upper limit 
0.11  
Variability estimate 
Standard error of the mean


Dispersion value 
0.07


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.54  
upper limit 
0.25  
Variability estimate 
Standard error of the mean


Dispersion value 
0.07


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.07


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.07



End point title 
Change from Baseline to Weeks 4, 8 and 12 in the OABq Symptom Bother Score  
End point description 
The OABq was a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The symptom bother portion (seen in this endpoint) consisted 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 Weeks 4, 8, 12




No statistical analyses for this end point 


End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in HealthRelated Quality of Life Questionnaire (HRQL) Total Score  
End point description 
The OABq was a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion (seen in this endpoint) consisted of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1 6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.81


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.69  
upper limit 
5.94  
Variability estimate 
Standard error of the mean


Dispersion value 
1.08


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.16


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.03  
upper limit 
6.29  
Variability estimate 
Standard error of the mean


Dispersion value 
1.09


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
5.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.88  
upper limit 
7.15  
Variability estimate 
Standard error of the mean


Dispersion value 
1.09


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.002  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.17  
upper limit 
5.43  
Variability estimate 
Standard error of the mean


Dispersion value 
1.09



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Coping  
End point description 
The OABq was a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 16. The Coping score was calculated by adding 8 response 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.6  
upper limit 
6.65  
Variability estimate 
Standard error of the mean


Dispersion value 
1.29


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Lest squares mean difference  
Point estimate 
4.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.34  
upper limit 
7.4  
Variability estimate 
Standard error of the mean


Dispersion value 
1.29


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
6.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.55  
upper limit 
8.63  
Variability estimate 
Standard error of the mean


Dispersion value 
1.3


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.27  
upper limit 
6.33  
Variability estimate 
Standard error of the mean


Dispersion value 
1.29



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Concern  
End point description 
The OABq was a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 16. The Concern score was calculated by adding 7 response 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.24


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.84  
upper limit 
6.63  
Variability estimate 
Standard error of the mean


Dispersion value 
1.22


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.42  
upper limit 
7.22  
Variability estimate 
Standard error of the mean


Dispersion value 
1.22


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
5.34


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.93  
upper limit 
7.75  
Variability estimate 
Standard error of the mean


Dispersion value 
1.23


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.41


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.01  
upper limit 
6.81  
Variability estimate 
Standard error of the mean


Dispersion value 
1.22



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Sleep  
End point description 
The OABq was a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consisted of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 16. The Sleep score was calculated by adding 5 response 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.98  
upper limit 
6.85  
Variability estimate 
Standard error of the mean


Dispersion value 
1.24


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.42


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.98  
upper limit 
6.86  
Variability estimate 
Standard error of the mean


Dispersion value 
1.24


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.001  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
4.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.42  
upper limit 
7.32  
Variability estimate 
Standard error of the mean


Dispersion value 
1.25


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.008  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
3.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.84  
upper limit 
5.72  
Variability estimate 
Standard error of the mean


Dispersion value 
1.24



End point title 
Change from Baseline to Weeks 4, 8, 12 and EoT in HRQL Subscale Score: Social  
End point description 
The OABq was a selfreported questionnaire with items relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consisted of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 16. The Social score was calculated by adding 5 response 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 Weeks 4, 8, 12 and EoT (up to 12 weeks)




Statistical analysis title 
Difference vs. Solifenacin 5 mg (1) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.022  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.27


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.33  
upper limit 
4.21  
Variability estimate 
Standard error of the mean


Dispersion value 
0.99


Statistical analysis title 
Difference vs. Solifenacin 5 mg (2) (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (solifenacin 5 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1242


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.023  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.31  
upper limit 
4.19  
Variability estimate 
Standard error of the mean


Dispersion value 
0.99


Statistical analysis title 
Difference vs. Mirabegron 25 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 25 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 25 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron 25 mg v Solifenacin 5 mg + mirabegron 25 mg


Number of subjects included in analysis 
1237


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.005  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
2.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.85  
upper limit 
4.74  
Variability estimate 
Standard error of the mean


Dispersion value 
0.99


Statistical analysis title 
Difference vs. Mirabegron 50 mg (EoT)  
Statistical analysis description 
Difference of the adjusted mean calculated by subtracting the adjusted mean of the monotherapy group (mirabegron 50 mg) from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (<65, >=65 years), previous OAB medication (yes, no) and geographic region as fixed factors and baseline value as a covariate.


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


Number of subjects included in analysis 
1238


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.337  
Method 
ANCOVA  
Parameter type 
Least squares mean difference  
Point estimate 
0.95


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.99  
upper limit 
2.89  
Variability estimate 
Standard error of the mean


Dispersion value 
0.99



End point title 
Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Week 12 and EoT  
End point description 
The PGIC was 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 
Week 12 and EoT (up to 12 weeks)




No statistical analyses for this end point 


End point title 
PGIC Scale: Impression in General Health at Week 12 and EoT  
End point description 
The PGIC was 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 
Week 12 and EoT (up to 12 weeks)




No statistical analyses for this end point 


End point title 
Change from Baseline to EoT in European Quality of Life in 5 Dimensions (EQ5D) Questionnaire Subscale Score: Mobility  
End point description 
The EQ5D questionnaire was an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Selfcare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension had 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 EoT (up to 12 weeks)


