Clinical Trial Results:
A Phase 4, DoubleBlind, Randomized, Placebocontrolled, MultiCenter Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Men with Overactive Bladder (OAB) Symptoms While Taking the Alpha Blocker Tamsulosin Hydrochloride for Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH)
Summary


EudraCT number 
201500403636 
Trial protocol 
CZ DE PL ES GB IT 
Global end of trial date 
11 Sep 2018

Results information


Results version number 
v2(current) 
This version publication date 
18 Jun 2020

First version publication date 
30 Aug 2019

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 
178MA1008


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT02757768  
WHO universal trial number (UTN) 
  
Other trial identifiers 
Acronym: PLUS  
Sponsors


Sponsor organisation name 
Astellas Pharma Global Development, Inc.


Sponsor organisation address 
1 Astellas Way, Northbrook, IL, United States, 60062


Public contact 
Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com


Scientific contact 
Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., 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 
11 Sep 2018


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
11 Sep 2018


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
The primary objective of this study was to study the efficacy of mirabegron versus placebo in men with OAB symptoms while taking tamsulosin for LUTS due to BPH.


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 
13 Jun 2016


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Canada: 28


Country: Number of subjects enrolled 
Czech Republic: 105


Country: Number of subjects enrolled 
France: 3


Country: Number of subjects enrolled 
Germany: 91


Country: Number of subjects enrolled 
Italy: 92


Country: Number of subjects enrolled 
Poland: 150


Country: Number of subjects enrolled 
Spain: 49


Country: Number of subjects enrolled 
United Kingdom: 24


Country: Number of subjects enrolled 
United States: 173


Worldwide total number of subjects 
715


EEA total number of subjects 
514


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) 
312


From 65 to 84 years 
402


85 years and over 
1



Recruitment


Recruitment details 
The study enrolled male participants with overactive bladder (OAB) symptoms who were taking the alphablocker tamsulosin for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).  
Preassignment


Screening details 
Eligible participants who met inclusion criteria and none of the exclusion criteria were enrolled. Participants entered a 4week open label tamsulosin hydrochloride 0.4 mg once daily (QD) runin period prior to being randomized in a 1:1 ratio into the 12week doubleblind treatment period of either mirabegron or placebo once daily.  
Period 1


Period 1 title 
Overall Study (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Arms


Are arms mutually exclusive 
Yes


Arm title

Mirabegron  
Arm description 
Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.  
Arm type 
Experimental  
Investigational medicinal product name 
Mirabegron


Investigational medicinal product code 
YM178


Other name 
Myrbetriq, Betmiga


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks.


Investigational medicinal product name 
Tamsulosin Hydrochloride


Investigational medicinal product code 

Other name 
Flomax, Omnic


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received once daily treatment with tamsulosin hydrochloride 0.4 mg throughout the study.


Arm title

Placebo  
Arm description 
Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.  
Arm type 
Placebo  
Investigational medicinal product name 
Placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received initial dose of 25 mg of matching placebo which was increased to 50 mg after 4 weeks.


Investigational medicinal product name 
Tamsulosin Hydrochloride


Investigational medicinal product code 

Other name 
Flomax, Omnic


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Participants received once daily treatment with tamsulosin hydrochloride 0.4 mg throughout the study.





Baseline characteristics reporting groups


Reporting group title 
Mirabegron


Reporting group description 
Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.  
Reporting group title 
Placebo


Reporting group description 
Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.  



End points reporting groups


Reporting group title 
Mirabegron


Reporting group description 
Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.  
Reporting group title 
Placebo


Reporting group description 
Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study. 


End point title 
Change From Baseline to End of Treatment (EoT) in Mean Number of Micturitions Per Day  
End point description 
Participants recorded micturitions in the ediary during three days. The mean number of micturitions was calculated as the average number of times a participant recorded a micturition per day during the 3day period. Only voluntary micturitions were counted and the episodes of incontinence were not included. The analysis population was the full analysis set (FAS), which consisted of all randomized participants who took at least 1 dose of doubleblind study drug, reported at least 1 baseline micturition recorded in the 3day ediary and at least 1 postbaseline micturition. Last observation carried forward (LOCF) was used for missing values in the EoT.


End point type 
Primary


End point timeframe 
Baseline and Week 12




Statistical analysis title 
Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.039  
Method 
ANCOVA  
Parameter type 
Least Squares (LS) Mean of Difference  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19



End point title 
Change From Baseline to Week 4, Week 8, and Week 12 in Mean Number of Micturitions Per Day  
End point description 
Participants recorded micturitions in the ediary during three days. The mean number of micturitions was calculated as the average number of times a participant recorded a micturition per day during the 3day period. Only voluntary micturitions were counted and the episodes of incontinence were not included. The analysis population was the FAS. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.558  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.46  
upper limit 
0.25  
Variability estimate 
Standard error of the mean


Dispersion value 
0.18


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.007 ^{[1]}  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
0.14  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19


Notes [1]  Pvalue indicates statistical significance at the 0.05 level. 

Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.041 ^{[2]}  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.76  
upper limit 
0.02  
Variability estimate 
Standard error of the mean


Dispersion value 
0.19


Notes [2]  Pvalue indicates statistical significance at the 0.05 level. 


End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Volume Voided Per Micturition  
End point description 
The mean volume voided per micturition collected in the micturition diary during the 3day period. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.167  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
3.87


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.63  
upper limit 
9.37  
Variability estimate 
Standard error of the mean


Dispersion value 
2.8


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.056  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
6.29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.15  
upper limit 
12.73  
Variability estimate 
Standard error of the mean


Dispersion value 
3.28


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.012  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
8.99


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.97  
upper limit 
16.01  
Variability estimate 
Standard error of the mean


Dispersion value 
3.58


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.007  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
9.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.53  
upper limit 
15.98  
Variability estimate 
Standard error of the mean


Dispersion value 
3.43



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Incontinence Episodes Per Day  
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 as the average number of times a participant recorded an incontinence episode per day during the 3day micturition diary period. The analysis population was the full analysis set  incontinence (FASI), which consisted of all randomized participants who took at least 1 dose of doubleblind study drug and reported 1 micturition at baseline and postbaseline in the 3day ediary. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.747  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.63  
upper limit 
0.38  
Variability estimate 
Standard error of the mean


Dispersion value 
0.26


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.393  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
0.54  
Variability estimate 
Standard error of the mean


Dispersion value 
0.32


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.672  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.87  
upper limit 
0.38  
Variability estimate 
Standard error of the mean


Dispersion value 
0.32


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.64  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.31



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per Day  
End point description 
Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode with a severity of grade 3 or 4, assessed by participants based on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The mean number of urgency episodes (grade 3 and/or 4) per day was calculated as the average number of times a participant recorded an urgency episode (grade 3 and/or 4) with or without incontinence per day during the 3day micturition diary period. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.222  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.68  
upper limit 
0.16  
Variability estimate 
Standard error of the mean


Dispersion value 
0.21


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.003 ^{[3]}  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.18  
upper limit 
0.24  
Variability estimate 
Standard error of the mean


Dispersion value 
0.24


Notes [3]  Pvalue indicates statistical significance at the 0.05 level. 

Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.008 ^{[4]}  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.65


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.13  
upper limit 
0.17  
Variability estimate 
Standard error of the mean


Dispersion value 
0.24


Notes [4]  Pvalue indicates statistical significance at the 0.05 level. 

Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004 ^{[5]}  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.67


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.13  
upper limit 
0.21  
Variability estimate 
Standard error of the mean


Dispersion value 
0.23


Notes [5]  Pvalue indicates statistical significance at the 0.05 level. 


End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in International Prostate Symptom Score (IPSS) Total Score  
End point description 
The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.723  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.7  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.5


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.812  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Voiding Score  
End point description 
The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.121  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.241  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.843  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.679  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3



End point title 
Change From Baseline to Week 4, Week 8, Week 12, and EoT in IPSS Subscale Storage Score  
End point description 
The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.175  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.2


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.43  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


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


Dispersion value 
0.2


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.141  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.2


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.288  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.2



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in IPSS Subscale Quality of Life (QoL) Score  
End point description 
The International Prostate Symptom Score (IPSS) consists of 7 questions concerning urinary symptoms and 1 question concerning quality of life (QoL) with total score and subscores (voiding, storage and QoL). The IPSS total score classification ranges from mild (0 to 7) to moderate (8 to 19) or severe (20 to 35). Higher IPSS scored indicated more severe symptoms. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.128  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.054  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.079  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.148  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


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


Dispersion value 
0.1



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Urgency Incontinence Episodes Per Day  
End point description 
Urgency Incontinence was defined as the complaint of involuntary leakage accompanied by or immediately proceeded by urgency. The mean number of urgency incontinence episodes was calculated as the average number of times a participant recorded an urgency incontinence episode per day during the 3day micturition diary period. The analysis population was the FASI. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8 and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.66  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.61  
upper limit 
0.39  
Variability estimate 
Standard error of the mean


Dispersion value 
0.25


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.767  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.72  
upper limit 
0.53  
Variability estimate 
Standard error of the mean


Dispersion value 
0.32


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.372  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
0.34  
Variability estimate 
Standard error of the mean


Dispersion value 
0.31


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
261


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.272  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.92  
upper limit 
0.26  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Symptom Bother Score  
End point description 
Overactive bladder symptoms were assessed using the Symptom Bother Scale of the Overactive Bladder questionnaire (OABq). The OABq is a selfreported questionnaire with 33 questions relating to symptom bother and healthrelated quality of life (HRQoL). The symptom bother portion consists of 8 questions, 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). Lower scores on OABq symptom bother indicate a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.179  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.75


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.29  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
1.3


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.006  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
3.84


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.6  
upper limit 
1.08  
Variability estimate 
Standard error of the mean


Dispersion value 
1.41


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.055  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
2.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.86  
upper limit 
0.06  
Variability estimate 
Standard error of the mean


Dispersion value 
1.51


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.154  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
2.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.02  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
1.48



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Health Related Quality of Life (HRQL) Score  
End point description 
The OABq is a selfreported questionnaire with 33 questions relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A higher score on OABq HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.233  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.57  
upper limit 
0.87  
Variability estimate 
Standard error of the mean


Dispersion value 
1.13


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.698  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.46


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.89  
upper limit 
2.82  
Variability estimate 
Standard error of the mean


Dispersion value 
1.2


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Week 12 Difference vs. Mirabegron: Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.486  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.62  
upper limit 
3.4  
Variability estimate 
Standard error of the mean


Dispersion value 
1.28


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.968  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.52  
upper limit 
2.42  
Variability estimate 
Standard error of the mean


Dispersion value 
1.26



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Coping Score  
End point description 
The OABq is a selfreported questionnaire with 33 questions relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. A higher score on OABq HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.165  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.89


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.56  
upper limit 
0.78  
Variability estimate 
Standard error of the mean


Dispersion value 
1.36


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.592  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.76


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.02  
upper limit 
3.54  
Variability estimate 
Standard error of the mean


Dispersion value 
1.41


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.559  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.12  
upper limit 
3.92  
Variability estimate 
Standard error of the mean


Dispersion value 
1.54


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.985  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.94  
upper limit 
3  
Variability estimate 
Standard error of the mean


Dispersion value 
1.51



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Concern Score  
End point description 
The OABq is a selfreported questionnaire with 33 questions relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. A higher score on OABq HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron:  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.161  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.82


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.35  
upper limit 
0.72  
Variability estimate 
Standard error of the mean


Dispersion value 
1.29


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.798  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.35


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.36  
upper limit 
3.07  
Variability estimate 
Standard error of the mean


Dispersion value 
1.38


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.408  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.17


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.61  
upper limit 
3.95  
Variability estimate 
Standard error of the mean


Dispersion value 
1.42


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.919  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.6  
upper limit 
2.88  
Variability estimate 
Standard error of the mean


Dispersion value 
1.39



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Sleep Score  
End point description 
The OABq is a selfreported questionnaire with 33 questions relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. A higher score on OABq HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8 and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.99  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.94  
upper limit 
2.91  
Variability estimate 
Standard error of the mean


Dispersion value 
1.49


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.554  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.92


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.12  
upper limit 
3.96  
Variability estimate 
Standard error of the mean


Dispersion value 
1.55


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.348  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.53


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.67  
upper limit 
4.73  
Variability estimate 
Standard error of the mean


Dispersion value 
1.63


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.876  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.89  
upper limit 
3.38  
Variability estimate 
Standard error of the mean


Dispersion value 
1.6



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in HRQL Subscale Social Interaction Score  
End point description 
The OABq is a selfreported questionnaire with 33 questions relating to symptom bother and healthrelated quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 16. A higher score on OABq HRQL indicated a better response. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.293  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.16  
upper limit 
0.95  
Variability estimate 
Standard error of the mean


Dispersion value 
1.05


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.773  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.52  
upper limit 
1.87  
Variability estimate 
Standard error of the mean


Dispersion value 
1.12


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.94  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.28  
upper limit 
2.11  
Variability estimate 
Standard error of the mean


Dispersion value 
1.12


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.516  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.71


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.86  
upper limit 
1.44  
Variability estimate 
Standard error of the mean


Dispersion value 
1.1



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in European Quality of Life in 5 Dimensions and 5 Levels (EQ5D5L Questionnaire) Utilities  
End point description 
The EQ5D5L is an international standardized nondisease specific generic instrument for describing and valuing health status. It has a multidimensional measure of healthrelated QoL, capable of being expressed as a single index value and specifically designed to complement other health status measures. The EQ5D5L has five dimensions: Mobility, SelfCare, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels (e.g., 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems/unable to perform the activity). Healthstate utility (HSU) data are estimates of the preference for a given state of health on a cardinal numeric scale, where a value of 1.0 represents full health, 0.0 represents dead, and negative values represent states worse than death. The analysis population was the FAS. Missing EoT values were imputed using LOCF method.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4591 ^{[6]}  
Method 
ttest, 2 sided  
Confidence interval 

Notes [6]  Statistical comparisons were be made using 2sided tests at α = 0.05 significance level. 

Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4073 ^{[7]}  
Method 
ttest, 2 sided  
Confidence interval 

Notes [7]  Statistical comparisons were be made using 2sided tests at α = 0.05 significance level. 

Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.774 ^{[8]}  
Method 
ttest, 2 sided  
Confidence interval 

Notes [8]  Statistical comparisons were be made using 2sided tests at α = 0.05 significance level. 

Statistical analysis title 
EoT Placebo vs. Mirabegron  
Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5121 ^{[9]}  
Method 
ttest, 2 sided  
Confidence interval 

Notes [9]  Statistical comparisons were be made using 2sided tests at α = 0.05 significance level. 


End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Patient Perception of Bladder Condition (PPBC)  
End point description 
The PPBC is a validated, global assessment tool using a 6point Likert scale that asks participants to rate 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. A higher score indicated a worse perception of bladder condition. The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.223  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.598  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.312  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Placebo v Mirabegron


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.525  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.1



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Total Urgency and Frequency Score (TUFS)  
End point description 
The TUFS was calculated by adding the PPIUS scores of every void in a participant’s 3day diary, and dividing this by the number of days recorded in the diary. The analysis population was the FAS. Due to a programming failure in the ediary data for the number of pads used was not collected. Data not calculable is denoted as "99999" as applicable.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8 and 12




No statistical analyses for this end point 


End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours  
End point description 
A nocturia episode was defined as waking at night one or more time to void (i.e., any voiding associated with sleep disturbance between the date/time the participant goes to bed with the intention to sleep until the date/time the participant gets up in the morning with the intention to stay awake). A night time episode of incontinence is not considered a nocturia episode. The mean number of nocturia episodes per day (24 hours) was calculated as the average number of times a participant recorded a nocturia episode per day during the 3day micturition diary period. The analysis population was the full analysis set  nocturia (FASN), which consisted of all randomized participants who took at least 1 dose of doubleblind study drug and reported 1 micturition at baseline and postbaseline in the 3day ediary. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
266


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.226  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.08  
upper limit 
0.34  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
266


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.501  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.14  
upper limit 
0.28  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
266


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.984  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.22  
upper limit 
0.23  
Variability estimate 
Standard error of the mean


Dispersion value 
0.12


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
266


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.78  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
0.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.18  
upper limit 
0.24  
Variability estimate 
Standard error of the mean


Dispersion value 
0.11



End point title 
Change From Baseline to Week 4, Week 8, Week 12 and EoT in Treatment Satisfaction Visual Analog Scale (TSVAS)  
End point description 
The TSVAS is a visual analog scale that asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) to 100 (Yes, completely). The analysis population was the FAS. Missing values in the EoT were imputed using the LOCF method. N is the number of participants with available data at each time point.


End point type 
Secondary


End point timeframe 
Baseline and Weeks 4, 8, and 12




Statistical analysis title 
Week 4 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.107  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
3.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
6.8  
Variability estimate 
Standard error of the mean


Dispersion value 
1.9


Statistical analysis title 
Week 8 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.19  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
2.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
6.3  
Variability estimate 
Standard error of the mean


Dispersion value 
1.9


Statistical analysis title 
Week 12 Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.297  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
2.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
6.3  
Variability estimate 
Standard error of the mean


Dispersion value 
2.1


Statistical analysis title 
EoT Placebo vs. Mirabegron  
Statistical analysis description 
Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, age group (<65, >=65 years) and geographical region as fixed factors and baseline value as a covariate.


Comparison groups 
Mirabegron v Placebo


Number of subjects included in analysis 
676


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.493  
Method 
ANCOVA  
Parameter type 
LS Mean of Difference  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.7  
upper limit 
5.5  
Variability estimate 
Standard error of the mean


Dispersion value 
2.1



Adverse events information


Timeframe for reporting adverse events 
From first doubleblind medication intake until 30 days after last doubleblind medication intake; 16 weeks


Assessment type 
Systematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
20.1


Reporting groups


Reporting group title 
Mirabegron


Reporting group description 
Participants received initial dose of 25 mg of mirabegron which was increased to 50 mg after 4 weeks. In addition to mirabegron participants received 0.4 mg of oral tamsulosin hydrochloride daily throughout the study.  
Reporting group title 
Placebo


Reporting group description 
Participants received matching placebo in addition to oral tamsulosin hydrochloride daily throughout the study.  


Frequency threshold for reporting nonserious adverse events: 2%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

16 May 2016 
The changes include:
● Updated mode of administration of tamsulosin to include capsules in the US and tablets in the EU and Canada.
Nonsubstantial changes were as follows:
● Added study name PLUS to protocol title
● Updated patient ediary – micturition and incontinence section
● Made minor administrative type corrections 

10 May 2017 
The changes include:
● Updated acceptable PSA range to ≥ 4 ng/mL but < 10 ng/mL if a negative biopsy was obtained within the last year
Nonsubstantial changes were minor administrative type corrections. 

24 Oct 2017 
The changes include:
● Updated the sample size by reducing the power from 90% to 80%, where approximately 640 patients would be randomized 1:1; with 320 to mirabegron and 320 to placebo
● Updated acceptable PSA range if negative biopsy was obtained within the past 2 years Nonsubstantial changes were implemented in addition to the substantial changes mentioned
above. 

22 Jan 2018 
The changes include:
● Updated reference safety information from the US package insert, Canadian monograph and SmPC to the company core data sheet for mirabegron 

Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
The analysis of the EQ5D endpoint was completed by an external vendor outside of the main study report. Astellas had previously anticipated to post the results in April 2020. 