Download PDF

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

Summary
EudraCT number	2012-005401-41
Trial protocol	SK CZ GB SE IE BE PT NO AT FI GR HU ES SI NL DK PL
Global end of trial date	25 Nov 2014

Results information
Results version number	v3(current)
This version publication date	28 Apr 2018
First version publication date	21 Jul 2016
Other versions	v1 , v2
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

905-EC-012

ISRCTN number

US NCT number

NCT01908829

WHO universal trial number (UTN)

Other trial identifiers

Acronym: BESIDE

Sponsor organisation name

Astellas Pharma Europe Ltd

Sponsor organisation address

2000 Hillswood Drive, Chertsey, United Kingdom, KT16 0RS

Public contact

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

Scientific contact

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

Is trial part of an agreed paediatric investigation plan (PIP)

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

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

Analysis stage

Final

Date of interim/final analysis

25 Nov 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

25 Nov 2014

Was the trial ended prematurely?

Main objective of the trial

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

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Jul 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Algeria: 15

Country: Number of subjects enrolled

Armenia: 52

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Austria: 24

Country: Number of subjects enrolled

Belgium: 24

Country: Number of subjects enrolled

Canada: 57

Country: Number of subjects enrolled

Czech Republic: 129

Country: Number of subjects enrolled

Denmark: 39

Country: Number of subjects enrolled

Egypt: 11

Country: Number of subjects enrolled

Finland: 6

Country: Number of subjects enrolled

France: 11

Country: Number of subjects enrolled

Georgia: 23

Country: Number of subjects enrolled

Germany: 106

Country: Number of subjects enrolled

Greece: 53

Country: Number of subjects enrolled

Hungary: 53

Country: Number of subjects enrolled

Ireland: 8

Country: Number of subjects enrolled

Israel: 43

Country: Number of subjects enrolled

Italy: 49

Country: Number of subjects enrolled

Kazakhstan: 23

Country: Number of subjects enrolled

Norway: 9

Country: Number of subjects enrolled

Poland: 234

Country: Number of subjects enrolled

Portugal: 12

Country: Number of subjects enrolled

Romania: 84

Country: Number of subjects enrolled

Russian Federation: 241

Country: Number of subjects enrolled

Slovakia: 93

Country: Number of subjects enrolled

Slovenia: 26

Country: Number of subjects enrolled

Spain: 76

Country: Number of subjects enrolled

Sweden: 54

Country: Number of subjects enrolled

Switzerland: 11

Country: Number of subjects enrolled

Turkey: 164

Country: Number of subjects enrolled

Ukraine: 28

Country: Number of subjects enrolled

United Kingdom: 78

Country: Number of subjects enrolled

United States: 320

Country: Number of subjects enrolled

Netherlands: 15

Worldwide total number of subjects

2174

EEA total number of subjects

1183

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1492

From 65 to 84 years

671

85 years and over

Subject disposition

Top of page

Recruitment details

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

Screening details

Participants who met the screening inclusion/exclusion criteria went through a two week wash-out period and maintained a micturition diary during that the wash-out period. A total of 3815 participants were screened of which 2401 participants received solifenacin 5 mg run-in medication. A total of 2174 participants were randomized.

Number of subjects started

3815 ^[1]

Intermediate milestone: Number of subjects

Received 1 dose, single-blind run-in: 2401

Number of subjects completed

2174

Reason: Number of subjects

Discontinued before run-in solifenacin 5 mg: 1414

Reason: Number of subjects

Exclusion/inclusion criteria not met: 169

Reason: Number of subjects

Patient withdrawn: 32

Reason: Number of subjects

Adverse event: 16

Reason: Number of subjects

Other reasons: 7

Reason: Number of subjects

Lost to follow-up: 3

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The number of participants included in the pre-assignment period were the total number screened. The number of participants included in the worldwide number enrolled were the total number of participants randomized.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

The study was comprised of a 12 week double-blind treatment period (participants were randomized into the double-blind period if they experienced 1 or more incontinence episodes over the 3-day diary period prior to randomization to double-blind period and warranted additional relief for their OAB symptoms). There was 2 week safety follow up period (placebo administered). The active and placebo tablets were made indistinguishable by using a double-dummy packaging system.

Are arms mutually exclusive

Yes

Combination (solifenacin + mirabegron)

Arm description

Participants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.

Arm type

Experimental

Investigational medicinal product name

solifenacin 5 mg

Investigational medicinal product code

YM905

Other name

Vesicare, Vesitrim, Vesikur, solifenacin succinate

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

solifenacin 10 mg matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

mirabegron 25 mg

Investigational medicinal product code

YM178

Other name

Betanis, Betmiga, Myrbetriq

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

mirabegron 50 mg

Investigational medicinal product code

YM178

Other name

Betanis, Betmiga, Myrbetriq

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Solifenacin 5 mg

Arm description

Participants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

Arm type

Active comparator

Investigational medicinal product name

solifenacin 5 mg

Investigational medicinal product code

YM905

Other name

Vesicare, Vesitrim, Vesikur, solifenacin succinate

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

solifenacin 10 mg matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

mirabegron 25 mg matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

mirabegron 50 mg matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Solifenacin 10 mg

Arm description

Participants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.

Arm type

Active comparator

Investigational medicinal product name

solifenacin 5 mg matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

solifenacin 10 mg

Investigational medicinal product code

YM905

Other name

Vesicare, Vesitrim, Vesikur, solifenacin succinate

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

mirabegron 25 mg matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Investigational medicinal product name

mirabegron 50 mg matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Number of subjects in period 1	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Started	727	728	719
Treated with double-blind drug	725	728	719
Completed	678	679	680
Not completed	49	49	39
Randomized no double-blind drug received	1	-	1
Discontinued (no EoT page)	2	-	-
Miscellaneous	-	2	-
Adverse event	13	11	13
Protocol Violation	2	2	-
Lost to follow-up	4	2	1
Lack of efficacy	1	3	2
Withdrawal by subject	26	29	22

Baseline characteristics

Top of page

Reporting group title

Combination (solifenacin + mirabegron)

Reporting group description

Reporting group title

Solifenacin 5 mg

Reporting group description

Reporting group title

Solifenacin 10 mg

Reporting group description

Reporting group values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg	Total
Number of subjects	727	728	719
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	58.2 ( 13.1 )	56.9 ( 13.5 )	57.4 ( 13.2 )	-
Gender categorical
Units:
Male	123	124	119	366
Female	604	604	600	1808

End points

Top of page

Reporting group title

Combination (solifenacin + mirabegron)

Reporting group description

Reporting group title

Solifenacin 5 mg

Reporting group description

Reporting group title

Solifenacin 10 mg

Reporting group description

Primary: Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

Top of page

End point title

Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

End point description

The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. The analysis population consisted of the Full Analysis Set (FAS) which comprised of all the Randomized Analysis Set's (RAS) participants who met the following criteria: took at least 1 dose of double-blind study drug after randomization, reported at least 1 micturition in the baseline diary & at least 1 micturition postbaseline & reported at least 1 incontinence episode in the baseline diary. For participants who withdrew before EoT (week 12) and have no measurement available for that diary period, the Last Observation Carried Forward (LOCF) value during the double-blind study period was used as EoT value to derive the primary variable.

End point type

Primary

End point timeframe

Baseline and end of treatment (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	706	704	697
Units: incontinence episodes
least squares mean (standard error)	-1.8 ( 0.08 )	-1.53 ( 0.08 )	-1.67 ( 0.08 )

Adjusted Difference Combination vs Solifenacin 5mg

Statistical analysis description

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

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1410

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[1]

Method

stratified rank ANCOVA

Parameter type

Least Squares (LS) Means

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.11

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

Secondary: Change from Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes per 24 Hours

Top of page

End point title

Change from Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes per 24 Hours

End point description

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: incontinence episodes
least squares mean (standard error)
Week 4 (N= 690, 690, 679)	-1.24 ( 0.07 )	-0.91 ( 0.07 )	-1.12 ( 0.07 )
Week 8 (N= 661, 674, 673)	-1.68 ( 0.07 )	-1.29 ( 0.07 )	-1.49 ( 0.07 )
Week 12 (N= 653, 645, 664)	-1.81 ( 0.08 )	-1.57 ( 0.08 )	-1.67 ( 0.08 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

stratified rank ANCOVA

Parameter type

LS Means

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.52

upper limit

-0.14

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[3]

Method

stratified rank ANCOVA

Parameter type

LS Means

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[4]

Method

stratified rank ANCOVA

Parameter type

LS Means

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.11

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

Secondary: Change from Baseline in Mean Number of Micturitions per 24 Hours

Top of page

End point title

Change from Baseline in Mean Number of Micturitions per 24 Hours

End point description

The average number of micturitions (voluntary urinations (excluding incontinence only episodes)) per 24 hours was derived from number of micturitions recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period (excluding incontinence only episodes). LOCF was used for EoT. The analysis population included the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: micturitions
least squares mean (standard error)
Week 4 (N= 690, 690, 679)	-0.95 ( 0.07 )	-0.69 ( 0.07 )	-0.79 ( 0.07 )
Week 8 (N= 661, 674, 673)	-1.36 ( 0.08 )	-0.94 ( 0.08 )	-1.00 ( 0.08 )
Week 12 (N= 653, 645, 664)	-1.63 ( 0.08 )	-1.16 ( 0.09 )	-1.11 ( 0.08 )
EoT (N= 706, 704, 697)	-1.59 ( 0.08 )	-1.14 ( 0.08 )	-1.12 ( 0.08 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Adjusted change from baseline values as well as 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[5]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[6]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.65

upper limit

-0.19

Variability estimate

Standard error of the mean

Dispersion value

0.12

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[7]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.23

Variability estimate

Standard error of the mean

Dispersion value

0.12

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[8]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.12

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

Secondary: Number of Incontinence Episodes Reported During the 3-Day Diary

Top of page

End point title

Number of Incontinence Episodes Reported During the 3-Day Diary

End point description

The number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from total number of incontinence episodes on valid diary days recorded during the 3-day micturition diary period. LOCF was used for EoT. The analysis population included the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: incontinence episodes
arithmetic mean (standard error)
Week 4 (N= 690, 690, 679)	5.81 ( 0.30 )	6.68 ( 0.31 )	6.41 ( 0.33 )
Week 8 (N= 661, 674, 673)	4.55 ( 0.30 )	5.43 ( 0.30 )	5.28 ( 0.32 )
Week 12 (N= 653, 645, 664)	4.03 ( 0.29 )	4.56 ( 0.28 )	4.62 ( 0.31 )
EoT (N= 706, 704, 697)	4.25 ( 0.29 )	4.87 ( 0.28 )	4.72 ( 0.31 )

Rate Ratio Combination vs 5 mg Solifenacin Week 4

Statistical analysis description

Rate ratio, 95% CIs, & p-value for number of incontinence episodes during EoT 3-day diary between combination & solifenacin treatment was calculated from Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of incontinence episodes/valid diary days) at baseline as covariate & log of number of valid diary days as the offset variable.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[9]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

0.96

Variability estimate

Standard error of the mean

Dispersion value

0.05

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

Rate Ratio Combination vs 5 mg Solifenacin Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[10]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.86

Variability estimate

Standard error of the mean

Dispersion value

0.07

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

Rate Ratio Combination vs 5 mg Solifenacin Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021 ^[11]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.97

Variability estimate

Standard error of the mean

Dispersion value

0.08

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

Rate Ratio Combination vs 5 mg Solifenacin EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014 ^[12]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.96

Variability estimate

Standard error of the mean

Dispersion value

0.08

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

Secondary: Change from Baseline in Mean Volume Voided (MVV) per Micturition

Top of page

End point title

Change from Baseline in Mean Volume Voided (MVV) per Micturition

End point description

MVV per micturition was defined as MVV (mL) per micturition during last 3 days of the 3-day micturition diary period. MVV per micturition was calculated as the sum of each volume voided for each record with volume voided > 0 on valid diary days divided by the total number of records with a volume voided > 0 on valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: mL
least squares mean (standard error)
Week 4 (N= 665, 669, 664)	15.06 ( 1.55 )	11.20 ( 1.55 )	14.99 ( 1.55 )
Week 8 (N= 638, 648, 655)	25.21 ( 1.89 )	14.02 ( 1.87 )	21.08 ( 1.86 )
Week 12 (N= 627, 617, 642)	29.54 ( 2.06 )	17.16 ( 2.08 )	20.99 ( 2.04 )
EoT (N= 680, 682, 682)	28.05 ( 1.97 )	16.52 ( 1.97 )	20.30 ( 1.97 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.078 ^[13]

Method

ANCOVA

Parameter type

LS Means

Point estimate

3.86

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

8.16

Variability estimate

Standard error of the mean

Dispersion value

2.19

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[14]

Method

ANCOVA

Parameter type

LS Means

Point estimate

11.19

Confidence interval

level

95%

sides

2-sided

lower limit

5.98

upper limit

16.4

Variability estimate

Standard error of the mean

Dispersion value

2.66

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

ANCOVA

Parameter type

LS Means

Point estimate

12.38

Confidence interval

level

95%

sides

2-sided

lower limit

6.65

upper limit

18.12

Variability estimate

Standard error of the mean

Dispersion value

2.92

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

ANCOVA

Parameter type

LS Means

Point estimate

11.52

Confidence interval

level

95%

sides

2-sided

lower limit

6.06

upper limit

16.99

Variability estimate

Standard error of the mean

Dispersion value

2.79

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

Secondary: Change from Baseline to EoT in Corrected Micturition Frequency (CMF)

Top of page

End point title

Change from Baseline to EoT in Corrected Micturition Frequency (CMF)

End point description

CMF was defined as the mean number of micturitions per 24 hours that participants would have at EoT if their fluid intake had remained unchanged since baseline. This was calculated by the MVV per Micturition at baseline multiplied by the mean number of micturitions per 24 hours at baseline divided by the MVV per micturition at EoT. LOCF was used. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and EoT (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	706	704	697
Units: micturitions
least squares mean (standard error)	-0.96 ( 0.10 )	-0.52 ( 0.10 )	-0.71 ( 0.10 )

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1410

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[17]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.16

Variability estimate

Standard error of the mean

Dispersion value

0.15

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

Secondary: Change from Baseline in Mean Number of Urgency Incontinence (UI) Episodes per 24 Hours

Top of page

End point title

Change from Baseline in Mean Number of Urgency Incontinence (UI) Episodes per 24 Hours

End point description

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

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: UI episodes
least squares mean (standard error)
Week 4 (N= 676, 670, 650)	-1.26 ( 0.07 )	-0.91 ( 0.07 )	-1.14 ( 0.07 )
Week 8 (N= 649, 654, 645)	-1.70 ( 0.07 )	-1.25 ( 0.07 )	-1.45 ( 0.07 )
Week 12 (N= 643, 627, 635)	-1.84 ( 0.07 )	-1.58 ( 0.07 )	-1.62 ( 0.07 )
EoT (N= 691, 683, 666)	-1.82 ( 0.07 )	-1.54 ( 0.07 )	-1.63 ( 0.07 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

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

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[18]

P-value

< 0.001 ^[19]

Method

stratified rank ANCOVA

Parameter type

LS Means

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

0.09

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[20]

P-value

< 0.001 ^[21]

Method

stratified rank ANCOVA

Parameter type

LS Means

Point estimate

-0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.65

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

= 0.004 ^[23]

Method

stratified rank ANCOVA

Parameter type

LS Means

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.11

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[24]

P-value

= 0.003 ^[25]

Method

stratified rank ANCOVA

Parameter type

LS Means

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.07

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Secondary: Number of UI Episodes Reported During the 3-Day Diary

Top of page

End point title

Number of UI Episodes Reported During the 3-Day Diary

End point description

Number of UI episodes was calculated using the number of UI episodes recorded on valid diary days during the 3-day micturition diary period. NOTE: Only urgency incontinence episodes recorded on a valid diary day were counted. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: UI episodes
arithmetic mean (standard error)
Week 4 (N= 676, 670, 650)	4.96 ( 0.27 )	5.86 ( 0.29 )	5.50 ( 0.30 )
Week 8 (N= 649, 654, 645)	3.55 ( 0.25 )	4.76 ( 0.27 )	4.50 ( 0.30 )
Week 12 (N= 643, 627, 635)	3.10 ( 0.24 )	3.78 ( 0.25 )	3.91 ( 0.30 )
EoT (N= 691, 683, 666)	3.33 ( 0.24 )	4.00 ( 0.25 )	3.96 ( 0.29 )

Rate Ratio Combination vs 5 mg Solifenacin Week 4

Statistical analysis description

Rate ratio, 95% CIs, and p-value for number of UI episodes during EoT 3-day diary between combination and solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of UI episodes/number of valid diary days) at baseline as covariate and log of number of valid diary as the offset variable.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[26]

P-value

= 0.003 ^[27]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

0.94

Variability estimate

Standard error of the mean

Dispersion value

0.05

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

Rate Ratio Combination vs 5 mg Solifenacin Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[28]

P-value

< 0.001 ^[29]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

0.86

Variability estimate

Standard error of the mean

Dispersion value

0.08

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

Rate Ratio Combination vs 5 mg Solifenacin Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[30]

P-value

= 0.038 ^[31]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.99

Variability estimate

Standard error of the mean

Dispersion value

0.09

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

Rate Ratio Combination vs 5 mg Solifenacin EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[32]

P-value

= 0.022 ^[33]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.97

Variability estimate

Standard error of the mean

Dispersion value

0.09

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

Secondary: Change from Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) per 24 Hours

Top of page

End point title

Change from Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) per 24 Hours

End point description

An urgency episode was defined as the complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes (severity of 3 or 4) per 24 hours was defined as the average number of times a participant recorded an urgency episode (severity of 3 or 4) with or without incontinence per day during the 3-day micturition diary period. Measured using the PPIUS scale. This was calculated using the sum of each record with an urgency episode (severity of 3 or 4) recorded on a valid diary day divided by the number of valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: urgency episodes
least squares mean (standard error)
Week 4 (N= 684, 681, 663)	-1.84 ( 0.09 )	-1.39 ( 0.09 )	-1.74 ( 0.10 )
Week 8 (N= 654, 665, 659)	-2.64 ( 0.10 )	-2.00 ( 0.10 )	-2.29 ( 0.10 )
Week 12 (N= 647, 638, 648)	-2.97 ( 0.11 )	-2.44 ( 0.11 )	-2.55 ( 0.11 )
EoT (N= 699, 694, 680)	-2.95 ( 0.10 )	-2.41 ( 0.10 )	-2.54 ( 0.11 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[34]

P-value

= 0.001 ^[35]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.72

upper limit

-0.19

Variability estimate

Standard error of the mean

Dispersion value

0.13

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[36]

P-value

< 0.001 ^[37]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.15

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[38]

P-value

= 0.001 ^[39]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.15

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[40]

P-value

< 0.001 ^[41]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.15

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

Secondary: Change from Baseline in Mean Number of Pads per 24 hours

Top of page

End point title

Change from Baseline in Mean Number of Pads per 24 hours

End point description

The mean number of pads per 24 hours was defined as the average number of times a participant recorded a new pad used per day during the 3-day micturition diary period. This was calculated using the number of new pads used during valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: pads
least squares mean (standard error)
Week 4 (N= 497, 467, 474)	-1.12 ( 0.07 )	-0.86 ( 0.07 )	-1.04 ( 0.07 )
Week 8 (N= 482, 459, 469)	-1.50 ( 0.07 )	-1.17 ( 0.08 )	-1.36 ( 0.08 )
Week 12 (N= 477, 440, 468)	-1.65 ( 0.07 )	-1.38 ( 0.07 )	-1.43 ( 0.07 )
EoT (N= 510, 476, 487)	-1.66 ( 0.07 )	-1.35 ( 0.07 )	-1.43 ( 0.07 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

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

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[42]

P-value

= 0.008 ^[43]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

-0.07

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

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

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[44]

P-value

= 0.002 ^[45]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.55

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.11

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

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

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[46]

P-value

= 0.006 ^[47]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

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

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[48]

P-value

= 0.002 ^[49]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.51

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Secondary: Number of Pads Used During the 3-Day Diary

Top of page

End point title

Number of Pads Used During the 3-Day Diary

End point description

The number of pads used was defined as the number of times a participant recorded a new pad used during the 3-day micturition diary period. This was calculated using the sum of each record with new pad checked. Only records with new pad checked on a valid diary day were counted. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: pads
arithmetic mean (standard error)
Week 4 (N= 497, 467, 474)	4.80 ( 0.28 )	5.69 ( 0.36 )	5.41 ( 0.29 )
Week 8 (N= 482, 459, 469)	3.64 ( 0.24 )	4.71 ( 0.37 )	4.50 ( 0.29 )
Week 12 (N= 477, 440, 468)	3.23 ( 0.22 )	4.13 ( 0.28 )	4.07 ( 0.28 )
EoT (N= 510, 476, 487)	3.29 ( 0.22 )	4.27 ( 0.28 )	4.17 ( 0.29 )

Rate Ratio Combination vs 5 mg Solifenacin Week 4

Statistical analysis description

Rate ratio, 95% CIs, and p-value for number of pads used during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region and 4-week incontinence episode reduction group as factors, log of (number of pads used/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[50]

P-value

= 0.545 ^[51]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.08

Variability estimate

Standard error of the mean

Dispersion value

0.06

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

Rate Ratio Combination vs 5 mg Solifenacin Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[52]

P-value

= 0.01 ^[53]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.95

Variability estimate

Standard error of the mean

Dispersion value

0.08

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

Rate Ratio Combination vs 5 mg Solifenacin Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[54]

P-value

= 0.007 ^[55]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

0.94

Variability estimate

Standard error of the mean

Dispersion value

0.09

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

Rate Ratio Combination vs 5 mg Solifenacin EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[56]

P-value

= 0.003 ^[57]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.92

Variability estimate

Standard error of the mean

Dispersion value

0.08

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

Secondary: Change from Baseline in Mean Number of Nocturia Episodes

Top of page

End point title

Change from Baseline in Mean Number of Nocturia Episodes

End point description

Mean number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) while sleeping during the 3-day diary period, divided by the number of valid diary days during the diary period. Night time episode of incontinence only was not considered a nocturia episode. Nocturia episodes were counted for each micturition record which occurred between the date/time of going to bed with intention to sleep and the date/time of getting up with intention to stay awake on a valid diary day & which was accompanied by a sleep interruption. Nocturia only determined for those who were not night-shift workers. LOCF used for EoT.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: nocturia episodes
least squares mean (standard error)
Week 4 (N= 526, 514, 517)	-0.28 ( 0.03 )	-0.27 ( 0.03 )	-0.29 ( 0.03 )
Week 8 (N= 500, 501, 514)	-0.37 ( 0.03 )	-0.35 ( 0.03 )	-0.37 ( 0.03 )
Week 12 (N= 492, 480, 510)	-0.46 ( 0.03 )	-0.38 ( 0.03 )	-0.41 ( 0.03 )
EoT (N= 537, 523, 531)	-0.43 ( 0.03 )	-0.37 ( 0.03 )	-0.41 ( 0.03 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[58]

P-value

= 0.836 ^[59]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.05

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[60]

P-value

= 0.617 ^[61]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.07

Variability estimate

Standard error of the mean

Dispersion value

0.05

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[62]

P-value

= 0.134 ^[63]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.05

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[64]

P-value

= 0.174 ^[65]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.03

Variability estimate

Standard error of the mean

Dispersion value

0.05

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

Secondary: Number of Nocturia Episodes Reported Over 3-Day Diary

Top of page

End point title

Number of Nocturia Episodes Reported Over 3-Day Diary

End point description

The number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) during sleeping time during the 3-day micturition diary period. This was calculated using the sum of each nocturia episode recorded on valid diary days during the 3-day micturition diary period. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: nocturia episodes
arithmetic mean (standard error)
Week 4 (N= 526, 514, 517)	3.63 ( 0.12 )	3.59 ( 0.12 )	3.58 ( 0.12 )
Week 8 (N= 500, 501, 514)	3.33 ( 0.12 )	3.35 ( 0.12 )	3.32 ( 0.12 )
Week 12 (N= 492, 480, 510)	3.12 ( 0.13 )	3.26 ( 0.12 )	3.23 ( 0.12 )
EoT (N= 537, 523, 531)	3.16 ( 0.12 )	3.28 ( 0.11 )	3.19 ( 0.12 )

Rate Ratio Combination vs 5 mg Solifenacin Week 4

Statistical analysis description

Rate ratio, 95% CIs, & p-value for number of nocturia episodes during the 3-day diary between combination & solifenacin treatment was calculated from a Mixed Effects Poisson (negative binomial) regression model including treatment group, sex, age group (<65, >=65 years), geographic region & 4-week incontinence episode reduction group as factors, log of (number of nocturia episodes/number of valid diary days) at baseline as covariate and log of number of valid diary days as the offset variable.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[66]

P-value

= 0.993 ^[67]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.08

Variability estimate

Standard error of the mean

Dispersion value

0.04

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

Rate Ratio Combination vs 5 mg Solifenacin Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[68]

P-value

= 0.736 ^[69]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.07

Variability estimate

Standard error of the mean

Dispersion value

0.04

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

Rate Ratio Combination vs 5 mg Solifenacin Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[70]

P-value

= 0.121 ^[71]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.02

Variability estimate

Standard error of the mean

Dispersion value

0.05

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

Rate Ratio Combination vs 5 mg Solifenacin EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority ^[72]

P-value

= 0.172 ^[73]

Method

Mixed Effects Poisson

Parameter type

Rate Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.03

Variability estimate

Standard error of the mean

Dispersion value

0.04

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

Secondary: Number of Participants with Change from Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility

Top of page

End point title

Number of Participants with Change from Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility

End point description

The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and EoT (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: participants
number (not applicable)
No problems -> no problems	409	370	374
No problems -> slight problems	33	35	36
No problems -> moderate problems	14	11	11
No problems -> severe problems	0	7	4
No problems -> extreme problems	0	1	0
No problems -> no data	2	4	5
Slight problems -> no problems	52	58	60
Slight problems -> slight problems	43	46	40
Slight problems -> moderate problems	15	28	16
Slight problems -> severe problems	1	3	3
Slight problems -> extreme problems	0	0	0
Slight problems -> no data	2	0	0
Moderate problems -> no problems	24	36	25
Moderate problems -> slight problems	25	18	23
Moderate problems -> moderate problems	28	28	40
Moderate problems -> severe problems	2	3	7
Moderate problems -> extreme problems	0	1	0
Moderate problems -> no data	1	0	0
Severe problems -> no problems	7	8	2
Severe problems -> slight problems	6	7	7
Severe problems -> moderate problems	17	11	11
Severe problems -> severe problems	12	10	14
Severe problems -> extreme problems	0	0	0
Severe problems -> no data	1	1	0
Extreme problems -> no problems	3	2	2
Extreme problems -> slight problems	1	0	0
Extreme problems -> moderate problems	1	1	1
Extreme problems -> severe problems	1	0	0
Extreme problems -> extreme problems	0	0	0
Extreme problems -> no data	0	0	0
No data -> no problems	4	9	13
No data -> slight problems	2	4	1
No data -> moderate problems	0	3	3
No data -> severe problems	0	0	0
No data -> extreme problems	0	0	0
No data -> no data	1	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Self-care

Top of page

End point title

Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Self-care

End point description

End point type

Secondary

End point timeframe

Baseline and EoT (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: participants
number (not applicable)
No problems -> no problems	548	541	548
No problems -> slight problems	28	26	25
No problems -> moderate problems	0	14	7
No problems -> severe problems	3	0	2
No problems -> extreme problems	0	0	0
No problems -> no data	6	5	4
Slight problems -> no problems	37	25	32
Slight problems -> slight problems	23	24	22
Slight problems -> moderate problems	9	7	9
Slight problems -> severe problems	1	0	0
Slight problems -> extreme problems	0	0	0
Slight problems -> no data	0	0	1
Moderate problems -> no problems	12	16	7
Moderate problems -> slight problems	9	9	5
Moderate problems -> moderate problems	11	7	12
Moderate problems -> severe problems	0	2	2
Moderate problems -> extreme problems	0	0	0
Moderate problems -> no data	0	0	0
Severe problems -> no problems	7	5	0
Severe problems -> slight problems	2	2	2
Severe problems -> moderate problems	2	1	2
Severe problems -> severe problems	1	4	1
Severe problems -> extreme problems	0	0	0
Severe problems -> no data	0	0	0
Extreme problems -> no problems	0	0	0
Extreme problems -> slight problems	0	1	0
Extreme problems -> moderate problems	0	0	0
Extreme problems -> severe problems	1	0	0
Extreme problems -> extreme problems	0	0	0
Extreme problems -> no data	0	0	0
No data -> no problems	6	14	17
No data -> slight problems	0	2	0
No data -> moderate problems	0	0	0
No data -> severe problems	0	0	0
No data -> extreme problems	0	0	0
No data -> no data	1	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Usual Activities

Top of page

End point title

Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Usual Activities

End point description

End point type

Secondary

End point timeframe

Baseline and EoT (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: participants
number (not applicable)
No problems -> no problems	397	384	379
No problems -> slight problems	38	30	42
No problems -> moderate problems	12	19	11
No problems -> severe problems	1	4	1
No problems -> extreme problems	0	0	1
No problems -> no data	4	3	3
Slight problems -> no problems	75	81	78
Slight problems -> slight problems	46	45	37
Slight problems -> moderate problems	12	16	15
Slight problems -> severe problems	1	1	3
Slight problems -> extreme problems	0	1	0
Slight problems -> no data	0	1	2
Moderate problems -> no problems	29	35	25
Moderate problems -> slight problems	22	20	28
Moderate problems -> moderate problems	22	18	21
Moderate problems -> severe problems	3	3	4
Moderate problems -> extreme problems	1	0	0
Moderate problems -> no data	2	1	0
Severe problems -> no problems	9	8	12
Severe problems -> slight problems	7	5	1
Severe problems -> moderate problems	7	6	9
Severe problems -> severe problems	5	7	9
Severe problems -> extreme problems	0	0	0
Severe problems -> no data	0	0	0
Extreme problems -> no problems	2	0	0
Extreme problems -> slight problems	1	0	0
Extreme problems -> moderate problems	3	1	0
Extreme problems -> severe problems	1	0	0
Extreme problems -> extreme problems	0	0	0
Extreme problems -> no data	0	0	0
No data -> no problems	5	11	15
No data -> slight problems	1	4	1
No data -> moderate problems	0	1	1
No data -> severe problems	0	0	0
No data -> extreme problems	0	0	0
No data -> no data	1	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort

Top of page

End point title

Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort

End point description

End point type

Secondary

End point timeframe

Baseline and EoT (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: participants
number (not applicable)
No pain -> no pain	299	290	283
No pain -> slight pain	45	62	51
No pain -> moderate pain	12	14	17
No pain -> severe pain	3	9	2
No pain -> extreme pain	0	0	1
No pain -> no data	4	4	3
Slight pain -> no pain	79	82	81
Slight pain -> slight pain	58	64	55
Slight pain -> moderate pain	28	17	31
Slight pain -> severe pain	0	2	5
Slight pain -> extreme pain	1	2	0
Slight pain -> no data	0	0	2
Moderate pain -> no pain	39	36	21
Moderate pain -> slight pain	37	36	39
Moderate pain -> moderate pain	34	30	39
Moderate pain -> severe pain	7	4	8
Moderate pain -> extreme pain	0	1	0
Moderate pain -> no data	2	1	0
Severe pain -> no pain	7	4	10
Severe pain -> slight pain	12	7	4
Severe pain -> moderate pain	11	16	16
Severe pain -> severe pain	10	4	9
Severe pain -> extreme pain	0	1	1
Severe pain -> no data	0	0	0
Extreme pain -> no pain	4	1	0
Extreme pain -> slight pain	0	1	1
Extreme pain -> moderate pain	1	0	1
Extreme pain -> severe pain	6	1	1
Extreme pain -> extreme pain	1	0	0
Extreme pain -> no data	0	0	0
No data -> no pain	4	8	11
No data -> slight pain	1	3	4
No data -> moderate pain	1	5	2
No data -> severe pain	0	0	0
No data -> extreme pain	0	0	0
No data -> no data	1	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression

Top of page

End point title

Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression

End point description

End point type

Secondary

End point timeframe

Baseline and EoT (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: participants
number (not applicable)
Not anxious -> not anxious	322	300	307
Not anxious -> slightly anxious	43	39	43
Not anxious -> moderately anxious	11	17	15
Not anxious -> severely anxious	2	2	3
Not anxious-> extremely anxious	0	0	0
Not anxious -> no data	4	3	3
Slightly anxious -> not anxious	107	99	90
Slightly anxious -> slightly anxious	56	60	69
Slightly anxious -> moderately anxious	13	11	23
Slightly anxious -> severely anxious	1	2	2
Slightly anxious -> extremely anxious	0	0	0
Slightly anxious -> no data	1	2	2
Moderately anxious -> not anxious	36	38	34
Moderately anxious -> slightly anxious	36	40	33
Moderately anxious -> moderately anxious	22	26	17
Moderately anxious -> severely anxious	3	7	1
Moderately anxious -> extremely anxious	0	3	1
Moderately anxious -> no data	0	0	0
Severely anxious -> not anxious	10	8	8
Severely anxious -> slightly anxious	9	5	5
Severely anxious -> moderately anxious	6	6	11
Severely anxious -> severely anxious	5	8	7
Severely anxious -> extremely anxious	0	3	0
Severely anxious -> no data	0	0	0
Extremely anxious -> not anxious	1	4	1
Extremely anxious -> slightly anxious	2	1	1
Extremely anxious -> moderately anxious	4	2	3
Extremely anxious -> severely anxious	4	1	1
Extremely anxious -> extremely anxious	1	2	1
Extremely anxious -> no data	1	0	0
No data -> not anxious	5	13	11
No data -> slightly anxious	0	2	5
No data -> moderately anxious	1	1	1
No data -> severely anxious	0	0	0
No data -> extremely anxious	0	0	0
No data -> no data	1	0	0

No statistical analyses for this end point

Secondary: Change from Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score

Top of page

End point title

Change from Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score

End point description

The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 682, 677, 669)	-16.68 ( 0.65 )	-13.79 ( 0.65 )	-15.82 ( 0.65 )
Week 8 (N= 670, 660, 658)	-22.86 ( 0.68 )	-18.36 ( 0.69 )	-19.34 ( 0.69 )
Week 12 (N= 644, 641, 647)	-27.90 ( 0.71 )	-22.31 ( 0.71 )	-24.09 ( 0.71 )
EoT (N= 694, 683, 676)	-26.89 ( 0.69 )	-21.93 ( 0.70 )	-23.59 ( 0.70 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Adjusted change from baseline values as well as 95% CIs & p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors & baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[74]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-2.89

Confidence interval

level

95%

sides

2-sided

lower limit

-4.68

upper limit

-1.1

Variability estimate

Standard error of the mean

Dispersion value

0.91

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[75]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.4

upper limit

-2.6

Variability estimate

Standard error of the mean

Dispersion value

0.97

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[76]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-5.59

Confidence interval

level

95%

sides

2-sided

lower limit

-7.56

upper limit

-3.62

Variability estimate

Standard error of the mean

Dispersion value

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[77]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-4.96

Confidence interval

level

95%

sides

2-sided

lower limit

-6.88

upper limit

-3.04

Variability estimate

Standard error of the mean

Dispersion value

0.98

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

Secondary: Change from Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score

Top of page

End point title

Change from Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score

End point description

The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 682, 677, 669)	12.95 ( 0.59 )	11.03 ( 0.59 )	12.44 ( 0.59 )
Week 8 (N= 670, 660, 658)	17.58 ( 0.63 )	15.26 ( 0.63 )	14.60 ( 0.64 )
Week 12 (N= 644, 641, 647)	21.40 ( 0.66 )	17.91 ( 0.67 )	17.72 ( 0.66 )
EoT (N= 694, 683, 676)	20.78 ( 0.65 )	17.63 ( 0.65 )	17.40 ( 0.65 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021

Method

ANCOVA

Parameter type

LS Means

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

3.55

Variability estimate

Standard error of the mean

Dispersion value

0.83

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[78]

Method

ANCOVA

Parameter type

LS Means

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

4.06

Variability estimate

Standard error of the mean

Dispersion value

0.89

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[79]

Method

ANCOVA

Parameter type

LS Means

Point estimate

3.49

Confidence interval

level

95%

sides

2-sided

lower limit

1.65

upper limit

5.33

Variability estimate

Standard error of the mean

Dispersion value

0.94

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[80]

Method

ANCOVA

Parameter type

LS Means

Point estimate

3.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

4.95

Variability estimate

Standard error of the mean

Dispersion value

0.92

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

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Coping

Top of page

End point title

Change from Baseline in OAB-q HRQL Subscale Score: Coping

End point description

The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 682, 677, 669)	15.17 ( 0.68 )	12.27 ( 0.68 )	14.25 ( 0.68 )
Week 8 (N= 670, 660, 658)	20.82 ( 0.74 )	17.47 ( 0.74 )	16.87 ( 0.74 )
Week 12 (N= 644, 641, 647)	25.16 ( 0.78 )	20.45 ( 0.78 )	20.20 ( 0.78 )
EoT (N= 694, 683, 676)	24.48 ( 0.75 )	20.19 ( 0.76 )	19.90 ( 0.76 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[81]

Method

ANCOVA

Parameter type

LS Means

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

4.78

Variability estimate

Standard error of the mean

Dispersion value

0.96

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[82]

Method

ANCOVA

Parameter type

LS Means

Point estimate

3.35

Confidence interval

level

95%

sides

2-sided

lower limit

1.29

upper limit

5.4

Variability estimate

Standard error of the mean

Dispersion value

1.05

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[83]

Method

ANCOVA

Parameter type

LS Means

Point estimate

4.71

Confidence interval

level

95%

sides

2-sided

lower limit

2.55

upper limit

6.87

Variability estimate

Standard error of the mean

Dispersion value

1.1

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[84]

Method

ANCOVA

Parameter type

LS Means

Point estimate

4.29

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

6.39

Variability estimate

Standard error of the mean

Dispersion value

1.07

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

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Concern

Top of page

End point title

Change from Baseline in OAB-q HRQL Subscale Score: Concern

End point description

The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 682, 677, 669)	13.79 ( 0.68 )	11.85 ( 0.68 )	13.82 ( 0.69 )
Week 8 (N= 670, 660, 658)	18.87 ( 0.70 )	16.36 ( 0.71 )	15.88 ( 0.71 )
Week 12 (N= 644, 641, 647)	22.85 ( 0.74 )	19.24 ( 0.75 )	19.67 ( 0.74 )
Week EoT (N= 694, 683, 676)	22.28 ( 0.72 )	19.00 ( 0.73 )	19.28 ( 0.73 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.044 ^[85]

Method

ANCOVA

Parameter type

LS Means

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

3.83

Variability estimate

Standard error of the mean

Dispersion value

0.96

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[86]

Method

ANCOVA

Parameter type

LS Means

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

4.46

Variability estimate

Standard error of the mean

Dispersion value

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[87]

Method

ANCOVA

Parameter type

LS Means

Point estimate

3.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

5.67

Variability estimate

Standard error of the mean

Dispersion value

1.05

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[88]

Method

ANCOVA

Parameter type

LS Means

Point estimate

3.28

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

5.29

Variability estimate

Standard error of the mean

Dispersion value

1.03

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

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Sleep

Top of page

End point title

Change from Baseline in OAB-q HRQL Subscale Score: Sleep

End point description

The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 682, 677, 669)	11.58 ( 0.68 )	11.04 ( 0.68 )	11.16 ( 0.69 )
Week 8 (N= 670, 660, 658)	16.18 ( 0.71 )	14.57 ( 0.71 )	13.72 ( 0.71 )
Week 12 (N= 644, 641, 647)	20.00 ( 0.74 )	17.74 ( 0.74 )	16.84 ( 0.74 )
Week EoT (N= 694, 683, 676)	19.16 ( 0.72 )	17.30 ( 0.73 )	16.55 ( 0.73 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.575 ^[89]

Method

ANCOVA

Parameter type

LS Means

Point estimate

0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-1.35

upper limit

2.43

Variability estimate

Standard error of the mean

Dispersion value

0.96

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.109 ^[90]

Method

ANCOVA

Parameter type

LS Means

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

3.58

Variability estimate

Standard error of the mean

Dispersion value

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032 ^[91]

Method

ANCOVA

Parameter type

LS Means

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

4.32

Variability estimate

Standard error of the mean

Dispersion value

1.05

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.069 ^[92]

Method

ANCOVA

Parameter type

LS Means

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

3.87

Variability estimate

Standard error of the mean

Dispersion value

1.02

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

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Social Interaction

Top of page

End point title

Change from Baseline in OAB-q HRQL Subscale Score: Social Interaction

End point description

The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 682, 677, 669)	9.58 ( 0.59 )	7.85 ( 0.59 )	8.95 ( 0.59 )
Week 8 (N= 670, 660, 658)	11.93 ( 0.60 )	10.84 ( 0.60 )	10.16 ( 0.60 )
Week 12 (N= 644, 641, 647)	14.70 ( 0.61 )	12.08 ( 0.61 )	11.98 ( 0.61 )
Week EoT (N= 694, 683, 676)	14.39 ( 0.60 )	11.91 ( 0.60 )	11.72 ( 0.61 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.037 ^[93]

Method

ANCOVA

Parameter type

LS Means

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

3.36

Variability estimate

Standard error of the mean

Dispersion value

0.83

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.199 ^[94]

Method

ANCOVA

Parameter type

LS Means

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

2.76

Variability estimate

Standard error of the mean

Dispersion value

0.85

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[95]

Method

ANCOVA

Parameter type

LS Means

Point estimate

2.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

4.31

Variability estimate

Standard error of the mean

Dispersion value

0.87

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[96]

Method

ANCOVA

Parameter type

LS Means

Point estimate

2.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

4.15

Variability estimate

Standard error of the mean

Dispersion value

0.85

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

Secondary: Change from Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score

Top of page

End point title

Change from Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score

End point description

The TS-VAS rated participant satisfaction with treatment on a scale from 0 (No, not at all) to 10 (Yes, completely). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 680, 677, 668)	1.2 ( 0.1 )	0.8 ( 0.1 )	1.1 ( 0.1 )
Week 8 (N= 668, 660, 656)	1.5 ( 0.1 )	1.2 ( 0.1 )	1.3 ( 0.1 )
Week 12 (N= 644, 641, 646)	1.9 ( 0.1 )	1.4 ( 0.1 )	1.6 ( 0.1 )
EoT (N= 693, 683, 675)	1.8 ( 0.1 )	1.4 ( 0.1 )	1.6 ( 0.1 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Adjusted change from baseline values as well as the 95% CIs and p-value were generated from an ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Differences of adjusted means were calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[97]

Method

ANCOVA

Parameter type

LS Means

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019 ^[98]

Method

ANCOVA

Parameter type

LS Means

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[99]

Method

ANCOVA

Parameter type

LS Means

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[100]

Method

ANCOVA

Parameter type

LS Means

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Secondary: Change from Baseline in Patient Perception Bladder Control (PPBC) Score

Top of page

End point title

Change from Baseline in Patient Perception Bladder Control (PPBC) Score

End point description

The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. PPBC score: 1-no problem, 2- some very minor problems, 3-some minor problems, 4-moderate problems, 5-severe problems, 6-many severe problems. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: units on a scale
least squares mean (standard error)
Week 4 (N= 687, 685, 677)	-0.9 ( 0.0 )	-0.6 ( 0.0 )	-0.7 ( 0.0 )
Week 8 (N= 673, 667, 669)	-1.2 ( 0.0 )	-1.0 ( 0.0 )	-1.0 ( 0.0 )
Week 12 (N= 647, 648, 655)	-1.5 ( 0.0 )	-1.2 ( 0.0 )	-1.3 ( 0.0 )
EoT (N= 697, 688, 683)	-1.5 ( 0.0 )	-1.2 ( 0.0 )	-1.3 ( 0.0 )

Adj. Diff. Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Adjusted change from baseline values as well as the 95% CIs and p-value were generated from ANCOVA model with treatment group, sex, age group (<65, >=65 years), 4-week incontinence reduction group and geographic region as fixed factors and baseline value as a covariate. Difference of adjusted mean was calculated by subtracting adjusted mean of solifenacin monotherapy groups from adjusted mean of combination group.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[101]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[102]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[103]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Adj. Diff. Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[104]

Method

ANCOVA

Parameter type

LS Means

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.1

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

Secondary: Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)

Top of page

End point title

Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)

End point description

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

End point type

Secondary

End point timeframe

End of treatment (up to 12 weeks)

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: participants
number (not applicable)
PIBS Very Much Improved	227	152	171
PIBS Much Improved	257	264	284
PIBS Minimally Improved	135	170	152
PIBS No Change	25	55	56
PIBS Minimally Worse	7	11	4
PIBS Much Worse	4	4	6
PIBS Very Much Worse	0	1	1
PIGH Very Much Improved	144	104	108
PIGH Much Improved	239	236	244
PIGH Minimally Improved	143	147	146
PIGH No Change	113	142	160
PIGH Minimally Worse	14	23	10
PIGH Much Worse	1	4	4
PIGH Very Much Worse	1	1	2
CIBS Very Much Improved	184	118	141
CIBS Much Improved	311	316	329
CIBS Minimally Improved	141	164	155
CIBS No Change	23	56	40
CIBS Minimally Worse	4	8	5
CIBS Much Worse	4	3	5
CIBS Very Much Worse	3	3	4

No statistical analyses for this end point

Secondary: Percentage of Participants with at Least a 50% Decrease from Baseline in Mean Number of Incontinence Episodes per 24 Hours

Top of page

End point title

Percentage of Participants with at Least a 50% Decrease from Baseline in Mean Number of Incontinence Episodes per 24 Hours

End point description

Incontinence was defined as any involuntary leakage of urine. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: percentage of participants
number (not applicable)
Week 4 (N= 690, 690, 679)	52.5	43.3	49.0
Week 8 (N= 661, 674, 673)	66.9	57.6	61.8
Week 12 (N= 653, 645, 664)	72.4	64.0	66.9
EoT (N= 706, 704, 697)	71.2	63.1	66.6

Odds Ratio Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Odds ratios, 95% Two sided CIs for Odds ratios and p-values were from a logistic regression model including treatment group, sex, age group (<65, >=65 years), 4-week incontinence episode reduction group, geographic region as factors and baseline value as covariate.

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[105]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

1.84

Notes
[105] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[106]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.57

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

1.98

Notes
[106] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[107]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

1.21

upper limit

1.95

Notes
[107] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[108]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

1.9

Notes
[108] - p<0.05 indicated superiority in favor of treatment group with highest response.

Secondary: Percentage of Participants with Zero Incontinence Episodes Postbaseline

Top of page

End point title

Percentage of Participants with Zero Incontinence Episodes Postbaseline

End point description

Incontinence was defined as any involuntary leakage of urine. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: percentage of participants
number (not applicable)
Week 4 (N= 690, 690, 679)	23.5	20.0	22.1
Week 8 (N= 661, 674, 673)	40.4	31.6	34.3
Week 12 (N= 653, 645, 664)	47.3	39.5	40.7
EoT (N= 706, 704, 697)	46.0	37.9	40.2

Odds Ratio Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.119 ^[109]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.63

Notes
[109] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[110]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

1.98

Notes
[110] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[111]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

1.82

Notes
[111] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[112]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.47

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

1.84

Notes
[112] - p<0.05 indicated superiority in favor of treatment group with highest response.

Secondary: Percentage of Participants with a Mean of at Least 8 Micturitions per 24 Hours at Baseline and Less than 8 Micturitions per 24 Hours Postbaseline

Top of page

End point title

Percentage of Participants with a Mean of at Least 8 Micturitions per 24 Hours at Baseline and Less than 8 Micturitions per 24 Hours Postbaseline

End point description

Micturitions were defined as voluntary urinations (excluding incontinence only episodes). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: percentage of participants
number (not applicable)
Week 4 (N= 690, 690, 679)	21.0	18.7	20.2
Week 8 (N= 661 674, 673)	28.1	22.4	26.3
Week 12 (N= 653, 645, 664)	31.4	24.8	28.0
EoT (N= 706, 704, 697)	30.2	25.0	27.7

Odds Ratio Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.305 ^[113]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.5

Notes
[113] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014 ^[114]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

1.76

Notes
[114] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[115]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

1.76

Notes
[115] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.036 ^[116]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

1.64

Notes
[116] - p<0.05 indicated superiority in favor of treatment group with highest response.

Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in OAB-q Symptom Bother Score

Top of page

End point title

Percentage of Participants with at Least a 10-Point Improvement from Baseline in OAB-q Symptom Bother Score

End point description

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: percentage of participants
number (not applicable)
Week 4 (N= 682, 677, 669)	67.9	58.2	61.9
Week 8 (N= 670, 660, 658)	77.2	66.4	69.1
Week 12 (N= 644, 641, 647)	83.5	72.1	75.4
EoT (N= 694, 683, 676)	81.7	71.7	74.6

OAB-q Odds Ratio Comb. vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[117]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.49

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

1.88

Notes
[117] - p<0.05 indicated superiority in favor of treatment group with highest response.

OAB-q Odds Ratio Comb. vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[118]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

2.18

Notes
[118] - p<0.05 indicated superiority in favor of treatment group with highest response.

OAB-q Odds Ratio Comb. vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[119]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.96

Confidence interval

level

95%

sides

2-sided

lower limit

1.47

upper limit

2.61

Notes
[119] - p<0.05 indicated superiority in favor of treatment group with highest response.

OAB-q Odds Ratio Comb. vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[120]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

2.3

Notes
[120] - p<0.05 indicated superiority in favor of treatment group with highest response.

Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in HRQL Total Score

Top of page

End point title

Percentage of Participants with at Least a 10-Point Improvement from Baseline in HRQL Total Score

End point description

HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life). LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: percentage of participants
number (not applicable)
Week 4 (N= 682, 677, 669)	52.6	44.5	48.1
Week 8 (N= 670, 660, 658)	63.6	54.8	53.8
Week 12 (N= 644, 641, 647)	70.5	60.8	60.4
EoT (N= 694, 683, 676)	68.6	60.6	60.1

HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[121]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

1.82

Notes
[121] - p<0.05 indicates superiority in favor of treatment group with highest response.

HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[122]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

1.93

Notes
[122] - p<0.05 indicates superiority in favor of treatment group with highest response.

HRQL Odds Ratio Comb. vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[123]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.13

Notes
[123] - p<0.05 indicates superiority in favor of treatment group with highest response.

HRQL Odds Ratio Comb. vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[124]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

1.91

Notes
[124] - p<0.05 indicates superiority in favor of treatment group with highest response.

Secondary: Percentage of Participants with at Least a 1-Point Improvement from Baseline in PPBC

Top of page

End point title

Percentage of Participants with at Least a 1-Point Improvement from Baseline in PPBC

End point description

The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. LOCF was used for EoT. The analysis population consisted of the FAS.

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: percentage of participants
number (not applicable)
Week 4 (N= 687, 685, 677)	61.1	52.1	56.3
Week 8 (N= 673, 667, 669)	70.1	62.1	64.6
Week 12 (N= 647, 648, 655)	77.9	70.4	72.7
EoT (N= 697, 688, 683)	76.5	69.5	71.9

Odds Ratio Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[125]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.42

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

1.79

Notes
[125] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[126]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

1.84

Notes
[126] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[127]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.15

upper limit

1.96

Notes
[127] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[128]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

1.84

Notes
[128] - p<0.05 indicated superiority in favor of treatment group with highest response.

Secondary: Percentage of Participants with Major (at Least 2-Point) Improvement from Baseline in PPBC

Top of page

End point title

Percentage of Participants with Major (at Least 2-Point) Improvement from Baseline in PPBC

End point description

End point type

Secondary

End point timeframe

Weeks 4, 8 and 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	707	705	698
Units: percentage of participants
number (not applicable)
Week 4 (N= 687, 685, 677)	26.6	21.6	21.6
Week 8 (N= 673, 667, 669)	39.5	31.5	31.8
Week 12 (N= 647, 648, 655)	51.8	39.8	43.8
EoT (N= 697, 688, 683)	49.8	39.1	43.2

Odds Ratio Combination vs Solifenacin 5mg Week 4

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.065 ^[129]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.66

Notes
[129] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 8

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[130]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

1.79

Notes
[130] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg Week 12

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[131]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

2.07

Notes
[131] - p<0.05 indicated superiority in favor of treatment group with highest response.

Odds Ratio Combination vs Solifenacin 5mg EoT

Statistical analysis description

Comparison groups

Combination (solifenacin + mirabegron) v Solifenacin 5 mg

Number of subjects included in analysis

1412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[132]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.55

Confidence interval

level

95%

sides

2-sided

lower limit

1.24

upper limit

1.94

Notes
[132] - p<0.05 indicated superiority in favor of treatment group with highest response.

Secondary: Number of Participants with Adverse Events (AEs)

Top of page

End point title

Number of Participants with Adverse Events (AEs)

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	725	728	719
Units: participants
AEs	260	241	283
Drug-related AEs	141	125	161
Serious Adverse Events (SAEs)	13	10	15
Drug-related SAEs	1	0	3
AEs Leading to Perm. Disc. of Study Drug	11	11	11
Drug-related AEs Leading to Perm. Disc. of Drug	9	10	9
Deaths	0	0	0

No statistical analyses for this end point

Secondary: Change From Baseline in Post Void Residual (PVR) Volume

Top of page

End point title

Change From Baseline in Post Void Residual (PVR) Volume

End point description

PVR Volume was assessed by bladder scan. The analysis population consisted of the SAF with data available at each time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 & 12

End point values	Combination (solifenacin + mirabegron)	Solifenacin 5 mg	Solifenacin 10 mg
Number of subjects analysed	725	728	719
Units: mL
arithmetic mean (standard deviation)
Week 4 (N= 705, 712, 704)	1.545 ( 40.313 )	2.821 ( 38.588 )	7.308 ( 72.122 )
Week 8 (N= 683, 694, 690)	2.245 ( 38.347 )	1.117 ( 36.470 )	7.232 ( 60.096 )
Week 12 (N= 669, 680, 681)	6.356 ( 51.067 )	2.337 ( 42.147 )	6.552 ( 48.505 )
EoT (N= 706, 713, 707)	5.478 ( 51.595 )	3.046 ( 43.499 )	7.354 ( 54.121 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

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

Adverse event reporting additional description

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

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

Combination (solifenacin + mirabegron)

Reporting group description

Reporting group title

Solifenacin 10 mg

Reporting group description

Reporting group title

Solifenacin 5 mg

Reporting group description

Serious adverse events	Combination (solifenacin + mirabegron)	Solifenacin 10 mg	Solifenacin 5 mg
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 725 (1.79%)	15 / 719 (2.09%)	10 / 728 (1.37%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal adenoma
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal cancer
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intraductal proliferative breast lesion
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertensive crisis
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Joint resurfacing surgery
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin neoplasm excision
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Adhesion
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 725 (0.14%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Cervix haemorrhage uterine
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Respiratory tract oedema
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriogram coronary normal
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthroscopy
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colonoscopy
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Polyneuropathy
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal hernia
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic pain
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Liver disorder
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Goitre
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 725 (0.00%)	0 / 719 (0.00%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fracture pain
subjects affected / exposed	0 / 725 (0.00%)	1 / 719 (0.14%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mobility decreased
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 725 (0.14%)	1 / 719 (0.14%)	1 / 728 (0.14%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Encephalitis herpes
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 725 (0.14%)	0 / 719 (0.00%)	0 / 728 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Combination (solifenacin + mirabegron)	Solifenacin 10 mg	Solifenacin 5 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	43 / 725 (5.93%)	68 / 719 (9.46%)	41 / 728 (5.63%)
Gastrointestinal disorders
Dry mouth
subjects affected / exposed	43 / 725 (5.93%)	68 / 719 (9.46%)	41 / 728 (5.63%)
occurrences all number	44	70	44

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

One participant was randomized to the Combination arm, but actually received Solifenacin 10 mg. In terms of actual treatment received, the participant was allocated to the solifenacin 10 mg arm.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

Primary: Change from Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

Secondary: Change from Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes per 24 Hours

Secondary: Change from Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes per 24 Hours

Secondary: Change from Baseline in Mean Number of Micturitions per 24 Hours

Secondary: Change from Baseline in Mean Number of Micturitions per 24 Hours

Secondary: Number of Incontinence Episodes Reported During the 3-Day Diary

Secondary: Number of Incontinence Episodes Reported During the 3-Day Diary

Secondary: Change from Baseline in Mean Volume Voided (MVV) per Micturition

Secondary: Change from Baseline in Mean Volume Voided (MVV) per Micturition

Secondary: Change from Baseline to EoT in Corrected Micturition Frequency (CMF)

Secondary: Change from Baseline to EoT in Corrected Micturition Frequency (CMF)

Secondary: Change from Baseline in Mean Number of Urgency Incontinence (UI) Episodes per 24 Hours

Secondary: Change from Baseline in Mean Number of Urgency Incontinence (UI) Episodes per 24 Hours

Secondary: Number of UI Episodes Reported During the 3-Day Diary

Secondary: Number of UI Episodes Reported During the 3-Day Diary

Secondary: Change from Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) per 24 Hours

Secondary: Change from Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) per 24 Hours

Secondary: Change from Baseline in Mean Number of Pads per 24 hours

Secondary: Change from Baseline in Mean Number of Pads per 24 hours

Secondary: Number of Pads Used During the 3-Day Diary

Secondary: Number of Pads Used During the 3-Day Diary

Secondary: Change from Baseline in Mean Number of Nocturia Episodes

Secondary: Change from Baseline in Mean Number of Nocturia Episodes

Secondary: Number of Nocturia Episodes Reported Over 3-Day Diary

Secondary: Number of Nocturia Episodes Reported Over 3-Day Diary

Secondary: Number of Participants with Change from Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility

Secondary: Number of Participants with Change from Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Self-care

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Self-care

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Usual Activities

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Usual Activities

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression

Secondary: Number of Participants with Change from Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression

Secondary: Change from Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score

Secondary: Change from Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score

Secondary: Change from Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score

Secondary: Change from Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Coping

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Coping

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Concern

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Concern

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Sleep

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Sleep

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Social Interaction

Secondary: Change from Baseline in OAB-q HRQL Subscale Score: Social Interaction

Secondary: Change from Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score

Secondary: Change from Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score

Secondary: Change from Baseline in Patient Perception Bladder Control (PPBC) Score

Secondary: Change from Baseline in Patient Perception Bladder Control (PPBC) Score

Secondary: Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)

Secondary: Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)

Secondary: Percentage of Participants with at Least a 50% Decrease from Baseline in Mean Number of Incontinence Episodes per 24 Hours

Secondary: Percentage of Participants with at Least a 50% Decrease from Baseline in Mean Number of Incontinence Episodes per 24 Hours

Secondary: Percentage of Participants with Zero Incontinence Episodes Postbaseline

Secondary: Percentage of Participants with Zero Incontinence Episodes Postbaseline

Secondary: Percentage of Participants with a Mean of at Least 8 Micturitions per 24 Hours at Baseline and Less than 8 Micturitions per 24 Hours Postbaseline

Secondary: Percentage of Participants with a Mean of at Least 8 Micturitions per 24 Hours at Baseline and Less than 8 Micturitions per 24 Hours Postbaseline

Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in OAB-q Symptom Bother Score

Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in OAB-q Symptom Bother Score

Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in HRQL Total Score

Secondary: Percentage of Participants with at Least a 10-Point Improvement from Baseline in HRQL Total Score

Secondary: Percentage of Participants with at Least a 1-Point Improvement from Baseline in PPBC

Secondary: Percentage of Participants with at Least a 1-Point Improvement from Baseline in PPBC

Secondary: Percentage of Participants with Major (at Least 2-Point) Improvement from Baseline in PPBC

Secondary: Percentage of Participants with Major (at Least 2-Point) Improvement from Baseline in PPBC

Secondary: Number of Participants with Adverse Events (AEs)

Secondary: Number of Participants with Adverse Events (AEs)

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