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Clinical Trial Results:
A Randomized, Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate the Long-term Safety and Efficacy of Combination of Solifenacin Succinate with Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in Patients with Overactive Bladder

Summary
EudraCT number	2012-005736-29
Trial protocol	NL BE HU IT FI GB EE SE SK CZ LV DK SI PL ES LT BG GR
Global end of trial date	08 Sep 2016

Results information
Results version number	v1
This version publication date	17 Aug 2017
First version publication date	17 Aug 2017
Other versions	v2

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

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Trial information

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Sponsor protocol code

178-CL-102

ISRCTN number

US NCT number

NCT02045862

WHO universal trial number (UTN)

Sponsor organisation name

Astellas Pharma Europe B.V.

Sponsor organisation address

Sylviusweg 62, Leiden, Netherlands, 2333 BE

Public contact

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

Scientific contact

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

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

08 Sep 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

08 Sep 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the safety and tolerability of long-term combination treatment with solifenacin (5 mg) and mirabegron (50 mg) compared to solifenacin and mirabegron monotherapy. The study comprised a single-blind, 2-week placebo run-in period followed by a randomized, double-blind, active-controlled, 12-month treatment period and then by a 2-week follow-up period.

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Mar 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 71

Country: Number of subjects enrolled

United States: 311

Country: Number of subjects enrolled

Mexico: 8

Country: Number of subjects enrolled

Belgium: 6

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

Finland: 1

Country: Number of subjects enrolled

Germany: 94

Country: Number of subjects enrolled

Italy: 29

Country: Number of subjects enrolled

Norway: 32

Country: Number of subjects enrolled

Spain: 27

Country: Number of subjects enrolled

Sweden: 13

Country: Number of subjects enrolled

United Kingdom: 7

Country: Number of subjects enrolled

Netherlands: 14

Country: Number of subjects enrolled

Bulgaria: 61

Country: Number of subjects enrolled

Czech Republic: 142

Country: Number of subjects enrolled

Estonia: 6

Country: Number of subjects enrolled

Hungary: 75

Country: Number of subjects enrolled

Latvia: 24

Country: Number of subjects enrolled

Lithuania: 39

Country: Number of subjects enrolled

Poland: 278

Country: Number of subjects enrolled

Romania: 32

Country: Number of subjects enrolled

Russian Federation: 86

Country: Number of subjects enrolled

Slovakia: 108

Country: Number of subjects enrolled

Slovenia: 2

Country: Number of subjects enrolled

Ukraine: 154

Country: Number of subjects enrolled

Malaysia: 3

Country: Number of subjects enrolled

Singapore: 8

Country: Number of subjects enrolled

Korea, Republic of: 122

Country: Number of subjects enrolled

Thailand: 4

Country: Number of subjects enrolled

Australia: 30

Country: Number of subjects enrolled

New Zealand: 12

Country: Number of subjects enrolled

South Africa: 26

Worldwide total number of subjects

1829

EEA total number of subjects

994

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)

1201

From 65 to 84 years

622

85 years and over

Subject disposition

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Recruitment details

Participants who had symptoms of “wet” overactive bladder (OAB) (urgency, urinary frequency and urgency incontinence) for ≥ 3 months were enrolled in 251 centers globally. A majority of the participants were recruited from participants who enrolled and completed studies 178-CL-101 or 905-EC-012.

Screening details

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

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Mirabegron 50 mg

Arm description

Participants who received mirabegron 50 mg once a day for 52 weeks.

Arm type

Active comparator

Investigational medicinal product name

Mirabegron

Investigational medicinal product code

YM178

Other name

Myrbetriq, Myrbetric, Betanis, Betmiga

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received mirabegron 50 mg orally once a day at the same time each day.

Investigational medicinal product name

Placebo to solifenacin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received placebo to match solifenacin 5 mg orally once a day at the same time each day.

Solifenacin 5 mg

Arm description

Participants who received solifenacin 5 mg once a day for 52 weeks.

Arm type

Active comparator

Investigational medicinal product name

Solifenacin succinate

Investigational medicinal product code

YM905

Other name

Solifenacin, Vesicare, Vesikur, Vesitrim

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received solifenacin 5 mg orally once a day at the same time each day.

Investigational medicinal product name

Placebo to mirabegron

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received placebo to match mirabegron 50 mg orally once a day at the same time each day.

Solifenacin 5 mg + mirabegron 50 mg

Arm description

Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.

Arm type

Experimental

Investigational medicinal product name

Solifenacin succinate

Investigational medicinal product code

YM905

Other name

Solifenacin, Vesicare, Vesikur, Vesitrim

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received solifenacin 5 mg orally once a day at the same time each day.

Investigational medicinal product name

Mirabegron

Investigational medicinal product code

YM178

Other name

Myrbetriq, Myrbetric, Betanis, Betmiga

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received mirabegron 50 mg orally once a day at the same time each day.

Number of subjects in period 1	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Started	306	305	1218
Treated	306	303	1210
Safety Analysis Set (SAF)	305	303	1206
Full Analysis Set (FAS)	302	299	1193
Completed	267	265	1092
Not completed	39	40	126
Lack of Efficacy	8	4	13
Adverse Event	7	5	27
Randomized but not received study drug	-	2	8
Lost to Follow-up	1	2	6
Death	-	-	1
Miscellaneous	5	-	8
Protocol Violation	-	-	6
Withdrawal by patient	18	27	57

Baseline characteristics

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Reporting group title

Mirabegron 50 mg

Reporting group description

Participants who received mirabegron 50 mg once a day for 52 weeks.

Reporting group title

Solifenacin 5 mg

Reporting group description

Participants who received solifenacin 5 mg once a day for 52 weeks.

Reporting group title

Solifenacin 5 mg + mirabegron 50 mg

Reporting group description

Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.

Reporting group values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg	Total
Number of subjects	306	305	1218
Age categorical
Units: Subjects
Age continuous
Randomized analysis set (RAS), comprised of all randomized participants.
Units: years
arithmetic mean (standard deviation)	58.8 ( 12.7 )	59 ( 13.3 )	58.3 ( 13 )	-
Gender categorical
RAS
Units:
Male	63	60	245	368
Female	243	245	973	1461
Mean Number of Incontinence Episodes per 24 Hours
RAS; data only available for 1818 participants [306, 303, 1209].
Units: incontinence episodes
arithmetic mean (standard deviation)	3.17 ( 3.58 )	3.08 ( 3.56 )	3.03 ( 3.16 )	-
Mean Number of Micturitions per 24 Hours
RAS; data only available for 1818 participants [306, 303, 1209].
Units: micturitions
arithmetic mean (standard deviation)	10.51 ( 2.4 )	10.74 ( 2.82 )	10.56 ( 2.73 )	-
Mean Volume Voided per Micturition
RAS; data only available for 1815 participants [306, 303, 1206].
Units: mL
arithmetic mean (standard deviation)	161.37 ( 59.92 )	159.98 ( 58.58 )	158.74 ( 58.41 )	-
Number of Incontinence Episodes per Week
RAS; data only available for 1818 participants [306, 303, 1209].
Units: incontinence episodes/week
arithmetic mean (standard deviation)	21.96 ( 24.91 )	21.45 ( 24.91 )	20.88 ( 21.82 )	-
Mean Number of Urgency Incontinence Episodes per 24 Hours
RAS; data only available for 1809 participants [306, 301, 1202]. Only participants with ≥ 1 urgency incontinence episode at baseline were included. An urgency incontinence episode is defined as the involuntary leakage of urine accompanied by or immediately proceeded by urgency.
Units: urgency incontinence episodes
arithmetic mean (standard deviation)	2.88 ( 3.32 )	2.89 ( 3.47 )	2.74 ( 2.78 )	-
Number of Urgency Incontinence Episodes per Week
RAS; data only available for 1809 participants [306, 301, 1202]. Only participants with ≥ 1 urgency incontinence episode at baseline were included.
Units: urgency incontinence episodes/week
arithmetic mean (standard deviation)	19.92 ( 23.04 )	20.13 ( 24.33 )	18.87 ( 19.07 )	-
Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours
RAS; data only available for 1818 participants [306, 303, 1209]. Only participants with ≥ 1 urgency episode at baseline were included. An urgency episode is a complaint of a sudden, compelling desire to pass urine, which is difficult to defer; it is recorded when a micturition or incontinence episode is recorded and the severity of urinary urgency recorded is 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS).
Units: urgency episodes
arithmetic mean (standard deviation)	6.38 ( 4.15 )	6.62 ( 4.07 )	6.55 ( 3.69 )	-
Mean Number of Nocturia Episodes per 24 Hours
RAS; data only available for 1563 participants [265, 256, 1042]. Only participants with ≥ 1 nocturia episode at baseline were included. A nocturia episode is defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the patients gets up in the morning with the intention to stay awake).
Units: nocturia episodes
arithmetic mean (standard deviation)	1.49 ( 0.95 )	1.57 ( 0.94 )	1.5 ( 0.94 )	-
Number of Nocturia Episodes per Week
RAS; data only available for 1563 participants [265, 256, 1042]. Only participants with ≥ 1 nocturia episode at baseline were included.
Units: nocturia episodes/week
arithmetic mean (standard deviation)	10.38 ( 6.68 )	10.93 ( 6.58 )	10.36 ( 6.48 )	-
Mean Number of Pads Used per 24 Hours
RAS; data only available for 1187 participants [204, 197, 786]. Only participants with ≥ 1 pad used at baseline were included.
Units: pads
arithmetic mean (standard deviation)	2.49 ( 3.74 )	2.75 ( 3.12 )	2.57 ( 2.58 )	-
Number of Pads Used per Week
RAS; data only available for 1187 participants [204, 197, 786]. Only participants with ≥ 1 pad used at baseline were included.
Units: pads/week
arithmetic mean (standard deviation)	17.13 ( 25.93 )	19.06 ( 21.84 )	17.66 ( 17.53 )	-

End points

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Reporting group title

Mirabegron 50 mg

Reporting group description

Participants who received mirabegron 50 mg once a day for 52 weeks.

Reporting group title

Solifenacin 5 mg

Reporting group description

Participants who received solifenacin 5 mg once a day for 52 weeks.

Reporting group title

Solifenacin 5 mg + mirabegron 50 mg

Reporting group description

Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.

Primary: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

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End point title

Number of Participants with Treatment-Emergent Adverse Events (TEAEs) ^[1]

End point description

A TEAE is defined as an adverse event (AE) observed after taking the first dose of double-blind treatment until 14 days after taking the last dose of double-blind treatment for non-serious AEs and until 30 days after taking the last dose of double-blind treatment for serious adverse events (SAEs). This includes abnormal laboratory tests, vital signs or electrocardiogram data that were defined as AEs if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant in the investigator's opinion. The severity of an AE was measured by: Mild (No disruption of normal daily activities); Moderate (Affected normal daily activities) and Severe (Inability to perform daily activities). The analysis population was the Safety Analysis Set (SAF), which consisted of all participants who received ≥ 1 dose of double-blind study drug and excluded participants from site 10153.

End point type

Primary

End point timeframe

From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 56 weeks)

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

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	305	303	1206
Units: participants
Any TEAEs	126	134	596
Mild TEAEs	61	69	306
Moderate TEAEs	52	58	238
Severe TEAEs	13	7	52
Drug-related TEAEs	35	42	200
Serious TEAEs	8	8	51
Drug-related serious TEAEs	1	0	0
TEAEs leading to discontuation of study drug	7	5	25
Drug-related TEAEs leading to discont. of drug	4	4	17
TEAEs leading to death	0	0	1

No statistical analyses for this end point

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

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End point title

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

End point description

An incontinence episode is defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period. The analysis population was the Full Analysis Set (FAS), which was comprised of all randomized participants who took ≥ 1 dose of double-blind treatment, reported ≥ 1 micturition in the baseline diary and ≥ 1 micturition postbaseline, reported ≥ 1 incontinence episode in the baseline diary and excluded participants from site 10153 and 42006. Last observation carried forward (LOCF) was used for EoT.

End point type

Primary

End point timeframe

Baseline and Week 52

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	301	297	1184
Units: incontinence episodes
least squares mean (standard error)	-1.58 ( 0.11 )	-1.9 ( 0.11 )	-2.03 ( 0.05 )

Difference vs. Mirabegron 50 mg

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1485

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.12

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

Difference vs. Solifenacin 5 mg

Statistical analysis description

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

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1481

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[3]

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.12

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

Primary: Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours

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End point title

Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours

End point description

A micturition is defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period. The analysis population was the FAS. LOCF was used for EoT.

End point type

Primary

End point timeframe

Baseline and Week 52

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	301	297	1184
Units: micturitions
least squares mean (standard error)	-2.1 ( 0.13 )	-2.16 ( 0.13 )	-2.58 ( 0.07 )

Difference vs. Mirabegron 50 mg

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1485

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[4]

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.48

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.15

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

Difference vs. Solifenacin 5 mg

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1481

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[5]

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.15

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

Secondary: Change from Baseline to EoT in Mean Volume Voided per Micturition

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End point title

Change from Baseline to EoT in Mean Volume Voided per Micturition

End point description

The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period. The analysis population was the FAS. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	289	293	1162
Units: mL
least squares mean (standard error)	21.83 ( 3.12 )	24.9 ( 3.1 )	37.67 ( 1.55 )

Difference vs. Mirabegron 50 mg

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1451

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

15.84

Confidence interval

level

95%

sides

2-sided

lower limit

8.99

upper limit

22.69

Variability estimate

Standard error of the mean

Dispersion value

3.49

Difference vs. Solifenacin 5 mg

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1455

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

12.77

Confidence interval

level

95%

sides

2-sided

lower limit

5.98

upper limit

19.57

Variability estimate

Standard error of the mean

Dispersion value

3.47

Secondary: Change from Baseline to EoT in OAB Questionnaire (OAB-q) Symptom Bother Score

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End point title

Change from Baseline to EoT in OAB Questionnaire (OAB-q) Symptom Bother Score

End point description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicates an improvement. The analysis population was the FAS. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	290	294	1163
Units: units on a scale
least squares mean (standard error)	-21.96 ( 1.14 )	-24.91 ( 1.13 )	-29.51 ( 0.57 )

Difference vs. Mirabegron 50 mg

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1453

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-7.55

Confidence interval

level

95%

sides

2-sided

lower limit

-10.05

upper limit

-5.05

Variability estimate

Standard error of the mean

Dispersion value

1.27

Difference vs. Solifenacin 5 mg

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1457

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-7.09

upper limit

-2.12

Variability estimate

Standard error of the mean

Dispersion value

1.27

Secondary: Change from Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

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End point title

Change from Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

End point description

The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicates improvement. The analysis population was the FAS. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	289	294	1163
Units: units on a scale
least squares mean (standard error)	2.19 ( 0.12 )	2.15 ( 0.12 )	2.73 ( 0.06 )

Difference vs. Mirabegron 50 mg

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1452

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

0.82

Variability estimate

Standard error of the mean

Dispersion value

0.14

Difference vs. Solifenacin 5 mg

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1457

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

0.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

0.86

Variability estimate

Standard error of the mean

Dispersion value

0.14

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes per 24 Hours

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End point title

Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes per 24 Hours

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: incontinence episodes
least squares mean (standard error)
Month 1 [N=291, 288, 1158]	-0.97 ( 0.1 )	-1.29 ( 0.11 )	-1.45 ( 0.05 )
Month 3 [N=282, 288, 1137]	-1.31 ( 0.11 )	-1.71 ( 0.11 )	-1.78 ( 0.05 )
Month 6 [N=266, 273, 1107]	-1.42 ( 0.11 )	-1.78 ( 0.11 )	-1.93 ( 0.05 )
Month 9 [N=264, 261, 1070]	-1.53 ( 0.11 )	-1.9 ( 0.11 )	-2 ( 0.06 )
Month 12 [N=258, 256, 1048]	-1.67 ( 0.11 )	-1.92 ( 0.11 )	-2.06 ( 0.06 )

No statistical analyses for this end point

Secondary: Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Top of page

End point title

Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

End point description

The number of incontinence episodes is the number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: incontinence episodes
arithmetic mean (standard error)
Month 1 [N=291, 288, 1158]	14.88 ( 1.52 )	12.41 ( 1.22 )	10.8 ( 0.58 )
Month 3 [N=282, 288, 1137]	12.23 ( 1.12 )	9.23 ( 1.02 )	8.33 ( 0.52 )
Month 6 [N=266, 273, 1107]	10.62 ( 1.08 )	8.18 ( 1.01 )	7.28 ( 0.48 )
Month 9 [N=264, 261, 1070]	10.53 ( 1.19 )	7.28 ( 0.91 )	6.74 ( 0.45 )
Month 12 [N=258, 266, 1048]	9.09 ( 1.1 )	7.06 ( 0.94 )	6.1 ( 0.46 )
EoT [N=301, 297, 1184]	10.32 ( 1.08 )	8.09 ( 0.94 )	6.85 ( 0.47 )

Rate ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed Effects Poisson-negative binomial

Parameter type

Rate ratio

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

0.84

Variability estimate

Standard error of the mean

Dispersion value

0.12

Rate ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

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

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

Mixed Effects Poisson-negative binomial

Parameter type

Rate ratio

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

0.97

Variability estimate

Standard error of the mean

Dispersion value

0.12

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

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End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: incontinence episodes
least squares mean (standard error)
Month 1 [N=291, 288, 1158]	-6.77 ( 0.73 )	-9.17 ( 0.73 )	-10.31 ( 0.36 )
Month 3 [N=282, 288, 1137]	-9.21 ( 0.76 )	-12.05 ( 0.75 )	-12.55 ( 0.38 )
Month 6 [N=266, 273, 1107]	-10.36 ( 0.76 )	-12.5 ( 0.75 )	-13.49 ( 0.37 )
Month 9 [N=264, 261, 1070]	-10.62 ( 0.76 )	-13.51 ( 0.77 )	-14.06 ( 0.38 )
Month 12 [N=258, 256, 1048]	-11.84 ( 0.77 )	-13.47 ( 0.77 )	-14.43 ( 0.38 )
EoT [N=301, 297, 1184]	-11.17 ( 0.75 )	-13.37 ( 0.75 )	-14.29 ( 0.37 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-3.12

Confidence interval

level

95%

sides

2-sided

lower limit

-4.76

upper limit

-1.49

Variability estimate

Standard error of the mean

Dispersion value

0.83

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

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

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.93

Confidence interval

level

95%

sides

2-sided

lower limit

-2.57

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

0.84

Secondary: Number of Incontinence-Free Days Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

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End point title

Number of Incontinence-Free Days Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

End point description

The number of incontinence-free days is the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: incontinence-free days
arithmetic mean (standard error)
Month 1 [N=291, 288, 1158]	2.73 ( 0.15 )	3.35 ( 0.17 )	3.46 ( 0.08 )
Month 3 [N=282, 288, 1137]	3.3 ( 0.17 )	3.98 ( 0.17 )	4.17 ( 0.08 )
Month 6 [N=266, 273, 1107]	3.64 ( 0.17 )	4.08 ( 0.17 )	4.44 ( 0.08 )
Month 9 [N=264, 261, 1070]	3.97 ( 0.18 )	4.33 ( 0.17 )	4.56 ( 0.08 )
Month 12 [N=258, 256, 1048]	4.23 ( 0.18 )	4.5 ( 0.18 )	4.81 ( 0.08 )
EoT [N=301, 297, 1184]	3.98 ( 0.17 )	4.29 ( 0.16 )	4.64 ( 0.08 )

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Overdispersed binomial regression

Parameter type

Odds ratio (OR)

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.01

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009

Method

Overdispersed binomial regression

Parameter type

Odds ratio (OR)

Point estimate

1.38

Confidence interval

level

95%

sides

2-sided

lower limit

1.08

upper limit

1.75

Secondary: Number of Incontinence-Free Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Top of page

End point title

Number of Incontinence-Free Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

End point description

The number of incontinence-free days with < 8 micturitions per day is the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded and with < 8 micturitions per day. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: days
arithmetic mean (standard error)
Month 1 [N=291, 288, 1158]	1.03 ( 0.11 )	1.01 ( 0.1 )	1.33 ( 0.06 )
Month 3 [N=282, 288, 1137]	1.24 ( 0.12 )	1.48 ( 0.13 )	1.91 ( 0.07 )
Month 6 [N=266, 273, 1107]	1.56 ( 0.14 )	1.66 ( 0.14 )	2.13 ( 0.08 )
Month 9 [N=264, 261, 1070]	1.56 ( 0.14 )	1.64 ( 0.14 )	2.2 ( 0.08 )
Month 12 [N=258, 256, 1048]	1.87 ( 0.15 )	1.92 ( 0.15 )	2.54 ( 0.08 )
EoT [N=301, 297, 1184]	1.75 ( 0.14 )	1.9 ( 0.14 )	2.43 ( 0.07 )

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Overdispersed binomial regression

Parameter type

Odds ratio (OR)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.05

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Overdispersed binomial regression

Parameter type

Odds ratio (OR)

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

1.85

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours

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End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours

End point description

An urgency incontinence episode is defined as the involuntary leakage of urine accompanied by or immediately proceeded by urgency. The mean number of urgency incontinence episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: urgency incontinence episodes
least squares mean (standard error)
Month 1 [N=291, 286, 1152]	-0.93 ( 0.1 )	-1.25 ( 0.1 )	-1.43 ( 0.05 )
Month 3 [N=282, 286, 1132]	-1.3 ( 0.1 )	-1.64 ( 0.1 )	-1.71 ( 0.05 )
Month 6 [N=266, 271, 1101]	-1.4 ( 0.1 )	-1.67 ( 0.1 )	-1.86 ( 0.05 )
Month 9 [N=264, 259, 1066]	-1.6 ( 0.11 )	-1.78 ( 0.11 )	-1.92 ( 0.05 )
Month 12 [N=258, 254, 1043]	-1.6 ( 0.1 )	-1.82 ( 0.1 )	-1.98 ( 0.05 )
EoT [N=301, 295, 1178]	-1.51 ( 0.1 )	-1.81 ( 0.1 )	-1.94 ( 0.05 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-0.65

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.11

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.11

Secondary: Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Top of page

End point title

Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

End point description

The number of urgency incontinence episodes is the number of times a participant recorded an urgency incontinence episode during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: urgency incontinence episodes
arithmetic mean (standard error)
Month 1 [N=291, 286, 1152]	13.14 ( 1.42 )	11.21 ( 1.19 )	8.99 ( 0.47 )
Month 3 [N=282, 286, 1132]	10.37 ( 1 )	8.12 ( 0.98 )	6.95 ( 0.44 )
Month 6 [N=266, 271, 1101]	8.97 ( 0.95 )	7.31 ( 0.96 )	5.88 ( 0.41 )
Month 9 [N=264, 259, 1066]	8.08 ( 1.01 )	6.51 ( 0.89 )	5.47 ( 0.4 )
Month 12 [N=258, 254, 1043]	7.73 ( 1 )	6.06 ( 0.85 )	4.88 ( 0.38 )
EoT [N=301, 295, 1178]	8.86 ( 0.98 )	7.04 ( 0.86 )	5.57 ( 0.4 )

Rate ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Negative binomial regression

Parameter type

Rate ratio

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

0.79

Variability estimate

Standard error of the mean

Dispersion value

0.13

Rate ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

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

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.023

Method

Negative binomial regression

Parameter type

Rate ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

0.96

Variability estimate

Standard error of the mean

Dispersion value

0.13

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: urgency incontinence episodes
least squares mean (standard error)
Month 1 [N=291, 286, 1152]	-6.45 ( 0.69 )	-8.77 ( 0.69 )	-10.1 ( 0.34 )
Month 3 [N=282, 286, 1132]	-9.06 ( 0.72 )	-11.48 ( 0.71 )	-11.99 ( 0.36 )
Month 6 [N=266, 271, 1101]	-10.09 ( 0.72 )	-11.71 ( 0.71 )	-13 ( 0.35 )
Month 9 [N=264, 259, 1066]	-11.1 ( 0.72 )	-12.6 ( 0.73 )	-13.44 ( 0.36 )
Month 12 [N=258, 254, 1043]	-11.27 ( 0.71 )	-12.8 ( 0.71 )	-13.8 ( 0.35 )
EoT [N=301, 295, 1178]	-10.61 ( 0.7 )	-12.66 ( 0.7 )	-13.59 ( 0.35 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[6]

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-2.98

Confidence interval

level

95%

sides

2-sided

lower limit

-4.51

upper limit

-1.46

Variability estimate

Standard error of the mean

Dispersion value

0.78

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

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[7]

Method

Stratified rank ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.93

Confidence interval

level

95%

sides

2-sided

lower limit

-2.47

upper limit

0.61

Variability estimate

Standard error of the mean

Dispersion value

0.78

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

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions per 24 Hours

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions per 24 Hours

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: micturitions
least squares mean (standard error)
Month 1 [N=291, 288, 1158]	-1.09 ( 0.12 )	-1.36 ( 0.12 )	-1.64 ( 0.06 )
Month 3 [N=282, 288, 1137]	-1.63 ( 0.13 )	-1.87 ( 0.12 )	-2.16 ( 0.06 )
Month 6 [N=266, 273, 1107]	-1.85 ( 0.13 )	-2.04 ( 0.13 )	-2.39 ( 0.06 )
Month 9 [N=264, 261, 1070]	-2.03 ( 0.13 )	-2.03 ( 0.13 )	-2.42 ( 0.06 )
Month 12 [N=258, 256, 1048]	-2.2 ( 0.13 )	-2.13 ( 0.14 )	-2.64 ( 0.07 )

No statistical analyses for this end point

Secondary: Number of Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Top of page

End point title

Number of Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

End point description

The number of days with < 8 micturitions is the number of valid diary days during the 7-day micturition diary period with with less than 8 micturitions per day. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: days
arithmetic mean (standard error)
Month 1 [N=291, 288, 1158]	1.9 ( 0.13 )	1.6 ( 0.12 )	2.08 ( 0.07 )
Month 3 [N=282, 288, 1137]	2.07 ( 0.14 )	2.14 ( 0.14 )	2.66 ( 0.08 )
Month 6 [N=266, 273, 1107]	2.35 ( 0.15 )	2.34 ( 0.15 )	2.87 ( 0.08 )
Month 9 [N=264, 261, 1070]	2.38 ( 0.16 )	2.33 ( 0.15 )	2.93 ( 0.08 )
Month 12 [N=258, 256, 1048]	2.61 ( 0.16 )	2.58 ( 0.16 )	3.17 ( 0.08 )
EoT [N=301, 297, 1184]	2.52 ( 0.15 )	2.58 ( 0.15 )	3.1 ( 0.08 )

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Overdispersed binomial regression

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

1.8

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

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

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Overdispersed binomial regression

Parameter type

Odds ratio (OR)

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

1.73

Secondary: Change from Baseline to EoT in Corrected Micturition Frequency

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End point title

Change from Baseline to EoT in Corrected Micturition Frequency

End point description

Corrected micturition frequency is defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline. The analysis population was the FAS. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	301	297	1184
Units: micturitions
least squares mean (standard error)	-0.72 ( 0.17 )	-1.11 ( 0.17 )	-1.51 ( 0.08 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1485

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.16

upper limit

-0.41

Variability estimate

Standard error of the mean

Dispersion value

0.19

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1481

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.037

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.19

Secondary: Change from Baseline to Months 3, 6 and 12 in Mean Volume Voided per Micturition

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End point title

Change from Baseline to Months 3, 6 and 12 in Mean Volume Voided per Micturition

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.

End point type

Secondary

End point timeframe

Baseline and Months 3, 6, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: mL
least squares mean (standard error)
Month 3 [N=274, 280, 1125]	15.34 ( 2.96 )	23.71 ( 2.92 )	34.89 ( 1.45 )
Month 6 [N=265, 268, 1102]	20.87 ( 3.21 )	27.08 ( 3.19 )	38.56 ( 1.57 )
Month 12 [N=248, 254, 1028]	21.85 ( 3.42 )	24.05 ( 3.37 )	38.72 ( 1.67 )

No statistical analyses for this end point

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours

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End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours

End point description

An urgency episode is a complaint of a sudden, compelling desire to pass urine, which is difficult to defer; it is recorded when a micturition or incontinence episode is recorded and the severity of urinary urgency recorded is 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS). The mean number of urgency episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 urgency episode at baseline were included in the analysis. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: urgency episodes
least squares mean (standard error)
Month 1 [N=291, 288, 1158]	-1.93 ( 0.17 )	-2.31 ( 0.17 )	-2.68 ( 0.09 )
Month 3 [N=282, 288, 1137]	-2.68 ( 0.17 )	-3.02 ( 0.17 )	-3.36 ( 0.08 )
Month 6 [N=266, 273, 1107]	-2.93 ( 0.17 )	-3.17 ( 0.17 )	-3.72 ( 0.08 )
Month 9 [N=264, 261, 1070]	-3.4 ( 0.18 )	-3.55 ( 0.18 )	-3.87 ( 0.09 )
Month 12 [N=258, 256, 1048]	-3.4 ( 0.17 )	-3.56 ( 0.17 )	-3.95 ( 0.09 )
EoT [N=301, 297, 1184]	-3.11 ( 0.17 )	-3.45 ( 0.17 )	-3.84 ( 0.08 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

-0.37

Variability estimate

Standard error of the mean

Dispersion value

0.19

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.036

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.19

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours

End point description

A nocturia episode is defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the patients gets up in the morning with the intention to stay awake). The mean number of nocturia episodes was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: nocturia episodes
least squares mean (standard error)
Month 1 [N=253, 244, 1000]	-0.2 ( 0.04 )	-0.22 ( 0.04 )	-0.34 ( 0.02 )
Month 3 [N=247, 244, 985]	-0.34 ( 0.04 )	-0.38 ( 0.04 )	-0.46 ( 0.02 )
Month 6 [N=231, 231, 958]	-0.41 ( 0.05 )	-0.39 ( 0.05 )	-0.49 ( 0.02 )
Month 9 [N=229, 221, 927]	-0.42 ( 0.05 )	-0.44 ( 0.05 )	-0.5 ( 0.02 )
Month 12 [N=225, 217, 906]	-0.46 ( 0.05 )	-0.44 ( 0.05 )	-0.56 ( 0.02 )
EoT [N=262, 251, 1023]	-0.45 ( 0.04 )	-0.45 ( 0.04 )	-0.55 ( 0.02 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.059

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.05

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.068

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.05

Secondary: Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Top of page

End point title

Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

End point description

The number of nocturia episodes is the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: nocturia episodes
arithmetic mean (standard error)
Month 1 [N=253, 244, 1000]	8.76 ( 0.41 )	9.23 ( 0.44 )	8 ( 0.2 )
Month 3 [N=247, 244, 985]	7.93 ( 0.39 )	7.92 ( 0.4 )	7.17 ( 0.19 )
Month 6 [N=231, 231, 958]	7.12 ( 0.35 )	7.86 ( 0.43 )	6.96 ( 0.2 )
Month 9 [N=229, 221, 927]	7.4 ( 0.38 )	7.48 ( 0.41 )	6.84 ( 0.2 )
Month 12 [N=225, 217, 906]	6.88 ( 0.38 )	7.39 ( 0.44 )	6.33 ( 0.19 )
EoT [N=262, 251, 1023]	7.13 ( 0.37 )	7.47 ( 0.42 )	6.51 ( 0.19 )

Rate ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.067

Method

Negative binomial regression

Parameter type

Rate ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.01

Variability estimate

Standard error of the mean

Dispersion value

0.06

Rate ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

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

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.131

Method

Negative binomial regression

Parameter type

Rate ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.03

Variability estimate

Standard error of the mean

Dispersion value

0.06

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: nocturia episodes
least squares mean (standard error)
Month 1 [N=253, 244, 1000]	-1.56 ( 0.29 )	-1.58 ( 0.29 )	-2.39 ( 0.15 )
Month 3 [N=247, 244, 985]	-2.45 ( 0.29 )	-2.78 ( 0.3 )	-3.26 ( 0.15 )
Month 6 [N=231, 231, 958]	-3.08 ( 0.33 )	-2.81 ( 0.33 )	-3.44 ( 0.16 )
Month 9 [N=229, 221, 927]	-2.91 ( 0.32 )	-3.13 ( 0.32 )	-3.55 ( 0.16 )
Month 12 [N=225, 217, 906]	-3.29 ( 0.32 )	-3.08 ( 0.33 )	-3.97 ( 0.16 )
EoT [N=262, 251, 1023]	-3.24 ( 0.31 )	-3.2 ( 0.32 )	-3.9 ( 0.16 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.055

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1.34

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.35

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.048

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.39

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.35

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used per 24 Hours

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used per 24 Hours

End point description

The mean number of pads used was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 pads used at baseline were included in the analysis. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: pads
least squares mean (standard error)
Month 1 [N=193, 185, 741]	-0.67 ( 0.1 )	-0.96 ( 0.11 )	-1.25 ( 0.05 )
Month 3 [N=188, 184, 734]	-1.12 ( 0.11 )	-1.3 ( 0.11 )	-1.49 ( 0.06 )
Month 6 [N=174, 173, 712]	-1.3 ( 0.12 )	-1.24 ( 0.12 )	-1.59 ( 0.06 )
Month 9 [N=173, 166, 689]	-1.38 ( 0.12 )	-1.31 ( 0.13 )	-1.65 ( 0.06 )
Month 12 [N=170, 162, 678]	-1.35 ( 0.12 )	-1.37 ( 0.13 )	-1.67 ( 0.06 )
EoT [N=200, 191, 762]	-1.23 ( 0.12 )	-1.38 ( 0.12 )	-1.66 ( 0.06 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

-0.16

Variability estimate

Standard error of the mean

Dispersion value

0.13

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.039

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.55

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.14

Secondary: Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Top of page

End point title

Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

End point description

The number of pads used is the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit. The analysis population was the FAS. Only participants with ≥ 1 pad used at baseline were included in the analysis. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: pads
arithmetic mean (standard error)
Month 1 [N=193, 185, 741]	12.67 ( 1.98 )	12.55 ( 1.59 )	8.75 ( 0.5 )
Month 3 [N=188, 184, 734]	9.61 ( 1.12 )	9.47 ( 1.28 )	7.23 ( 0.5 )
Month 6 [N=174, 173, 712]	7.99 ( 1.03 )	9.16 ( 1.28 )	6.51 ( 0.47 )
Month 9 [N=173, 166, 689]	7.65 ( 1.08 )	8.91 ( 1.28 )	6.18 ( 0.46 )
Month 12 [N=170, 162, 678]	7.6 ( 1.05 )	8.09 ( 1.23 )	5.7 ( 0.44 )
EoT [N=200, 191, 762]	9.09 ( 1.07 )	8.54 ( 1.1 )	6.33 ( 0.45 )

Rate ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Negative binomial regression

Parameter type

Rate ratio

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

0.76

Variability estimate

Standard error of the mean

Dispersion value

0.14

Rate ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

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

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.044

Method

Negative binomial regression

Parameter type

Rate ratio

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

0.99

Variability estimate

Standard error of the mean

Dispersion value

0.14

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. Only participants with ≥ 1 pad used at baseline were included in the analysis. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: pads
least squares mean (standard error)
Month 1 [N=193, 185, 741]	-4.74 ( 0.71 )	-6.72 ( 0.72 )	-8.89 ( 0.36 )
Month 3 [N=188, 184, 734]	-7.83 ( 0.77 )	-9.21 ( 0.78 )	-10.47 ( 0.39 )
Month 6 [N=174, 173, 712]	-9.09 ( 0.85 )	-8.86 ( 0.85 )	-11.12 ( 0.42 )
Month 9 [N=173, 166, 689]	-9.59 ( 0.87 )	-9.33 ( 0.89 )	-11.44 ( 0.43 )
Month 12 [N=170, 162, 678]	-9.39 ( 0.85 )	-9.92 ( 0.87 )	-11.66 ( 0.42 )
EoT [N=200, 191, 762]	-8.59 ( 0.82 )	-9.89 ( 0.84 )	-11.58 ( 0.42 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-2.98

Confidence interval

level

95%

sides

2-sided

lower limit

-4.78

upper limit

-1.18

Variability estimate

Standard error of the mean

Dispersion value

0.92

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.072

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-1.68

Confidence interval

level

95%

sides

2-sided

lower limit

-3.52

upper limit

0.15

Variability estimate

Standard error of the mean

Dispersion value

0.93

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=281, 286, 1132]	-16.37 ( 1.08 )	-20.82 ( 1.07 )	-22.86 ( 0.54 )
Month 3 [N=278, 286, 1137]	-19.69 ( 1.08 )	-23.13 ( 1.07 )	-26.88 ( 0.53 )
Month 6 [N=260, 272, 1108]	-20.97 ( 1.14 )	-24.27 ( 1.12 )	-27.73 ( 0.55 )
Month 9 [N=261, 264, 1077]	-21.41 ( 1.15 )	-25.82 ( 1.14 )	-28.45 ( 0.56 )
Month 12 [N=250, 255, 1049]	-23.41 ( 1.19 )	-25.38 ( 1.18 )	-30.18 ( 0.58 )

No statistical analyses for this end point

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQL): Total score

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQL): Total score

End point description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=281, 286, 1132]	11.67 ( 0.92 )	14.01 ( 0.91 )	15.69 ( 0.45 )
Month 3 [N=278, 286, 1137]	15.25 ( 0.95 )	16.41 ( 0.94 )	19.26 ( 0.47 )
Month 6 [N=260, 272, 1108]	16.63 ( 1.02 )	17.96 ( 1 )	20.03 ( 0.49 )
Month 9 [N=261, 264, 1077]	16.69 ( 1.02 )	18.53 ( 1.01 )	20.75 ( 0.5 )
Month 12 [N=250, 255, 1049]	17.33 ( 1.04 )	18.8 ( 1.03 )	21.82 ( 0.51 )
EoT [N=290, 294, 1163]	16.57 ( 1 )	18.47 ( 0.99 )	21.33 ( 0.5 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

4.76

Confidence interval

level

95%

sides

2-sided

lower limit

2.56

upper limit

6.96

Variability estimate

Standard error of the mean

Dispersion value

1.12

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

2.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

5.04

Variability estimate

Standard error of the mean

Dispersion value

1.11

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Coping

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Coping

End point description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=281, 286, 1132]	13.05 ( 1.09 )	15.4 ( 1.08 )	17.58 ( 0.54 )
Month 3 [N=278, 286, 1137]	17.57 ( 1.14 )	18.38 ( 1.13 )	21.64 ( 0.56 )
Month 6 [N=260, 272, 1108]	19.68 ( 1.22 )	20.53 ( 1.19 )	22.73 ( 0.59 )
Month 9 [N=261, 264, 1077]	19.54 ( 1.21 )	21.21 ( 1.2 )	23.58 ( 0.59 )
Month 12 [N=250, 255, 1049]	19.47 ( 1.25 )	21.9 ( 1.23 )	24.86 ( 0.61 )
EoT [N=290, 294, 1163]	18.54 ( 1.19 )	21.13 ( 1.18 )	24.14 ( 0.59 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.99

upper limit

8.2

Variability estimate

Standard error of the mean

Dispersion value

1.33

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

3.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

5.6

Variability estimate

Standard error of the mean

Dispersion value

1.32

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Concern

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Concern

End point description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=281, 286, 1132]	13.24 ( 1.03 )	15.49 ( 1.02 )	17.6 ( 0.51 )
Month 3 [N=278, 286, 1137]	16.37 ( 1.05 )	17.64 ( 1.04 )	21.23 ( 0.52 )
Month 6 [N=260, 272, 1108]	17.77 ( 1.1 )	19.05 ( 1.07 )	21.73 ( 0.53 )
Month 9 [N=261, 264, 1077]	18.15 ( 1.11 )	19.74 ( 1.1 )	22.3 ( 0.54 )
Month 12 [N=250, 255, 1049]	19.1 ( 1.12 )	19.4 ( 1.1 )	23.3 ( 0.54 )
EoT [N=290, 294, 1163]	17.98 ( 1.08 )	19.22 ( 1.07 )	23 ( 0.54 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

5.01

Confidence interval

level

95%

sides

2-sided

lower limit

2.65

upper limit

7.38

Variability estimate

Standard error of the mean

Dispersion value

1.21

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

3.78

Confidence interval

level

95%

sides

2-sided

lower limit

1.43

upper limit

6.13

Variability estimate

Standard error of the mean

Dispersion value

1.2

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Sleep

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Sleep

End point description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=281, 286, 1132]	10.96 ( 1.08 )	14.24 ( 1.07 )	15.82 ( 0.54 )
Month 3 [N=278, 286, 1137]	14.09 ( 1.12 )	16.71 ( 1.1 )	19.75 ( 0.55 )
Month 6 [N=260, 272, 1108]	14.84 ( 1.22 )	17.7 ( 1.19 )	20.09 ( 0.59 )
Month 9 [N=261, 264, 1077]	14.86 ( 1.22 )	17.73 ( 1.21 )	21.15 ( 0.6 )
Month 12 [N=250, 255, 1049]	16.53 ( 1.29 )	18.28 ( 1.27 )	22.17 ( 0.63 )
EoT [N=290, 294, 1163]	16.44 ( 1.22 )	18.32 ( 1.21 )	21.59 ( 0.61 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

5.15

Confidence interval

level

95%

sides

2-sided

lower limit

2.47

upper limit

7.83

Variability estimate

Standard error of the mean

Dispersion value

1.36

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

3.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

5.93

Variability estimate

Standard error of the mean

Dispersion value

1.35

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Social

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Social

End point description

The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=281, 286, 1132]	7.99 ( 0.84 )	9.41 ( 0.83 )	9.89 ( 0.42 )
Month 3 [N=278, 286, 1137]	11.14 ( 0.85 )	11.19 ( 0.84 )	12.22 ( 0.42 )
Month 6 [N=260, 272, 1108]	11.89 ( 0.89 )	12.54 ( 0.87 )	13.3 ( 0.43 )
Month 9 [N=261, 264, 1077]	11.92 ( 0.9 )	13.33 ( 0.89 )	13.64 ( 0.44 )
Month 12 [N=250, 255, 1049]	12.25 ( 0.9 )	13.47 ( 0.89 )	14.52 ( 0.44 )
EoT [N=290, 294, 1163]	11.57 ( 0.87 )	13.22 ( 0.87 )	14.25 ( 0.43 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

2.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

4.59

Variability estimate

Standard error of the mean

Dispersion value

0.98

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.287

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

2.93

Variability estimate

Standard error of the mean

Dispersion value

0.97

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

End point description

The analysis population was the FAS. N is the number of participants analyzed with data available at each time point.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=280, 286, 1131]	1.88 ( 0.12 )	1.95 ( 0.12 )	2.27 ( 0.06 )
Month 3 [N=277, 286, 1136]	2.1 ( 0.11 )	2.06 ( 0.11 )	2.57 ( 0.06 )
Month 6 [N=260, 272, 1108]	2.22 ( 0.12 )	2.25 ( 0.12 )	2.72 ( 0.06 )
Month 9 [N=261, 263, 1076]	2.24 ( 0.12 )	2.28 ( 0.12 )	2.74 ( 0.06 )
Month 12 [N=250, 255, 1049]	2.33 ( 0.12 )	2.34 ( 0.12 )	2.89 ( 0.06 )

No statistical analyses for this end point

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition Questionnaire (PPBC)

Top of page

End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition Questionnaire (PPBC)

End point description

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

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: units on a scale
least squares mean (standard error)
Month 1 [N=281, 287, 1133]	-0.84 ( 0.07 )	-0.89 ( 0.07 )	-1.05 ( 0.03 )
Month 3 [N=278, 286, 1137]	-1.09 ( 0.07 )	-1.08 ( 0.07 )	-1.33 ( 0.03 )
Month 6 [N=260, 272, 1108]	-1.11 ( 0.07 )	-1.18 ( 0.07 )	-1.42 ( 0.04 )
Month 9 [N=261, 264, 1077]	-1.25 ( 0.07 )	-1.31 ( 0.07 )	-1.48 ( 0.04 )
Month 12 [N=251, 255, 1049]	-1.29 ( 0.08 )	-1.36 ( 0.07 )	-1.59 ( 0.04 )
EoT [N=290, 294, 1163]	-1.22 ( 0.07 )	-1.34 ( 0.07 )	-1.54 ( 0.04 )

Difference vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.16

Variability estimate

Standard error of the mean

Dispersion value

0.08

Difference vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

ANCOVA

Parameter type

Least squares mean difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT

Top of page

End point title

Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT

End point description

The PGIC is a 2-part questionnaire, assessing both the change in the patient’s overall condition and change in bladder condition since the start of the study (from very much worse to very much improved). The analysis population was the FAS. The number of participants analyzed includes participants with data available. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 12: Very much improved	25.5	23.4	33.8
Month 12: Much improved	30.5	35.8	34
Month 12: Minimally improved	21.9	19.7	16.1
Month 12: No change	5	6.4	4.5
Month 12: Minimally worse	0.7	0.7	0.4
Month 12: Much worse	1	0.3	0.1
Month 12: Very much worse	0.3	0.3	0.5
EoT: Very much improved	25.8	24.4	34.1
EoT: Much improved	31.5	37.1	34.7
EoT: Minimally improved	22.2	20.4	16.6
EoT: No change	6.3	7	5.1
EoT: Minimally worse	0.7	0.7	0.4
EoT: Much worse	1.3	0.7	0.1
EoT: Very much worse	0.3	0.3	0.5

No statistical analyses for this end point

Secondary: PGIC Scale: Impression in General Health at Month 12 and EoT

Top of page

End point title

PGIC Scale: Impression in General Health at Month 12 and EoT

End point description

End point type

Secondary

End point timeframe

Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 12: Very much improved	12.9	14.7	18
Month 12: Much improved	23.8	26.8	28.7
Month 12: Minimally improved	18.9	17.1	18.7
Month 12: No change	24.2	24.7	20.7
Month 12: Minimally worse	3.6	2.7	2.7
Month 12: Much worse	0.7	0	0.4
Month 12: Very much worse	0.7	0.7	0.3
EoT: Very much improved	13.2	15.1	18.3
EoT: Much improved	24.5	27.8	28.9
EoT: Minimally improved	19.2	18.1	19.1
EoT: No change	25.8	25.8	21.6
EoT: Minimally worse	3.6	3	2.8
EoT: Much worse	1	0.3	0.5
EoT: Very much worse	0.7	0.7	0.3

No statistical analyses for this end point

Secondary: Change from Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility

Top of page

End point title

Change from Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility

End point description

The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The analysis population was the FAS. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: participants
number (not applicable)
No problems -> no problems	164	164	675
No problems -> slight problems	15	15	56
No problems -> moderate problems	10	4	26
No problems -> severe problems	1	1	2
No problems -> unable to walk about	1	0	0
No problems -> no data	3	0	7
Slight problems -> no problems	19	24	83
Slight problems -> slight problems	18	29	87
Slight problems -> moderate problems	4	6	26
Slight problems -> severe problems	3	1	2
Slight problems -> unable to walk about	0	0	0
Slight problems -> no data	2	1	0
Moderate problems -> no problems	14	11	38
Moderate problems -> slight problems	13	17	47
Moderate problems -> moderate problems	9	5	50
Moderate problems -> severe problems	2	4	8
Moderate problems -> unable to walk about	0	0	0
Moderate problems -> no data	0	0	1
Severe problems -> no problems	2	4	15
Severe problems -> slight problems	2	2	13
Severe problems -> moderate problems	6	4	16
Severe problems -> severe problems	5	3	15
Severe problems -> unable to walk about	1	0	2
Severe problems -> no data	0	0	0
Unable to walk about -> no problems	0	0	1
Unable to walk about -> slight problems	0	0	1
Unable to walk about -> moderate problems	0	0	0
Unable to walk about -> severe problems	0	0	0
Unable to walk about -> unable to walk about	0	0	0
Unable to walk about -> no data	0	0	0
No data -> no problems	4	3	19
No data -> slight problems	4	1	3
No data -> moderate problems	0	0	0
No data -> severe problems	0	0	0
No data -> unable to walk about	0	0	0
No data -> no data	0	0	0

No statistical analyses for this end point

Secondary: Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care

Top of page

End point title

Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care

End point description

End point type

Secondary

End point timeframe

Baseline and Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: participants
number (not applicable)
No problems -> no problems	223	232	906
No problems -> slight problems	12	9	40
No problems -> moderate problems	8	0	12
No problems -> severe problems	0	1	2
No problems -> unable to wash/dress myself	0	0	0
No problems -> no data	5	1	7
Slight problems -> no problems	16	18	64
Slight problems -> slight problems	9	14	44
Slight problems -> moderate problems	0	4	12
Slight problems -> severe problems	0	1	1
Slight problems -> unable to wash/dress myself	0	0	0
Slight problems -> no data	0	0	1
Moderate problems -> no problems	5	4	18
Moderate problems -> slight problems	5	6	20
Moderate problems -> moderate problems	5	3	21
Moderate problems -> severe problems	0	0	2
Moderate problems -> unable to wash/dress myself	0	0	0
Moderate problems -> no data	0	0	0
Severe problems -> no problems	0	1	8
Severe problems -> slight problems	1	0	3
Severe problems -> moderate problems	3	1	4
Severe problems -> severe problems	1	0	5
Severe problems -> unable to wash/dress myself	0	0	0
Severe problems -> no data	0	0	0
Unable to wash/dress myself -> no problems	0	0	0
Unable to wash/dress myself -> slight problems	0	0	1
Unable to wash/dress myself -> moderate problems	0	0	0
Unable to wash/dress myself -> severe problems	0	0	0
Unable to wash/dress myself -> unable to wash/dres	1	0	0
Unable to wash/dress myself -> no data	0	0	0
No data -> no problems	6	3	22
No data -> slight problems	2	1	0
No data -> moderate problems	0	0	0
No data -> severe problems	0	0	0
No data -> unable to wash/dress myself	0	0	0
No data -> no data	0	0	0

No statistical analyses for this end point

Secondary: Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities

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End point title

Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities

End point description

End point type

Secondary

End point timeframe

Baseline and Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: participants
No problems -> No problems	165	160	672
No problems -> Slight problems	13	16	65
No problems -> Moderate problems	8	4	15
No problems -> Severe problems	1	0	1
No problems -> unable to do usual activities	0	0	0
No problems -> no data	4	0	7
Slight problems -> no problems	27	39	131
Slight problems -> slight problems	28	33	85
Slight problems -> moderate problems	5	6	26
Slight problems -> severe problems	2	1	1
Slight problems ->unable to do usual activities	0	0	0
Slight problems -> no data	1	0	0
Moderate problems -> no problems	12	12	40
Moderate problems -> slight problems	11	9	44
Moderate problems -> moderate problems	7	4	43
Moderate problems -> severe problems	2	0	2
Moderate problems ->unable to do usual activities	0	0	0
Moderate problems -> no data	0	1	1
Severe problems -> no problems	2	1	10
Severe problems -> slight problems	0	2	9
Severe problems -> moderate problems	0	6	7
Severe problems -> severe problems	4	1	6
Severe problems -> unable to do usual activities	0	0	1
Severe problems -> no data	0	0	0
Unable to do usual activities -> no problems	0	0	0
Unable to do usual activities -> slight problems	0	0	1
Unable to do usual activities -> moderate problems	1	0	4
Unable to do usual activities -> severe problems	0	0	0
Unable to do usual activities -> unable to do	1	0	0
Unable to do usual activities -> no data	0	0	0
No data -> no problems	6	2	20
No data -> slight problems	1	2	2
No data -> moderate problems	1	0	0
No data -> severe problems	0	0	0
No data -> unable to do usual activities	0	0	0
No data -> no data	0	0	0

No statistical analyses for this end point

Secondary: Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort

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End point title

Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort

End point description

End point type

Secondary

End point timeframe

Baseline and Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: participants
No pain/discomfort -> no pain/discomfort	120	119	495
No pain/discomfort -> slight pain/discomfort	21	19	70
No pain/discomfort -> moderate pain/discomfort	7	1	20
No pain/discomfort -> severe pain/discomfort	1	0	3
No pain/discomfort -> extreme pain/discomfort	0	0	0
No pain/discomfort -> no data	2	1	6
Slight pain/discomfort -> no pain/discomfort	44	37	132
Slight pain/discomfort -> slight pain/discomfort	24	48	152
Slight pain/discomfort -> moderate pain/discomfort	11	9	26
Slight pain/discomfort -> severe pain/discomfort	2	1	5
Slight pain/discomfort -> exteme pain/discomfort	0	0	1
Slight pain/discomfort -> no data	0	0	1
Moderate pain/discomfort -> no pain/discomfort	9	11	49
Moderate pain/discomfort -> slight pain/discomfort	19	17	78
Moderate pain/discomfort -> moderate pain/discomf	16	10	65
Moderate pain/discomfort -> severe pain/discomfort	2	3	8
Moderate pain/discomfort -> extreme pain/discomf	0	0	1
Moderate pain/discomfort -> no data	1	0	1
Severe pain/discomfort -> no pain/discomfort	3	6	15
Severe pain/discomfort -> slight pain/discomfort	2	3	9
Severe pain/discomfort -> moderate pain/discomfort	5	5	13
Severe pain/discomfort -> severe pain/discomfort	2	3	11
Severe pain/discomfort -> extreme pain/discomfort	0	0	1
Severe pain/discomfort -> no data	1	0	0
Extreme pain/discomfort -> no pain/discomfort	0	0	0
Extreme pain/discomfort -> slight pain/discomfort	0	0	3
Extreme pain/discomfort -> moderate pain/discomf	1	0	2
Extreme pain/discomfort -> severe pain/discomfort	0	2	2
Extreme pain/discomfort -> extreme pain/discomfort	0	0	2
Extreme pain/discomfort -> no data	1	0	0
No data -> no pain/discomfort	5	1	11
No data -> slight pain/discomfort	3	3	11
No data -> moderate pain/discomfort	0	0	0
No data -> severe pain/discomfort	0	0	0
No data -> extreme pain/discomfort	0	0	0
No data -> no data	0	0	0

No statistical analyses for this end point

Secondary: Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression

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End point title

Change from Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression

End point description

End point type

Secondary

End point timeframe

Baseline and Month 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: participants
Not anxious -> not anxious	137	142	588
Not anxious -> slightly anxious	22	18	68
Not anxious -> moderately anxious	4	1	7
Not anxious -> severely anxious	1	0	1
Not anxious -> extremely anxious	0	0	0
Not anxious -> no data	3	1	5
Slightly anxious -> not anxious	35	43	177
Slightly anxious -> slightly anxious	30	33	106
Slightly anxious -> moderately anxious	4	8	21
Slightly anxious -> severely anxious	3	1	0
Slightly anxious -> extremely anxious	0	1	1
Slightly anxious -> no data	1	0	1
Moderately anxious -> not anxious	15	11	37
Moderately anxious -> slightly anxious	11	14	55
Moderately anxious -> moderately anxious	12	8	35
Moderately anxious -> severely anxious	1	1	5
Moderately anxious -> extremely anxious	0	0	0
Moderately anxious -> no data	0	0	1
Severely anxious -> not anxious	2	2	10
Severely anxious -> slightly anxious	3	2	14
Severely anxious -> moderately anxious	5	3	13
Severely anxious -> severely anxious	2	1	7
Severely anxious -> extremely anxious	1	0	1
Severely anxious -> no data	1	0	1
Extremely anxious -> not anxious	0	1	4
Extremely anxious -> slightly anxious	0	2	2
Extremely anxious -> moderately anxious	1	0	8
Extremely anxious -> severely anxious	0	2	2
Extremely anxious -> extremely anxious	0	0	1
Extremely anxious -> no data	0	0	0
No data -> not anxious	6	3	14
No data -> slightly anxious	1	1	7
No data -> moderately anxious	1	0	0
No data -> severely anxious	0	0	0
No data -> extremely anxious	0	0	1
No data -> no data	0	0	0

No statistical analyses for this end point

Secondary: Change from Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed

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End point title

Change from Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed

End point description

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

End point type

Secondary

End point timeframe

Baseline and Months 6,12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of work time missed
arithmetic mean (standard deviation)
Month 6 [N=86, 112, 379]	-0.49 ( 17.12 )	-0.59 ( 15.67 )	-3.11 ( 20.68 )
Month 12 [N=83, 110, 359]	0.39 ( 15.55 )	-1.95 ( 18.51 )	-3.74 ( 23.83 )
EoT [N=96, 124, 421]	-0.45 ( 18.51 )	-1.3 ( 18.04 )	-3.26 ( 22.88 )

No statistical analyses for this end point

Secondary: Change from Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working

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End point title

Change from Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working

End point description

End point type

Secondary

End point timeframe

Baseline and Months 6,12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of impairment while working
arithmetic mean (standard deviation)
Month 6 [N=85, 111, 372]	-16.94 ( 24.1 )	-12.97 ( 21.05 )	-13.41 ( 24.37 )
Month 12 [N=83, 108, 349]	-19.16 ( 23.38 )	-14.72 ( 27.32 )	-16.68 ( 24.16 )
EoT [N=96, 123, 414]	-17.81 ( 23.45 )	-13.9 ( 27.18 )	-15.63 ( 25.61 )

No statistical analyses for this end point

Secondary: Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 3 days prior to months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of particpants
number (not applicable)
Month 1 [N=291, 288, 1158]	24.4	39.9	38.3
Month 3 [N=282, 288, 1137]	40.1	44.8	49.6
Month 6 [N=266, 273, 1107]	40.6	50.5	54.7
Month 9 [N=264, 261, 1070]	47	54.4	55.8
Month 12 [N=258, 256, 1048]	51.6	55.5	61.2
EoT [N=301, 297, 1184]	47.8	53.2	58.8

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

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

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.15

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.08

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.67

Secondary: Percentage of Participants with ≥ 10 Points Improvement from Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with ≥ 10 Points Improvement from Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants with ≥ 10 points improvement from baseline to each visit (months 1, 3, 6, 9, 12 and EoT). The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=281, 286, 1132]	63.7	67.5	72.8
Month 3 [N=278, 286, 1137]	69.1	71.3	81.8
Month 6 [N=260, 272, 1108]	70.4	74.6	80.5
Month 9 [N=261, 264, 1077]	70.1	76.1	82.9
Month 12 [N=250, 255, 1049]	72.8	74.1	84.4
EoT [N=290, 294, 1163]	70.7	72.4	82.9

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OAB-q subscale as a covariate.

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

2.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.49

upper limit

2.78

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

1.37

upper limit

2.57

Secondary: Percentage of Participants with ≥ 10 Points Improvement from Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with ≥ 10 Points Improvement from Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT

End point description

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=281, 286, 1132]	46.6	53.8	57
Month 3 [N=278, 286, 1137]	53.6	59.4	64.6
Month 6 [N=260, 272, 1108]	56.9	62.9	66.1
Month 9 [N=261, 264, 1077]	57.1	62.9	67.7
Month 12 [N=250, 255, 1049]	58.4	62.4	69
EoT [N=290, 294, 1163]	56.2	61.6	68.4

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.82

Confidence interval

level

95%

sides

2-sided

lower limit

1.36

upper limit

2.43

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.08

upper limit

1.92

Secondary: Percentage of Participants with 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants with ≥ 50% decrease from baseline in mean number of incontinence episodes per 24 hours at each time point (months 1, 3, 6, 9, 12 and EoT). The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=291, 288, 1158]	46.7	55.2	62
Month 3 [N=282, 288, 1137]	58.2	67	73.3
Month 6 [N=266, 273, 1107]	63.2	71.8	76.6
Month 9 [N=264, 261, 1070]	67	73.6	77.8
Month 12 [N=258, 256, 1048]	72.9	75.4	81.3
EoT [N=301, 297, 1184]	69.1	73.1	79.5

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

2.41

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

1.95

Secondary: Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with Zero Incontinence Episodes per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 7 days prior to months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=291, 288, 1158]	17.2	26.4	27.9
Month 3 [N=282, 288, 1137]	27	35.1	40
Month 6 [N=266, 273, 1107]	32.3	39.9	44.7
Month 9 [N=264, 261, 1070]	37.1	43.7	46.9
Month 12 [N=258, 256, 1048]	41.9	47.3	52.5
EoT [N=301, 297, 1184]	38.9	45.1	49.7

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.19

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.133

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.62

Secondary: Percentage of Participants with Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT

End point description

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

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=290, 287, 1155]	34.5	29.3	36.8
Month 3 [N=281, 287, 1135]	36.7	36.6	46.6
Month 6 [N=265, 272, 1105]	42.3	43.4	51.4
Month 9 [N=263, 260, 1069]	44.5	41.9	52.5
Month 12 [N=257, 255, 1047]	46.3	44.7	56.4
EoT [N=300, 296, 1181]	46	46.3	55.9

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.55

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

2.03

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

1.95

Secondary: Percentage of Participants with ≥ 1 Point Improvement from Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with ≥ 1 Point Improvement from Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants with ≥ 1 point improvement from baseline in PPBC at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=281, 287, 1133]	53	59.2	64.1
Month 3 [N=278, 286, 1137]	61.9	65.7	72.5
Month 6 [N=260, 272, 1108]	64.6	68.8	73.8
Month 9 [N=261, 264, 1077]	65.5	68.9	75.1
Month 12 [N=251, 255, 1049]	69.7	73.7	76.9
EoT [N=290, 294, 1163]	66.2	71.4	76

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.68

Confidence interval

level

95%

sides

2-sided

lower limit

1.24

upper limit

2.29

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.109

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.77

Secondary: Percentage of Participants with Major (≥ 2 points) Improvement from Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants with Major (≥ 2 points) Improvement from Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants with a major (≥ 2 points) improvement from baseline in PPBC at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=281, 287, 1133]	24.9	28.2	30.7
Month 3 [N=278, 286, 1137]	31.3	33.9	42.8
Month 6 [N=260, 272, 1108]	35	38.2	45.4
Month 9 [N=261, 264, 1077]	37.5	40.9	47
Month 12 [N=251, 255, 1049]	40.6	40.4	51.9
EoT [N=290, 294, 1163]	38.3	39.8	50.3

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.25

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.16

Secondary: Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 10 Points Improvement on OAB-q Symptom Bother Scale) at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 10 Points Improvement on OAB-q Symptom Bother Scale) at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants considered as double responders, defined as participants with ≥ 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=274, 279, 1115]	36.1	46.6	52.6
Month 3 [N=270, 281, 1109]	47.8	55.5	65.1
Month 6 [N=250, 267, 1080]	50.4	56.9	65.8
Month 9 [N=254, 252, 1048]	53.1	61.9	69.2
Month 12 [N=245, 248, 1018]	59.2	60.9	73.2
EoT [N=289, 292, 1156]	55.7	58.2	70.8

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.99

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

2.62

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.79

Confidence interval

level

95%

sides

2-sided

lower limit

1.35

upper limit

2.36

Secondary: Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 10 Points Improvement on OAB-q HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 10 Points Improvement on OAB-q HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants considered as double responders, defined as participants with ≥ 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q HRQL total score at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=274, 279, 1115]	28.5	36.6	40.9
Month 3 [N=270, 281, 1109]	39.6	43.8	52.3
Month 6 [N=250, 267, 1080]	41.6	47.9	55.3
Month 9 [N=254, 252, 1048]	43.7	51.2	57.6
Month 12 [N=245, 248, 1018]	46.9	50.4	60.6
EoT [N=289, 292, 1156]	44.3	49	59.2

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.93

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

2.54

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

2.09

Secondary: Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours and at Least 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants considered as double responders, defined as participants with ≥ 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and ≥ 1 point improvement from baseline in PPBC at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=274, 280, 1116]	32.1	37.1	46
Month 3 [N=270, 281, 1109]	43.3	47.7	57.6
Month 6 [N=250, 267, 1080]	46.8	52.1	60.6
Month 9 [N=254, 252, 1048]	49.6	53.2	63
Month 12 [N=245, 248, 1018]	57.6	60.1	67
EoT [N=289, 292, 1156]	52.9	57.5	65.1

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.28

upper limit

2.26

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

1.86

Secondary: Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours, ≥ 10 Points Improvement on OAB-q Symptom Bother Scale and ≥1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours, ≥ 10 Points Improvement on OAB-q Symptom Bother Scale and ≥1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants considered as triple responders, defined as participants with ≥ 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score, and ≥ 1 point improvement from baseline in PPBC at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=274, 279, 1115]	29.9	35.5	42.8
Month 3 [N=270, 281, 1109]	38.9	44.8	54.1
Month 6 [N=250, 267, 1080]	42.4	46.1	55.9
Month 9 [N=254, 252, 1048]	46.5	50.8	59.2
Month 12 [N=245, 248, 1018]	51.4	53.6	63.7
EoT [N=289, 292, 1156]	47.4	51.4	61.7

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

2.46

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

2.09

Secondary: Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours, ≥ 10 Points Improvement on OAB-q HRQL Total Score and ≥ 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

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End point title

Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes per 24 Hours, ≥ 10 Points Improvement on OAB-q HRQL Total Score and ≥ 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT

End point description

The percentage of participants considered as triple responders, defined as participants with ≥ 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the HRQL total score, and ≥ 1 point improvement from baseline in PPBC at months 1, 3, 6, 9, 12 and EoT. The analysis population was the FAS. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	302	299	1193
Units: percentage of participants
number (not applicable)
Month 1 [N=274, 279, 1115]	25.2	29	35.5
Month 3 [N=270, 281, 1109]	33.3	39.1	45.9
Month 6 [N=250, 267, 1080]	36.8	41.2	49.6
Month 9 [N=254, 252, 1048]	39	44	51.3
Month 12 [N=245, 248, 1018]	44.1	47.6	54.6
EoT [N=289, 292, 1156]	40.1	45.2	53.3

Odds ratio vs. Mirabegron 50 mg (EoT)

Statistical analysis description

Comparison groups

Mirabegron 50 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1495

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.76

Confidence interval

level

95%

sides

2-sided

lower limit

1.33

upper limit

2.34

Odds ratio vs. Solifenacin 5 mg (EoT)

Statistical analysis description

Comparison groups

Solifenacin 5 mg v Solifenacin 5 mg + mirabegron 50 mg

Number of subjects included in analysis

1492

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Logistic regression

Parameter type

Odds ratio (OR)

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.08

upper limit

1.89

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume

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End point title

Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume

End point description

PVR volume was assessed by ultrasonography or a bladder scanner. The analysis population was the SAF. N is the number of participants analyzed with data available at each time point. LOCF was used for EoT.

End point type

Secondary

End point timeframe

Baseline and Months 1, 3, 6, 9, 12

End point values	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + mirabegron 50 mg
Number of subjects analysed	305	303	1206
Units: mL
arithmetic mean (standard deviation)
Month 1 [N=295, 298, 1170]	3.179 ( 27.491 )	4.549 ( 33.973 )	7.894 ( 38.369 )
Month 3 [N=293, 292, 1175]	4.686 ( 29.354 )	3.233 ( 32.679 )	7.033 ( 37.328 )
Month 6 [N=280, 282, 1144]	1.596 ( 29.399 )	3.418 ( 31.864 )	6.708 ( 35.881 )
Month 9 [N=272, 268, 1111]	3.074 ( 32.897 )	3.436 ( 32.17 )	8.229 ( 40.313 )
Month 12 [N=263, 266, 1084]	2.002 ( 32.453 )	4.818 ( 33.764 )	7.946 ( 38.118 )
EoT [N=300, 302, 1194]	1.747 ( 32.4 )	7.382 ( 42.916 )	8.522 ( 39.501 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 56 weeks)

Adverse event reporting additional description

The total number of deaths (all causes) includes deaths reported after the time frame above.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

Mirabegron 50 mg

Reporting group description

Participants who received mirabegron 50 mg once a day for 52 weeks.

Reporting group title

Solifenacin 5 mg + mirabegron 50 mg

Reporting group description

Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.

Reporting group title

Solifenacin 5 mg

Reporting group description

Participants who received solifenacin 5 mg once a day for 52 weeks.

Serious adverse events	Mirabegron 50 mg	Solifenacin 5 mg + mirabegron 50 mg	Solifenacin 5 mg
Total subjects affected by serious adverse events
subjects affected / exposed	8 / 305 (2.62%)	51 / 1206 (4.23%)	8 / 303 (2.64%)
number of deaths (all causes)	1	1	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 305 (0.00%)	3 / 1206 (0.25%)	0 / 303 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	1 / 305 (0.33%)	0 / 1206 (0.00%)	0 / 303 (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
Bowen's disease
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Breast cancer female
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Breast cancer recurrent
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Malignant melanoma
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Malignant melanoma in situ
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Metastatic uterine cancer
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Vascular disorders
Hypertension
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Surgical and medical procedures
Appendicectomy
subjects affected / exposed	1 / 305 (0.33%)	0 / 1206 (0.00%)	0 / 303 (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
Cholecystectomy
subjects affected / exposed	0 / 305 (0.00%)	2 / 1206 (0.17%)	0 / 303 (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
Colon polypectomy
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Cystocele repair
subjects affected / exposed	1 / 305 (0.33%)	0 / 1206 (0.00%)	0 / 303 (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
Hysterectomy
subjects affected / exposed	1 / 305 (0.33%)	0 / 1206 (0.00%)	0 / 303 (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
Spinal fusion surgery
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Spinal operation
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Pyrexia
subjects affected / exposed	1 / 305 (0.33%)	0 / 1206 (0.00%)	0 / 303 (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
Reproductive system and breast disorders
Hysterocele
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Pelvic pain
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Uterine prolapse
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Vaginal haemorrhage
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 305 (0.33%)	0 / 1206 (0.00%)	0 / 303 (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
Pneumothorax
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Psychiatric disorders
Delirium
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Investigations
Blood glucose increased
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Cervical vertebral fracture
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Clavicle fracture
subjects affected / exposed	0 / 305 (0.00%)	2 / 1206 (0.17%)	0 / 303 (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
Femur fracture
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Hip fracture
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Humerus fracture
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Incisional hernia
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Pelvic fracture
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Sternal fracture
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 305 (0.33%)	2 / 1206 (0.17%)	0 / 303 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Coronary artery occlusion
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Myocardial ischaemia
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Nervous system disorders
Carotid artery stenosis
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Dizziness
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Long thoracic nerve palsy
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Sciatica
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Eye disorders
Amaurosis fugax
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 305 (0.33%)	1 / 1206 (0.08%)	0 / 303 (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
Abdominal pain upper
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Enterocele
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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 disorder
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Gastrooesophageal sphincter insufficiency
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Inguinal hernia
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Pancreatitis acute
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 305 (0.00%)	2 / 1206 (0.17%)	0 / 303 (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
Endocrine disorders
Hyperparathyroidism
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Exostosis
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteitis
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Osteoarthritis
subjects affected / exposed	0 / 305 (0.00%)	2 / 1206 (0.17%)	0 / 303 (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
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 305 (0.33%)	2 / 1206 (0.17%)	0 / 303 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Cellulitis
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Erysipelas
subjects affected / exposed	0 / 305 (0.00%)	0 / 1206 (0.00%)	1 / 303 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematoma infection
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Meningitis aseptic
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Pneumonia
subjects affected / exposed	1 / 305 (0.33%)	2 / 1206 (0.17%)	0 / 303 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Superinfection bacterial
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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
Metabolism and nutrition disorders
Type 2 diabetes mellitus
subjects affected / exposed	0 / 305 (0.00%)	1 / 1206 (0.08%)	0 / 303 (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

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

Non-serious adverse events	Mirabegron 50 mg	Solifenacin 5 mg + mirabegron 50 mg	Solifenacin 5 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	27 / 305 (8.85%)	115 / 1206 (9.54%)	33 / 303 (10.89%)
Gastrointestinal disorders
Dry mouth
subjects affected / exposed	12 / 305 (3.93%)	74 / 1206 (6.14%)	18 / 303 (5.94%)
occurrences all number	12	77	20
Infections and infestations
Nasopharyngitis
subjects affected / exposed	16 / 305 (5.25%)	43 / 1206 (3.57%)	15 / 303 (4.95%)
occurrences all number	16	46	16

More information

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Were there any global substantial amendments to the protocol? Yes

06 Nov 2013

The changes for this amendment is summarized as: (1) Inclusion criterion 3 relating to female patients of childbearing potential and inclusion criterion 13 relating to the number of urgency episodes per 24 h, respectively, were clarified; (2) The sample size justification for change from baseline in mean number of incontinence episodes per 24 h was modified to accommodate the 7-day eDiary period; (3) The efficacy analysis was modified. If clear evidence for a normal distribution of change from baseline in mean number of incontinence episodes per 24 h was identified prior to hard locking of the database, then primary hypothesis testing for this variable would be performed within an analysis of covariance (ANCOVA) model; (4) Expected adverse drug reactions (ADRs) and expected risks (i.e., urinary retention) were updated in line with the company core data sheets; (5) Antidepressant drugs with anticholinergic ADRs were moved from the list of restricted medications to prohibited medications as these drugs are sometimes used to treat OAB. Nonsubstantial changes were also implemented.

11 Dec 2014

The changes for this amendment is summarized as: (1) Exclusion criteria 4, 10 and 24 relating to neurological cause for detrusor overactivity, QT interval corrected using Fridericia’s correction formula (QTcF) and UTI, respectively, were clarified; and (2) The list of prohibited or restricted medications was updated and removed from Appendix 1 of the protocol and was provided to investigational sites via separate communications. Nonsubstantial changes were also implemented.

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.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Primary: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

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

Primary: Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours

Primary: Change from Baseline to EoT in Mean Number of Micturitions per 24 Hours

Secondary: Change from Baseline to EoT in Mean Volume Voided per Micturition

Secondary: Change from Baseline to EoT in Mean Volume Voided per Micturition

Secondary: Change from Baseline to EoT in OAB Questionnaire (OAB-q) Symptom Bother Score

Secondary: Change from Baseline to EoT in OAB Questionnaire (OAB-q) Symptom Bother Score

Secondary: Change from Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

Secondary: Change from Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes per 24 Hours

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes per 24 Hours

Secondary: Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Number of Incontinence-Free Days Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Incontinence-Free Days Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Incontinence-Free Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Incontinence-Free Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes per 24 Hours

Secondary: Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions per 24 Hours

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions per 24 Hours

Secondary: Number of Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Days with < 8 Micturitions per Day Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Change from Baseline to EoT in Corrected Micturition Frequency

Secondary: Change from Baseline to EoT in Corrected Micturition Frequency

Secondary: Change from Baseline to Months 3, 6 and 12 in Mean Volume Voided per Micturition

Secondary: Change from Baseline to Months 3, 6 and 12 in Mean Volume Voided per Micturition

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes per 24 Hours

Secondary: Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used per 24 Hours

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used per 24 Hours

Secondary: Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used Reported During the 7-Day Micturition Diary Period Prior to Each Visit

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQL): Total score

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQL): Total score

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Coping

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Coping

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Concern

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Concern

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Sleep

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Sleep

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Social

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life (HRQL) Subscale Score: Social

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

Secondary: Change from Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition Questionnaire (PPBC)

Secondary: Change from Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition Questionnaire (PPBC)

Secondary: Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT

Secondary: Patient’s Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT

Secondary: PGIC Scale: Impression in General Health at Month 12 and EoT

Secondary: PGIC Scale: Impression in General Health at Month 12 and EoT

Secondary: Change from Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility