Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder (NCT NCT00689104)

Last Updated: 2024-11-20

Results Overview

The average number of incontinence episodes (any involuntary leakage of urine) per day was derived from the number of incontinence episodes recorded by the patient in a micturition diary for 3-days before the Baseline and Week 12 clinic visits. Least Squares (LS) Means were generated from an analysis of covariance (ANCOVA) model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2336 participants

Primary outcome timeframe

Baseline and Week 12 (final visit)

Results posted on

2024-11-20

Participant Flow

After screening, 2336 patients took placebo run-in study drug in a 2-week, single-blind, placebo run-in period. On completion of the run-in period, 1987 eligible patients were randomly assigned to receive placebo, mirabegron 50 mg, mirabegron 100 mg or tolterodine 4 mg for 12 weeks.

Participant milestones

Participant milestones
Measure	Placebo Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.	Mirabegron 50 mg Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.
Overall Study STARTED	497	497	498	495
Overall Study Safety Analysis Set (SAF)	494	493	496	495
Overall Study Full Analysis Set (FAS)	480	473	478	475
Overall Study Full Analysis Set Incontinence (FAS-I)	291	293	281	300
Overall Study COMPLETED	453	440	453	445
Overall Study NOT COMPLETED	44	57	45	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.	Mirabegron 50 mg Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.
Overall Study Eligibility criterion not met	5	8	0	4
Overall Study Adverse Event	13	25	16	24
Overall Study Lack of Efficacy	5	6	2	3
Overall Study Withdrawal by Subject	12	11	18	11
Overall Study Lost to Follow-up	4	3	2	5
Overall Study Protocol Violation	2	3	5	3
Overall Study Randomized but never received study drug	2	1	1	0
Overall Study Physician Decision	1	0	0	0
Overall Study Non-compliance with study procedures	0	0	1	0

Baseline Characteristics

Study to Assess the Efficacy and Safety of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=494 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.	Mirabegron 50 mg n=493 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=496 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=495 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Total n=1978 Participants Total of all reporting groups
Age, Continuous	59.2 years STANDARD_DEVIATION 12.30 • n=5 Participants	59.1 years STANDARD_DEVIATION 12.36 • n=7 Participants	59.0 years STANDARD_DEVIATION 12.71 • n=5 Participants	59.1 years STANDARD_DEVIATION 12.89 • n=4 Participants	59.1 years STANDARD_DEVIATION 12.56 • n=21 Participants
Sex: Female, Male Female	356 Participants n=5 Participants	357 Participants n=7 Participants	355 Participants n=5 Participants	361 Participants n=4 Participants	1429 Participants n=21 Participants
Sex: Female, Male Male	138 Participants n=5 Participants	136 Participants n=7 Participants	141 Participants n=5 Participants	134 Participants n=4 Participants	549 Participants n=21 Participants
Race/Ethnicity, Customized White	490 participants n=5 Participants	488 participants n=7 Participants	492 participants n=5 Participants	490 participants n=4 Participants	1960 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants	7 participants n=21 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	6 participants n=21 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	5 participants n=21 Participants
Type of overactive bladder (OAB) Urge Incontinence	204 participants n=5 Participants	200 participants n=7 Participants	188 participants n=5 Participants	190 participants n=4 Participants	782 participants n=21 Participants
Type of overactive bladder (OAB) Mixed	106 participants n=5 Participants	113 participants n=7 Participants	119 participants n=5 Participants	111 participants n=4 Participants	449 participants n=21 Participants
Type of overactive bladder (OAB) Frequency	184 participants n=5 Participants	180 participants n=7 Participants	189 participants n=5 Participants	194 participants n=4 Participants	747 participants n=21 Participants
Duration of OAB symptoms	76.0 months STANDARD_DEVIATION 91.38 • n=5 Participants	79.6 months STANDARD_DEVIATION 87.14 • n=7 Participants	84.8 months STANDARD_DEVIATION 94.12 • n=5 Participants	75.5 months STANDARD_DEVIATION 92.20 • n=4 Participants	79.0 months STANDARD_DEVIATION 91.25 • n=21 Participants
Mean number of micturitions per 24 Hours	11.72 micturitions STANDARD_DEVIATION 3.122 • n=5 Participants	11.64 micturitions STANDARD_DEVIATION 2.967 • n=7 Participants	11.49 micturitions STANDARD_DEVIATION 2.720 • n=5 Participants	11.53 micturitions STANDARD_DEVIATION 2.773 • n=4 Participants	11.59 micturitions STANDARD_DEVIATION 2.899 • n=21 Participants
Mean volume voided per micturition	156.8 mL STANDARD_DEVIATION 52.73 • n=5 Participants	160.3 mL STANDARD_DEVIATION 57.85 • n=7 Participants	158.9 mL STANDARD_DEVIATION 53.95 • n=5 Participants	157.4 mL STANDARD_DEVIATION 54.23 • n=4 Participants	158.3 mL STANDARD_DEVIATION 54.69 • n=21 Participants
Mean number of urgency episodes (grade 3 or 4) per 24 hours	5.72 urgency episodes STANDARD_DEVIATION 3.972 • n=5 Participants	5.68 urgency episodes STANDARD_DEVIATION 3.679 • n=7 Participants	5.95 urgency episodes STANDARD_DEVIATION 3.699 • n=5 Participants	5.79 urgency episodes STANDARD_DEVIATION 3.494 • n=4 Participants	5.79 urgency episodes STANDARD_DEVIATION 3.713 • n=21 Participants
Mean level of urgency	2.36 scores on a scale STANDARD_DEVIATION 0.563 • n=5 Participants	2.40 scores on a scale STANDARD_DEVIATION 0.547 • n=7 Participants	2.46 scores on a scale STANDARD_DEVIATION 0.528 • n=5 Participants	2.41 scores on a scale STANDARD_DEVIATION 0.561 • n=4 Participants	2.41 scores on a scale STANDARD_DEVIATION 0.551 • n=21 Participants
Mean number of nocturia episodes per 24 hours	1.98 nocturia episodes STANDARD_DEVIATION 1.405 • n=5 Participants	1.87 nocturia episodes STANDARD_DEVIATION 1.294 • n=7 Participants	1.91 nocturia episodes STANDARD_DEVIATION 1.374 • n=5 Participants	1.93 nocturia episodes STANDARD_DEVIATION 1.417 • n=4 Participants	1.92 nocturia episodes STANDARD_DEVIATION 1.373 • n=21 Participants
Mean number of pads used per 24 hours	1.12 pads STANDARD_DEVIATION 1.812 • n=5 Participants	1.12 pads STANDARD_DEVIATION 1.941 • n=7 Participants	1.25 pads STANDARD_DEVIATION 2.020 • n=5 Participants	1.04 pads STANDARD_DEVIATION 1.752 • n=4 Participants	1.13 pads STANDARD_DEVIATION 1.884 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12 (final visit)

Population: The full analysis set-Incontinence included all randomized patients who took at least 1 dose of double-blind study drug and who had a baseline and at least 1 post baseline micturition measurement in the visit diary and who had at least 1 incontinence episode at baseline. Last observation carried forward (LOCF) was utilized.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=293 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=281 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=300 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=291 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours	-1.57 Incontinence episodes Standard Error 0.113	-1.46 Incontinence episodes Standard Error 0.115	-1.27 Incontinence episodes Standard Error 0.112	-1.17 Incontinence episodes Standard Error 0.113

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all randomized patients who took at least 1 dose of double-blind study drug and who had a baseline and at least 1 post baseline micturition measurement in the visit diary. Last observation carried forward was utilized.

The average number of micturitions (urinations) per 24 hours was derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a micturition diary for 3-days before the Baseline and Week 12 clinic visits. LS Means generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Micturitions Per 24 Hours	-1.93 micturitions Standard Error 0.111	-1.77 micturitions Standard Error 0.110	-1.59 micturitions Standard Error 0.111	-1.34 micturitions Standard Error 0.110

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The Full analysis set included all randomized patients who took at least 1 dose of double-blind study drug and who had a baseline and at least 1 post baseline micturition measurement in the visit diary. Last observation carried forward was utilized.

The average volume voided per micturition was calculated from the volume of each micturition measured by the patient and recorded in a micturition diary for 3 days before the Baseline and Week 12 clinic visits. LS Means were generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=472 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Final Visit in Mean Volume Voided Per Micturition	24.2 mL Standard Error 2.01	25.6 mL Standard Error 2.00	25.0 mL Standard Error 2.00	12.3 mL Standard Error 1.99

SECONDARY outcome

Timeframe: Baseline and Week 4

The average number of incontinence episodes (any involuntary leakage of urine) per 24 hours was derived from the number of incontinence episodes recorded by the patient in a micturition diary for 3-days before the Baseline and Week 4 clinic visits. LS Means were generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=293 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=281 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=299 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=291 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4 in Mean Number of Incontinence Episodes Per 24 Hours	-1.04 Incontinence episodes Standard Error 0.118	-1.03 Incontinence episodes Standard Error 0.120	-1.00 Incontinence episodes Standard Error 0.117	-0.65 Incontinence episodes Standard Error 0.118

SECONDARY outcome

Timeframe: Baseline and Week 4

The average number of micturitions (urinations) per 24 hours was calculated from the number of micturitions recorded by the patient in a micturition diary for 3-days before the Baseline and Week 4 clinic visits. LS Means generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=471 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=477 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=474 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=479 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4 in Mean Number of Micturitions Per 24 Hours	-1.16 micturitions Standard Error 0.097	-1.29 micturitions Standard Error 0.096	-1.10 micturitions Standard Error 0.096	-0.77 micturitions Standard Error 0.096

SECONDARY outcome

Timeframe: Baseline and Weeks 8 and 12

Population: The full analysis set-incontinence included all randomized patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 post baseline micturition measurement in the visit diary and at least 1 incontinence episode at baseline. The number of patients included at each time point is noted as "N". LOCF was not utilized.

The average number of incontinence episodes (any involuntary leakage of urine) per 24 hours was derived from the number of incontinence episodes recorded by the patient in a micturition diary for 3-days before the Baseline, Week 8 and Week 12 clinic visits. LS Means were generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=293 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=281 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=300 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=291 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours Week 8 [N=280; 277; 268; 292]	-1.29 Incontinence episodes Standard Error 0.128	-1.40 Incontinence episodes Standard Error 0.130	-1.02 Incontinence episodes Standard Error 0.125	-1.00 Incontinence episodes Standard Error 0.127
Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours Week 12 [N=275; 272; 262; 276]	-1.62 Incontinence episodes Standard Error 0.117	-1.45 Incontinence episodes Standard Error 0.119	-1.27 Incontinence episodes Standard Error 0.116	-1.18 Incontinence episodes Standard Error 0.116

SECONDARY outcome

Timeframe: Baseline and Weeks 8 and 12

The average number of micturitions (urinations) per 24 hours was calculated from the number of micturitions recorded by the patient in a micturition diary for 3-days before the Baseline, Week 8 and 12 clinic visits. LS Means were generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours Week 8 [N=463; 450; 455; 461]	-1.64 micturitions Standard Error 0.107	-1.66 micturitions Standard Error 0.106	-1.43 micturitions Standard Error 0.106	-1.15 micturitions Standard Error 0.106
Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours Week 12 [N=452; 437; 447; 438]	-2.02 micturitions Standard Error 0.115	-1.78 micturitions Standard Error 0.113	-1.60 micturitions Standard Error 0.114	-1.33 micturitions Standard Error 0.113

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

The average volume voided per micturition was calculated from the volume of each micturition measured by the patient and recorded in a micturition diary for 3 days before the Baseline and Week 4, 8 and 12 clinic visits. LS Means generated from an ANCOVA model with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition Week 4 [N=479; 470; 477; 474]	20.1 mL Standard Error 1.75	20.3 mL Standard Error 1.74	21.4 mL Standard Error 1.74	9.8 mL Standard Error 1.73
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition Week 8 [N=463; 449; 455; 461]	20.7 mL Standard Error 2.00	25.3 mL Standard Error 1.99	25.9 mL Standard Error 1.97	11.7 mL Standard Error 1.97
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition Week 12 [N=452; 437; 447; 438]	25.3 mL Standard Error 2.11	25.7 mL Standard Error 2.08	25.8 mL Standard Error 2.10	11.9 mL Standard Error 2.07

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set-incontinence included all patients who took at least 1 dose of double-blind study drug \& had a baseline \& at least 1 post baseline micturition measurement in the visit diary \& at least 1 urgency incontinence episode at baseline. LOCF was used for the Final Visit analysis. N = the number of patients included at each time point.

The involuntary leakage of urine accompanied by or immediately proceeded by urgency, derived from the number of incontinence episodes classified by the patient in a 3-day micturition diary as 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. LS Means are from an ANCOVA with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=293 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=281 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=300 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=291 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Week 4 [N=283; 286; 276; 288]	-0.98 Urgency incontinence episodes Standard Error 0.107	-1.00 Urgency incontinence episodes Standard Error 0.109	-1.01 Urgency incontinence episodes Standard Error 0.107	-0.63 Urgency incontinence episodes Standard Error 0.108
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Week 8 [N=273; 272; 263; 281]	-1.27 Urgency incontinence episodes Standard Error 0.118	-1.32 Urgency incontinence episodes Standard Error 0.120	-0.99 Urgency incontinence episodes Standard Error 0.116	-0.94 Urgency incontinence episodes Standard Error 0.118
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Week 12 [N=269; 267; 257; 265]	-1.52 Urgency incontinence episodes Standard Error 0.112	-1.32 Urgency incontinence episodes Standard Error 0.114	-1.19 Urgency incontinence episodes Standard Error 0.122	-1.12 Urgency incontinence episodes Standard Error 0.111
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Final Visit (LOCF) [N=283; 286; 276; 289]	-1.46 Urgency incontinence episodes Standard Error 0.109	-1.33 Urgency incontinence episodes Standard Error 0.111	-1.18 Urgency incontinence episodes Standard Error 0.109	-1.11 Urgency incontinence episodes Standard Error 0.110

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 post baseline micturition measurement in the visit diary and at least 1 episode of urgency grade 3 or 4 at baseline. LOCF was used for the Final Visit analysis. N is the number of patients included at each time point.

The average number of urgency episodes (the sudden, compelling desire to pass urine, which is difficult to defer), derived from urgency episodes classified by the patient in a 3-day micturition diary as grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0: No urgency; 1: Mild urgency; 2: Moderate urgency, could delay voiding a short while; 3: Severe urgency, could not delay voiding; 4: Urge incontinence, leaked before arriving to the toilet. LS Means are from an ANCOVA with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours Week 4 [N=475; 469; 471; 470]	-1.39 Urgency episodes Standard Error 0.139	-1.54 Urgency episodes Standard Error 0.138	-1.63 Urgency episodes Standard Error 0.139	-0.89 Urgency episodes Standard Error 0.138
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours Week 8 [N=460; 446; 450; 456]	-1.90 Urgency episodes Standard Error 0.155	-1.90 Urgency episodes Standard Error 0.154	-1.91 Urgency episodes Standard Error 0.153	-1.28 Urgency episodes Standard Error 0.152
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours Week 12 [N=450; 433; 441; 434]	-2.35 Urgency episodes Standard Error 0.157	-2.00 Urgency episodes Standard Error 0.155	-2.16 Urgency episodes Standard Error 0.156	-1.65 Urgency episodes Standard Error 0.154
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours Final Visit (LOCF) [N=479; 470; 474; 472]	-2.25 Urgency episodes Standard Error 0.152	-1.96 Urgency episodes Standard Error 0.151	-2.07 Urgency episodes Standard Error 0.152	-1.65 Urgency episodes Standard Error 0.151

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 post baseline micturition measurement in the visit diary. LOCF was used for the Final Visit analysis. The number of participants included in the calculation for each time point is noted as "N".

Average of patients' ratings on the degree of urgency associated with each micturition and/or incontinence episode recorded in a 3-day micturition diary according to the following 5-point categorical scale (Patient Perception of Intensity of Urgency Scale): 0: No urgency; 1: Mild urgency; 2: Moderate urgency, could delay voiding a short while; 3: Severe urgency, could not delay voiding; 4: Urge incontinence, leaked before arriving to the toilet. LS Means are from an ANCOVA with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Level of Urgency Week 4 [N=476; 469; 472; 471]	-0.19 Scores on a scale Standard Error 0.023	-0.21 Scores on a scale Standard Error 0.023	-0.21 Scores on a scale Standard Error 0.023	-0.08 Scores on a scale Standard Error 0.023
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Level of Urgency Week 8 [N=460; 447; 451; 456]	-0.26 Scores on a scale Standard Error 0.027	-0.27 Scores on a scale Standard Error 0.027	-0.25 Scores on a scale Standard Error 0.027	-0.16 Scores on a scale Standard Error 0.027
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Level of Urgency Week 12 [N=450; 434; 442; 434]	-0.33 Scores on a scale Standard Error 0.029	-0.31 Scores on a scale Standard Error 0.029	-0.30 Scores on a scale Standard Error 0.029	-0.22 Scores on a scale Standard Error 0.029
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Level of Urgency Final Visit (LOCF) [N=480; 472; 475; 473]	-0.31 Scores on a scale Standard Error 0.028	-0.30 Scores on a scale Standard Error 0.028	-0.29 Scores on a scale Standard Error 0.028	-0.22 Scores on a scale Standard Error 0.028

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 post baseline micturition measurement in the visit diary and who had at least one nocturia episode at baseline. LOCF was used for the Final Visit analysis. N is the number of participants included at each time point.

Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinated (excluding incontinence only episodes) during sleeping time per day was derived from the 3-day patient micturition diary. LS Means are from an ANCOVA with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Week 4 [N=428; 422; 422; 432]	-0.27 nocturia episodes Standard Error 0.045	-0.34 nocturia episodes Standard Error 0.045	-0.29 nocturia episodes Standard Error 0.045	-0.25 nocturia episodes Standard Error 0.045
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Week 8 [N=414; 404; 403; 419]	-0.41 nocturia episodes Standard Error 0.048	-0.48 nocturia episodes Standard Error 0.048	-0.39 nocturia episodes Standard Error 0.047	-0.30 nocturia episodes Standard Error 0.047
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Week 12 [N=404; 393; 395; 399]	-0.57 nocturia episodes Standard Error 0.049	-0.47 nocturia episodes Standard Error 0.049	-0.44 nocturia episodes Standard Error 0.048	-0.41 nocturia episodes Standard Error 0.048
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Final Visit (LOCF) [N=428; 423; 422; 433]	-0.56 nocturia episodes Standard Error 0.047	-0.50 nocturia episodes Standard Error 0.047	-0.45 nocturia episodes Standard Error 0.047	-0.41 nocturia episodes Standard Error 0.047

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary and who had at least one use of a pad at baseline. LOCF was used for the Final Visit analysis. N is the number of participants included at each time point.

The average number of times a patient records a new pad used per day during the 3-day micturition diary period. LS Means are from an ANCOVA with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Week 4 [N=209; 183; 195; 181]	-0.73 pads Standard Error 0.110	-0.81 pads Standard Error 0.107	-0.67 pads Standard Error 0.111	-0.45 pads Standard Error 0.103
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Week 8 [N=204; 176; 183; 177]	-1.02 pads Standard Error 0.125	-1.03 pads Standard Error 0.122	-0.77 pads Standard Error 0.124	-0.72 pads Standard Error 0.116
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Week 12 [N=200; 172; 181; 165]	-1.26 pads Standard Error 0.126	-1.11 pads Standard Error 0.123	-0.95 pads Standard Error 0.128	-0.99 pads Standard Error 0.117
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Final Visit (LOCF) [N=209; 183; 195; 181]	-1.17 pads Standard Error 0.123	-1.12 pads Standard Error 0.119	-0.95 pads Standard Error 0.123	-0.95 pads Standard Error 0.115

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: The full analysis set-incontinence included all patients who took at least 1 dose of double-blind study drug \& had a baseline \& at least 1 postbaseline micturition measurement in the visit diary \& who had at least 1 incontinence episode at baseline. LOCF was used for the Final Visit analysis. N is the number of patients included at each time point.

The percentage of participants with no incontinence episodes for the 3 days prior to each clinic visit derived from the micturition diary recorded by the patient.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=293 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=281 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=300 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=291 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Percentage of Participants With Zero Incontinence Episodes at Week 4, Week 8, Week 12 and the Final Visit Week 4 [N=291; 293; 281; 299]	32.1 percentage of participants	32.0 percentage of participants	33.4 percentage of participants	28.9 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Week 4, Week 8, Week 12 and the Final Visit Week 8 [N=280; 277; 268; 292]	42.6 percentage of participants	45.1 percentage of participants	41.8 percentage of participants	34.3 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Week 4, Week 8, Week 12 and the Final Visit Week 12 [N=275; 272; 262; 276]	46.3 percentage of participants	43.9 percentage of participants	48.6 percentage of participants	41.1 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Week 4, Week 8, Week 12 and the Final Visit Final Visit (LOCF) [N=291; 293; 281; 300]	45.1 percentage of participants	43.8 percentage of participants	47.3 percentage of participants	40.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set-incontinence included all patients who took at least 1 dose of double-blind study drug \& had a baseline \& at least 1 postbaseline micturition measurement in the visit diary \& who had at least 1 incontinence episode at baseline. LOCF was used for the Final Visit analysis. N is the number of patients included at each time point.

The percentage of participants with at least 50% decrease from baseline in mean number of incontinence episodes per 24 hours during the 3 days prior to each clinic visit derived from the patient micturition diary.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=293 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=281 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=300 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=291 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 8 [N=280; 277; 268; 292]	67.9 percentage of participants	68.3 percentage of participants	64.4 percentage of participants	53.9 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 4 [N=291; 293; 281; 299]	57.3 percentage of participants	54.4 percentage of participants	56.5 percentage of participants	46.0 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 12 [N=275; 272; 262; 276]	73.5 percentage of participants	67.9 percentage of participants	69.6 percentage of participants	61.5 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Final Visit (LOCF) [N=291; 293; 281; 300]	72.2 percentage of participants	67.6 percentage of participants	68.3 percentage of participants	60.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for the Final Visit analysis. The number of participants included in the calculation for each time point is noted as "N".

Overactive bladder symptoms were assessed using the symptom bother scale of the overactive bladder questionnaire. The symptom bother scale consists of 8 questions answered by the participant on a scale from 1-6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from Baseline in symptom bother score indicates improvements. LS Means are from an ANCOVA with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Week 4 [N=472; 460; 470; 467]	-13.0 Scores on a scale Standard Error 0.76	-13.8 Scores on a scale Standard Error 0.75	-13.8 Scores on a scale Standard Error 0.76	-9.7 Scores on a scale Standard Error 0.75
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Week 8 [N=455; 441; 450; 451]	-17.8 Scores on a scale Standard Error 0.85	-17.6 Scores on a scale Standard Error 0.84	-17.1 Scores on a scale Standard Error 0.84	-13.3 Scores on a scale Standard Error 0.84
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Week 12 [N=445; 424; 435; 433]	-20.3 Scores on a scale Standard Error 0.89	-20.0 Scores on a scale Standard Error 0.88	-18.5 Scores on a scale Standard Error 0.88	-15.3 Scores on a scale Standard Error 0.87
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Final Visit (LOCF) [N=475; 465; 473; 469]	-19.6 Scores on a scale Standard Error 0.85	-19.9 Scores on a scale Standard Error 0.84	-18.4 Scores on a scale Standard Error 0.85	-14.9 Scores on a scale Standard Error 0.84

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. LOCF was utilized for the Final Visit analysis. The number of participants included in the calculation for each time point is noted as "N".

Health-related quality of life was assessed by the HRQL subscales (coping, concern, sleep and social interaction) of the overactive bladder questionnaire (OABq). The HRQL total score was calculated by adding the 4 HRQL subscale scores, and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from Baseline in HRQL score indicates improvements. LS Means are from an ANCOVA with treatment group, gender, and geographic region as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Week 4 [N=471; 463; 469; 467]	9.5 Scores on a scale Standard Error 0.68	11.2 Scores on a scale Standard Error 0.68	9.4 Scores on a scale Standard Error 0.68	8.8 Scores on a scale Standard Error 0.68
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Week 8 [N=454; 446; 450; 453]	13.7 Scores on a scale Standard Error 0.76	14.8 Scores on a scale Standard Error 0.76	13.2 Scores on a scale Standard Error 0.76	11.9 Scores on a scale Standard Error 0.76
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Week 12 [N=445; 426; 435; 432]	16.6 Scores on a scale Standard Error 0.80	17.2 Scores on a scale Standard Error 0.80	15.1 Scores on a scale Standard Error 0.80	14.1 Scores on a scale Standard Error 0.79
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Final Visit (LOCF) [N=473; 468; 472; 470]	16.1 Scores on a scale Standard Error 0.77	17.0 Scores on a scale Standard Error 0.77	14.8 Scores on a scale Standard Error 0.77	13.7 Scores on a scale Standard Error 0.76

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug \& had a baseline \& at least 1 postbaseline micturition measurement in the visit diary. The number of patients at each time point (N) includes those with both baseline and post-baseline values who were employed. LOCF was used for the Final Visit analysis.

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with work productivity in the last 7 days. Percent of work time missed is derived from the number of hours of work missed due to OAB symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Week 12 [N=111; 120; 109; 113]	-1.9 percent work time missed Standard Deviation 13.42	-1.7 percent work time missed Standard Deviation 18.83	-1.2 percent work time missed Standard Deviation 12.68	-0.2 percent work time missed Standard Deviation 7.31
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Final Visit (LOCF) [N=113; 122; 110; 114]	-1.8 percent work time missed Standard Deviation 13.31	-1.7 percent work time missed Standard Deviation 18.74	-1.2 percent work time missed Standard Deviation 12.62	-0.2 percent work time missed Standard Deviation 7.24

SECONDARY outcome

Timeframe: Baseline and Week 12

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with work productivity in the last 7 days. Percent impairment while working was derived from the patient's assessment of the degree to which OAB affected their productivity while working. A higher percentage indicates greater impairment and less productivity. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Week 12 [N=116; 128; 104; 114]	-12.5 percent impairment while working Standard Deviation 23.24	-10.8 percent impairment while working Standard Deviation 25.19	-6.7 percent impairment while working Standard Deviation 28.40	-8.3 percent impairment while working Standard Deviation 24.50
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Final Visit (LOCF) [N=118; 130; 106; 115]	-12.8 percent impairment while working Standard Deviation 23.24	-10.8 percent impairment while working Standard Deviation 25.04	-6.6 percent impairment while working Standard Deviation 28.28	-8.1 percent impairment while working Standard Deviation 24.43

SECONDARY outcome

Timeframe: Baseline and Week 12

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with work productivity in the last 7 days. Percent overall work impairment takes into account both hours missed due to OAB symptoms and the patient's assessment of the degree to which OAB affected their productivity while working. A higher percentage indicates greater impairment and less productivity. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Week 12 [N=104; 117; 98; 104]	-13.2 percent overall work impairment Standard Deviation 25.70	-11.6 percent overall work impairment Standard Deviation 27.09	-5.8 percent overall work impairment Standard Deviation 28.32	-7.9 percent overall work impairment Standard Deviation 23.86
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Final Visit (LOCF) [N=106; 119; 99; 105]	-13.6 percent overall work impairment Standard Deviation 25.64	-11.5 percent overall work impairment Standard Deviation 26.97	-5.8 percent overall work impairment Standard Deviation 28.19	-7.7 percent overall work impairment Standard Deviation 23.79

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. The number of participants at each time point (N) included patients with both baseline and post-baseline values. LOCF was used for the Final Visit analysis.

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with daily activities over the last 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which OAB affected their regular daily activities. A higher percentage indicates greater impairment. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Week 12 [N=409; 395; 409; 400]	-15.0 percent activity impairment Standard Deviation 27.93	-14.5 percent activity impairment Standard Deviation 28.67	-14.7 percent activity impairment Standard Deviation 29.50	-11.2 percent activity impairment Standard Deviation 27.73
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Final Visit (LOCF) [N=419; 400; 417; 409]	-14.9 percent activity impairment Standard Deviation 27.84	-14.4 percent activity impairment Standard Deviation 28.70	-14.3 percent activity impairment Standard Deviation 29.70	-11.0 percent activity impairment Standard Deviation 27.78

SECONDARY outcome

Timeframe: Baseline and Week 12

The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems in walking about; I have some problems in walking about; I am confined to bed. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available for that Visit.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> No problem	340 participants	334 participants	330 participants	334 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> Some problems	26 participants	18 participants	28 participants	27 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> Confined to bed	1 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> Missing data	2 participants	1 participants	1 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> No problems	44 participants	40 participants	38 participants	37 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> Some problems	59 participants	82 participants	73 participants	78 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> Confined to bed	0 participants	0 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> Missing data	0 participants	1 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined -> No problems	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined -> Some problems	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined -> Confined to bed	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined -> Missing data	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Missing data -> No problem	1 participants	2 participants	3 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Missing data -> Some problems	0 participants	0 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Missing data -> Confined to bed	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Missing data -> Missing data	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems with self-care; I have some problems washing or dressing myself; I am unable to wash or dress myself. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available for that Visit.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Some problems -> Some problems	6 participants	10 participants	15 participants	14 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Some problems -> Unable to wash or dress myself	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Some problems -> Missing data	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Unable to wash or dress myself -> Some problems	1 participants	1 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Unable to wash or dress -> Unable to wash or dress	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Missing data -> Missing data	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score No problem -> No problem	445 participants	439 participants	432 participants	437 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score No problem -> Some problems	9 participants	17 participants	12 participants	7 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score No problem -> Unable to wash or dress myself	0 participants	0 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score No problem -> Missing data	2 participants	2 participants	1 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Some problems -> No problems	9 participants	8 participants	9 participants	18 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Unable to wash or dress myself -> No problems	0 participants	0 participants	0 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Unable to wash or dress myself -> Missing data	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Missing data -> No problem	1 participants	1 participants	4 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Missing data -> Some problems	0 participants	0 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score Missing data -> Unable to wash or dress myself	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

The EQ-5D is a standardized, nondisease-specific instrument for describing health status. Participants were asked which statement best describes their health state with regard to usual activities (work, study or leisure): I have no problems performing my usual activities; I have some problems performing my usual activities; I am unable to perform my usual activities. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available at that Visit.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Missing data -> Missing data	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> No problem	316 participants	327 participants	283 participants	298 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> Some problems	18 participants	25 participants	39 participants	25 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> Unable to perform usual activities	2 participants	3 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> Missing data	1 participants	1 participants	1 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> No problems	82 participants	51 participants	68 participants	73 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> Some problems	48 participants	63 participants	73 participants	75 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems-> Unable to perform usual activities	0 participants	0 participants	0 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> Missing data	1 participants	1 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Unable to perform usual activities -> No problems	1 participants	1 participants	2 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Unable to perform usual activities-> Some problems	1 participants	3 participants	3 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Unable to perform -> Unable to perform	1 participants	2 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Unable to perform usual activities -> Missing data	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Missing data -> No problem	2 participants	1 participants	4 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Missing data -> Some problems	0 participants	0 participants	1 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Missing data -> Unable to perform usual activities	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no pain or discomfort; I have moderate pain or discomfort; I have extreme pain or discomfort. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available for that Visit.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> Moderate pain	12 participants	12 participants	12 participants	13 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> Extreme pain	4 participants	5 participants	9 participants	10 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> Missing data	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Missing data -> No pain	1 participants	1 participants	3 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Missing data -> Moderate pain	0 participants	1 participants	1 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Missing data -> Extreme pain	0 participants	0 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> No pain	211 participants	209 participants	197 participants	210 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> Moderate pain	32 participants	50 participants	37 participants	36 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> No pain	2 participants	1 participants	4 participants	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> Extreme pain	2 participants	2 participants	2 participants	4 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> Missing data	2 participants	1 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> No pain	71 participants	76 participants	69 participants	70 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> Moderate pain	128 participants	114 participants	132 participants	129 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> Extreme pain	8 participants	5 participants	7 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain ->Missing data	0 participants	1 participants	0 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Missing data -> Missing data	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I am not anxious or depressed; I am moderately anxious or depressed; I am extremely anxious or depressed. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available for that Visit.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Not anxious -> Moderately anxious	30 participants	19 participants	21 participants	37 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Moderately anxious -> Not anxious	74 participants	88 participants	71 participants	76 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Moderately anxious -> Moderately anxious	111 participants	105 participants	122 participants	108 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Moderately anxious -> Extremely anxious	5 participants	10 participants	12 participants	9 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Moderately anxious -> Missing data	1 participants	0 participants	1 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Extremely anxious -> Not anxious	4 participants	1 participants	4 participants	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Extremely anxious -> Moderately anxious	12 participants	11 participants	18 participants	12 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Extremely anxious -> Extremely anxious	9 participants	8 participants	2 participants	9 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Extremely anxious -> Missing data	1 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Missing data -> Not anxious	1 participants	1 participants	3 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Missing data -> Moderately anxious	0 participants	0 participants	1 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Missing data -> Extremely anxious	0 participants	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Not anxious -> Not anxious	224 participants	232 participants	217 participants	219 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Not anxious -> Extremely anxious	1 participants	1 participants	3 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Not anxious -> Missing data	0 participants	2 participants	0 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score Missing data -> Missing data	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug \& had a baseline \& at least 1 postbaseline micturition measurement in the visit diary. The number of participants at each time point (N) includes only patients with both baseline and post-baseline values. LOCF was used for the Final Visit analysis.

The EQ-5D is an international, standardized, generic instrument for describing and evaluating health status. Health status is assessed by patients evaluating their health on a vertical, visual analog scale from 0 to 100 where the endpoints are labeled 'Worst imaginable health state' (=0) and 'Best imaginable health state' (=100). On the EQ-5D VAS, a positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Week 12 [N=443; 423; 437; 429]	7.1 Scores on a scale Standard Deviation 18.89	8.2 Scores on a scale Standard Deviation 17.56	6.9 Scores on a scale Standard Deviation 17.62	6.7 Scores on a scale Standard Deviation 19.01
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Final Visit (LOCF) [N=470; 466; 472; 467]	6.5 Scores on a scale Standard Deviation 18.67	8.1 Scores on a scale Standard Deviation 17.74	6.4 Scores on a scale Standard Deviation 18.23	6.4 Scores on a scale Standard Deviation 19.03
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Week 4 [N=466; 459; 468; 461]	3.3 Scores on a scale Standard Deviation 15.74	4.4 Scores on a scale Standard Deviation 16.75	3.2 Scores on a scale Standard Deviation 17.68	3.1 Scores on a scale Standard Deviation 15.64
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Week 8 [N=451; 443; 447; 447]	5.5 Scores on a scale Standard Deviation 16.79	6.8 Scores on a scale Standard Deviation 17.42	6.0 Scores on a scale Standard Deviation 17.31	4.5 Scores on a scale Standard Deviation 16.81

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. The number of participants included at each time point (N) only includes those with baseline and post-baseline values. LOCF was used for the Final Visit analysis.

The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 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' and 6: 'Causes me many severe problems'. LS means are from an ANCOVA model with treatment group, gender, and geographical regions as fixed factors and baseline as a covariate. A negative change from Baseline score indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) Week 12 [N=425; 410; 421; 417]	-1.1 Scores on a scale Standard Error 0.06	-0.1 Scores on a scale Standard Error 0.06	-1.0 Scores on a scale Standard Error 0.06	-0.8 Scores on a scale Standard Error 0.06
Change From Baseline to Week 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) Final Visit (LOCF) [N=433; 416; 429; 426]	-1.0 Scores on a scale Standard Error 0.06	-1.1 Scores on a scale Standard Error 0.05	-1.0 Scores on a scale Standard Error 0.06	-0.8 Scores on a scale Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. The number of participants included at each time point (N) only includes those with baseline and post-baseline values. LOCF was used for the Final Visit analysis.

The TS-VAS is a visual analog scale (VAS) that asks patients to rate their satisfaction with treatment by placing a vertical mark on a 10 cm line where the endpoints are labeled 'No, not at all' on the left (=0) to 'Yes, completely satisfied' on the right (=10). LS means are from an ANCOVA model with treatment group, gender, and geographical regions as fixed factors and baseline as a covariate. A positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS) Week 12 [N=421; 410; 420; 416]	2.57 Scores on a scale Standard Error 0.149	2.67 Scores on a scale Standard Error 0.147	2.44 Scores on a scale Standard Error 0.148	1.92 Scores on a scale Standard Error 0.147
Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS) Final Visit (LOCF) [N=428; 414; 427; 425]	2.55 Scores on a scale Standard Error 0.149	2.66 Scores on a scale Standard Error 0.146	2.44 Scores on a scale Standard Error 0.147	1.89 Scores on a scale Standard Error 0.146

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. The number of participants at each time point (N) includes only patients with both baseline and post-baseline values. LOCF was used for the Final Visit analysis.

The number of times the patient visited a physician's office during the 4 weeks prior to each study visit (excluding study visits) because of the patient's bladder condition.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Week 4 [N=477; 467; 473; 474]	-0.0 Physician visits Standard Deviation 0.14	-0.0 Physician visits Standard Deviation 0.19	0.0 Physician visits Standard Deviation 0.23	-0.0 Physician visits Standard Deviation 0.20
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Week 8 [N=462; 448; 453; 460]	0.0 Physician visits Standard Deviation 0.18	-0.0 Physician visits Standard Deviation 0.21	-0.0 Physician visits Standard Deviation 0.15	-0.0 Physician visits Standard Deviation 0.17
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Week 12 [N=451; 435; 443; 439]	-0.0 Physician visits Standard Deviation 0.16	-0.0 Physician visits Standard Deviation 0.18	-0.0 Physician visits Standard Deviation 0.18	-0.0 Physician visits Standard Deviation 0.16
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Final Visit (LOCF) [N=478; 469; 475; 474]	-0.0 Physician visits Standard Deviation 0.17	-0.0 Physician visits Standard Deviation 0.18	-0.0 Physician visits Standard Deviation 0.19	-0.0 Physician visits Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. The number of participants at each time point (N) only includes those with baseline and post-baseline values. LOCF was used for the Final Visit analysis.

The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 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' and 6: 'Causes me many severe problems'. Improvement was defined as at least a 1 point improvement from Baseline to post-baseline and a major improvement was defined as at least a 2 point improvement from Baseline to post-baseline in PPBC score.

Outcome measures

Outcome measures
Measure	Mirabegron 50 mg n=473 Participants Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=478 Participants Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=475 Participants Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.	Placebo n=480 Participants Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Improvement: Final Visit [N=433; 416; 429; 426]	61.3 percentage of participants	62.2 percentage of participants	65.0 percentage of participants	56.6 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Improvement: Week 12 [N=425; 410;421; 417]	61.5 percentage of participants	62.7 percentage of participants	65.2 percentage of participants	56.9 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Major Improvement: Week 12 [N=425; 410; 421; 417]	29.5 percentage of participants	34.0 percentage of participants	31.7 percentage of participants	28.5 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Major Improvement: Final Visit [N=433;416;429;426]	29.1 percentage of participants	33.6 percentage of participants	31.5 percentage of participants	28.2 percentage of participants

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 49 other events

Deaths: 0 deaths

Mirabegron 50 mg

Serious events: 14 serious events

Other events: 42 other events

Deaths: 0 deaths

Mirabegron 100 mg

Serious events: 12 serious events

Other events: 41 other events

Deaths: 0 deaths

Tolterodine SR 4 mg

Serious events: 11 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=494 participants at risk Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks.	Mirabegron 50 mg n=493 participants at risk Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Mirabegron 100 mg n=496 participants at risk Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks.	Tolterodine SR 4 mg n=495 participants at risk Participants received Tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks.
Vascular disorders hypertension	7.7% 38/494 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.	5.9% 29/493 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.	5.4% 27/496 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.	7.9% 39/495 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.
Gastrointestinal disorders Dry mouth	2.6% 13/494 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.	2.8% 14/493 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.	2.8% 14/496 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.	10.1% 50/495 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.

Additional Information

Director Medical Science

Astellas Pharma Europe B.V.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Primary publication of the multi-center data. Sponsor must receive a site's manuscript at least 45 days prior to planned submission to ensure that no confidential information of Sponsor is included in the document. Sponsor will respond within 30 days and may request changes or delay the publication to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER