Trial Outcomes & Findings for Study to Test the Long Term Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder (NCT NCT00688688)

Last Updated: 2024-11-20

Results Overview

An adverse event (AE) was defined as any untoward medical occurrence in a patient administered a study drug and which did not necessarily have a causal relationship with the treatment. The investigator assessed the severity of each AE, including abnormal laboratory values, as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2792 participants

Primary outcome timeframe

From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.

Results posted on

2024-11-20

Participant Flow

Patients who completed the 12-week treatment and safety follow-up periods of studies 178-CL-046 (NCT00689104) or 178-CL-047 (NCT00662909), as well as patients that did not participate in these studies were enrolled into this study if they met all inclusion criteria and none of the exclusion criteria.

After screening, 2792 patients took placebo run-in study drug in a 2-week, single-blind, placebo run-in period. On completion of the run-in period, 2452 eligible patients were randomly assigned to receive mirabegron 50 mg, or mirabegron 100 mg or tolterodine ER 4 mg once daily for 12 months.

Participant milestones

Participant milestones
Measure	Mirabegron 50 mg Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Mirabegron 100 mg Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Overall Study STARTED	815	824	813
Overall Study Safety Analysis Set (SAF)	812	820	812
Overall Study Full Analysis Set (FAS)	789	802	791
Overall Study Full Analysis Set Incontinence (FAS-I)	479	483	488
Overall Study COMPLETED	629	645	621
Overall Study NOT COMPLETED	186	179	192

Reasons for withdrawal

Reasons for withdrawal
Measure	Mirabegron 50 mg Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Mirabegron 100 mg Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Overall Study Eligibility criterion not met	7	7	10
Overall Study Adverse Event	52	51	50
Overall Study Lack of Efficacy	34	25	45
Overall Study Withdrawal by Subject	66	75	65
Overall Study Lost to Follow-up	14	7	7
Overall Study Protocol Violation	6	9	11
Overall Study Randomized but never received study drug	1	0	0
Overall Study Non-compliance with study procedures	5	3	4
Overall Study Taking exclusionary medications	1	0	0
Overall Study Site closure	0	1	0
Overall Study Violation of exclusion criterion	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mirabegron 50 mg n=812 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Mirabegron 100 mg n=820 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=812 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Total n=2444 Participants Total of all reporting groups
Age, Continuous	59.2 years STANDARD_DEVIATION 12.56 • n=5 Participants	60.1 years STANDARD_DEVIATION 11.92 • n=7 Participants	59.6 years STANDARD_DEVIATION 12.47 • n=5 Participants	59.6 years STANDARD_DEVIATION 12.32 • n=4 Participants
Sex: Female, Male Female	602 Participants n=5 Participants	608 Participants n=7 Participants	600 Participants n=5 Participants	1810 Participants n=4 Participants
Sex: Female, Male Male	210 Participants n=5 Participants	212 Participants n=7 Participants	212 Participants n=5 Participants	634 Participants n=4 Participants
Type of overactive bladder (OAB) Urge incontinence	296 participants n=5 Participants	305 participants n=7 Participants	317 participants n=5 Participants	918 participants n=4 Participants
Type of overactive bladder (OAB) Mixed	232 participants n=5 Participants	228 participants n=7 Participants	210 participants n=5 Participants	670 participants n=4 Participants
Type of overactive bladder (OAB) Frequency	284 participants n=5 Participants	287 participants n=7 Participants	285 participants n=5 Participants	856 participants n=4 Participants
Duration of OAB symptoms	87.4 months STANDARD_DEVIATION 96.28 • n=5 Participants	87.9 months STANDARD_DEVIATION 91.52 • n=7 Participants	83.8 months STANDARD_DEVIATION 87.34 • n=5 Participants	86.4 months STANDARD_DEVIATION 91.77 • n=4 Participants
Summary of previous treatment Placebo	190 participants n=5 Participants	174 participants n=7 Participants	180 participants n=5 Participants	544 participants n=4 Participants
Summary of previous treatment Mirabegron 50 mg	170 participants n=5 Participants	180 participants n=7 Participants	171 participants n=5 Participants	521 participants n=4 Participants
Summary of previous treatment Mirabegron 100 mg	183 participants n=5 Participants	198 participants n=7 Participants	197 participants n=5 Participants	578 participants n=4 Participants
Summary of previous treatment Tolterodine ER 4 mg	130 participants n=5 Participants	107 participants n=7 Participants	108 participants n=5 Participants	345 participants n=4 Participants
Summary of previous treatment Naive	139 participants n=5 Participants	161 participants n=7 Participants	156 participants n=5 Participants	456 participants n=4 Participants
Mean number of micturitions per 24 Hours	11.12 micturitions STANDARD_DEVIATION 2.809 • n=5 Participants	11.16 micturitions STANDARD_DEVIATION 2.917 • n=7 Participants	10.94 micturitions STANDARD_DEVIATION 2.668 • n=5 Participants	11.08 micturitions STANDARD_DEVIATION 2.801 • n=4 Participants
Mean volume voided per micturition	160.4 mL STANDARD_DEVIATION 58.80 • n=5 Participants	164.6 mL STANDARD_DEVIATION 58.62 • n=7 Participants	160.8 mL STANDARD_DEVIATION 56.98 • n=5 Participants	162.0 mL STANDARD_DEVIATION 58.15 • n=4 Participants
Mean number of urgency episodes (grade 3 or 4) per 24 hours	5.66 urgency episodes STANDARD_DEVIATION 3.601 • n=5 Participants	5.61 urgency episodes STANDARD_DEVIATION 3.722 • n=7 Participants	5.44 urgency episodes STANDARD_DEVIATION 3.453 • n=5 Participants	5.57 urgency episodes STANDARD_DEVIATION 3.594 • n=4 Participants
Mean level of urgency	2.45 scores on a scale STANDARD_DEVIATION 0.544 • n=5 Participants	2.44 scores on a scale STANDARD_DEVIATION 0.525 • n=7 Participants	2.43 scores on a scale STANDARD_DEVIATION 0.519 • n=5 Participants	2.44 scores on a scale STANDARD_DEVIATION 0.529 • n=4 Participants
Mean number of nocturia episodes per 24 hours	1.83 nocturia episodes STANDARD_DEVIATION 1.361 • n=5 Participants	1.85 nocturia episodes STANDARD_DEVIATION 1.404 • n=7 Participants	1.77 nocturia episodes STANDARD_DEVIATION 1.388 • n=5 Participants	1.82 nocturia episodes STANDARD_DEVIATION 1.384 • n=4 Participants
Mean number of pads used per 24 hours	1.06 pads STANDARD_DEVIATION 1.872 • n=5 Participants	0.98 pads STANDARD_DEVIATION 1.769 • n=7 Participants	0.98 pads STANDARD_DEVIATION 1.759 • n=5 Participants	1.01 pads STANDARD_DEVIATION 1.800 • n=4 Participants

PRIMARY outcome

Timeframe: From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.

Population: The number of participants analyzed represents the Safety Analysis Set (SAF), including all randomized patients who took at least one dose of double-blind study drug.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=820 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=812 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=812 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs) Mild adverse events	240 participants	251 participants	222 participants
Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs) Moderate adverse events	211 participants	218 participants	212 participants
Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs) Severe adverse events	52 participants	39 participants	51 participants

SECONDARY outcome

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

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

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 prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. Least squares (LS) means were generated from the analysis of covariance (ANCOVA) model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours Month 1 [N=786; 797; 786]	-1.10 micturitions Standard Error 0.068	-1.02 micturitions Standard Error 0.069	-0.94 micturitions Standard Error 0.069
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours Month 3 [N=742; 741; 735]	-1.46 micturitions Standard Error 0.079	-1.27 micturitions Standard Error 0.080	-1.13 micturitions Standard Error 0.079
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours Month 6 [N=684; 705; 684]	-1.43 micturitions Standard Error 0.082	-1.30 micturitions Standard Error 0.083	-1.25 micturitions Standard Error 0.083
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours Month 9 [N=656; 667; 645]	-1.37 micturitions Standard Error 0.086	-1.38 micturitions Standard Error 0.087	-1.33 micturitions Standard Error 0.086
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours Month 12 [N=627; 642; 623]	-1.46 micturitions Standard Error 0.088	-1.50 micturitions Standard Error 0.089	-1.30 micturitions Standard Error 0.089
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours Final Visit (LOCF) [N=789; 802; 791]	-1.41 micturitions Standard Error 0.082	-1.39 micturitions Standard Error 0.083	-1.27 micturitions Standard Error 0.083

SECONDARY outcome

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

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

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 prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. Least squares (LS) means were generated from the analysis of covariance (ANCOVA) model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=483 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=488 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=479 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours Month 1 [N=478; 479; 485]	-1.03 incontinence episodes Standard Error 0.079	-0.96 incontinence episodes Standard Error 0.078	-0.94 incontinence episodes Standard Error 0.079
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours Month 3 [N=447; 443; 452]	-1.28 incontinence episodes Standard Error 0.084	-1.09 incontinence episodes Standard Error 0.083	-1.10 incontinence episodes Standard Error 0.083
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours Month 6 [N=409; 428; 418]	-1.27 incontinence episodes Standard Error 0.086	-1.17 incontinence episodes Standard Error 0.087	-1.11 incontinence episodes Standard Error 0.088
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours Month 9 [N=387; 402; 391]	-1.32 incontinence episodes Standard Error 0.082	-1.26 incontinence episodes Standard Error 0.083	-1.17 incontinence episodes Standard Error 0.083
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours Month 12 [N=370; 387; 379]	-1.19 incontinence episodes Standard Error 0.092	-1.36 incontinence episodes Standard Error 0.093	-1.14 incontinence episodes Standard Error 0.094
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours Final Visit (LOCF) [N=479; 483; 488]	-1.24 incontinence episodes Standard Error 0.086	-1.26 incontinence episodes Standard Error 0.086	-1.01 incontinence episodes Standard Error 0.087

SECONDARY outcome

Timeframe: Baseline and Months 1, 3, 6, 9 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 prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. LS means were generated from the ANCOVA model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition Month 1 [N=785; 797; 786]	16.7 mL Standard Error 1.30	16.0 mL Standard Error 1.31	12.1 mL Standard Error 1.31
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition Month 3 [N=741; 741; 735]	20.4 mL Standard Error 1.50	17.4 mL Standard Error 1.51	14.8 mL Standard Error 1.50
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition Month 6 [N=684; 705; 684]	23.0 mL Standard Error 1.66	18.8 mL Standard Error 1.69	18.6 mL Standard Error 1.69
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition Month 9 [N=655; 667; 645]	23.5 mL Standard Error 1.77	17.9 mL Standard Error 1.80	20.5 mL Standard Error 1.78
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition Month 12 [N=626; 642; 623]	24.3 mL Standard Error 1.83	18.9 mL Standard Error 1.86	18.5 mL Standard Error 1.86
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition Final Visit (LOCF) [N=789; 802; 791]	21.5 mL Standard Error 1.63	18.1 mL Standard Error 1.64	17.5 mL Standard Error 1.65

SECONDARY outcome

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

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

The involuntary leakage of urine accompanied 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 time; 3=Severe urgency, could not postpone voiding; 4=Urge incontinence, leaked before arriving to toilet. LS means are from the ANCOVA model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=483 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=488 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=479 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Month 1 [N=471; 467; 471]	-1.04 urgency incontinence episodes Standard Error 0.073	-0.95 urgency incontinence episodes Standard Error 0.072	-0.92 urgency incontinence episodes Standard Error 0.072
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Month 3 [N=441; 432; 440]	-1.23 urgency incontinence episodes Standard Error 0.078	-1.06 urgency incontinence episodes Standard Error 0.077	-1.05 urgency incontinence episodes Standard Error 0.077
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Month 6 [N=404; 417; 408]	-1.32 urgency incontinence episodes Standard Error 0.079	-1.11 urgency incontinence episodes Standard Error 0.080	-1.13 urgency incontinence episodes Standard Error 0.080
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Month 9 [N=382; 392; 382]	-1.33 urgency incontinence episodes Standard Error 0.076	-1.25 urgency incontinence episodes Standard Error 0.077	-1.13 urgency incontinence episodes Standard Error 0.077
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Month 12 [N=366; 377; 371]	-1.20 urgency incontinence episodes Standard Error 0.085	-1.29 urgency incontinence episodes Standard Error 0.086	-1.17 urgency incontinence episodes Standard Error 0.087
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours Final Visit (LOCF) [N=472; 471; 474]	-1.23 urgency incontinence episodes Standard Error 0.082	-1.21 urgency incontinence episodes Standard Error 0.081	-1.01 urgency incontinence episodes Standard Error 0.082

SECONDARY outcome

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

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

The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from 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 delay voiding a short time; 3=Severe urgency, could not delay voiding; 4=Urge incontinence, leaked before arriving to the toilet. LS means are from an ANCOVA model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours Month 1 [N=783; 791; 780]	-1.31 urgency episodes Standard Error 0.091	-1.11 urgency episodes Standard Error 0.092	-1.30 urgency episodes Standard Error 0.092
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours Month 3 [N=738; 737; 733]	-1.83 urgency episodes Standard Error 0.103	-1.55 urgency episodes Standard Error 0.103	-1.37 urgency episodes Standard Error 0.103
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours Month 6 [N=683; 701; 680]	-1.95 urgency episodes Standard Error 0.106	-1.63 urgency episodes Standard Error 0.108	-1.75 urgency episodes Standard Error 0.108
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours Month 9 [N=653; 665; 643]	-1.71 urgency episodes Standard Error 0.113	-1.78 urgency episodes Standard Error 0.115	-1.77 urgency episodes Standard Error 0.114
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours Month 12 [N=621; 637; 621]	-1.79 urgency episodes Standard Error 0.115	-1.89 urgency episodes Standard Error 0.116	-1.81 urgency episodes Standard Error 0.116
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours Final Visit (LOCF) [N=788; 799; 788]	-1.80 urgency episodes Standard Error 0.107	-1.63 urgency episodes Standard Error 0.108	-1.62 urgency episodes Standard Error 0.108

SECONDARY outcome

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

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

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 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 generated from an ANCOVA model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency Month 1 [N=784; 793; 780]	-0.19 scores on a scale Standard Error 0.016	-0.17 scores on a scale Standard Error 0.016	-0.18 scores on a scale Standard Error 0.016
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency Month 3 [N=739; 738; 733]	-0.28 scores on a scale Standard Error 0.019	-0.24 scores on a scale Standard Error 0.019	-0.21 scores on a scale Standard Error 0.019
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency Month 6 [N=684; 702; 680]	-0.32 scores on a scale Standard Error 0.021	-0.27 scores on a scale Standard Error 0.021	-0.29 scores on a scale Standard Error 0.021
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency Month 9 [N=654; 666; 643]	-0.30 scores on a scale Standard Error 0.022	-0.31 scores on a scale Standard Error 0.022	-0.30 scores on a scale Standard Error 0.022
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency Month 12 [N=622; 638; 621]	-0.31 scores on a scale Standard Error 0.023	-0.32 scores on a scale Standard Error 0.023	-0.33 scores on a scale Standard Error 0.023
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency Final Visit (LOCF) [N=789; 801; 788]	-0.29 scores on a scale Standard Error 0.020	-0.27 scores on a scale Standard Error 0.020	-0.29 scores on a scale Standard Error 0.020

SECONDARY outcome

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

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

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 model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours Month 1 [N=324; 305; 313]	-0.79 pads Standard Error 0.086	-0.79 pads Standard Error 0.085	-0.75 pads Standard Error 0.084
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours Month 3 [N=307; 280; 286]	-0.94 pads Standard Error 0.097	-0.95 pads Standard Error 0.096	-0.80 pads Standard Error 0.093
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours Month 6 [N=277; 271; 264]	-0.94 pads Standard Error 0.098	-0.99 pads Standard Error 0.099	-0.88 pads Standard Error 0.097
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours Month 9 [N=264; 255; 250]	-0.96 pads Standard Error 0.094	-0.99 pads Standard Error 0.094	-0.99 pads Standard Error 0.092
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours Month 12 [N=254; 247; 241]	-0.92 pads Standard Error 0.101	-1.13 pads Standard Error 0.102	-0.87 pads Standard Error 0.100
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours Final Visit (LOCF) [N=325; 307; 314]	-0.88 pads Standard Error 0.092	-1.02 pads Standard Error 0.090	-0.81 pads Standard Error 0.089

SECONDARY outcome

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

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

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 model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Month 1 [N=690; 698; 690]	-0.29 nocturia episodes Standard Error 0.033	-0.29 nocturia episodes Standard Error 0.034	-0.26 nocturia episodes Standard Error 0.034
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Month 3 [N=654; 651; 643]	-0.45 nocturia episodes Standard Error 0.037	-0.37 nocturia episodes Standard Error 0.037	-0.41 nocturia episodes Standard Error 0.037
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Month 6 [N=604; 618; 602]	-0.38 nocturia episodes Standard Error 0.040	-0.35 nocturia episodes Standard Error 0.041	-0.42 nocturia episodes Standard Error 0.041
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Month 9 [N=580; 583; 567]	-0.41 nocturia episodes Standard Error 0.040	-0.39 nocturia episodes Standard Error 0.040	-0.50 nocturia episodes Standard Error 0.040
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Month 12 [N=554; 562; 550]	-0.40 nocturia episodes Standard Error 0.041	-0.46 nocturia episodes Standard Error 0.042	-0.48 nocturia episodes Standard Error 0.042
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Final Visit (LOCF) [N=693; 703; 693]	-0.39 nocturia episodes Standard Error 0.038	-0.43 nocturia episodes Standard Error 0.038	-0.46 nocturia episodes Standard Error 0.038

SECONDARY outcome

Timeframe: Months 1, 3, 6, 9 and 12

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 100 mg n=483 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=488 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=479 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Final Visit (LOCF) [N=479; 483; 488]	45.8 percentage of participants	45.1 percentage of participants	43.4 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 1 [N=478; 479; 485]	36.7 percentage of participants	33.4 percentage of participants	35.4 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 3 [N=447; 443; 452]	45.4 percentage of participants	39.2 percentage of participants	40.9 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 6 [N=409; 428; 418]	45.1 percentage of participants	43.5 percentage of participants	43.3 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 9 [N=387; 402; 391]	46.8 percentage of participants	44.2 percentage of participants	47.5 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 12 [N=370; 387; 379]	47.5 percentage of participants	49.1 percentage of participants	47.8 percentage of participants

SECONDARY outcome

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

The percentage of participants with at least a 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 100 mg n=483 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=488 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=479 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 1 [N=478; 479; 485]	57.0 percentage of participants	56.3 percentage of participants	58.2 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 3 [N=447; 443; 452]	66.1 percentage of participants	61.5 percentage of participants	61.7 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 6 [N=409; 428; 418]	66.8 percentage of participants	63.9 percentage of participants	65.5 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 9 [N=387; 402; 391]	67.2 percentage of participants	66.0 percentage of participants	65.6 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Month 12 [N=370; 387; 379]	68.5 percentage of participants	71.2 percentage of participants	67.6 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit Final Visit (LOCF) [N=479; 483; 488]	66.3 percentage of participants	66.8 percentage of participants	63.7 percentage of participants

SECONDARY outcome

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

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

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 patient 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 model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score Month 1 [N=775; 784; 771]	-12.5 scores on a scale Standard Error 0.55	-11.5 scores on a scale Standard Error 0.55	-10.5 scores on a scale Standard Error 0.55
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score Month 3 [N=736; 733; 739]	-16.1 scores on a scale Standard Error 0.61	-13.5 scores on a scale Standard Error 0.60	-13.4 scores on a scale Standard Error 0.61
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score Month 6 [N=680; 699; 682]	-16.5 scores on a scale Standard Error 0.64	-14.6 scores on a scale Standard Error 0.64	-14.5 scores on a scale Standard Error 0.65
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score Month 9 [N=649; 661; 639]	-15.6 scores on a scale Standard Error 0.68	-14.3 scores on a scale Standard Error 0.69	-14.2 scores on a scale Standard Error 0.68
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score Month 12 [N=622; 636; 612]	-15.7 scores on a scale Standard Error 0.69	-16.3 scores on a scale Standard Error 0.71	-14.1 scores on a scale Standard Error 0.70
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score Final Visit (LOCF) [N=779; 795; 781]	-14.8 scores on a scale Standard Error 0.65	-14.3 scores on a scale Standard Error 0.65	-13.1 scores on a scale Standard Error 0.65

SECONDARY outcome

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

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

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 model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Month 1 [N=774; 787; 773]	8.9 scores on a scale Standard Error 0.48	8.9 scores on a scale Standard Error 0.48	7.7 scores on a scale Standard Error 0.48
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Month 3 [N=736; 740; 739]	11.9 scores on a scale Standard Error 0.54	10.6 scores on a scale Standard Error 0.54	9.9 scores on a scale Standard Error 0.54
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Month 6 [N=681; 700; 686]	12.9 scores on a scale Standard Error 0.56	11.6 scores on a scale Standard Error 0.56	11.7 scores on a scale Standard Error 0.56
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Month 9 [N=650; 667; 644]	12.2 scores on a scale Standard Error 0.59	12.4 scores on a scale Standard Error 0.60	11.3 scores on a scale Standard Error 0.60
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Month 12 [N=619; 640; 613]	12.6 scores on a scale Standard Error 0.61	13.2 scores on a scale Standard Error 0.62	11.7 scores on a scale Standard Error 0.62
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Final Visit (LOCF) [N=779; 798; 783]	11.7 scores on a scale Standard Error 0.57	11.4 scores on a scale Standard Error 0.58	10.7 scores on a scale Standard Error 0.58

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug with a baseline \& 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 is used for the Final Visit.

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'. A negative change from Baseline score indicates improvement. LS means are from an ANCOVA model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) Month 12 [N=601; 616; 611]	-0.9 scores on a scale Standard Error 0.04	-0.9 scores on a scale Standard Error 0.04	-0.8 scores on a scale Standard Error 0.04
Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) Final Visit (LOCF) [N=655; 673; 673]	-0.9 scores on a scale Standard Error 0.04	-0.8 scores on a scale Standard Error 0.04	-0.8 scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug with a baseline \& 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 is used for the Final Visit.

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). A positive change from baseline indicates improvement. LS means are from an ANCOVA model with treatment group, previous study history, gender \& geographical regions as fixed factors and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS) Month 12 [N=599; 620; 613]	2.27 scores on a scale Standard Error 0.172	2.52 scores on a scale Standard Error 0.173	2.27 scores on a scale Standard Error 0.175
Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS) Final Visit (LOCF) [N=654; 676; 676]	2.11 scores on a scale Standard Error 0.164	2.27 scores on a scale Standard Error 0.164	2.08 scores on a scale Standard Error 0.167

SECONDARY outcome

Timeframe: Baseline and Months 3, 6 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 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Month 3 [N=215; 217; 211]	-1.0 Percent work time missed Standard Deviation 9.41	-0.6 Percent work time missed Standard Deviation 12.38	-0.06 Percent work time missed Standard Deviation 7.48
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Month 6 [N=183; 203; 200]	-1.5 Percent work time missed Standard Deviation 10.62	-0.7 Percent work time missed Standard Deviation 6.26	-1.3 Percent work time missed Standard Deviation 6.80
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Month 12 [N=181; 185; 188]	-0.8 Percent work time missed Standard Deviation 12.39	-1.2 Percent work time missed Standard Deviation 8.08	-0.5 Percent work time missed Standard Deviation 9.55
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Final Visit (LOCF) [N=245; 256; 249]	-0.9 Percent work time missed Standard Deviation 10.98	-0.8 Percent work time missed Standard Deviation 11.37	-0.5 Percent work time missed Standard Deviation 8.98

SECONDARY outcome

Timeframe: Baseline and Months 3, 6 and 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Month 3 [N=233; 236; 231]	-9.9 Percent impairment while working Standard Deviation 23.65	-10.9 Percent impairment while working Standard Deviation 22.56	-10.6 Percent impairment while working Standard Deviation 23.36
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Month 6 [N=207; 216; 213]	-11.9 Percent impairment while working Standard Deviation 21.88	-11.1 Percent impairment while working Standard Deviation 22.21	-13.0 Percent impairment while working Standard Deviation 22.44
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Month 12 [N=194; 196; 201]	-14.4 Percent impairment while working Standard Deviation 26.00	-12.3 Percent impairment while working Standard Deviation 24.60	-11.9 Percent impairment while working Standard Deviation 24.37
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Final Visit (LOCF) [N=261; 272; 265]	-11.8 Percent impairment while working Standard Deviation 25.12	-10.6 Percent impairment while working Standard Deviation 24.34	-10.9 Percent impairment while working Standard Deviation 24.51

SECONDARY outcome

Timeframe: Baseline and Months 3, 6 and 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Month 3 [N=208; 208; 204]	-10.9 Percent overall work impairment Standard Deviation 24.50	-11.0 Percent overall work impairment Standard Deviation 23.10	-11.4 Percent overall work impairment Standard Deviation 23.92
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Month 6 [N=181; 195; 193]	-13.0 Percent overall work impairment Standard Deviation 23.99	-11.1 Percent overall work impairment Standard Deviation 22.48	-12.4 Percent overall work impairment Standard Deviation 22.29
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Month 12 [N=175; 177; 183]	-14.1 Percent overall work impairment Standard Deviation 27.02	-13.6 Percent overall work impairment Standard Deviation 25.75	-11.5 Percent overall work impairment Standard Deviation 25.36
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Final Visit (LOCF) [N=240; 250; 244]	-12.4 Percent overall work impairment Standard Deviation 25.56	-11.5 Percent overall work impairment Standard Deviation 24.74	-11.2 Percent overall work impairment Standard Deviation 25.21

SECONDARY outcome

Timeframe: Baseline and Months 3, 6 and 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 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 and less productivity. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Month 3 [N=691; 690; 692]	-13.7 Percent activity impairment Standard Deviation 25.75	-12.3 Percent activity impairment Standard Deviation 25.34	-12.0 Percent activity impairment Standard Deviation 24.21
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Month 6 [N=640; 663; 651]	-15.6 Percent activity impairment Standard Deviation 26.38	-13.4 Percent activity impairment Standard Deviation 26.25	-14.0 Percent activity impairment Standard Deviation 25.47
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Month 12 [N=582; 603; 598]	-15.2 Percent activity impairment Standard Deviation 28.84	-15.0 Percent activity impairment Standard Deviation 28.07	-13.3 Percent activity impairment Standard Deviation 26.50
Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Final Visit (LOCF) [N=728; 737; 733]	-13.9 Percent activity impairment Standard Deviation 28.53	-12.8 Percent activity impairment Standard Deviation 28.10	-12.5 Percent activity impairment Standard Deviation 26.37

SECONDARY outcome

Timeframe: Baseline and Month 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 this analysis.

The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and evaluating 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> No problem	601 participants	573 participants	567 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> Some problems	42 participants	39 participants	36 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	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> Missing data	3 participants	2 participants	4 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> No problems	55 participants	62 participants	64 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> Some problems	97 participants	106 participants	105 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
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> Missing data	1 participants	2 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined to bed -> No problems	1 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined to bed -> Some problems	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined to bed -> Confined to bed	0 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined to bed -> Missing data	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	7 participants	11 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	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
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

SECONDARY outcome

Timeframe: Baseline and Month 12

The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and evaluating 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score No problem -> No problem	735 participants	720 participants	718 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score No problem -> Some problems	15 participants	23 participants	16 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	3 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score No problem -> Missing data	4 participants	4 participants	4 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score Some problems -> No problems	19 participants	13 participants	19 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score Some problems -> Some problems	25 participants	20 participants	18 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
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
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	2 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	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
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
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score Missing data -> No problem	1 participants	8 participants	13 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	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
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

SECONDARY outcome

Timeframe: Baseline and Month 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
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	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> No problem	569 participants	542 participants	536 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> Some problems	55 participants	53 participants	40 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	1 participants	2 participants	2 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	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> No problems	88 participants	96 participants	97 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> Some problems	76 participants	79 participants	94 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	2 participants	1 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> Missing data	2 participants	3 participants	1 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	2 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-> Some problems	4 participants	5 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	0 participants	1 participants	2 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	2 participants	7 participants	10 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Missing data -> No problem	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
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

SECONDARY outcome

Timeframe: Baseline and Month 12

The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and evaluating 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
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
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> No pain	396 participants	398 participants	398 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> Moderate pain	69 participants	63 participants	54 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	4 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	2 participants	4 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> No pain	107 participants	105 participants	104 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> Moderate pain	196 participants	182 participants	173 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> Extreme pain	5 participants	8 participants	14 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> Missing data	2 participants	2 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> No pain	4 participants	4 participants	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> Moderate pain	6 participants	9 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	10 participants	8 participants	10 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Missing data-> No pain	3 participants	6 participants	8 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	0 participants	3 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	0 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

SECONDARY outcome

Timeframe: Baseline and Month 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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Missing data -> Not anxious	0 participants	3 participants	7 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Not anxious -> Not anxious	453 participants	429 participants	413 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Not anxious -> Moderately anxious	34 participants	43 participants	43 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Not anxious -> Extremely anxious	3 participants	1 participants	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Not anxious -> Missing data	1 participants	2 participants	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Moderately anxious -> Not anxious	99 participants	105 participants	108 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Moderately anxious -> Moderately anxious	181 participants	169 participants	174 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Moderately anxious -> Extremely anxious	9 participants	11 participants	7 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Moderately anxious -> Missing data	2 participants	2 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	5 participants	3 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	9 participants	14 participants	8 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Extremely anxious -> Extremely anxious	5 participants	6 participants	15 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Extremely anxious -> Missing data	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 -> Moderately anxious	1 participants	2 participants	4 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	1 participants	0 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

SECONDARY outcome

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

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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Month 1 [N=767; 787; 770]	3.9 scores on a scale Standard Deviation 13.64	3.1 scores on a scale Standard Deviation 12.78	3.8 scores on a scale Standard Deviation 12.85
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Month 3 [N=734; 740; 731]	5.4 scores on a scale Standard Deviation 15.27	4.3 scores on a scale Standard Deviation 13.48	5.0 scores on a scale Standard Deviation 15.33
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Month 6 [N=676; 697; 678]	6.4 scores on a scale Standard Deviation 16.54	5.2 scores on a scale Standard Deviation 15.40	6.5 scores on a scale Standard Deviation 16.97
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Month 9 [N=645; 665; 637]	6.5 scores on a scale Standard Deviation 16.55	6.3 scores on a scale Standard Deviation 15.91	6.6 scores on a scale Standard Deviation 17.52
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Month 12 [N=615; 637; 612]	6.8 scores on a scale Standard Deviation 17.56	7.9 scores on a scale Standard Deviation 16.48	8.2 scores on a scale Standard Deviation 17.39
Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Final Visit (LOCF) [N=776; 797; 777]	5.9 scores on a scale Standard Deviation 17.35	6.0 scores on a scale Standard Deviation 16.64	6.8 scores on a scale Standard Deviation 17.47

SECONDARY outcome

Timeframe: Baseline and Months 3, 6 and 12

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 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician Month 3 [N=748; 750; 744]	0.0 Physician visits Standard Deviation 0.15	0.0 Physician visits Standard Deviation 0.14	0.0 Physician visits Standard Deviation 0.22
Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician Month 6 [N=690; 705; 687]	0.0 Physician visits Standard Deviation 0.13	0.0 Physician visits Standard Deviation 0.18	0.0 Physician visits Standard Deviation 0.17
Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician Month 12 [N=628; 640; 622]	0.0 Physician visits Standard Deviation 0.13	0.0 Physician visits Standard Deviation 0.11	0.0 Physician visits Standard Deviation 0.25
Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician Final Visit (LOCF) [N=773; 769; 760]	0.0 Physician visits Standard Deviation 0.15	0.0 Physician visits Standard Deviation 0.14	0.0 Physician visits Standard Deviation 0.25

SECONDARY outcome

Timeframe: Baseline and Month 12

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 one point improvement from Baseline to post-baseline and a major improvement was defined as at least a two point improvement from Baseline to post-baseline in PPBC score.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=802 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=791 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=789 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) Improvement: Month12 [N=616; 630; 620]	60.6 percentage of participants	56.6 percentage of participants	55.7 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) Improvement: Final Visit [N=671; 688; 684]	59.6 percentage of participants	54.4 percentage of participants	52.9 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) Major Improvement: Month 12 [N=616; 630; 620]	29.7 percentage of participants	28.2 percentage of participants	27.4 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) Major Improvement: Final Visit [N=671; 688; 684]	28.2 percentage of participants	26.6 percentage of participants	26.2 percentage of participants

SECONDARY outcome

Timeframe: From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.

Population: The number of participants analyzed represents the Safety Analysis Set (SAF), including all randomized patients who took at least one dose of double-blind study drug.

An abnormality identified during a medical test was defined as an AE if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant. The Investigator assessed each AE for causal relationship (not related, possible or probable) to study drug. A serious AE (SAE) was any untoward medical occurrence that: resulted in death, was life-threatening, resulted in significant disability/incapacity or congenital anomaly/birth defect, required or prolonged hospitalization or was a medically important event. The data reported represent the number of participants with adverse events in each category.

Outcome measures

Outcome measures
Measure	Mirabegron 100 mg n=820 Participants Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=812 Participants Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Mirabegron 50 mg n=812 Participants Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram TRAEs leading to study drug discontinuation	29 participants	31 participants	35 participants
Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram Adverse events	503 participants	508 participants	485 participants
Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram Treatment-related adverse events (TRAEs)	192 participants	224 participants	213 participants
Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram Deaths	0 participants	2 participants	2 participants
Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram Serious adverse events (SAEs)	51 participants	44 participants	42 participants
Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram Treatment-related serious adverse events	4 participants	5 participants	10 participants
Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram AEs leading to study drug discontinuation	50 participants	46 participants	48 participants

Adverse Events

Mirabegron 50 mg

Serious events: 42 serious events

Other events: 136 other events

Deaths: 0 deaths

Mirabegron 100 mg

Serious events: 51 serious events

Other events: 137 other events

Deaths: 0 deaths

Tolterodine ER 4 mg

Serious events: 44 serious events

Other events: 181 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Mirabegron 50 mg n=812 participants at risk Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Mirabegron 100 mg n=820 participants at risk Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Tolterodine ER 4 mg n=812 participants at risk Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Vascular disorders Hypertension	9.1% 74/812 • 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.	9.8% 80/820 • 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.	9.6% 78/812 • 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.
Infections and infestations Urinary tract infection	5.9% 48/812 • 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.	5.5% 45/820 • 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.	6.4% 52/812 • 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	2.8% 23/812 • 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.	2.3% 19/820 • 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.	8.6% 70/812 • 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

Medical Director, Global Medical Sciences

Astellas Pharma Global Development, Inc.

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 Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER