Trial Outcomes & Findings for A Study to Test the Efficacy and Safety of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder (NCT NCT00912964)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2030 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2024-11-21

Participant Flow

After screening, 2030 patients took placebo run-in study drug in a 2-week, single-blind, placebo run-in period. On completion of the run-in period, 1306 eligible patients were randomly assigned to receive placebo, mirabegron 25 mg or mirabegron 50 mg for 12 weeks.

Participant milestones

Participant milestones
Measure	Placebo Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Overall Study STARTED	433	433	440
Overall Study Safety Analysis Set (SAF)	433	432	440
Overall Study Full Analysis Set (FAS)	415	410	426
Overall Study Full Analysis Set Incontinence (FAS-I)	262	254	257
Overall Study COMPLETED	367	387	386
Overall Study NOT COMPLETED	66	46	54

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Overall Study Eligibility criterion not met	1	1	0
Overall Study Adverse Event	15	18	12
Overall Study Lack of Efficacy	11	4	3
Overall Study Withdrawal by Subject	20	12	18
Overall Study Lost to Follow-up	4	3	3
Overall Study Protocol Violation	5	3	8
Overall Study Taking exclusionary medications	7	4	8
Overall Study Medical History	1	0	0
Overall Study Non-compliance with study procedures	2	0	0
Overall Study Violation of exclusion criterion	0	0	2
Overall Study Randomized but never received study drug	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=433 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=432 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=440 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Total n=1305 Participants Total of all reporting groups
Mean volume voided per micturition	163.5 mL STANDARD_DEVIATION 56.39 • n=5 Participants	165.4 mL STANDARD_DEVIATION 57.24 • n=7 Participants	158.4 mL STANDARD_DEVIATION 52.17 • n=5 Participants	162.4 mL STANDARD_DEVIATION 55.33 • n=4 Participants
Mean number of micturitions per 24 hours	11.54 micturitions STANDARD_DEVIATION 2.979 • n=5 Participants	11.66 micturitions STANDARD_DEVIATION 3.117 • n=7 Participants	11.69 micturitions STANDARD_DEVIATION 3.227 • n=5 Participants	11.63 micturitions STANDARD_DEVIATION 3.108 • n=4 Participants
Mean number of urgency episodes (grade 3 or 4) per 24 hours	5.43 urgency episodes STANDARD_DEVIATION 3.335 • n=5 Participants	5.54 urgency episodes STANDARD_DEVIATION 3.622 • n=7 Participants	5.81 urgency episodes STANDARD_DEVIATION 3.559 • n=5 Participants	5.60 urgency episodes STANDARD_DEVIATION 3.508 • n=4 Participants
Mean level of urgency	2.36 scores on a scale STANDARD_DEVIATION 0.550 • n=5 Participants	2.37 scores on a scale STANDARD_DEVIATION 0.573 • n=7 Participants	2.41 scores on a scale STANDARD_DEVIATION 0.556 • n=5 Participants	2.38 scores on a scale STANDARD_DEVIATION 0.560 • n=4 Participants
Mean number of nocturia episodes per 24 hours	1.82 nocturia episodes STANDARD_DEVIATION 1.332 • n=5 Participants	1.94 nocturia episodes STANDARD_DEVIATION 1.552 • n=7 Participants	2.03 nocturia episodes STANDARD_DEVIATION 1.528 • n=5 Participants	1.93 nocturia episodes STANDARD_DEVIATION 1.465 • n=4 Participants
Mean number of pads used per 24 hours	0.91 pads STANDARD_DEVIATION 1.786 • n=5 Participants	0.79 pads STANDARD_DEVIATION 1.449 • n=7 Participants	0.84 pads STANDARD_DEVIATION 1.700 • n=5 Participants	0.85 pads STANDARD_DEVIATION 1.666 • n=4 Participants
Type of overactive bladder (OAB) Urge Incontinence	126 participants n=5 Participants	168 participants n=7 Participants	169 participants n=5 Participants	463 participants n=4 Participants
Type of overactive bladder (OAB) Mixed	145 participants n=5 Participants	129 participants n=7 Participants	154 participants n=5 Participants	428 participants n=4 Participants
Type of overactive bladder (OAB) Frequency	162 participants n=5 Participants	135 participants n=7 Participants	117 participants n=5 Participants	414 participants n=4 Participants
Duration of OAB symptoms	91.3 months STANDARD_DEVIATION 96.82 • n=5 Participants	96.3 months STANDARD_DEVIATION 113.77 • n=7 Participants	92.7 months STANDARD_DEVIATION 97.88 • n=5 Participants	93.4 months STANDARD_DEVIATION 103.02 • n=4 Participants
Age, Continuous	58.2 years STANDARD_DEVIATION 13.73 • n=5 Participants	58.5 years STANDARD_DEVIATION 12.85 • n=7 Participants	60.3 years STANDARD_DEVIATION 12.22 • n=5 Participants	59.0 years STANDARD_DEVIATION 12.97 • n=4 Participants
Sex: Female, Male Female	301 Participants n=5 Participants	293 Participants n=7 Participants	303 Participants n=5 Participants	897 Participants n=4 Participants
Sex: Female, Male Male	132 Participants n=5 Participants	139 Participants n=7 Participants	137 Participants n=5 Participants	408 Participants n=4 Participants
Race/Ethnicity, Customized White	389 participants n=5 Participants	394 participants n=7 Participants	400 participants n=5 Participants	1183 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	35 participants n=5 Participants	32 participants n=7 Participants	33 participants n=5 Participants	100 participants n=4 Participants
Race/Ethnicity, Customized Asian	7 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	17 participants n=4 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=262 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=254 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=257 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours	-0.96 Incontinence episodes Standard Error 0.122	-1.36 Incontinence episodes Standard Error 0.124	-1.38 Incontinence episodes Standard Error 0.123

PRIMARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Micturitions Per 24 Hours	-1.18 micturitions Standard Error 0.124	-1.65 micturitions Standard Error 0.125	-1.60 micturitions Standard Error 0.122

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Volume Voided Per Micturition	8.3 mL Standard Error 2.23	12.8 mL Standard Error 2.24	20.7 mL Standard Error 2.20

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: The full analysis set-Incontinence included all randomized patients who took at least 1 dose of double-blind study drug and who had a baseline and at least 1 post baseline micturition measurement in the visit diary and who had at least 1 incontinence episode at baseline. Last observation carried forward (LOCF) was not utilized in this analysis.

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

Outcome measures

Outcome measures
Measure	Placebo n=262 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=254 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=255 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4 in Mean Number of Incontinence Episodes Per 24 Hours	-0.62 Incontinence episodes Standard Error 0.120	-0.96 Incontinence episodes Standard Error 0.122	-1.13 Incontinence episodes Standard Error 0.122

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: The full analysis set included all randomized patients who took at least 1 dose of double-blind study drug and who had a baseline and at least 1 post baseline micturition measurement in the visit diary. Last observation carried forward was not utilized in this analysis.

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=424 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4 in Mean Number of Micturitions Per 24 Hours	-0.78 micturitions Standard Error 0.124	-0.96 micturitions Standard Error 0.124	-1.14 micturitions Standard Error 0.122

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=413 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Level of Urgency	-0.15 scores on a scale Standard Error 0.028	-0.22 scores on a scale Standard Error 0.029	-0.29 scores on a scale Standard Error 0.028

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=247 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=251 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Urgency Incontinence Episodes Per 24 Hours	-0.95 urgency incontinence episodes Standard Error 0.110	-1.31 urgency incontinence episodes Standard Error 0.112	-1.33 urgency incontinence episodes Standard Error 0.111

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 post baseline micturition measurement in the visit diary and at least 1 episode of urgency grade 3 or 4 at baseline. Last observation carried forward was utilized.

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

Outcome measures

Outcome measures
Measure	Placebo n=413 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to End of Treatment (Final Visit) in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours	-1.35 urgency episodes Standard Error 0.154	-1.68 urgency episodes Standard Error 0.155	-1.94 urgency episodes Standard Error 0.152

SECONDARY outcome

Timeframe: Baseline and Weeks 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours Week 8 [N= 377; 395; 399]	-1.09 micturitions Standard Error 0.130	-1.52 micturitions Standard Error 0.127	-1.53 micturitions Standard Error 0.127
Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours Week 12 [N= 366; 387; 386]	-1.47 micturitions Standard Error 0.122	-1.68 micturitions Standard Error 0.119	-1.69 micturitions Standard Error 0.119

SECONDARY outcome

Timeframe: Baseline and Weeks 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=262 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=254 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=257 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours Week 8 [N= 236; 244; 241]	-1.04 Incontinence episodes Standard Error 0.117	-1.38 Incontinence episodes Standard Error 0.116	-1.39 Incontinence episodes Standard Error 0.116
Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours Week 12 [N= 231; 239; 232]	-1.08 Incontinence episodes Standard Error 0.120	-1.36 Incontinence episodes Standard Error 0.118	-1.43 Incontinence episodes Standard Error 0.119

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition Week 4 [N=415; 410; 424]	7.6 mL Standard Error 1.85	10.6 mL Standard Error 1.86	17.8 mL Standard Error 1.83
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition Week 8 [N=377; 395; 399]	9.8 mL Standard Error 2.21	15.7 mL Standard Error 2.16	17.9 mL Standard Error 2.15
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition Week 12 [N=366; 387; 386]	8.2 mL Standard Error 2.41	13.6 mL Standard Error 2.34	22.5 mL Standard Error 2.34

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set-Incontinence included all randomized patients who took at least 1 dose of double-blind study drug and who had a baseline and at least 1 post baseline micturition measurement in the visit diary and who had at least 1 urgency incontinence episode (grade 3 or 4) at baseline. LOCF was not utilized.

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

Outcome measures

Outcome measures
Measure	Placebo n=262 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=254 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=257 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Incontinence Episodes Per 24 Hours Week 4 [N=256; 247; 249]	-0.63 Urgency incontinence episodes Standard Error 0.107	-0.98 Urgency incontinence episodes Standard Error 0.109	-1.12 Urgency incontinence episodes Standard Error 0.109
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Incontinence Episodes Per 24 Hours Week 12 [N=226; 232; 227]	-1.06 Urgency incontinence episodes Standard Error 0.105	-1.32 Urgency incontinence episodes Standard Error 0.104	-1.39 Urgency incontinence episodes Standard Error 0.104
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Incontinence Episodes Per 24 Hours Week 8 [N=231; 237; 236]	-1.02 Urgency incontinence episodes Standard Error 0.101	-1.33 Urgency incontinence episodes Standard Error 0.100	-1.39 Urgency incontinence episodes Standard Error 0.100

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 post baseline micturition measurement in the visit diary and at least 1 episode of urgency grade 3 or 4 at baseline. LOCF was not utilized for this analysis. N is the number of patients included at each time point.

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours Week 4 [N=412; 409; 423]	-0.90 Urgency episodes Standard Error 0.143	-0.97 Urgency episodes Standard Error 0.143	-1.47 Urgency episodes Standard Error 0.141
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours Week 8 [N=377; 393; 398]	-1.17 Urgency episodes Standard Error 0.162	-1.51 Urgency episodes Standard Error 0.159	-1.73 Urgency episodes Standard Error 0.158
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours Week 12 [N=364; 385; 385]	-1.60 Urgency episodes Standard Error 0.162	-1.72 Urgency episodes Standard Error 0.157	-1.99 Urgency episodes Standard Error 0.157

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Level of Urgency Week 4 [N=412; 409; 423]	-0.10 scores on a scale Standard Error 0.025	-0.12 scores on a scale Standard Error 0.025	-0.20 scores on a scale Standard Error 0.025
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Level of Urgency Week 12 [N=364; 385; 385]	-0.19 scores on a scale Standard Error 0.030	-0.23 scores on a scale Standard Error 0.029	-0.30 scores on a scale Standard Error 0.029
Change From Baseline to Week 4, Week 8 and Week 12 in Mean Level of Urgency Week 8 [N=377; 393; 398]	-0.15 scores on a scale Standard Error 0.029	-0.19 scores on a scale Standard Error 0.028	-0.26 scores on a scale Standard Error 0.028

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Week 4 [N=362; 362; 376]	-0.30 nocturia episodes Standard Error 0.059	-0.27 nocturia episodes Standard Error 0.058	0.38 nocturia episodes Standard Error 0.057
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Week 8 [N=329; 349; 354]	-0.45 nocturia episodes Standard Error 0.059	-0.41 nocturia episodes Standard Error 0.057	-0.44 nocturia episodes Standard Error 0.057
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Week 12 [N=321; 342; 344]	-0.54 nocturia episodes Standard Error 0.058	-0.50 nocturia episodes Standard Error 0.056	-0.52 nocturia episodes Standard Error 0.056
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours Final Visit (LOCF) [N=362; 362; 378]	-0.48 nocturia episodes Standard Error 0.058	-0.49 nocturia episodes Standard Error 0.058	-0.52 nocturia episodes Standard Error 0.057

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Week 4 [N=145; 136; 136]	-0.72 pads Standard Error 0.117	-0.59 pads Standard Error 0.121	-0.81 pads Standard Error 0.120
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Week 8 [N=131; 131; 128]	-0.97 pads Standard Error 0.119	-0.79 pads Standard Error 0.119	-1.16 pads Standard Error 0.120
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Week 12 [N=129; 129; 124]	-1.06 pads Standard Error 0.125	-0.89 pads Standard Error 0.125	-1.17 pads Standard Error 0.127
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours Final Visit (LOCF) [N=145; 136; 137]	-0.99 pads Standard Error 0.118	-0.83 pads Standard Error 0.122	-1.16 pads Standard Error 0.121

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=262 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=254 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=257 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 4 [N=262; 254; 255]	28.2 percentage of participants	31.5 percentage of participants	36.5 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 8 [N=236; 244; 241]	41.9 percentage of participants	44.7 percentage of participants	41.9 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 12 [N=231; 239; 232]	42.0 percentage of participants	46.9 percentage of participants	47.4 percentage of participants
Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Final Visit (LOCF) [N=262; 254; 257]	39.7 percentage of participants	45.7 percentage of participants	47.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

The percentage of participants with at least 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	Placebo n=262 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=254 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=255 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Final Visit (LOCF) [N=262; 254; 257]	59.2 percentage of participants	72.8 percentage of participants	70.0 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 4 [N=262; 254; 255]	46.6 percentage of participants	54.7 percentage of participants	61.6 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 8 [N=236; 244; 241]	62.7 percentage of participants	71.7 percentage of participants	71.4 percentage of participants
Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit Week 12 [N=231; 239; 232]	61.5 percentage of participants	74.1 percentage of participants	71.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug \& had a baseline \& at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for this analysis.

Percentage of participants with a decrease from Baseline to Final Visit in mean level of urgency at least as large as the pre-specified minimally important difference (MID). The MID was determined to be 0.24 for mean level of urgency. Mean level of urgency was derived from the 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 which ranged from 0 (No urgency) to 4 (Urge incontinence).

Outcome measures

Outcome measures
Measure	Placebo n=413 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Percentage of Responders for Mean Level of Urgency	36.6 percentage of participants	40.5 percentage of participants	44.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug \& had a baseline \& at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for this analysis.

Percentage of participants with a decrease from baseline to final visit in mean number of urgency episodes (grade 3 or 4) at least as large as the pre-specified minimally important difference (MID). The MID was determined to be 1.54 for mean number of urgency episodes (grade 3 or 4). The mean number of urgency episodes was derived from urgency episodes classified by the patient in a 3-day micturition diary as grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale where a score 3=severe urgency and 4=urge incontinence.

Outcome measures

Outcome measures
Measure	Placebo n=413 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Percentage of Responders for Number of Grade 3 or 4 Urgency Episodes	44.6 percentage of participants	47.1 percentage of participants	57.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Week 8 [N=376; 389; 391]	-15.1 scores on a scale Standard Error 0.92	-17.4 scores on a scale Standard Error 0.91	-18.5 scores on a scale Standard Error 0.90
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Week 12 [N=360; 380; 378]	-17.5 scores on a scale Standard Error 0.94	-18.0 scores on a scale Standard Error 0.91	-19.6 scores on a scale Standard Error 0.92
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Week 4 [N=402; 406; 418]	-12.2 scores on a scale Standard Error 0.82	-13.7 scores on a scale Standard Error 0.82	-12.7 scores on a scale Standard Error 0.80
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score Final Visit (LOCF) [N=405; 407; 422]	-16.0 scores on a scale Standard Error 0.90	-17.9 scores on a scale Standard Error 0.90	-18.8 scores on a scale Standard Error 0.88

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Week 4 [N=403; 408; 417]	8.8 scores on a scale Standard Error 0.73	11.4 scores on a scale Standard Error 0.73	9.2 scores on a scale Standard Error 0.72
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Final Visit (LOCF) [N=406; 408; 419]	13.0 scores on a scale Standard Error 0.80	14.3 scores on a scale Standard Error 0.79	14.2 scores on a scale Standard Error 0.78
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Week 8 [N=373; 393; 390]	12.1 scores on a scale Standard Error 0.82	14.3 scores on a scale Standard Error 0.80	13.8 scores on a scale Standard Error 0.80
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score Week 12 [N=360; 383; 377]	13.8 scores on a scale Standard Error 0.84	14.4 scores on a scale Standard Error 0.81	14.7 scores on a scale Standard Error 0.82

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Week 12 [N=112; 118; 118]	0.6 percent work time missed Standard Deviation 14.42	0.7 percent work time missed Standard Deviation 15.63	-1.5 percent work time missed Standard Deviation 7.45
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Final Visit (LOCF) [N=119; 122; 123]	0.6 percent work time missed Standard Deviation 14.01	0.7 percent work time missed Standard Deviation 15.37	-1.3 percent work time missed Standard Deviation 7.35

SECONDARY outcome

Timeframe: Baseline and Week 12

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

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with work productivity in the last 7 days. Percent 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	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Week 12 [N=123; 130; 128]	-11.6 percent impairment while working Standard Deviation 26.44	-10.2 percent impairment while working Standard Deviation 22.01	-13.0 percent impairment while working Standard Deviation 23.89
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working Final Visit (LOCF) [N=130; 135; 134]	-11.5 percent impairment while working Standard Deviation 26.09	-10.1 percent impairment while working Standard Deviation 21.67	-13.1 percent impairment while working Standard Deviation 23.60

SECONDARY outcome

Timeframe: Baseline and Week 12

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

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with work productivity in the last 7 days. Percent 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	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Week 12 [N=110; 115; 118]	-14.1 percent overall work impairment Standard Deviation 26.57	-11.0 percent overall work impairment Standard Deviation 23.65	-13.3 percent overall work impairment Standard Deviation 24.45
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Final Visit (LOCF) [N=117; 119; 123]	-13.8 percent overall work impairment Standard Deviation 26.18	-10.8 percent overall work impairment Standard Deviation 23.33	-13.3 percent overall work impairment Standard Deviation 24.21

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Week 12 [N=353; 366; 362]	-11.4 percent activity impairment Standard Deviation 26.66	-12.3 percent activity impairment Standard Deviation 26.10	-13.1 percent activity impairment Standard Deviation 26.22
Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment Final Visit (LOCF) [N=373; 376; 378]	-11.0 percent activity impairment Standard Deviation 26.87	-11.9 percent activity impairment Standard Deviation 26.18	-13.3 percent activity impairment Standard Deviation 26.12

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for this analysis.

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> Some problems	39 participants	45 participants	48 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 No problem -> Some problems	16 participants	20 participants	33 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> 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 No problem -> Missing data	6 participants	1 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Some problems -> No problems	22 participants	31 participants	36 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	0 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score No problem -> No problem	327 participants	310 participants	304 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score Confined -> 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 -> 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 -> 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 -> 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	3 participants	3 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 Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for this analysis.

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score No problem -> Unable to wash or dress myself	0 participants	0 participants	1 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 Unable to wash or dress myself -> No 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 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 -> 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 No problem -> No problem	389 participants	385 participants	403 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score No problem -> Some problems	5 participants	10 participants	6 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score No problem -> Missing data	7 participants	1 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	5 participants	3 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score Some problems -> Some problems	6 participants	8 participants	9 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 -> Some problems	0 participants	0 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score Unable to wash or dress -> 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 Missing data -> No problem	3 participants	3 participants	0 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

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for this analysis.

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	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> Some problems	27 participants	27 participants	31 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> Some problems	30 participants	35 participants	44 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Missing data -> No problem	3 participants	2 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> Missing data	1 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Unable to perform usual activities -> No problems	0 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	0 participants	1 participants	1 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	0 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 -> Missing data	0 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Missing data -> Some problems	0 participants	1 participants	0 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
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> No problem	313 participants	303 participants	293 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	0 participants	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score No problem -> Missing data	6 participants	0 participants	4 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems -> No problems	35 participants	38 participants	51 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score Some problems->Unable to perform usual activities	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for this analysis.

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> No pain	209 participants	200 participants	185 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> Moderate pain	34 participants	36 participants	41 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	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score No pain -> Missing data	4 participants	0 participants	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> No pain	58 participants	65 participants	75 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain -> Moderate pain	85 participants	92 participants	87 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	0 participants	7 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Moderate pain ->Missing data	3 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> No pain	0 participants	0 participants	5 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> Moderate pain	9 participants	4 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	2 participants	5 participants	5 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Extreme pain -> Missing data	0 participants	1 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Missing data-> No pain	2 participants	1 participants	1 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score Missing data -> Moderate pain	2 participants	2 participants	0 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 Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. LOCF was used for this analysis.

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	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Moderately anxious -> Not anxious	52 participants	50 participants	58 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Extremely anxious -> Not anxious	1 participants	1 participants	2 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Extremely anxious -> Extremely anxious	4 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 -> Not anxious	239 participants	243 participants	225 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Not anxious -> Moderately anxious	20 participants	29 participants	33 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Not anxious -> Extremely anxious	1 participants	1 participants	3 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Not anxious -> Missing data	3 participants	0 participants	4 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Moderately anxious -> Moderately anxious	77 participants	74 participants	89 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Moderately anxious -> Extremely anxious	4 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 -> Missing data	4 participants	0 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Extremely anxious -> Moderately anxious	6 participants	5 participants	6 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	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Missing data -> Not anxious	3 participants	2 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	1 participants	0 participants
Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score Missing data -> Extremely anxious	0 participants	0 participants	0 participants
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 Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Week 4 [N=399; 401; 411]	0.38 scores on a scale Standard Deviation 15.312	2.43 scores on a scale Standard Deviation 13.929	1.67 scores on a scale Standard Deviation 13.712
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Week 8 [N=368; 386; 383]	3.14 scores on a scale Standard Deviation 15.389	3.95 scores on a scale Standard Deviation 15.766	4.13 scores on a scale Standard Deviation 14.795
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Week 12 [N=359; 379; 375]	4.26 scores on a scale Standard Deviation 15.535	4.40 scores on a scale Standard Deviation 15.282	5.59 scores on a scale Standard Deviation 17.112
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Final Visit (LOCF) [N=404; 406; 419]	3.43 scores on a scale Standard Deviation 16.076	4.12 scores on a scale Standard Deviation 15.082	4.96 scores on a scale Standard Deviation 17.225

SECONDARY outcome

Timeframe: Baseline and Week 12

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

The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. LS means are from an ANCOVA model with treatment group, gender, and geographical regions as fixed factors and baseline as a covariate. A negative change from Baseline score indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) Week 12 [N=357; 381; 378]	-0.7 scores on a scale Standard Error 0.06	-0.8 scores on a scale Standard Error 0.06	-0.8 scores on a scale Standard Error 0.06
Change From Baseline to Week 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) Final Visit (LOCF) [N=376; 391; 395]	-0.7 scores on a scale Standard Error 0.06	-0.8 scores on a scale Standard Error 0.06	-0.7 scores on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and Week 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS) Week 12 [N=357; 379; 371]	1.18 scores on a scale Standard Error 0.156	1.58 scores on a scale Standard Error 0.151	1.94 scores on a scale Standard Error 0.153
Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS) Final Visit (LOCF) [N=377; 389; 388]	1.05 scores on a scale Standard Error 0.154	1.54 scores on a scale Standard Error 0.152	1.88 scores on a scale Standard Error 0.152

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12

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

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

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Final Visit (LOCF) [N=410; 410; 424]	-0.0 Physician visits Standard Deviation 0.18	0.0 Physician visits Standard Deviation 0.15	-0.0 Physician visits Standard Deviation 0.12
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Week 4 [N=410; 410; 424]	0.0 Physician visits Standard Deviation 0.30	-0.0 Physician visits Standard Deviation 0.12	-0.0 Physician visits Standard Deviation 0.16
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Week 8 [N=381; 394; 399]	-0.0 Physician visits Standard Deviation 0.18	-0.0 Physician visits Standard Deviation 0.13	0.0 Physician visits Standard Deviation 0.16
Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician Week 12 [N=364; 386; 382]	-0.0 Physician visits Standard Deviation 0.17	0.0 Physician visits Standard Deviation 0.14	-0.0 Physician visits Standard Deviation 0.13

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. This assessment was completed by English speaking patients in the United States only. LOCF was used for the Final visit analysis.

The Clinician Global Impression Scale (CGI) assessed the change in the patient's bladder symptoms since the start of the study and was completed by the physician at Baseline and at Week 12/end of treatment. The degree of change was categorized as one of the following: 'Very much improved', 'Much improved', 'Minimally improved', 'No change', 'Minimally worse', 'Much worse', or 'Very much worse'.

Outcome measures

Outcome measures
Measure	Placebo n=188 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=194 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=202 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: Much Improved	48 participants	52 participants	58 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: Minimally Improved	53 participants	59 participants	42 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: Total	182 participants	188 participants	196 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: Very Much Improved	0 participants	2 participants	0 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: Much Improved	6 participants	6 participants	3 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: Minimally Improved	31 participants	32 participants	33 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: No Change	126 participants	134 participants	148 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: Minimally Worse	13 participants	9 participants	8 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: Much Worse	3 participants	5 participants	4 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Baseline: Very Much Worse	3 participants	0 participants	0 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: Total	158 participants	175 participants	171 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: Very Much Improved	13 participants	22 participants	28 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: No Change	32 participants	37 participants	41 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: Minimally Worse	6 participants	4 participants	2 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: Much Worse	5 participants	1 participants	0 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Week 12: Very Much Worse	1 participants	0 participants	0 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: Total	171 participants	183 participants	185 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: Very Much Improved	13 participants	22 participants	30 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: Much Improved	49 participants	54 participants	60 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: Minimally Improved	58 participants	60 participants	48 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: No Change	38 participants	41 participants	44 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: Minimally Worse	6 participants	4 participants	2 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: Much Worse	6 participants	2 participants	1 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale Final Visit: Very Much Worse	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. This assessment was completed by English speaking patients in the United States only. LOCF was used for the Final visit analysis.

The patient global impression (PGI) scale assessed the change in bladder symptoms since the start of the study and was completed by the patient at Baseline and at Week 12/end of treatment. The degree of change was categorized as one of the following: 'Very much improved', 'Much improved', 'Minimally improved', 'No change', 'Minimally worse', 'Much worse', or 'Very much worse'.

Outcome measures

Outcome measures
Measure	Placebo n=188 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=194 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=202 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Week 12: Minimally Improved	49 participants	57 participants	45 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Final Visit: Much Worse	8 participants	2 participants	3 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: Total	188 participants	194 participants	202 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: Very Much Improved	4 participants	4 participants	2 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: Much Improved	14 participants	15 participants	12 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: Minimally Improved	48 participants	52 participants	42 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: No Change	105 participants	105 participants	124 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: Minimally Worse	6 participants	11 participants	13 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: Much Worse	5 participants	5 participants	9 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Baseline: Very Much Worse	6 participants	2 participants	0 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Week 12: Total	160 participants	176 participants	174 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Week 12: Very Much Improved	18 participants	23 participants	37 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Week 12: Much Improved	54 participants	57 participants	48 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Week 12: No Change	26 participants	33 participants	42 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Week 12: Minimally Worse	5 participants	5 participants	1 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Week 12: Much Worse	8 participants	1 participants	1 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Final Visit: Total	173 participants	185 participants	188 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Final Visit: Very Much Improved	18 participants	23 participants	39 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Final Visit: Much Improved	54 participants	60 participants	51 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Final Visit: Minimally Improved	52 participants	57 participants	49 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Final Visit: No Change	35 participants	36 participants	45 participants
Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale Final Visit: Minimally Worse	6 participants	7 participants	1 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The full analysis set included all patients who took at least 1 dose of double-blind study drug and had a baseline and at least 1 postbaseline micturition measurement in the visit diary. This assessment was completed by English speaking patients in the United States only. LOCF was used for the Final visit analysis.

The patient global impression (PGI) scale assessed the change in the patient's overall condition since the start of the study and was completed by the patient at Baseline and at Week 12/end of treatment. The degree of change was categorized as one of the following: 'Very much improved', 'Much improved', 'Minimally improved', 'No change', 'Minimally worse', 'Much worse', or 'Very much worse'.

Outcome measures

Outcome measures
Measure	Placebo n=188 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=194 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=202 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: Total	188 participants	194 participants	202 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: Very Much Improved	3 participants	5 participants	2 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: Minimally Improved	46 participants	47 participants	41 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: No Change	112 participants	115 participants	132 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: Minimally Worse	6 participants	12 participants	11 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: Much Worse	3 participants	1 participants	5 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: Very Much Worse	5 participants	2 participants	0 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Week 12: Total	160 participants	176 participants	174 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Week 12: Very Much Improved	19 participants	19 participants	36 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Week 12: Much Improved	47 participants	60 participants	51 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Week 12: Minimally Improved	50 participants	54 participants	47 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Week 12: No Change	33 participants	39 participants	38 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Week 12: Much Worse	7 participants	1 participants	0 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Final Visit: Total	173 participants	185 participants	188 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Final Visit: Very Much Improved	19 participants	19 participants	38 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Final Visit: Much Improved	47 participants	62 participants	54 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Final Visit: Minimally Improved	53 participants	54 participants	49 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Final Visit: No Change	42 participants	43 participants	43 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Final Visit: Minimally Worse	4 participants	5 participants	3 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Final Visit: Much Worse	8 participants	2 participants	1 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Baseline: Much Improved	13 participants	12 participants	11 participants
Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale Week 12: Minimally Worse	4 participants	3 participants	2 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

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

The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. Improvement was defined as at least a 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	Placebo n=415 Participants Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=410 Participants Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=426 Participants Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Improvement: Final Visit [N=376; 391; 395]	55.1 percentage of participants	52.7 percentage of participants	55.2 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Major Improvement: Week 12 [N=357; 381; 378]	22.1 percentage of participants	23.6 percentage of participants	25.7 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Improvement: Week 12 [N=357; 381; 378]	56.0 percentage of participants	52.8 percentage of participants	55.8 percentage of participants
Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit Major Improvement: Final Visit [N=376; 391; 395]	21.5 percentage of participants	23.0 percentage of participants	25.6 percentage of participants

Adverse Events

Placebo

Serious events: 12 serious events

Other events: 51 other events

Deaths: 0 deaths

Mirabegron 25 mg

Serious events: 7 serious events

Other events: 64 other events

Deaths: 0 deaths

Mirabegron 50 mg

Serious events: 4 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=433 participants at risk Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=432 participants at risk Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=440 participants at risk Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Vascular disorders Hypertension	8.5% 37/433 • 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.	11.3% 49/432 • Adverse events starting or worsening in the period from first double-blind study drug intake until 30 days after last double-blind study drug intake.	10.7% 47/440 • 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 Nasopharyngitis	3.2% 14/433 • 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.	3.5% 15/432 • 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.	5.7% 25/440 • 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, Europe

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

Measure	Placebo n=433 participants at risk Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.	Mirabegron 25 mg n=432 participants at risk Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Mirabegron 50 mg n=440 participants at risk Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Infections and infestations Bronchitis acute	0.00% 0/433 • 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.	0.00% 0/432 • 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.	0.23% 1/440 • 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 Diverticulitis	0.00% 0/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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 Pyelonephritis acute	0.00% 0/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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 Viral upper respiratory tract infection	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Cardiac disorders Atrial fibrillation	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.23% 1/440 • 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 Inguinal hernia	0.00% 0/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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 Abdominal pain	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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 Pancreatitis	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
General disorders Chest pain	0.23% 1/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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.
General disorders Non-cardiac chest pain	0.00% 0/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/433 • 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.	0.00% 0/432 • 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.	0.23% 1/440 • 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.
Injury, poisoning and procedural complications Ligament rupture	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Investigations Liver function test abnormal	0.00% 0/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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.
Investigations Laparoscopy	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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.
Psychiatric disorders Bipolar disorder	0.00% 0/433 • 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.	0.00% 0/432 • 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.	0.23% 1/440 • 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.
Psychiatric disorders Delirium	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Psychiatric disorders Depression	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Vascular disorders Orthostatic hypotension	0.00% 0/433 • 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.	0.23% 1/432 • 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.	0.00% 0/440 • 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.
Nervous system disorders Carotid artery stenosis	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Nervous system disorders Cerebral ischaemia	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Nervous system disorders Cerebrovascular accident	0.46% 2/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Nervous system disorders Grand mal convulsion	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Nervous system disorders Hemianopia homonymous	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Nervous system disorders Petit mal epilepsy	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.
Surgical and medical procedures Appendicectomy	0.23% 1/433 • 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.	0.00% 0/432 • 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.	0.00% 0/440 • 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.