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

• Sponsor: Astellas Pharma Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00688688
• Collaborator: (none)
• Enrollment: 2,792
• Locations: 308
• Arms: 3
• Actual Duration (Months): 24.3
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The study is intended to test the safety, tolerability, efficacy of two doses of long term once daily (qd) treatment of Mirabegron in patients with symptoms of overactive bladder and secondly to compare these with active comparator.

Condition or Disease	Intervention/Treatment	Phase
Urinary Bladder, Overactive	Drug: Mirabegron; Drug: Tolterodine; Drug: Placebo to Mirabegron; Drug: Placebo to Tolterodine	Phase 3

Detailed Description

Patients who completed 178-CL-046 (NCT00689104) or 178-CL-047 (NCT00662909) or new patients could be enrolled in this study if eligible.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2792 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel Group, Active Controlled, Multi-center Long-term Study to Assess the Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) 50 mg qd and 100 mg qd in Subjects With Symptoms of Overactive Bladder
• Actual Study Start Date: Apr 25, 2008
• Actual Primary Completion Date: May 6, 2010
• Actual Study Completion Date: May 6, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirabegron 50 mg Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Drug: Mirabegron; Tablets; Other Names: Myrbetriq YM178 ; Drug: Placebo to Tolterodine; Matching tolterodine placebo capsules.
Experimental: Mirabegron 100 mg Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Drug: Mirabegron; Tablets; Other Names: Myrbetriq YM178 ; Drug: Placebo to Tolterodine; Matching tolterodine placebo capsules.
Active Comparator: Tolterodine ER 4 mg Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Drug: Tolterodine; Extended release capsules; Drug: Placebo to Mirabegron; Matching mirabegron placebo tablets.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs) [From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.]

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

Secondary Outcome Measures

1. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours [Baseline and Months 1, 3, 6, 9 and 12]

   The average number of micturitions (urinations) per 24 hours was derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a micturition diary for 3-days prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. Least squares (LS) means were generated from the analysis of covariance (ANCOVA) model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.

2. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours [Baseline and Months 1, 3, 6, 9 and 12]

   The average number of incontinence episodes (any involuntary leakage of urine) per day was derived from the number of incontinence episodes recorded by the patient in a micturition diary for 3-days prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. Least squares (LS) means were generated from the analysis of covariance (ANCOVA) model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.

3. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition [Baseline and Months 1, 3, 6, 9 and 12]

   The average volume voided per micturition was calculated from the volume of each micturition measured by the patient and recorded in a micturition diary for 3 days prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. LS means were generated from the ANCOVA model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.

4. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours [Baseline and Months 1, 3, 6, 9 and 12]

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

5. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours [Baseline and Months 1, 3, 6, 9 and 12]

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

6. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency [Baseline and Months 1, 3, 6, 9 and 12]

   Average of patients' ratings on the degree of urgency associated with each micturition and/or incontinence episode recorded in a 3-day micturition diary according to the Patient Perception of Intensity of Urgency Scale: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. LS means are generated from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.

7. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours [Baseline and Months 1, 3, 6, 9 and 12]

   The average number of times a patient records a new pad used per day during the 3-day micturition diary period. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.

8. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours [Baseline and Months 1, 3, 6, 9 and 12]

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

9. Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit [Months 1, 3, 6, 9 and 12]

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

10. Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit [Baseline and Months 1, 3, 6, 9 and 12]

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

11. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score [Baseline and Months 1, 3, 6, 9 and 12]

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

12. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score [Baseline and Months 1, 3, 6, 9 and 12]

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

13. Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC) [Baseline and Month 12]

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

14. Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS) [Baseline and Month 12]

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

15. Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed [Baseline and Months 3, 6 and 12]

    The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with work productivity in the last 7 days. Percent 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.

16. Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working [Baseline and Months 3, 6 and 12]

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

17. Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment [Baseline and Months 3, 6 and 12]

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

18. Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment [Baseline and Months 3, 6 and 12]

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

19. Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score [Baseline and Month 12]

    The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and evaluating health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems 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.

20. Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score [Baseline and Month 12]

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

21. Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score [Baseline and Month 12]

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

22. Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score [Baseline and Month 12]

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

23. Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score [Baseline and Month 12]

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

24. Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) [Baseline and Months 1, 3, 6, 9 and 12]

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

25. Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician [Baseline and Months 3, 6 and 12]

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

26. Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) [Baseline and Month 12]

    The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. Improvement was defined as at least a one point improvement from Baseline to post-baseline and a major improvement was defined as at least a two point improvement from Baseline to post-baseline in PPBC score.

27. Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram [From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient is willing and able to complete the micturition diary and questionnaires correctly

• Patient has symptoms of overactive bladder for ≥ 3 months

• Patient experiences frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period

• Patient must experience at least 3 episodes of urgency (grade 3 or 4) with or without incontinence, during the 3-day micturition diary period

Exclusion Criteria:

• Patient is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential, sexually active and not practicing a highly reliable method of birth control

• Patient has significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor

• Patient has an indwelling catheter or practices intermittent self-catheterization

• Patient has diabetic neuropathy

• Patient has evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs

• Patient receives non-drug treatment including electro-stimulation therapy

• Patient has severe hypertension

• Patient has a known or suspected hypersensitivity to tolterodine, other anticholinergics, YM178, other beta-adrenoreceptor (ß-AR) agonists, or lactose or any of the other inactive ingredients

• Patient has been treated with any investigational drug or device within 30 days (90 days in the UK for all clinical studies except 178-CL-046)

• Patient had an average total daily urine volume > 3000 mL as recorded in the 3-day micturition diary period

• Patient has serum creatinine >150 umol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2x upper limit of normal range (ULN), or gamma-glutamyl transpeptidase (γ-GT) > 3x ULN

• Patient has a clinically significant abnormal electrocardiogram (ECG)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Homewood	Alabama	United States	35209
2		Huntsville	Alabama	United States	35801
3		Mobile	Alabama	United States	36608
4		Montgomery	Alabama	United States	36117
5		Anchorage	Alaska	United States	99508
6		Phoenix	Arizona	United States	85051
7		Tucson	Arizona	United States	85712
8		Tucson	Arizona	United States	85741
9		Atherton	California	United States	94027
10		Beverly Hills	California	United States	90211
11		Buena Park	California	United States	90620
12		Fresno	California	United States	93720
13		La Mesa	California	United States	91942
14		Mission Hills	California	United States	91345
15		Newport Beach	California	United States	92660
16		Orange	California	United States	92869
17		Sacramento	California	United States	95831
18		San Bernardino	California	United States	92404
19		San Diego	California	United States	92108
20		San Diego	California	United States	92120
21		Tarzana	California	United States	91356
22		Torrance	California	United States	90505
23		Aurora	Colorado	United States	80012
24		Denver	Colorado	United States	80211
25		Denver	Colorado	United States	80218
26		Englewood	Colorado	United States	80112
27		New Britain	Connecticut	United States	06052
28		Waterbury	Connecticut	United States	06708
29		Aventura	Florida	United States	33180
30		Clearwater	Florida	United States	33756
31		Clearwater	Florida	United States	33761
32		Fort Myers	Florida	United States	33916
33		Miami	Florida	United States	33136
34		Ocala	Florida	United States	34471
35		Orlando	Florida	United States	32803
36		Pembroke Pines	Florida	United States	33024
37		Pembroke Pines	Florida	United States	33027
38		Sarasota	Florida	United States	34237
39		Tallahassee	Florida	United States	32308
40		Tampa	Florida	United States	33606
41		Wellington	Florida	United States	33414
42		West Palm Beach	Florida	United States	33407
43		Atlanta	Georgia	United States	30328
44		Decatur	Georgia	United States	30034
45		Marietta	Georgia	United States	30060
46		Roswell	Georgia	United States	30076
47		Coeur d'Alene	Idaho	United States	83814
48		Idaho Falls	Idaho	United States	83404
49		Melrose Park	Illinois	United States	60160
50		Fort Wayne	Indiana	United States	46825
51		Jeffersonville	Indiana	United States	47130
52		Newburgh	Indiana	United States	47630
53		Des Moines	Iowa	United States	50309
54		Wichita	Kansas	United States	57207
55		Greenbelt	Maryland	United States	20770
56		Watertown	Massachusetts	United States	02472
57		North Kansas City	Missouri	United States	64116
58		Billings	Montana	United States	59102
59		Lincoln	Nebraska	United States	68516
60		Omaha	Nebraska	United States	68114
61		Las Vegas	Nevada	United States	89148
62		New Brunswick	New Jersey	United States	08901
63		West Orange	New Jersey	United States	07052
64		Albuquerque	New Mexico	United States	87109
65		Albany	New York	United States	12205
66		Albany	New York	United States	12208
67		Endwell	New York	United States	13760
68		Garden City	New York	United States	11530
69		Kingston	New York	United States	12401
70		New York	New York	United States	10016
71		Poughkeepsie	New York	United States	12601
72		Cary	North Carolina	United States	27518
73		Charlotte	North Carolina	United States	28209
74		Concord	North Carolina	United States	28025
75		Wilmington	North Carolina	United States	28401
76		Winston-Salem	North Carolina	United States	27103
77		Fargo	North Dakota	United States	58104
78		Cincinnati	Ohio	United States	45212
79		Cleveland	Ohio	United States	44122
80		Columbus	Ohio	United States	43214
81		Lyndhurst	Ohio	United States	44124
82		Wadsworth	Ohio	United States	44281
83		Bethany	Oklahoma	United States	73008
84		Edmond	Oklahoma	United States	73008
85		Edmond	Oklahoma	United States	73034
86		Bala-Cynwyd	Pennsylvania	United States	19004
87		Jenkintown	Pennsylvania	United States	19046
88		Lancaster	Pennsylvania	United States	17604
89		Reading	Pennsylvania	United States	19611
90		Uniontown	Pennsylvania	United States	15401
91		Warwick	Rhode Island	United States	02886
92		Greer	South Carolina	United States	29650
93		Mount Pleasant	South Carolina	United States	29464
94		Simpsonville	South Carolina	United States	29681
95		Bristol	Tennessee	United States	37620
96		Arlington	Texas	United States	76017
97		Austin	Texas	United States	78759
98		Corpus Christi	Texas	United States	78414
99		Dallas	Texas	United States	75231
100		Houston	Texas	United States	77024
101		Salt Lake City	Utah	United States	84107
102		Virginia Beach	Virginia	United States	23454
103		Mountlake Terrace	Washington	United States	98043
104		Seattle	Washington	United States	98166
105		Spokane	Washington	United States	99204
106		Tacoma	Washington	United States	98405
107		Woolloongabba		Australia
108		Graz		Austria	8036
109		Innsbruck		Austria	6020
110		Linz		Austria	4020
111		Minsk		Belarus	220036
112		Minsk		Belarus	223041
113		Antwerp		Belgium	2020
114		Antwerp		Belgium	2030
115		Edegem		Belgium	2650
116		Gent		Belgium	9000
117		Kortrijk		Belgium	8500
118		Leper		Belgium	8900
119		Leuven		Belgium	3000
120		Liege		Belgium	4000
121		Sint Truiden		Belgium	3800
122		Calgary	Alberta	Canada	T2V 4R6
123		Edmonton	Alberta	Canada	T5H 3V9
124		Surrey	British Columbia	Canada	V3V 1N1
125		Victoria	British Columbia	Canada	V8T 5G1
126		Victoria	British Columbia	Canada	V8V 3N1
127		Saint John	New Brunswick	Canada	E2L 3J8
128		Dartmouth	Nova Scotia	Canada	B2W 2S7
129		Kentville	Nova Scotia	Canada	B4N 4K9
130		Barrie	Ontario	Canada	L4M 7G1
131		Brampton	Ontario	Canada	L6T 4S5
132		Kitchener	Ontario	Canada	N2N 2B9
133		Markham	Ontario	Canada	L6B 1A1
134		Newmarket	Ontario	Canada	L3X 1W1
135		North Bay	Ontario	Canada	P1B 7K8
136		Oshawa	Ontario	Canada	L1H 1B9
137		Saint Denis	Ontario	Canada	H2X 3J4
138		Thunder Bay	Ontario	Canada	P7E 6E7
139		Toronto	Ontario	Canada	M4N 3M5
140		Toronto	Ontario	Canada	M5T 2S8
141		Granby	Quebec	Canada	J2G 8Z9
142		Montreal	Quebec	Canada	H3A 1A1
143		Point Claire	Quebec	Canada	H9R 4S3
144		Montreal		Canada
145		Brno		Czechia	60200
146		Melnik		Czechia	27601
147		Olomouc		Czechia	77200
148		Ostrava-Poruba		Czechia	70853
149		Plzen		Czechia	30599
150		Prague		Czechia	12851
151		Prague		Czechia	14056
152		Prague		Czechia	18081
153		Steti		Czechia	41108
154		Usti nad Labem		Czechia	40001
155		Aalborg		Denmark	9100
156		Aarhus		Denmark	8200
157		Glostrup		Denmark	2600
158		Roskilde		Denmark
159		Helsinki		Finland	00029
160		Oulu		Finland	90220
161		Tampere		Finland	33521
162		Turku		Finland	20100
163		Paris	Cedex 10	France	75020
164		Colmar		France	68024
165		Marseille Cedex 9		France	13274
166		Mulhouse		France	68070
167		Nimes Cedex 9		France	30029
168		Orleans Cedex 2		France	45067
169		Paris-Cedex12		France	75571
170		Saint Priest en Jarez		France	42055
171		Strasbourg		France	67000
172		Toulouse Cedex 9		France	31059
173		AIchach		Germany	86551
174		Bad Ems		Germany	56130
175		Bautzen		Germany	02625
176		Berlin		Germany	13347
177		Duisburg		Germany	47051
178		Frankfurt		Germany	65933
179		Ganderkesee		Germany	27777
180		Hagenow		Germany	19230
181		Halle/Saale		Germany	06132
182		Hamburg		Germany	20253
183		Henningsdorf		Germany	16761
184		Hettstedt		Germany	06333
185		Kiel		Germany
186		Koblenz		Germany	56068
187		Leipzig		Germany	04105
188		Lutherstadt Eisleben		Germany	06295
189		Muenchen-Bogenhausen		Germany	81925
190		Munich		Germany
191		Neustadt I. Sachsen		Germany	01844
192		Oranienburg		Germany	16151
193		Radebeul		Germany	01445
194		Sangerhausen		Germany	06526
195		Trier		Germany	54290
196		Uetersen		Germany	25436
197		Budapest		Hungary	1047
198		Budapest		Hungary	1076
199		Nyiregyhaza		Hungary	4400
200		Sopron		Hungary
201		Szeged		Hungary	6725
202		Szekesfehervar		Hungary	8000
203		Szekszard		Hungary	7100
204		Tatabanya		Hungary	2800
205		Reykjavik		Iceland	101
206		Dublin 9		Ireland
207		Mullingar		Ireland
208		Bari		Italy	70124
209		Catanzaro		Italy	88100
210		Genoa		Italy	16128
211		Latina		Italy	04100
212		Milan		Italy	20142
213		Modena		Italy	41100
214		Naples		Italy	80131
215		Perugia		Italy	06122
216		Treviglio		Italy	24047
217		Varese		Italy	21100
218		Liepaja		Latvia
219		Riga		Latvia
220		Kaunas		Lithuania
221		Amsterdam		Netherlands	1105 AZ
222		Apeldoorn		Netherlands	7334 DZ
223		Eindhoven		Netherlands	5623 EJ
224		Enschede		Netherlands	7511 JX
225		Leiden		Netherlands	2334 CK
226		Nijmegen		Netherlands	6532 SZ
227		Sneek		Netherlands	8600 BA
228		Tilburg		Netherlands	5022 GC
229		Winterswijk		Netherlands	7101 BN
230		Bergen		Norway	5021
231		Drammen		Norway	3016
232		Hamar		Norway	2317
233		Oslo		Norway	0257
234		Tonsberg		Norway	3103
235		Bialystok		Poland	15-278
236		Lodz		Poland	93-338
237		Lodz		Poland	93-513
238		Lublin		Poland	20-954
239		Warsaw		Poland	00-846
240		Warsaw		Poland	02-005
241		Warsaw		Poland	02-507
242		Warsaw		Poland
243		Wroclaw		Poland	50-556
244		Amadora		Portugal	2700
245		Porto		Portugal	4099-005
246		Tomar		Portugal	2304-909
247		Bucharest		Romania	22328
248		Bucharest		Romania
249		Lasi		Romania
250		Oradea		Romania
251		Moscow		Russian Federation	101000
252		Moscow		Russian Federation	105425
253		Moscow		Russian Federation	111020
254		Moscow		Russian Federation	111123
255		Moscow		Russian Federation	117049
256		Moscow		Russian Federation	117815
257		Moscow		Russian Federation	119435
258		Moscow		Russian Federation	123836
259		Moscow		Russian Federation	125206
260		St Petersburg		Russian Federation	197089
261		St. Petersburg		Russian Federation	115516
262		St. Petersburg		Russian Federation	198013
263		Martin		Slovakia	03659
264		Poprad		Slovakia	05801
265		Skalica		Slovakia	90982
266		Trencin		Slovakia	91101
267		Zilina		Slovakia	01207
268		Hatfield		South Africa
269		Lyttelton		South Africa
270		Paarl		South Africa
271		Pietermaritzburg		South Africa
272		Roodepoort		South Africa
273		Barcelona		Spain	08020
274		Barcelona		Spain	08036
275		Bilbao		Spain	48013
276		Getafe		Spain	28905
277		Madrid		Spain	28016
278		Madrid		Spain	28046
279		Mataro		Spain	8304
280		Miranda de Ebro		Spain	09200
281		Sevilla		Spain	41013
282		Toledo		Spain	45071
283		Valencia		Spain	46010
284		Huddinge		Sweden	75185
285		Orebro		Sweden	70185
286		Skovde		Sweden	54130
287		Sonkoping		Sweden	11883
288		Stockholm		Sweden	14186
289		Stockholm		Sweden	17176
290		Stockholm		Sweden	18288
291		Umea		Sweden	90185
292		Frauenfeld		Switzerland	8501
293		Luzern		Switzerland	6000
294		Kiev		Ukraine	01023
295		Kiev		Ukraine	04053
296		Bristol		United Kingdom	B15 2TG
297		Chorley		United Kingdom	PR7 7NA
298		Croydon		United Kingdom	CR7 7YE
299		Liverpool		United Kingdom	L22 OLG
300		London		United Kingdom	SE5 9RS
301		London		United Kingdom	W2 2YP
302		Manchester		United Kingdom	M15 6SX
303		Newcastle Upon Tyne		United Kingdom	NE7 7DN
304		Northwood		United Kingdom	HA6 2RN
305		Reading		United Kingdom	RG1 5AN
306		Reading		United Kingdom	RG2 7AG
307		Sheffield		United Kingdom	S10 2JF
308		Swansea		United Kingdom	SA6 6NL

Sponsors and Collaborators

• Astellas Pharma Inc

Investigators

• Study Director: Central Contact, Astellas Pharma Europe B.V.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Link to results on Astellas Clinical Study Results website

Publications

• Chapple CR, Kaplan SA, Mitcheson D, Klecka J, Cummings J, Drogendijk T, Dorrepaal C, Martin N. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder. Eur Urol. 2013 Feb;63(2):296-305. doi: 10.1016/j.eururo.2012.10.048. Epub 2012 Nov 6.

• Responsible Party: Astellas Pharma Inc
• ClinicalTrials.gov Identifier: NCT00688688
• Other Study ID Numbers: 178-CL-049; 2007-001452-39
• First Posted: Jun 3, 2008
• Last Update Posted: Dec 11, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Astellas Pharma Inc: Frequency; Overactive Bladder; Urgency; Urinary urge incontinence; Urinary incontinence; Micturition
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Mirabegron; Tolterodine Tartrate

Study Results

Participant Flow

Recruitment Details	Patients who completed the 12-week treatment and safety follow-up periods of studies 178-CL-046 (NCT00689104) or 178-CL-047 (NCT00662909), as well as patients that did not participate in these studies were enrolled into this study if they met all inclusion criteria and none of the exclusion criteria.
Pre-assignment Detail	After screening, 2792 patients took placebo run-in study drug in a 2-week, single-blind, placebo run-in period. On completion of the run-in period, 2452 eligible patients were randomly assigned to receive mirabegron 50 mg, or mirabegron 100 mg or tolterodine ER 4 mg once daily for 12 months.

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

Baseline Characteristics

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg	Total
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.	Total of all reporting groups
Overall Participants	812	820	812	2444
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (12.56)	60.1 (11.92)	59.6 (12.47)	59.6 (12.32)
Sex: Female, Male (Count of Participants)
Female	602 74.1%	608 74.1%	600 73.9%	1810 74.1%
Male	210 25.9%	212 25.9%	212 26.1%	634 25.9%
Type of overactive bladder (OAB) (participants) [Number]
Urge incontinence	296 36.5%	305 37.2%	317 39%	918 37.6%
Mixed	232 28.6%	228 27.8%	210 25.9%	670 27.4%
Frequency	284 35%	287 35%	285 35.1%	856 35%
Duration of OAB symptoms (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	87.4 (96.28)	87.9 (91.52)	83.8 (87.34)	86.4 (91.77)
Summary of previous treatment (participants) [Number]
Placebo	190 23.4%	174 21.2%	180 22.2%	544 22.3%
Mirabegron 50 mg	170 20.9%	180 22%	171 21.1%	521 21.3%
Mirabegron 100 mg	183 22.5%	198 24.1%	197 24.3%	578 23.6%
Tolterodine ER 4 mg	130 16%	107 13%	108 13.3%	345 14.1%
Naive	139 17.1%	161 19.6%	156 19.2%	456 18.7%
Mean number of micturitions per 24 Hours (micturitions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micturitions]	11.12 (2.809)	11.16 (2.917)	10.94 (2.668)	11.08 (2.801)
Mean volume voided per micturition (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	160.4 (58.80)	164.6 (58.62)	160.8 (56.98)	162.0 (58.15)
Mean number of urgency episodes (grade 3 or 4) per 24 hours (urgency episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [urgency episodes]	5.66 (3.601)	5.61 (3.722)	5.44 (3.453)	5.57 (3.594)
Mean level of urgency (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	2.45 (0.544)	2.44 (0.525)	2.43 (0.519)	2.44 (0.529)
Mean number of nocturia episodes per 24 hours (nocturia episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nocturia episodes]	1.83 (1.361)	1.85 (1.404)	1.77 (1.388)	1.82 (1.384)
Mean number of pads used per 24 hours (pads) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pads]	1.06 (1.872)	0.98 (1.769)	0.98 (1.759)	1.01 (1.800)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was defined as any untoward medical occurrence in a patient administered a study drug and which did not necessarily have a causal relationship with the treatment. The investigator assessed the severity of each AE, including abnormal laboratory values, as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities.
Time Frame	From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	812	820	812
Mild adverse events	222 27.3%	240 29.3%	251 30.9%
Moderate adverse events	212 26.1%	211 25.7%	218 26.8%
Severe adverse events	51 6.3%	52 6.3%	39 4.8%

2. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours
Description	The average number of micturitions (urinations) per 24 hours was derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a micturition diary for 3-days prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. Least squares (LS) means were generated from the analysis of covariance (ANCOVA) model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=786; 797; 786]	-0.94 (0.069)	-1.10 (0.068)	-1.02 (0.069)
Month 3 [N=742; 741; 735]	-1.13 (0.079)	-1.46 (0.079)	-1.27 (0.080)
Month 6 [N=684; 705; 684]	-1.25 (0.083)	-1.43 (0.082)	-1.30 (0.083)
Month 9 [N=656; 667; 645]	-1.33 (0.086)	-1.37 (0.086)	-1.38 (0.087)
Month 12 [N=627; 642; 623]	-1.30 (0.089)	-1.46 (0.088)	-1.50 (0.089)
Final Visit (LOCF) [N=789; 802; 791]	-1.27 (0.083)	-1.41 (0.082)	-1.39 (0.083)

3. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours
Description	The average number of incontinence episodes (any involuntary leakage of urine) per day was derived from the number of incontinence episodes recorded by the patient in a micturition diary for 3-days prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. Least squares (LS) means were generated from the analysis of covariance (ANCOVA) model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	479	483	488
Month 1 [N=478; 479; 485]	-0.94 (0.079)	-1.03 (0.079)	-0.96 (0.078)
Month 3 [N=447; 443; 452]	-1.10 (0.083)	-1.28 (0.084)	-1.09 (0.083)
Month 6 [N=409; 428; 418]	-1.11 (0.088)	-1.27 (0.086)	-1.17 (0.087)
Month 9 [N=387; 402; 391]	-1.17 (0.083)	-1.32 (0.082)	-1.26 (0.083)
Month 12 [N=370; 387; 379]	-1.14 (0.094)	-1.19 (0.092)	-1.36 (0.093)
Final Visit (LOCF) [N=479; 483; 488]	-1.01 (0.087)	-1.24 (0.086)	-1.26 (0.086)

4. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition
Description	The average volume voided per micturition was calculated from the volume of each micturition measured by the patient and recorded in a micturition diary for 3 days prior to clinic visits at Baseline and months 1, 3, 6, 9 and 12/end of treatment. LS means were generated from the ANCOVA model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=785; 797; 786]	12.1 (1.31)	16.7 (1.30)	16.0 (1.31)
Month 3 [N=741; 741; 735]	14.8 (1.50)	20.4 (1.50)	17.4 (1.51)
Month 6 [N=684; 705; 684]	18.6 (1.69)	23.0 (1.66)	18.8 (1.69)
Month 9 [N=655; 667; 645]	20.5 (1.78)	23.5 (1.77)	17.9 (1.80)
Month 12 [N=626; 642; 623]	18.5 (1.86)	24.3 (1.83)	18.9 (1.86)
Final Visit (LOCF) [N=789; 802; 791]	17.5 (1.65)	21.5 (1.63)	18.1 (1.64)

5. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours
Description	The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes classified by the patient in a 3-day micturition diary as 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0=No urgency; 1=Mild urgency; 2=Moderate urgency, could postpone voiding a short time; 3=Severe urgency, could not postpone voiding; 4=Urge incontinence, leaked before arriving to toilet. LS means are from the ANCOVA model with treatment group, previous study history, gender and geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	479	483	488
Month 1 [N=471; 467; 471]	-0.92 (0.072)	-1.04 (0.073)	-0.95 (0.072)
Month 3 [N=441; 432; 440]	-1.05 (0.077)	-1.23 (0.078)	-1.06 (0.077)
Month 6 [N=404; 417; 408]	-1.13 (0.080)	-1.32 (0.079)	-1.11 (0.080)
Month 9 [N=382; 392; 382]	-1.13 (0.077)	-1.33 (0.076)	-1.25 (0.077)
Month 12 [N=366; 377; 371]	-1.17 (0.087)	-1.20 (0.085)	-1.29 (0.086)
Final Visit (LOCF) [N=472; 471; 474]	-1.01 (0.082)	-1.23 (0.082)	-1.21 (0.081)

6. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours
Description	The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from episodes classified by the patient in a 3-day micturition diary as 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0=No urgency; 1=Mild urgency; 2=Moderate urgency, could delay voiding a short time; 3=Severe urgency, could not delay voiding; 4=Urge incontinence, leaked before arriving to the toilet. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=783; 791; 780]	-1.30 (0.092)	-1.31 (0.091)	-1.11 (0.092)
Month 3 [N=738; 737; 733]	-1.37 (0.103)	-1.83 (0.103)	-1.55 (0.103)
Month 6 [N=683; 701; 680]	-1.75 (0.108)	-1.95 (0.106)	-1.63 (0.108)
Month 9 [N=653; 665; 643]	-1.77 (0.114)	-1.71 (0.113)	-1.78 (0.115)
Month 12 [N=621; 637; 621]	-1.81 (0.116)	-1.79 (0.115)	-1.89 (0.116)
Final Visit (LOCF) [N=788; 799; 788]	-1.62 (0.108)	-1.80 (0.107)	-1.63 (0.108)

7. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency
Description	Average of patients' ratings on the degree of urgency associated with each micturition and/or incontinence episode recorded in a 3-day micturition diary according to the Patient Perception of Intensity of Urgency Scale: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. LS means are generated from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=784; 793; 780]	-0.18 (0.016)	-0.19 (0.016)	-0.17 (0.016)
Month 3 [N=739; 738; 733]	-0.21 (0.019)	-0.28 (0.019)	-0.24 (0.019)
Month 6 [N=684; 702; 680]	-0.29 (0.021)	-0.32 (0.021)	-0.27 (0.021)
Month 9 [N=654; 666; 643]	-0.30 (0.022)	-0.30 (0.022)	-0.31 (0.022)
Month 12 [N=622; 638; 621]	-0.33 (0.023)	-0.31 (0.023)	-0.32 (0.023)
Final Visit (LOCF) [N=789; 801; 788]	-0.29 (0.020)	-0.29 (0.020)	-0.27 (0.020)

8. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours
Description	The average number of times a patient records a new pad used per day during the 3-day micturition diary period. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=324; 305; 313]	-0.75 (0.084)	-0.79 (0.086)	-0.79 (0.085)
Month 3 [N=307; 280; 286]	-0.80 (0.093)	-0.94 (0.097)	-0.95 (0.096)
Month 6 [N=277; 271; 264]	-0.88 (0.097)	-0.94 (0.098)	-0.99 (0.099)
Month 9 [N=264; 255; 250]	-0.99 (0.092)	-0.96 (0.094)	-0.99 (0.094)
Month 12 [N=254; 247; 241]	-0.87 (0.100)	-0.92 (0.101)	-1.13 (0.102)
Final Visit (LOCF) [N=325; 307; 314]	-0.81 (0.089)	-0.88 (0.092)	-1.02 (0.090)

9. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours
Description	Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinated (excluding incontinence only episodes) during sleeping time per day was derived from the 3-day patient micturition diary. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=690; 698; 690]	-0.26 (0.034)	-0.29 (0.033)	-0.29 (0.034)
Month 3 [N=654; 651; 643]	-0.41 (0.037)	-0.45 (0.037)	-0.37 (0.037)
Month 6 [N=604; 618; 602]	-0.42 (0.041)	-0.38 (0.040)	-0.35 (0.041)
Month 9 [N=580; 583; 567]	-0.50 (0.040)	-0.41 (0.040)	-0.39 (0.040)
Month 12 [N=554; 562; 550]	-0.48 (0.042)	-0.40 (0.041)	-0.46 (0.042)
Final Visit (LOCF) [N=693; 703; 693]	-0.46 (0.038)	-0.39 (0.038)	-0.43 (0.038)

10. Secondary Outcome

Title	Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit
Description	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.
Time Frame	Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	479	483	488
Month 1 [N=478; 479; 485]	35.4 4.4%	36.7 4.5%	33.4 4.1%
Month 3 [N=447; 443; 452]	40.9 5%	45.4 5.5%	39.2 4.8%
Month 6 [N=409; 428; 418]	43.3 5.3%	45.1 5.5%	43.5 5.4%
Month 9 [N=387; 402; 391]	47.5 5.8%	46.8 5.7%	44.2 5.4%
Month 12 [N=370; 387; 379]	47.8 5.9%	47.5 5.8%	49.1 6%
Final Visit (LOCF) [N=479; 483; 488]	43.4 5.3%	45.8 5.6%	45.1 5.6%

11. Secondary Outcome

Title	Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit
Description	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.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	479	483	488
Month 1 [N=478; 479; 485]	58.2 7.2%	57.0 7%	56.3 6.9%
Month 3 [N=447; 443; 452]	61.7 7.6%	66.1 8.1%	61.5 7.6%
Month 6 [N=409; 428; 418]	65.5 8.1%	66.8 8.1%	63.9 7.9%
Month 9 [N=387; 402; 391]	65.6 8.1%	67.2 8.2%	66.0 8.1%
Month 12 [N=370; 387; 379]	67.6 8.3%	68.5 8.4%	71.2 8.8%
Final Visit (LOCF) [N=479; 483; 488]	63.7 7.8%	66.3 8.1%	66.8 8.2%

12. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score
Description	Overactive bladder symptoms were assessed using the symptom bother scale of the overactive bladder questionnaire. The symptom bother scale consists of 8 questions answered by the patient on a scale from 1-6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from Baseline in symptom bother score indicates improvements. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=775; 784; 771]	-10.5 (0.55)	-12.5 (0.55)	-11.5 (0.55)
Month 3 [N=736; 733; 739]	-13.4 (0.61)	-16.1 (0.61)	-13.5 (0.60)
Month 6 [N=680; 699; 682]	-14.5 (0.65)	-16.5 (0.64)	-14.6 (0.64)
Month 9 [N=649; 661; 639]	-14.2 (0.68)	-15.6 (0.68)	-14.3 (0.69)
Month 12 [N=622; 636; 612]	-14.1 (0.70)	-15.7 (0.69)	-16.3 (0.71)
Final Visit (LOCF) [N=779; 795; 781]	-13.1 (0.65)	-14.8 (0.65)	-14.3 (0.65)

13. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score
Description	Health-related quality of life was assessed by the HRQL subscales (coping, concern, sleep and social interaction) of the overactive bladder questionnaire (OABq). The HRQL total score was calculated by adding the 4 HRQL subscale scores, and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from Baseline in HRQL score indicates improvements. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=774; 787; 773]	7.7 (0.48)	8.9 (0.48)	8.9 (0.48)
Month 3 [N=736; 740; 739]	9.9 (0.54)	11.9 (0.54)	10.6 (0.54)
Month 6 [N=681; 700; 686]	11.7 (0.56)	12.9 (0.56)	11.6 (0.56)
Month 9 [N=650; 667; 644]	11.3 (0.60)	12.2 (0.59)	12.4 (0.60)
Month 12 [N=619; 640; 613]	11.7 (0.62)	12.6 (0.61)	13.2 (0.62)
Final Visit (LOCF) [N=779; 798; 783]	10.7 (0.58)	11.7 (0.57)	11.4 (0.58)

14. Secondary Outcome

Title	Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC)
Description	The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. A negative change from Baseline score indicates improvement. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 12 [N=601; 616; 611]	-0.8 (0.04)	-0.9 (0.04)	-0.9 (0.04)
Final Visit (LOCF) [N=655; 673; 673]	-0.8 (0.04)	-0.9 (0.04)	-0.8 (0.04)

15. Secondary Outcome

Title	Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS)
Description	The TS-VAS is a visual analog scale (VAS) that asks patients to rate their satisfaction with treatment by placing a vertical mark on a 10 cm line where the endpoints are labeled 'No, not at all' on the left (=0) to 'Yes, completely satisfied' on the right (=10). A positive change from baseline indicates improvement. LS means are from an ANCOVA model with treatment group, previous study history, gender & geographical regions as fixed factors and baseline as a covariate.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 12 [N=599; 620; 613]	2.27 (0.175)	2.27 (0.172)	2.52 (0.173)
Final Visit (LOCF) [N=654; 676; 676]	2.08 (0.167)	2.11 (0.164)	2.27 (0.164)

16. Secondary Outcome

Title	Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed
Description	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.
Time Frame	Baseline and Months 3, 6 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 3 [N=215; 217; 211]	-0.06 (7.48)	-1.0 (9.41)	-0.6 (12.38)
Month 6 [N=183; 203; 200]	-1.3 (6.80)	-1.5 (10.62)	-0.7 (6.26)
Month 12 [N=181; 185; 188]	-0.5 (9.55)	-0.8 (12.39)	-1.2 (8.08)
Final Visit (LOCF) [N=245; 256; 249]	-0.5 (8.98)	-0.9 (10.98)	-0.8 (11.37)

17. Secondary Outcome

Title	Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working
Description	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.
Time Frame	Baseline and Months 3, 6 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 3 [N=233; 236; 231]	-10.6 (23.36)	-9.9 (23.65)	-10.9 (22.56)
Month 6 [N=207; 216; 213]	-13.0 (22.44)	-11.9 (21.88)	-11.1 (22.21)
Month 12 [N=194; 196; 201]	-11.9 (24.37)	-14.4 (26.00)	-12.3 (24.60)
Final Visit (LOCF) [N=261; 272; 265]	-10.9 (24.51)	-11.8 (25.12)	-10.6 (24.34)

18. Secondary Outcome

Title	Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment
Description	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.
Time Frame	Baseline and Months 3, 6 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 3 [N=208; 208; 204]	-11.4 (23.92)	-10.9 (24.50)	-11.0 (23.10)
Month 6 [N=181; 195; 193]	-12.4 (22.29)	-13.0 (23.99)	-11.1 (22.48)
Month 12 [N=175; 177; 183]	-11.5 (25.36)	-14.1 (27.02)	-13.6 (25.75)
Final Visit (LOCF) [N=240; 250; 244]	-11.2 (25.21)	-12.4 (25.56)	-11.5 (24.74)

19. Secondary Outcome

Title	Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment
Description	The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess the degree and extent to which overactive bladder (OAB) symptoms interfered with daily activities over the last 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which OAB affected their regular daily activities. A higher percentage indicates greater impairment and less productivity. A negative change from baseline indicates improvement.
Time Frame	Baseline and Months 3, 6 and 12

Outcome Measure Data

Analysis Population Description

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 value. LOCF was used for the Final Visit analysis.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 3 [N=691; 690; 692]	-12.0 (24.21)	-13.7 (25.75)	-12.3 (25.34)
Month 6 [N=640; 663; 651]	-14.0 (25.47)	-15.6 (26.38)	-13.4 (26.25)
Month 12 [N=582; 603; 598]	-13.3 (26.50)	-15.2 (28.84)	-15.0 (28.07)
Final Visit (LOCF) [N=728; 737; 733]	-12.5 (26.37)	-13.9 (28.53)	-12.8 (28.10)

20. Secondary Outcome

Title	Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score
Description	The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and evaluating health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems in walking about; I have some problems in walking about; I am confined to bed. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available for that Visit.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
No problem -> No problem	567 69.8%	601 73.3%	573 70.6%
No problem -> Some problems	36 4.4%	42 5.1%	39 4.8%
No problem -> Confined to bed	1 0.1%	1 0.1%	0 0%
No problem -> Missing data	4 0.5%	3 0.4%	2 0.2%
Some problems -> No problems	64 7.9%	55 6.7%	62 7.6%
Some problems -> Some problems	105 12.9%	97 11.8%	106 13.1%
Some problems -> Confined to bed	1 0.1%	0 0%	0 0%
Some problems -> Missing data	0 0%	1 0.1%	2 0.2%
Confined to bed -> No problems	0 0%	1 0.1%	0 0%
Confined to bed -> Some problems	0 0%	0 0%	0 0%
Confined to bed -> Confined to bed	0 0%	0 0%	0 0%
Confined to bed -> Missing data	0 0%	0 0%	0 0%
Missing data -> No problem	11 1.4%	1 0.1%	7 0.9%
Missing data -> Some problems	0 0%	0 0%	0 0%
Missing data -> Confined to bed	0 0%	0 0%	0 0%
Missing data -> Missing data	0 0%	0 0%	0 0%

21. Secondary Outcome

Title	Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score
Description	The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and evaluating health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems with self-care; I have some problems washing or dressing myself; I am unable to wash or dress myself. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available for that Visit.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
No problem -> No problem	718 88.4%	735 89.6%	720 88.7%
No problem -> Some problems	16 2%	15 1.8%	23 2.8%
No problem -> Unable to wash or dress myself	1 0.1%	0 0%	3 0.4%
No problem -> Missing data	4 0.5%	4 0.5%	4 0.5%
Some problems -> No problems	19 2.3%	19 2.3%	13 1.6%
Some problems -> Some problems	18 2.2%	25 3%	20 2.5%
Some problems -> Unable to wash or dress myself	0 0%	0 0%	0 0%
Some problems -> Missing data	0 0%	0 0%	0 0%
Unable to wash or dress myself -> No problems	0 0%	2 0.2%	0 0%
Unable to wash or dress myself -> Some problems	0 0%	1 0.1%	0 0%
Unable to wash or dress -> Unable to wash or dress	0 0%	0 0%	0 0%
Unable to wash or dress myself -> Missing data	0 0%	0 0%	0 0%
Missing data -> No problem	13 1.6%	1 0.1%	8 1%
Missing data -> Some problems	0 0%	0 0%	0 0%
Missing data -> Unable to wash or dress myself	0 0%	0 0%	0 0%
Missing data -> Missing data	0 0%	0 0%	0 0%

22. Secondary Outcome

Title	Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
No problem -> No problem	536 66%	569 69.4%	542 66.7%
No problem -> Some problems	40 4.9%	55 6.7%	53 6.5%
No problem -> Unable to perform usual activities	2 0.2%	1 0.1%	2 0.2%
No problem -> Missing data	3 0.4%	1 0.1%	1 0.1%
Some problems -> No problems	97 11.9%	88 10.7%	96 11.8%
Some problems -> Some problems	94 11.6%	76 9.3%	79 9.7%
Some problems-> Unable to perform usual activities	1 0.1%	2 0.2%	1 0.1%
Some problems -> Missing data	1 0.1%	2 0.2%	3 0.4%
Unable to perform usual activities -> No problems	0 0%	2 0.2%	0 0%
Unable to perform usual activities-> Some problems	2 0.2%	4 0.5%	5 0.6%
Unable to perform -> Unable to perform	2 0.2%	0 0%	1 0.1%
Unable to perform usual activities -> Missing data	10 1.2%	2 0.2%	7 0.9%
Missing data -> No problem	1 0.1%	0 0%	1 0.1%
Missing data -> Some problems	0 0%	0 0%	0 0%
Missing data -> Unable to perform usual activities	0 0%	0 0%	0 0%
Missing data -> Missing data	0 0%	0 0%	0 0%

23. Secondary Outcome

Title	Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score
Description	The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and evaluating health status. Participants were asked to indicate which of the following statements best describes their health state: I have no pain or discomfort; I have moderate pain or discomfort; I have extreme pain or discomfort. In the table below, each row title lists Baseline health status first followed by Final Visit health status and reports the number of patients in that category. Missing data indicates patients with no data available for that Visit.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
No pain -> No pain	398 49%	396 48.3%	398 49%
No pain -> Moderate pain	54 6.7%	69 8.4%	63 7.8%
No pain -> Extreme pain	4 0.5%	2 0.2%	4 0.5%
No pain -> Missing data	4 0.5%	2 0.2%	2 0.2%
Moderate pain -> No pain	104 12.8%	107 13%	105 12.9%
Moderate pain -> Moderate pain	173 21.3%	196 23.9%	182 22.4%
Moderate pain -> Extreme pain	14 1.7%	5 0.6%	8 1%
Moderate pain -> Missing data	1 0.1%	2 0.2%	2 0.2%
Extreme pain -> No pain	3 0.4%	4 0.5%	4 0.5%
Extreme pain -> Moderate pain	13 1.6%	6 0.7%	9 1.1%
Extreme pain -> Extreme pain	10 1.2%	10 1.2%	8 1%
Extreme pain -> Missing data	0 0%	0 0%	0 0%
Missing data-> No pain	8 1%	3 0.4%	6 0.7%
Missing data -> Moderate pain	3 0.4%	0 0%	0 0%
Missing data -> Extreme pain	0 0%	0 0%	0 0%
Missing data -> Missing data	0 0%	0 0%	0 0%

24. Secondary Outcome

Title	Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Not anxious -> Not anxious	413 50.9%	453 55.2%	429 52.8%
Not anxious -> Moderately anxious	43 5.3%	34 4.1%	43 5.3%
Not anxious -> Extremely anxious	3 0.4%	3 0.4%	1 0.1%
Not anxious -> Missing data	3 0.4%	1 0.1%	2 0.2%
Moderately anxious -> Not anxious	108 13.3%	99 12.1%	105 12.9%
Moderately anxious -> Moderately anxious	174 21.4%	181 22.1%	169 20.8%
Moderately anxious -> Extremely anxious	7 0.9%	9 1.1%	11 1.4%
Moderately anxious -> Missing data	1 0.1%	2 0.2%	2 0.2%
Extremely anxious -> Not anxious	3 0.4%	5 0.6%	3 0.4%
Extremely anxious -> Moderately anxious	8 1%	9 1.1%	14 1.7%
Extremely anxious -> Extremely anxious	15 1.8%	5 0.6%	6 0.7%
Extremely anxious -> Missing data	0 0%	0 0%	0 0%
Missing data -> Not anxious	7 0.9%	0 0%	3 0.4%
Missing data -> Moderately anxious	4 0.5%	1 0.1%	2 0.2%
Missing data -> Extremely anxious	0 0%	0 0%	1 0.1%
Missing data -> Missing data	0 0%	0 0%	0 0%

25. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)
Description	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.
Time Frame	Baseline and Months 1, 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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. LOCF was used for the Final Visit analysis.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 1 [N=767; 787; 770]	3.8 (12.85)	3.9 (13.64)	3.1 (12.78)
Month 3 [N=734; 740; 731]	5.0 (15.33)	5.4 (15.27)	4.3 (13.48)
Month 6 [N=676; 697; 678]	6.5 (16.97)	6.4 (16.54)	5.2 (15.40)
Month 9 [N=645; 665; 637]	6.6 (17.52)	6.5 (16.55)	6.3 (15.91)
Month 12 [N=615; 637; 612]	8.2 (17.39)	6.8 (17.56)	7.9 (16.48)
Final Visit (LOCF) [N=776; 797; 777]	6.8 (17.47)	5.9 (17.35)	6.0 (16.64)

26. Secondary Outcome

Title	Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician
Description	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.
Time Frame	Baseline and Months 3, 6 and 12

Outcome Measure Data

Analysis Population Description

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. LOCF was used for the Final Visit analysis.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Month 3 [N=748; 750; 744]	0.0 (0.22)	0.0 (0.15)	0.0 (0.14)
Month 6 [N=690; 705; 687]	0.0 (0.17)	0.0 (0.13)	0.0 (0.18)
Month 12 [N=628; 640; 622]	0.0 (0.25)	0.0 (0.13)	0.0 (0.11)
Final Visit (LOCF) [N=773; 769; 760]	0.0 (0.25)	0.0 (0.15)	0.0 (0.14)

27. Secondary Outcome

Title	Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC)
Description	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.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

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. LOCF was used for the Final Visit analysis.

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	789	802	791
Improvement: Month12 [N=616; 630; 620]	55.7 6.9%	60.6 7.4%	56.6 7%
Improvement: Final Visit [N=671; 688; 684]	52.9 6.5%	59.6 7.3%	54.4 6.7%
Major Improvement: Month 12 [N=616; 630; 620]	27.4 3.4%	29.7 3.6%	28.2 3.5%
Major Improvement: Final Visit [N=671; 688; 684]	26.2 3.2%	28.2 3.4%	26.6 3.3%

28. Secondary Outcome

Title	Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram
Description	An abnormality identified during a medical test was defined as an AE if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant. The Investigator assessed each AE for causal relationship (not related, possible or probable) to study drug. A serious AE (SAE) was any untoward medical occurrence that: resulted in death, was life-threatening, resulted in significant disability/incapacity or congenital anomaly/birth defect, required or prolonged hospitalization or was a medically important event. The data reported represent the number of participants with adverse events in each category.
Time Frame	From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Mirabegron 50 mg	Mirabegron 100 mg	Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.	Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.	Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Measure Participants	812	820	812
Adverse events	485 59.7%	503 61.3%	508 62.6%
Treatment-related adverse events (TRAEs)	213 26.2%	192 23.4%	224 27.6%
Deaths	2 0.2%	0 0%	2 0.2%
Serious adverse events (SAEs)	42 5.2%	51 6.2%	44 5.4%
Treatment-related serious adverse events	10 1.2%	4 0.5%	5 0.6%
AEs leading to study drug discontinuation	48 5.9%	50 6.1%	46 5.7%
TRAEs leading to study drug discontinuation	35 4.3%	29 3.5%	31 3.8%

Adverse Events

Time Frame	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.
Arm/Group Title	Mirabegron 50 mg		Mirabegron 100 mg		Tolterodine ER 4 mg
Arm/Group Description	Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.		Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.		Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
All Cause Mortality
	Mirabegron 50 mg		Mirabegron 100 mg		Tolterodine ER 4 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Mirabegron 50 mg		Mirabegron 100 mg		Tolterodine ER 4 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/812 (5.2%)		51/820 (6.2%)		44/812 (5.4%)
Blood and lymphatic system disorders
Anaemia	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Haemolytic anaemia	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Thrombocytopenia	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Coagulopathy	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Cardiac disorders
Atrial fibrillation	2/812 (0.2%)		0/820 (0%)		3/812 (0.4%)
Acute myocardial infarction	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Arrhythmia	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Atrial flutter	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Atrioventricular block first degree	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Cardiac arrest	1/812 (0.1%)		0/820 (0%)		1/812 (0.1%)
Cardiac failure	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Coronary artery disease	0/812 (0%)		1/820 (0.1%)		1/812 (0.1%)
Myocardial infarction	1/812 (0.1%)		0/820 (0%)		2/812 (0.2%)
Myocardial ischaemia	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Sick sinus syndrome	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Ventricular fibrillation	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Ventricular tachycardia	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Angina pectoris	0/812 (0%)		0/820 (0%)		2/812 (0.2%)
Aortic valve incompetence	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Coronary artery stenosis	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Ear and labyrinth disorders
Tympanic membrane perforation	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Vertigo	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Eye disorders
Angle closure glaucoma	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Open angle glaucoma	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Blepharospasm	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Gastrointestinal disorders
Gastritis	1/812 (0.1%)		1/820 (0.1%)		0/812 (0%)
Upper gastrointestinal haemorrhage	1/812 (0.1%)		1/820 (0.1%)		0/812 (0%)
Colitis ischaemic	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Diverticular perforation	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Gastric ulcer	1/812 (0.1%)		0/820 (0%)		1/812 (0.1%)
Gastritis erosive	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Inguinal hernia	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Oesophagitis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Pancreatitis acute	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Volvulus	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Duodenal ulcer	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Gastrointestinal haemorrhage	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Ileus	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
General disorders
Chest pain	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Gait disturbance	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Multi-organ failure	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Non-cardiac chest pain	1/812 (0.1%)		0/820 (0%)		1/812 (0.1%)
Fatigue	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Hepatobiliary disorders
Cholecystitis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Cholelithiasis	0/812 (0%)		1/820 (0.1%)		2/812 (0.2%)
Biliary colic	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Infections and infestations
Abscess intestinal	1/812 (0.1%)		1/820 (0.1%)		0/812 (0%)
Cellulitis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Clostridium difficile colitis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Diverticulitis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Intestinal gangrene	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Localised infection	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Pneumonia	1/812 (0.1%)		0/820 (0%)		1/812 (0.1%)
Staphylococcal sepsis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Escherichia bacteraemia	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Pyelonephritis	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Sinusitis	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Injury, poisoning and procedural complications
Anaemia postoperative	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Cardiac pacemaker malfunction	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Concussion	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Fall	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Femoral neck fracture	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Hip fracture	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Humerus fracture	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Joint dislocation	0/812 (0%)		1/820 (0.1%)		1/812 (0.1%)
Ligament rupture	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Muscle injury	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Pelvic fracture	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Postoperative fever	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Rib fracture	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Thoracic vertebral fracture	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Upper limb fracture	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Lower limb fracture	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Investigations
Liver function test abnormal	0/812 (0%)		2/820 (0.2%)		0/812 (0%)
Arthroscopy	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Gamma-glutamyltransferase increased	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Metabolism and nutrition disorders
Dehydration	1/812 (0.1%)		0/820 (0%)		1/812 (0.1%)
Obesity	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	2/812 (0.2%)		1/820 (0.1%)		1/812 (0.1%)
Arthritis	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Lumbar spinal stenosis	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Rotator cuff syndrome	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Spinal column stenosis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Tenosynovitis	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Musculoskeletal pain	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/812 (0%)		2/820 (0.2%)		2/812 (0.2%)
Lung neoplasm malignant	0/812 (0%)		2/820 (0.2%)		0/812 (0%)
Prostate cancer	0/812 (0%)		2/820 (0.2%)		0/812 (0%)
Endometrial cancer	0/812 (0%)		1/820 (0.1%)		1/812 (0.1%)
Endometrial cancer stage I	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Fibroma	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Pancreatic carcinoma	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Thyroid neoplasm	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Transitional cell carcinoma	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Benign lung neoplasm	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Uterine leiomyoma	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Nervous system disorders
Cerebrovascular accident	3/812 (0.4%)		0/820 (0%)		1/812 (0.1%)
Balance disorder	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Carpal tunnel syndrome	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Paraesthesia	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Transient ischaemic attack	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Carotid artery stenosis	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Cerebral circulatory failure	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Cerebral infarction	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Global amnesia	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Psychiatric disorders
Mental disorder	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Renal and urinary disorders
Hypertonic bladder	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Nephrolithiasis	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Renal cyst	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Renal mass	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Renal vein thrombosis	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Urinary incontinence	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Azotaemia	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Calculus ureteric	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Renal failure acute	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Reproductive system and breast disorders
Uterine polyp	1/812 (0.1%)		1/820 (0.1%)		0/812 (0%)
Uterine prolapse	0/812 (0%)		2/820 (0.2%)		0/812 (0%)
Dysmenorrhoea	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Menorrhagia	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Rectocele	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Erectile dysfunction	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Metrorrhagia	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Ovarian cyst	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Pelvic pain	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Pelvic prolapse	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Postmenopausal haemorrhage	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Uterine haemorrhage	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Vaginal haemorrhage	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Chronic obstructive pulmonary disease	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Respiratory failure	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Pneumonia aspiration	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Skin and subcutaneous tissue disorders
Dermal cyst	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Urticaria	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Surgical and medical procedures
Hysterectomy	1/812 (0.1%)		1/820 (0.1%)		0/812 (0%)
Cataract operation	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Cystocele repair	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Gastrectomy	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Gastric bypass	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Hip arthroplasty	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Knee arthroplasty	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Spinal fusion surgery	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Uterine prolapse repair	0/812 (0%)		1/820 (0.1%)		0/812 (0%)
Cystopexy	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Foot operation	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Spinal laminectomy	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Thyroidectomy	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Vascular disorders
Hypertension	1/812 (0.1%)		1/820 (0.1%)		0/812 (0%)
Aortic aneurysm	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Arterial thrombosis limb	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Haemorrhage	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Varicose vein	1/812 (0.1%)		0/820 (0%)		0/812 (0%)
Aortic stenosis	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Ischaemia	0/812 (0%)		0/820 (0%)		1/812 (0.1%)
Other (Not Including Serious) Adverse Events
	Mirabegron 50 mg		Mirabegron 100 mg		Tolterodine ER 4 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	136/812 (16.7%)		137/820 (16.7%)		181/812 (22.3%)
Gastrointestinal disorders
Dry mouth	23/812 (2.8%)		19/820 (2.3%)		70/812 (8.6%)
Infections and infestations
Urinary tract infection	48/812 (5.9%)		45/820 (5.5%)		52/812 (6.4%)
Vascular disorders
Hypertension	74/812 (9.1%)		80/820 (9.8%)		78/812 (9.6%)

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Principal Investigators are NOT employed by the organization sponsoring the study.

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.