Symphony: A Study to Evaluate the Efficacy, Safety and Tolerability of Mirabegron and Solifenacin Succinate Alone and in Combination for the Treatment of Overactive Bladder

Sponsor

Astellas Pharma Europe B.V. (Industry)

Overall Status

Completed

CT.gov ID

NCT01340027

Collaborator

(none)

1,307

Enrollment

133

Locations

Arms

Actual Duration (Months)

9.8

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to examine how well two medicines in combination (solifenacin succinate and mirabegron) work in the treatment of bladder problems over a 12-week period.

Condition or Disease	Intervention/Treatment	Phase
Urologic Diseases Urinary Bladder Diseases Urological Manifestations Signs and Symptoms Urinary Bladder, Overactive	Drug: Mirabegron Drug: Solifenacin succinate Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

1307 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Factorial, Parallel-Group, Active and Placebo-Controlled, Multicenter Dose-Ranging Study to Evaluate the Efficacy, Safety and Tolerability of Six Dose Combinations of Solifenacin Succinate and Mirabegron Compared to Mirabegron and Solifenacin Succinate Monotherapies in the Treatment of Overactive Bladder.

Actual Study Start Date :

Mar 29, 2011

Actual Primary Completion Date :

Jun 28, 2012

Actual Study Completion Date :

Jun 28, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received matching placebo tablets orally once a day for 12 weeks	Drug: Placebo oral
Active Comparator: Mirabegron 25 mg Participants received mirabegron 25 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178
Active Comparator: Mirabegron 50 mg Participants received mirabegron 50 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178
Active Comparator: Solifenacin 2.5 mg Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks	Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Active Comparator: Solifenacin 5 mg Participants received solifenacin 5 mg tablets orally once a day for 12 weeks	Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Active Comparator: Solifenacin 10 mg Participants received solifenacin 10 mg tablets orally once a day for 12 weeks	Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Experimental: Solifenacin 2.5 mg and Mirabegron 25 mg Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178 Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Experimental: Solifenacin 2.5 mg and Mirabegron 50 mg Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178 Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Experimental: Solifenacin 5 mg and Mirabegron 25 mg Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178 Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Experimental: Solifenacin 5 mg and Mirabegron 50 mg Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178 Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Experimental: Solifenacin 10 mg and Mirabegron 25 mg Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178 Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare
Experimental: Solifenacin 10 mg and Mirabegron 50 mg Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks	Drug: Mirabegron oral Other Names: Betmiga Myrbetric Myrbetriq Betanis YM178 Drug: Solifenacin succinate oral Other Names: Vesikur Vesicare

Outcome Measures

Primary Outcome Measures

Change From Baseline to End of Treatment (EOT) in Mean Volume Voided Per Micturition [Baseline and Week 12]
The average volume voided per micturition was calculated from the volume of each micturition measured by the participant and recorded in a micturition diary for 3 days before the Baseline and Week 12 clinic visits.

Secondary Outcome Measures

Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours [Baseline and Week 12]
The average number of micturitions (urinations) per 24 hours was derived from the number of urinations (excluding incontinence only episodes) per day recorded by the participant in the micturition diary for 3-days before the Baseline and Week 12 clinic visits.
Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours [Baseline and Week 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 participant in the micturition diary for 3-days before the Baseline and Week 12 clinic visits.
Change From Baseline to Each Visit in Mean Volume Voided Per Micturition [Baseline and Weeks 2, 4, 8 and 12]
The average volume voided per micturition was calculated from the volume of each micturition measured by the participant and recorded in a micturition diary for 3 days before the Baseline and each post-baseline clinic visit.
Change From Baseline to Each Visit in Mean Number of Micturitions Per 24 Hours [Baseline and Weeks 2, 4, 8 and 12]
The average number of micturitions (urinations) per 24 hours was derived from the number of urinations (excluding incontinence only episodes) per day recorded by the participant in the micturition diary for 3-days before the Baseline and each post-baseline clinic visit.
Percentage of Participants With a Micturition Response [Baseline and Weeks 2, 4, 8 and 12]
A responder is defined as a participant with at most 8 micturitions per 24 hours post-baseline and a negative change (i.e. an improvement) from Baseline.
Change From Baseline to Each Visit in Mean Number of Incontinence Episodes Per 24 Hours [Baseline and Weeks 2, 4, 8 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 participant in the micturition diary for 3-days before the Baseline and each post-baseline clinic visit.
Percentage of Participants With Zero Incontinence Episodes Post-baseline [Weeks 2, 4, 8 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 participant.
Percentage of Participants With 50% Reduction in Incontinence Episodes [Baseline and Weeks 2, 4, 8 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 participant's micturition diary.
Change From Baseline to Each Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours [Baseline and Weeks 2, 4, 8 and 12]
Urgency incontinence is the involuntary leakage of urine accompanied by or immediately preceded by urgency, and was derived from the number of incontinence episodes classified by the participant in a 3-day micturition diary as Grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet.
Change From Baseline to Each Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours [Baseline and Weeks 2, 4, 8 and 12]
The average number of urgency episodes (the sudden, compelling desire to pass urine, which is difficult to defer), derived from urgency episodes classified by the participant in the 3-day micturition diary as grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0: No urgency; 1: Mild urgency; 2: Moderate urgency, could delay voiding a short while; 3: Severe urgency, could not delay voiding; 4: Urge incontinence, leaked before arriving to the toilet.
Change From Baseline to Each Visit in Mean Level of Urgency [Baseline and Weeks 2, 4, 8 and 12]
Average of participants' ratings on the degree of urgency associated with each micturition and/or incontinence episode recorded in the 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.
Change From Baseline to Each Visit in Mean Number of Pads Used Per 24 Hours [Baseline and Weeks 2, 4, 8 and 12]
The average number of times a participant recorded a new pad used per day during the 3-day micturition diary period.
Change From Baseline to Each Visit in Mean Number of Nocturia Episodes Per 24-Hours [Baseline and Weeks 2, 4, 8 and 12]
Nocturia is defined as waking at night one or more times to void. The average number of times a participant urinated (excluding incontinence only episodes) during sleeping time per day was derived from the 3-day micturition diary.
Change From Baseline to End of Treatment in Patient Perception of Bladder Condition (PPBC) [Baseline and Week 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.
Percentage of Participants With Improvement in PPBC [Baseline and Week 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 1-point improvement (decrease) from Baseline in PPBC score.
Percentage of Participants With Major Improvement in PPBC [Baseline and Week 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'. Major improvement was defined as at least a 2-point improvement (decrease) from Baseline in PPBC score.
Percentage of Participants With Deterioration in PPBC [Baseline and Week 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'. Deterioration was defined as at least a 1 point increase from Baseline in PPBC score.
Change From Baseline to End of Treatment in Symptom Bother Score as Assessed by the Overactive Bladder Questionnaire (OAB-q) [Baseline and Week 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 participant on a scale from 1-6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from Baseline in symptom bother score indicates improvements.
Percentage of Participants With a Symptom Bother Response [Baseline and Week 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 participant on a scale from 1-6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. Symptom bother response is defined as improvement (decrease) of at least 10 points from Baseline.
Change From Baseline to End of Treatment in Health-related Quality of Life (HRQL) Total Score [Baseline and Week 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.
Percentage of Participants With a Health-related Quality of Life Total Score Response [Baseline and Week 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. HRQL response is defined as improvement (decrease) of at least 10 points from Baseline.
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score [Baseline and Week 12]
The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems in walking about; I have some problems in walking about; I am confined to bed. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of patients in that category.
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score [Baseline and Week 12]
The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems with self-care; I have some problems washing or dressing myself; I am unable to wash or dress myself. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of patients in that category.
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score [Baseline and Week 12]
The EQ-5D is a standardized, nondisease-specific instrument for describing health status. Participants were asked which statement best describes their health state with regard to usual activities (work, study or leisure): I have no problems performing my usual activities; I have some problems performing my usual activities; I am unable to perform my usual activities. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of patients in that category.
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score [Baseline and Week 12]
The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no pain or discomfort; I have moderate pain or discomfort; I have extreme pain or discomfort. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of participants in that category.
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score [Baseline and Week 12]
The EQ-5D is an international, standardized, nondisease-specific (i.e., generic) instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I am not anxious or depressed; I am moderately anxious or depressed; I am extremely anxious or depressed. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of patients in that category.
Change From Baseline to End of Treatment in European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) [Baseline and Week 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.
Change From Baseline to End of Treatment in Work Productivity and Activity Impairment (WPAI) [Baseline and Week 12]
This 6-item assessment measures productivity losses during the past 7 days and includes measures on work time missed due to health, impairment while working due to health (the participant's assessment of the degree to which health affected their productivity while working), overall work impairment due to health (takes into account both hours missed due to health and the participant's assessment of the degree to which health affected their productivity while working) and activity impairment due to health (the degree in which health problems affected their ability to do regular daily activities). Scores for each measure are expressed from 0 to 100 with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicates improvement.
Change From Baseline to End of Treatment in Treatment Satisfaction on Visual Analog Scale (TS-VAS) [Baseline and Week 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inclusion Criteria at Visit 1/Screening:
Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m^2 and a total body weight between 50 and 95 kg;
Subject is willing and able to complete the micturition diary and questionnaires correctly and is willing and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;
Subject has symptoms of overactive bladder (OAB; urinary frequency, urgency and/or urgency incontinence) for at least 3 months.
Inclusion Criteria at Visit 3/Baseline:
Subject has experienced frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period (incontinence episode should not be counted as a micturition);
Subject must experience at least 1 episode of urgency (grade 3 or 4) per 24-hour period (with or without urgency incontinence) during the 3 day micturition diary period.

Exclusion Criteria:

Exclusion Criteria at Visit 1/Screening:
Subject is breastfeeding, pregnant or intends to become pregnant during the study. The pregnancy test (Beta Human Chorionic Gonadotropin in serum) at Screening must be negative in women of childbearing potential;
Female subjects of childbearing potential and not using a highly effective method of birth control during the study and for 30 days after final study drug administration.
Male subjects (unless surgically sterile) with female spouses/partners who are of childbearing potential, and not using a barrier method of contraception during the study and for 30 days after final study drug administration. In addition, female spouses/partners of male subjects and who are of childbearing potential should also use a highly effective method of birth control during the study and for 30 days after final study drug administration. Highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
Subject has significant post-void residual (PVR) volume (> 150 mL);
Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the Investigator (for female subjects confirmed by the cough provocation test);
Subject has a neurological cause for detrusor overactivity;
Subject has an indwelling catheter or practices intermittent self-catheterization;
Subject has diabetic neuropathy;
Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
Subject has had previous lower urinary tract or pelvic floor surgery (except cystoscopy);
Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis or Crohn's Disease, toxic megacolon, myasthenia gravis or any other condition which makes the use of anticholinergics contraindicated;
Subject has clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to Screening, such as myocardial infarction, uncontrolled angina, significant ventricular arrhythmias, heart failure and stroke;
Subject is receiving current non-drug treatment including electro-stimulation therapy (with the exception of a bladder training program or pelvic floor exercises which started more than 30 days prior to Screening);
Subject is using medications intended to treat OAB or prohibited medications.
Subject has known or suspected hypersensitivity to solifenacin succinate, mirabegron or any of their excipients;
Subject has any significant neurological disease or defect affecting bladder function (e.g., neurogenic bladder, systemic or central neurological disease such as multiple sclerosis [MS] and Parkinson's disease);
Subject has severe hypertension which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg;
Exclusion Criteria at Visit 2/Placebo Run-In:
Subject has evidence of a urinary tract infection (UTI) (urine culture containing

100,000 cfu/mL). The subject can be enrolled into the study after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture). However, the subject must be re screened if the initial screening visit was > 28 days;

Subject has a QT interval > 450 ms or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia) or is on drug treatment known to be associated with QT prolongation;
Subject has clinically significant abnormalities on the 12 lead electrocardiogram (ECG);
Subject has serum creatinine > 150 µmol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2x upper limit of normal (ULN), gamma-glutamyltransferase (γ-GT) > 3x ULN, or total bilirubin > 2x ULN, as assessed in Screening samples;
Exclusion Criteria at Visit 3/Baseline:
Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period;
Subject has severe hypertension which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	BY37101	Minsk	Belarus	220036
2	BY37102	Minsk	Belarus	220119
3	BY37103	Minsk	Belarus	223010
4	BY37104	Vitebsk	Belarus	210037
5	BE32102	Brussels	Belgium	1090
6	BE32104	Edegem	Belgium	2650
7	BE32103	Gent	Belgium	9000
8	BE32101	Leuven	Belgium	3000
9	CZ42005	Bohumín	Czechia	73581
10	CZ42003	Hradec Kralove	Czechia	500 02
11	CZ42011	Ostrava	Czechia	700 30
12	CZ42006	Plzen	Czechia	301 24
13	CZ42007	Prague 4	Czechia	14000
14	CZ42001	Prague	Czechia	128 51
15	CZ42009	Prague	Czechia	15006
16	CZ42010	Roudnice nad Labem	Czechia	413 01
17	CZ42012	Sternberk	Czechia	78501
18	CZ42002	Uherske Hradiste	Czechia	68608
19	DK45101	Aarhus N	Denmark	8200
20	DK45102	Herlev	Denmark	2730
21	DK45104	Holstebro	Denmark	7500
22	FI35803	Helsinki	Finland	00029
23	FI35804	Kouvola	Finland	45200
24	FI35801	Oulu	Finland	90220
25	FI35802	Tampere	Finland	33521
26	FR33104	Colmar Cedex	France	68024
27	FR33108	Dijon	France	21079
28	FR33103	Orleans	France	45067
29	FR33111	Paris Cedex 13	France	75651
30	FR33112	Paris cedex 20	France	75970
31	FR33106	Toulouse	France	31059
32	FR33110	Tours	France	37044
33	DE49109	Bad Ems	Germany	56130
34	DE49103	Göttingen	Germany	37075
35	DE49117	Hagenow	Germany	19230
36	DE49105	Hettstedt	Germany	06333
37	DE49108	Leipzig	Germany	04105
38	DE49110	Neustadt I. Sachsen	Germany	01844
39	DE49118	Reutlingen	Germany	72764
40	DE49101	Rostock	Germany	18107
41	DE49111	Sangerhausen	Germany	06526
42	DE49104	Wismar	Germany	23970
43	HU36108	Csongrád	Hungary	6640
44	HU36101	Gyor	Hungary	9024
45	HU36106	Körmend	Hungary	9900
46	HU36110	Miskolc	Hungary	3526
47	HU36104	Sopron	Hungary	9400
48	HU36103	Szekszárd	Hungary	7100
49	HU36107	Tatabánya	Hungary	2800
50	IT39103	Avellino	Italy	83100
51	IT39101	Catanzaro	Italy	88100
52	IT39105	Florence	Italy	50139
53	IT39102	Treviglio (BG)	Italy	24047
54	NL31104	Amsterdam	Netherlands	1100 AD
55	NL31106	Maastricht	Netherlands
56	NL31102	Sneek	Netherlands	8601 ZK
57	NL31101	Winterswijk	Netherlands	7101 BN
58	NO47104	Elverum	Norway	2408
59	NO47102	Hamar	Norway	2317
60	PL48107	Krakow	Poland	31-530
61	PL48103	Lodz	Poland	90-602
62	PL48108	Lublin	Poland	20-954
63	PL48106	Piaseczno	Poland	05-500
64	PL48104	Pulawy	Poland	24-100
65	PL48101	Warsaw	Poland	02-507
66	PL48105	Warsaw	Poland	02-929
67	PL48112	Wiecbork	Poland	89-410
68	PL48111	Wroclaw	Poland	01-432
69	PT35102	Coimbra	Portugal	3000-075
70	PT35105	Coimbra	Portugal	3041-801
71	PT35104	Lisbon	Portugal	1050-199
72	PT35107	Lisbon	Portugal	1649-035
73	PT35110	Porto	Portugal	4099-001
74	PT35101	Porto	Portugal	4200-319
75	PT35106	Tomar	Portugal	2304-909
76	RO40106	Brasov	Romania	500152
77	RO40102	Bucharest	Romania	042122
78	RO40104	Bucharest	Romania	050659
79	RO40103	Bucharest	Romania	200642
80	RO40108	Bucharest	Romania	22328
81	RO40101	Craiova	Romania	20116
82	RO40105	Craiova	Romania	20116
83	RO40107	Sibiu	Romania	550245
84	RU70112	Kazan	Russian Federation	420012
85	RU70108	Moscow	Russian Federation	105425
86	RU70110	Moscow	Russian Federation	115682
87	RU70102	Saint Petersburg	Russian Federation	191015
88	RU70103	Saint Petersburg	Russian Federation	194178
89	RU70101	Saint Petersburg	Russian Federation	197136
90	RU70107	Saint Petersburg	Russian Federation	198013
91	RU70106	St. Petersburg	Russian Federation	197089
92	RU70109	St. Petersburg	Russian Federation	198103
93	RU70113	Ufa	Russian Federation	450096
94	SK42109	Banska Bystrica	Slovakia	975 01
95	SK42112	Bratislava	Slovakia	832 63
96	SK42107	Kosice	Slovakia	04011
97	SK42113	Malacky	Slovakia	90101
98	SK42104	Nitra	Slovakia	949 01
99	SK42106	Piestany	Slovakia	921 01
100	SK42105	Pieštany	Slovakia	921 01
101	SK42102	Presov	Slovakia	08001
102	SK42108	Trencin	Slovakia	911 01
103	SK42101	Trenčín	Slovakia	91101
104	SK42103	Zilina	Slovakia
105	ES34103	Madrid	Spain	28031
106	ES34101	Madrid	Spain	28041
107	ES34109	Madrid	Spain	28046
108	ES34102	Madrid	Spain	28905
109	ES34105	Pamplona	Spain	31008
110	ES34104	San Juan de Alicante	Spain	03550
111	ES34107	Sevilla	Spain	41014
112	SE46101	Gothenburg	Sweden	41263
113	SE46103	Karlshamn	Sweden	37435
114	SE46104	Malmo	Sweden	21152
115	SE46102	Stockholm	Sweden	14186
116	SE46105	Tanumshede	Sweden	45781
117	UA38104	Dnepropetrovsk	Ukraine	49005
118	UA38102	Donetsk	Ukraine	83003
119	UA38111	Donetsk	Ukraine	83114
120	UA38106	Kiev	Ukraine	01023
121	UA38109	Kiev	Ukraine	04053
122	UA38107	Lviv	Ukraine	79044
123	UA38101	Odessa	Ukraine
124	UA38103	Zaporizhzhya	Ukraine	69600
125	GB44103	Bristol	United Kingdom	BS10 5NB
126	GB44108	Cambridge	United Kingdom	CB2 2QQ
127	GB44106	Garston	United Kingdom	WD25 0EA
128	GB44111	Glasgow	United Kingdom	G20 0XA
129	GB44104	Nantwich	United Kingdom	CW5 5NX
130	GB44110	Northwood	United Kingdom	HA6 2RN
131	GB44107	Plymouth	United Kingdom	PL6 8DH
132	GB44101	Reading	United Kingdom	RG1 5AN
133	GB44105	Sandbach	United Kingdom	CW11 1EQ

Sponsors and Collaborators

Astellas Pharma Europe B.V.

Investigators

Study Director: Study Physician, Astellas Pharma Europe B.V.
Principal Investigator: Principal Investigator, Bristol Urological Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Link to results on the Astellas Clinical Study Results website

Publications

None provided.

Responsible Party:

Astellas Pharma Europe B.V.

ClinicalTrials.gov Identifier:

NCT01340027

Other Study ID Numbers:

178-CL-100
2010-020601-32

First Posted:

Apr 21, 2011

Last Update Posted:

Dec 27, 2019

Last Verified:

Dec 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Astellas Pharma Europe B.V.

Urinary incontinence

Overactive bladder (OAB)

Additional relevant MeSH terms:

Urinary Bladder, Overactive

Urologic Diseases

Urinary Bladder Diseases

Urological Manifestations

Solifenacin Succinate

Mirabegron

Study Results

Participant Flow

Recruitment Details	Male and female patients with symptoms of overactive bladder (OAB; urgency, urinary frequency and/or urgency incontinence) for at least 3 months. The study was conducted at 141 sites in 20 countries in Europe.
Pre-assignment Detail	After screening, 1658 participants entered a 2-week, single-blind, placebo run-in period. After completion of the run-in period, 1307 participants were randomly assigned to 1 of the 12 treatment arms in a 1:1:1:1:2:1:2:2:2:2:1:1 ratio.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Period Title: Overall Study
STARTED	81	78	79	79	156	78	149	149	144	152	81	81
Received Treatment	81	78	78	79	156	78	149	149	144	152	81	81
COMPLETED	76	71	75	75	146	74	142	142	136	146	79	77
NOT COMPLETED	5	7	4	4	10	4	7	7	8	6	2	4

Baseline Characteristics

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg +Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg	Total
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Total of all reporting groups
Overall Participants	81	77	78	79	156	78	149	149	144	153	81	81	1306
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (13.37)	55.2 (14.45)	53.4 (13.98)	56.1 (11.71)	54.2 (15.53)	55.0 (12.82)	55.8 (13.82)	53.7 (14.55)	55.0 (14.57)	54.1 (14.09)	56.5 (12.34)	55.5 (13.82)	54.8 (13.97)
Sex: Female, Male (Count of Participants)
Female	54 66.7%	52 67.5%	52 66.7%	51 64.6%	103 66%	53 67.9%	100 67.1%	100 67.1%	95 66%	101 66%	52 64.2%	54 66.7%	867 66.4%
Male	27 33.3%	25 32.5%	26 33.3%	28 35.4%	53 34%	25 32.1%	49 32.9%	49 32.9%	49 34%	52 34%	29 35.8%	27 33.3%	439 33.6%
Race/Ethnicity, Customized (participants) [Number]
White	81 100%	77 100%	78 100%	78 98.7%	156 100%	77 98.7%	149 100%	148 99.3%	143 99.3%	153 100%	81 100%	81 100%	1302 99.7%
Black or African American	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%	0 0%	2 0.2%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%	2 0.2%
Other	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Type of Overactive Bladder (OAB) (participants) [Number]
Urge Incontinence	14 17.3%	27 35.1%	19 24.4%	18 22.8%	39 25%	19 24.4%	42 28.2%	33 22.1%	35 24.3%	35 22.9%	23 28.4%	20 24.7%	324 24.8%
Mixed	9 11.1%	10 13%	10 12.8%	10 12.7%	27 17.3%	11 14.1%	22 14.8%	20 13.4%	19 13.2%	18 11.8%	14 17.3%	10 12.3%	180 13.8%
Frequency	56 69.1%	39 50.6%	48 61.5%	50 63.3%	89 57.1%	48 61.5%	84 56.4%	95 63.8%	90 62.5%	100 65.4%	44 54.3%	50 61.7%	793 60.7%
Missing	2 2.5%	1 1.3%	1 1.3%	1 1.3%	1 0.6%	0 0%	1 0.7%	1 0.7%	0 0%	0 0%	0 0%	1 1.2%	9 0.7%
Duration of OAB Symptoms (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	48.3 (38.37)	61.2 (68.03)	56.9 (66.62)	60.2 (67.85)	61.8 (78.21)	52.4 (56.98)	57.7 (68.91)	57.0 (66.85)	56.3 (84.78)	57.4 (81.53)	64.9 (100.57)	57.4 (80.12)	57.8 (73.82)
Mean Number of Micturitions per 24 Hours (micturitions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micturitions]	10.36 (2.036)	11.29 (2.581)	10.78 (2.254)	11.10 (3.056)	11.34 (3.158)	11.29 (2.896)	11.25 (3.643)	11.00 (2.260)	10.92 (2.386)	11.25 (3.171)	11.14 (2.268)	11.24 (2.453)	11.10 (2.794)
Mean Volume Voided per Micturition (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	156.4 (52.80)	152.7 (56.70)	156.8 (52.33)	162.4 (57.59)	145.5 (59.34)	148.0 (52.74)	156.8 (61.97)	149.8 (50.05)	155.0 (55.55)	153.1 (51.88)	141.4 (51.29)	155.3 (62.13)	152.5 (55.65)
Mean Number of Urgency Episodes per 24 Hours (urgency episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [urgency episodes]	5.26 (3.079)	6.25 (3.332)	6.58 (3.981)	6.20 (3.870)	6.41 (4.154)	6.37 (4.530)	6.05 (3.749)	6.78 (3.419)	6.26 (3.928)	6.49 (4.238)	6.91 (4.319)	6.81 (4.312)	6.37 (3.931)
Mean Level of Urgency (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.45 (0.503)	2.53 (0.439)	2.55 (0.508)	2.53 (0.539)	2.49 (0.508)	2.48 (0.503)	2.49 (0.445)	2.59 (0.446)	2.50 (0.491)	2.51 (0.441)	2.57 (0.493)	2.53 (0.473)	2.52 (0.479)
Mean Number of Nocturia Episodes per 24 Hours (nocturia episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nocturia episodes]	2.19 (1.584)	2.18 (1.392)	2.31 (1.517)	2.46 (1.852)	2.19 (1.399)	2.50 (1.859)	2.64 (2.259)	2.05 (1.219)	2.28 (1.449)	2.27 (1.305)	2.65 (2.525)	2.41 (2.001)	2.33 (1.701)
Mean Number of Incontinence Episodes per 24 Hours (incontinence episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [incontinence episodes]	0.95 (0.765)	1.87 (1.578)	1.26 (1.000)	1.80 (1.167)	1.33 (1.242)	1.40 (1.280)	1.27 (1.096)	1.14 (0.791)	1.24 (1.108)	1.17 (1.196)	1.53 (1.235)	1.25 (0.858)	1.31 (1.109)
Mean Number of Urgency Incontinence Episodes per 24 Hours (urgency incontinence episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [urgency incontinence episodes]	0.78 (0.807)	1.54 (1.337)	1.19 (1.043)	1.56 (1.052)	1.32 (1.227)	1.18 (1.308)	0.96 (0.903)	1.06 (0.757)	1.23 (1.118)	1.08 (1.193)	1.51 (1.247)	1.20 (0.901)	1.20 (1.072)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to End of Treatment (EOT) in Mean Volume Voided Per Micturition
Description	The average volume voided per micturition was calculated from the volume of each micturition measured by the participant and recorded in a micturition diary for 3 days before the Baseline and Week 12 clinic visits.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
The Full Analysis Set (FAS) comprised all participants took at least 1 dose of double-blind study medication after randomization and had primary efficacy data (mean volume voided) derived from the diary at Baseline and at least 1 post-baseline visit. Last observation carried forward imputation (LOCF) was utilized.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Least Squares Mean (Standard Error) [mL]	14.0 (5.91)	24.9 (6.06)	34.5 (6.02)	36.4 (6.02)	36.0 (4.32)	36.2 (6.06)	39.4 (4.37)	41.9 (4.36)	53.6 (4.45)	54.2 (4.31)	57.6 (5.99)	62.3 (5.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	Statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model for all pairwise comparisons includes the 2 main factors mirabegron dose and solifenacin succinate dose and their interaction, sex, age group and geographic region as fixed factors and Baseline value as a covariate. Least squares (LS) mean differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95% -14.3 to 14.9
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.44
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95% -8.6 to 15.5
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.15
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95% -6.1 to 18.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.13
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	17.6
	Confidence Interval	(2-Sided) 95% 5.4 to 29.8
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.20
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	18.2
	Confidence Interval	(2-Sided) 95% 6.2 to 30.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.10
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	21.7
	Confidence Interval	(2-Sided) 95% 7.2 to 36.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.37
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	26.3
	Confidence Interval	(2-Sided) 95% 11.9 to 40.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.32
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.0
	Confidence Interval	(2-Sided) 95% -5.6 to 27.6
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.46
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	20.5
	Confidence Interval	(2-Sided) 95% 4.0 to 37.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.43
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.4
	Confidence Interval	(2-Sided) 95% 5.9 to 39.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.43
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.0
	Confidence Interval	(2-Sided) 95% 7.6 to 36.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.32
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.2
	Confidence Interval	(2-Sided) 95% 5.6 to 38.8
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.46
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25.4
	Confidence Interval	(2-Sided) 95% 11.0 to 39.8
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.35
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	27.9
	Confidence Interval	(2-Sided) 95% 13.5 to 42.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.34
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	39.6
	Confidence Interval	(2-Sided) 95% 25.1 to 54.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.39
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean DIfference
	Estimated Value	40.2
	Confidence Interval	(2-Sided) 95% 25.8 to 54.5
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.31
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	43.6
	Confidence Interval	(2-Sided) 95% 27.1 to 60.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.42
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	48.3
	Confidence Interval	(2-Sided) 95% 31.9 to 64.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.35
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours
Description	The average number of micturitions (urinations) per 24 hours was derived from the number of urinations (excluding incontinence only episodes) per day recorded by the participant in the micturition diary for 3-days before the Baseline and Week 12 clinic visits.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set; LOCF was used.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Least Squares Mean (Standard Error) [micturitions]	-2.43 (0.291)	-2.48 (0.298)	-2.56 (0.296)	-2.44 (0.296)	-2.54 (0.212)	-3.22 (0.298)	-2.58 (0.215)	-2.93 (0.215)	-2.56 (0.219)	-3.34 (0.212)	-3.42 (0.294)	-3.52 (0.291)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	Statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model for all pairwise comparisons includes the 2 main factors mirabegron dose and solifenacin succinate dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95% -1.40 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.366
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.91
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.63 to 0.56
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.302
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95% -0.98 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.302
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95% -0.62 to 0.58
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.305
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95% -1.39 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.300
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.88
	Confidence Interval	(2-Sided) 95% -1.59 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.363
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95% -1.68 to -0.27
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.360
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.91
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95% -0.87 to 0.77
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.417
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95% -0.94 to 0.69
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.415
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95% -0.82 to 0.81
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.416
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95% -0.82 to 0.60
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.361
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95% -1.61 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.417
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95% -0.85 to 0.57
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.362
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95% -1.21 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.362
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95% -0.84 to 0.59
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.364
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.91
	Confidence Interval	(2-Sided) 95% -1.62 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.361
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95% -1.80 to -0.17
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.414
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.08
	Confidence Interval	(2-Sided) 95% -1.89 to -0.28
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.412
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to End of Treatment 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 participant in the micturition diary for 3-days before the Baseline and Week 12 clinic visits.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
The Full Analysis Set-Incontinence comprised participants in the FAS who reported at least 1 incontinence episode in the baseline diary. LOCF was used.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	17	13	18	15	35	15	35	33	32	24	24	20
Least Squares Mean (Standard Error) [incontinence episodes]	-0.95 (0.365)	-0.74 (0.415)	-0.90 (0.353)	-1.26 (0.386)	-0.88 (0.252)	-0.97 (0.386)	-0.75 (0.251)	-0.85 (0.260)	-1.22 (0.266)	-1.14 (0.306)	-0.27 (0.304)	-0.97 (0.333)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	The ANCOVA model including the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and Baseline measurement as a covariate was used to calculate point estimates and 95% confidence intervals (CI) for change from Baseline within each treatment group and for differences between combination treatment groups and solifenacin 5 mg as well as for differences between active treatment groups and placebo.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.51
	Comments	Statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed.
	Method	Stratified Rank ANCOVA
	Comments	P-values are from pairwise comparisons of the combination/active treatment groups vs. solifenacin 5 mg/placebo within a stratified rank ANCOVA model.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95% -1.00 to 0.82
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.460
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95% -0.57 to 0.83
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.355
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95% -0.68 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.361
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.001
	Comments	P values were calculated from a pairwise comparison of the combination treatment groups vs solifenacin succinate 5 mg or placebo within the ANCOVA model.
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95% -1.06 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.365
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95% -1.04 to 0.52
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.397
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95% -0.17 to 1.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.395
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95% -0.91 to 0.73
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.417
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95% -0.88 to 1.30
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.554
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -0.95 to 1.04
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.505
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95% -1.36 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.533
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95% -0.80 to 0.95
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.444
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95% -1.07 to 1.03
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.534
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95% -0.67 to 1.07
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.443
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 2% -0.78 to 0.99
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.448
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95% -1.16 to 0.63
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.454
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95% -1.12 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.472
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95% -0.26 to 1.61
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.475
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95% -0.99 to 0.95
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.494
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Each 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 participant and recorded in a micturition diary for 3 days before the Baseline and each post-baseline clinic visit.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full analysis set including participants with available data at Baseline and each post-baseline visit (indicated by "n")..

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Week 2; n=80,71,76,74,148,73,145,145,136,141,76,77	8.7 (4.44)	14.3 (4.71)	26.0 (4.55)	22.7 (4.62)	23.1 (3.26)	16.1 (4.64)	22.5 (3.30)	29.2 (3.30)	29.9 (3.40)	32.3 (3.34)	29.5 (4.56)	42.1 (4.52)
Week 4; n=79,72,74,76,146,72,141,142,138,144,77,75	10.2 (4.93)	16.8 (5.16)	29.4 (5.09)	24.8 (5.02)	29.6 (3.63)	28.3 (5.16)	29.2 (3.69)	36.5 (3.67)	42.7 (3.73)	44.5 (3.65)	45.7 (5.00)	54.5 (5.06)
Week 8; n=77,70,73,75,147,73,143,142,134,143,76,74	13.5 (5.56)	24.6 (5.83)	35.4 (5.71)	28.3 (5.63)	30.1 (4.03)	37.7 (5.71)	35.6 (4.08)	42.3 (4.09)	49.7 (4.21)	52.2 (4.08)	55.8 (5.60)	68.5 (5.67)
Week 12;n=75,68,73,73,144,72,138,138,133,140,72,73	14.7 (6.12)	23.0 (6.43)	35.5 (6.20)	36.9 (6.20)	34.6 (4.42)	35.8 (6.25)	38.6 (4.52)	43.7 (4.51)	54.7 (4.60)	56.6 (4.48)	59.8 (6.26)	66.2 (6.20)

5. Secondary Outcome

Title	Change From Baseline to Each 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 urinations (excluding incontinence only episodes) per day recorded by the participant in the micturition diary for 3-days before the Baseline and each post-baseline clinic visit.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full analysis set including participants with available data at Baseline and each post-baseline visit (indicated by "n").

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Week 2; n=80,71,76,74,148,73,145,145,136,141,77,77	-1.18 (0.240)	-1.69 (0.255)	-1.60 (0.246)	-1.49 (0.249)	-1.16 (0.176)	-1.32 (0.251)	-1.52 (0.178)	-1.95 (0.178)	-1.68 (0.184)	-2.21 (0.181)	-1.74 (0.244)	-2.35 (0.244)
Week 4; n=79,72,74,76,147,73,141,142,138,144,77,75	-1.68 (0.261)	-2.02 (0.273)	-1.99 (0.269)	-2.10 (0.266)	-1.80 (0.191)	-2.25 (0.271)	-2.03 (0.195)	-2.11 (0.194)	-2.29 (0.197)	-2.77 (0.193)	-2.55 (0.264)	-2.69 (0.267)
Week 8; n=77,70,73,75,147,74,143,142,134,145,77,74	-2.27 (0.270)	-2.27 (0.283)	-2.42 (0.277)	-2.46 (0.273)	-2.22 (0.196)	-2.97 (0.275)	-2.58 (0.198)	-2.66 (0.199)	-2.43 (0.205)	-3.20 (0.197)	-3.04 (0.270)	-3.49 (0.275)
Week 12;n=75,69,73,73,144,73,138,138,133,144,75,73	-2.59 (0.302)	-2.51 (0.314)	-2.67 (0.306)	-2.38 (0.306)	-2.58 (0.218)	-3.31 (0.306)	-2.64 (0.222)	-3.02 (0.222)	-2.64 (0.227)	-3.35 (0.218)	-3.47 (0.302)	-3.63 (0.306)

6. Secondary Outcome

Title	Percentage of Participants With a Micturition Response
Description	A responder is defined as a participant with at most 8 micturitions per 24 hours post-baseline and a negative change (i.e. an improvement) from Baseline.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with at least 8 micturitions per 24 hours at Baseline and including participants with available data at Baseline and each post-baseline visit (indicated by "n"); LOCF imputation was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Week 2; n=79,70,75,71,144,72,143,143,135,137,77,76	27.8 34.3%	25.7 33.4%	37.3 47.8%	29.6 37.5%	26.4 16.9%	34.7 44.5%	36.4 24.4%	38.5 25.8%	34.1 23.7%	36.5 23.9%	36.4 44.9%	46.1 56.9%
Week 4; n=78,72,73,73,144,72,139,140,137,140,77,74	42.3 52.2%	27.8 36.1%	43.8 56.2%	35.6 45.1%	34.0 21.8%	44.4 56.9%	45.3 30.4%	42.1 28.3%	48.2 33.5%	56.4 36.9%	48.1 59.4%	41.9 51.7%
Week 8; n=76,70,73,72,145,73,141,140,133,142,77,73	53.9 66.5%	35.7 46.4%	50.7 65%	43.1 54.6%	40.0 25.6%	56.2 72.1%	46.8 31.4%	54.3 36.4%	49.6 34.4%	56.3 36.8%	57.1 70.5%	64.4 79.5%
Week 12;n=74,69,72,69,142,72,136,136,132,142,75,72	55.4 68.4%	46.4 60.3%	47.2 60.5%	53.6 67.8%	47.9 30.7%	55.6 71.3%	55.1 37%	55.1 37%	53.8 37.4%	62.0 40.5%	65.3 80.6%	61.1 75.4%
EOT; n=79,75,76,73,146,75,144,145,140,146,78,79	53.2 65.7%	42.7 55.5%	47.4 60.8%	54.8 69.4%	47.9 30.7%	54.7 70.1%	54.2 36.4%	53.1 35.6%	52.1 36.2%	61.6 40.3%	65.4 80.7%	58.2 71.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The logistic regression model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95% 0.69 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95% 0.72 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95% 0.67 to 1.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95% 0.61 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 95% 1.14 to 3.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 95% 1.11 to 3.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.54
	Confidence Interval	(2-Sided) 95% 0.84 to 2.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95% 0.45 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95% 0.45 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95% 0.74 to 2.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95% 0.63 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95% 0.73 to 2.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95% 0.75 to 2.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95% 0.70 to 2.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95% 0.64 to 2.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.16
	Confidence Interval	(2-Sided) 95% 1.18 to 3.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.33
	Confidence Interval	(2-Sided) 95% 1.16 to 4.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.74
	Confidence Interval	(2-Sided) 95% 0.88 to 3.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline to Each 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 participant in the micturition diary for 3-days before the Baseline and each post-baseline clinic visit.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full Analysis Set-Incontinence including participants with available data at Baseline and each post-baseline visit (indicated by "n").

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	17	13	18	15	35	15	35	33	32	24	24	19
Week 2; n=17,13,18,15,33,14,35,33,32,21,24,19	-0.83 (0.168)	-0.43 (0.191)	-0.85 (0.162)	-0.98 (0.178)	-0.67 (0.119)	-0.71 (0.184)	-0.49 (0.116)	-0.64 (0.120)	-0.70 (0.122)	-0.65 (0.150)	-1.14 (0.140)	-0.77 (0.157)
Week 4; n=17,10,18,15,34,14,34,30,32,23,24,19	-0.87 (0.146)	-0.48 (0.189)	-0.89 (0.141)	-1.20 (0.155)	-0.80 (0.102)	-0.84 (0.160)	-0.73 (0.102)	-0.67 (0.109)	-0.81 (0.106)	-0.88 (0.125)	-1.18 (0.122)	-0.71 (0.137)
Week 8; n=17,10,18,14,34,15,35,30,32,22,24,20	-0.82 (0.163)	-0.65 (0.210)	-0.92 (0.157)	-1.12 (0.178)	-0.72 (0.114)	-1.04 (0.172)	-0.78 (0.112)	-0.82 (0.122)	-1.01 (0.118)	-0.95 (0.142)	-0.93 (0.136)	-0.91 (0.149)
Week 12; n=17,10,18,13,34,14,33,30,30,23,24,20	-0.93 (0.373)	-0.59 (0.482)	-0.89 (0.361)	-1.21 (0.424)	-0.84 (0.261)	-0.95 (0.409)	-0.74 (0.265)	-0.88 (0.279)	-1.20 (0.280)	-1.11 (0.319)	-0.27 (0.311)	-0.96 (0.341)

8. Secondary Outcome

Title	Percentage of Participants With Zero Incontinence Episodes Post-baseline
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 participant.
Time Frame	Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full Analysis Set-Incontinence including participants with available data at Baseline and each post-baseline visit (indicated by "n"); LOCF imputation was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	17	13	18	15	35	15	35	33	32	24	24	20
Week 2; n=17,13,18,15,33,14,35,33,32,21,24,19	47.1 58.1%	23.1 30%	44.4 56.9%	40.0 50.6%	45.5 29.2%	50.0 64.1%	40.0 26.8%	51.5 34.6%	65.6 45.6%	52.4 34.2%	70.8 87.4%	52.6 64.9%
Week 4; n=17,10,18,15,34,14,34,30,32,23,24,19	64.7 79.9%	20.0 26%	55.6 71.3%	73.3 92.8%	64.7 41.5%	71.4 91.5%	55.9 37.5%	46.7 31.3%	62.5 43.4%	52.2 34.1%	79.2 97.8%	52.6 64.9%
Week 8; n=17,10,18,14,34,15,35,30,32,22,24,20	58.8 72.6%	50.0 64.9%	61.1 78.3%	71.4 90.4%	50.0 32.1%	73.3 94%	54.3 36.4%	50.0 33.6%	71.9 49.9%	77.3 50.5%	79.2 97.8%	65.0 80.2%
Week 12; n=17,10,18,13,34,14,33,30,30,23,24,20	82.4 101.7%	50.0 64.9%	61.1 78.3%	69.2 87.6%	58.8 37.7%	57.1 73.2%	51.5 34.6%	63.3 42.5%	86.7 60.2%	87.0 56.9%	79.2 97.8%	75.0 92.6%
EOT; n=17,13,18,15,35,15,35,33,32,24,24,20	82.4 101.7%	46.2 60%	61.1 78.3%	66.7 84.4%	60.0 38.5%	53.3 68.3%	54.3 36.4%	60.6 40.7%	87.5 60.8%	87.5 57.2%	79.2 97.8%	75.0 92.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The logistic regression model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.52
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95% 0.16 to 2.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95% 0.23 to 1.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95% 0.32 to 2.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.12
	Confidence Interval	(2-Sided) 95% 1.47 to 25.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.49
	Confidence Interval	(2-Sided) 95% 1.17 to 25.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.84
	Confidence Interval	(2-Sided) 95% 0.95 to 15.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 95% 0.48 to 7.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95% 0.05 to 2.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95% 0.08 to 2.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95% 0.17 to 6.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95% 0.09 to 2.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95% 0.05 to 1.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95% 0.06 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95% 0.09 to 1.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.67
	Confidence Interval	(2-Sided) 95% 0.44 to 16.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.39
	Confidence Interval	(2-Sided) 95% 0.37 to 15.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.68
	Confidence Interval	(2-Sided) 95% 0.29 to 9.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.15 to 4.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With 50% Reduction in Incontinence Episodes
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 participant's micturition diary.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full Analysis Set-Incontinence including participants with available data at Baseline and each post-baseline visit (indicated by "n"); LOCF imputation was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	17	13	18	15	35	15	35	33	32	24	24	20
Week 2; n=17,13,18,15,33,14,35,33,32,21,24,19	64.7 79.9%	30.8 40%	66.7 85.5%	73.3 92.8%	57.6 36.9%	57.1 73.2%	51.4 34.5%	66.7 44.8%	71.9 49.9%	66.7 43.6%	91.7 113.2%	68.4 84.4%
Week 4; n=17,10,18,15,34,14,34,30,32,23,24,19	82.4 101.7%	40.0 51.9%	72.2 92.6%	86.7 109.7%	76.5 49%	78.6 100.8%	64.7 43.4%	63.3 42.5%	75.0 52.1%	78.3 51.2%	95.8 118.3%	68.4 84.4%
Week 8; n=17,10,18,14,34,15,35,30,32,22,24,20	76.5 94.4%	60.0 77.9%	77.8 99.7%	85.7 108.5%	58.8 37.7%	86.7 111.2%	82.9 55.6%	73.3 49.2%	90.6 62.9%	81.8 53.5%	91.7 113.2%	75.0 92.6%
Week 12; n=17,10,18,13,34,14,33,30,30,23,24,20	94.1 116.2%	70.0 90.9%	77.8 99.7%	84.6 107.1%	73.5 47.1%	64.3 82.4%	66.7 44.8%	80.0 53.7%	96.7 67.2%	95.7 62.5%	95.8 118.3%	90.0 111.1%
EOT; n=17,13,18,15,35,15,35,33,32,24,24,20	94.1 116.2%	61.5 79.9%	77.8 99.7%	86.7 109.7%	74.3 47.6%	66.7 85.5%	68.6 46%	75.8 50.9%	96.9 67.3%	95.8 62.6%	95.8 118.3%	90.0 111.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The logistic regression model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95% 0.16 to 2.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95% 0.25 to 2.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95% 0.34 to 3.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	12.16
	Confidence Interval	(2-Sided) 95% 1.40 to 105.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.042
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.48
	Confidence Interval	(2-Sided) 95% 1.08 to 83.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.03
	Confidence Interval	(2-Sided) 95% 1.03 to 79.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.79
	Confidence Interval	(2-Sided) 95% 0.52 to 14.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95% 0.01 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95% 0.02 to 1.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95% 0.04 to 5.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95% 0.02 to 1.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95% 0.01 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95% 0.01 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95% 0.02 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 95% 0.11 to 35.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95% 0.09 to 27.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95% 0.08 to 26.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95% 0.04 to 5.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline to Each Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours
Description	Urgency incontinence is the involuntary leakage of urine accompanied by or immediately preceded by urgency, and was derived from the number of incontinence episodes classified by the participant in a 3-day micturition diary as Grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full Analysis Set-Incontinence participants who had at least 1 urgency (grade 3 or 4) incontinence episode at Baseline, including participants with available data at Baseline and each post-baseline visit (indicated by "n"). LOCF was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	17	13	18	15	35	15	35	33	32	24	24	20
Week 2; n=14,13,17,15,33,12,29,33,31,21,24,18	-0.80 (0.178)	-0.59 (0.184)	-0.83 (0.161)	-0.96 (0.171)	-0.66 (0.115)	-0.77 (0.191)	-0.52 (0.123)	-0.68 (0.115)	-0.68 (0.120)	-0.64 (0.145)	-1.12 (0.135)	-0.76 (0.156)
Week 4; n=14,10,17,15,34,12,28,30,31,22,24,18	-0.83 (0.157)	-0.48 (0.185)	-0.93 (0.142)	-1.13 (0.151)	-0.77 (0.100)	-1.00 (0.169)	-0.73 (0.111)	-0.70 (0.107)	-0.81 (0.106)	-0.86 (0.125)	-1.20 (0.120)	-0.68 (0.138)
Week 8; n=14,10,17,14,34,13,29,30,31,21,24,19	-0.86 (0.173)	-0.65 (0.204)	-1.00 (0.157)	-1.04 (0.172)	-0.76 (0.110)	-1.16 (0.179)	-0.86 (0.119)	-0.84 (.118)	-0.99 (0.117)	-0.89 (0.141)	-0.91 (0.132)	-0.88 (0.148)
Week 12; n=14,10,17,13,34,12,28,30,29,22,24,19	-0.84 (0.420)	-0.54 (0.493)	-0.87 (0.379)	-1.13 (0.433)	-0.83 (0.267)	-1.13 (0.451)	-0.81 (0.295)	-0.91 (0.286)	-1.19 (0.292)	-1.06 (0.334)	-0.28 (0.319)	-0.93 (0.358)
EOT; n=14,13,17,15,35,13,29,33,31,23,24,19	-0.86 (0.411)	-0.80 (0.424)	-0.88 (0.372)	-1.17 (0.394)	-0.86 (0.258)	-1.13 (0.424)	-0.81 (0.283)	-0.87 (0.266)	-1.20 (0.277)	-1.08 (0.321)	-0.28 (0.312)	-0.94 (0.351)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	The ANCOVA model including the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and Baseline measurement as a covariate was used to calculate point estimates and 95% confidence intervals for change from Baseline within each treatment group and for differences between combination treatment groups and solifenacin 5 mg as well as for differences between active treatment groups and placebo.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.25
	Comments	All statistical comparisons are for change from Baseline to End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed.
	Method	Stratified Rank ANCOVA
	Comments	P-values are from pairwise comparisons of the combination/active treatment groups vs. solifenacin 5 mg/placebo within a stratified rank ANCOVA model.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95% -1.24 to 0.71
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.495
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -0.70 to 0.81
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.383
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95% -0.74 to 0.72
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.371
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95% -1.08 to 0.41
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.377
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95% -1.04 to 0.59
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.413
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95% -0.21 to 1.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.405
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95% -0.94 to 0.78
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.435
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95% -1.10 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.590
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95% -1.11 to 1.07
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.552
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95% -1.43 to 0.82
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.570
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95% -0.96 to 0.96
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.487
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95% -1.44 to 0.90
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.593
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.46
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -0.93 to 1.04
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.500
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95% -0.97 to 0.96
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.490
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95% -1.32 to 0.65
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.499
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95% -1.24 to 0.80
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.517
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.72
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95% -0.43 to 1.60
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.516
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Stratified Rank ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95% -1.15 to 0.98
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.541
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline to Each 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, which is difficult to defer), derived from urgency episodes classified by the participant in the 3-day micturition diary as grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale: 0: No urgency; 1: Mild urgency; 2: Moderate urgency, could delay voiding a short while; 3: Severe urgency, could not delay voiding; 4: Urge incontinence, leaked before arriving to the toilet.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full analysis set including participants with available data at Baseline and each post-baseline visit (indicated by "n"). LOCF was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Week 2; n=80,71,76,74,148,73,145,145,136,141,77,77	-2.07 (0.276)	-2.06 (0.292)	-1.91 (0.282)	-2.49 (0.286)	-1.63 (0.202)	-1.97 (0.288)	-1.84 (0.205)	-2.59 (0.205)	-2.30 (0.211)	-2.57 (0.207)	-2.35 (0.281)	-2.23 (0.281)
Week 4; n=79,72,74,76,147,73,141,142,138,144,77,75	-2.55 (0.308)	-2.70 (0.322)	-2.70 (0.317)	-3.16 (0.313)	-2.24 (0.225)	-3.02 (0.320)	-2.64 (0.230)	-3.14 (0.229)	-3.08 (0.233)	-3.17 (0.228)	-3.04 (0.311)	-2.81 (0.316)
Week 8; n=77,70,73,75,147,74,143,142,134,145,77,74	-3.42 (0.318)	-2.86 (0.332)	-3.27 (0.325)	-3.61 (0.321)	-2.67 (0.229)	-3.63 (0.323)	-3.34 (0.232)	-3.60 (0.233)	-3.60 (0.240)	-3.85 (0.231)	-3.53 (0.317)	-3.63 (0.323)
Week 12;n=75,69,73,73,144,73,138,138,133,144,75,73	-3.69 (0.334)	-3.31 (0.347)	-3.65 (0.338)	-3.54 (0.338)	-2.71 (0.240)	-4.15 (0.337)	-3.26 (0.246)	-4.24 (0.246)	-3.98 (0.250)	-4.09 (0.240)	-3.76 (0.333)	-3.93 (0.338)
EOT; n=80,76,77,77,150,76,146,147,141,150,78,80	-3.53 (0.328)	-3.23 (0.336)	-3.44 (0.334)	-3.62 (0.334)	-2.73 (0.239)	-3.98 (0.336)	-3.21 (0.242)	-3.97 (0.242)	-3.86 (0.247)	-4.10 (0.239)	-3.71 (0.332)	-3.91 (0.327)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for change from Baseline to End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.26
	Confidence Interval	(2-Sided) 95% -2.06 to -0.45
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.412
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95% -1.15 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.340
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.24
	Confidence Interval	(2-Sided) 95% -1.91 to -0.57
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.340
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.13
	Confidence Interval	(2-Sided) 95% -1.80 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.343
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.37
	Confidence Interval	(2-Sided) 95% -2.03 to -0.70
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.338
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95% -1.78 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.409
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.18
	Confidence Interval	(2-Sided) 95% -1.98 to -0.39
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.405
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95% -0.63 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.469
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95% -0.83 to 1.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.468
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95% -1.01 to 0.83
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.468
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.050
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% -0.00 to 1.59
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.406
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95% -1.38 to 0.46
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.469
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95% -0.48 to 1.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.407
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95% -1.24 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.408
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95% -1.14 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.410
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95% -1.37 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.406
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95% -1.10 to 0.73
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.467
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95% -1.30 to 0.52
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.464
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline to Each Visit in Mean Level of Urgency
Description	Average of participants' ratings on the degree of urgency associated with each micturition and/or incontinence episode recorded in the 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.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full analysis set including participants with available data at Baseline and each post-baseline visit (indicated by "n"). LOCF was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Week 2; n=80,71,76,74,148,73,145,145,136,141,77,77	-0.24 (0.043)	-0.19 (0.046)	-0.15 (0.044)	-0.25 (0.045)	-0.14 (0.032)	-0.21 (0.045)	-0.19 (0.032)	-0.26 (0.032)	-0.26 (0.033)	-0.28 (0.033)	-0.31 (0.044)	-0.20 (0.044)
Week 4; n=79,72,74,76,147,73,141,142,138,144,77,75	-0.32 (0.052)	-0.28 (0.054)	-0.26 (0.053)	-0.33 (0.053)	-0.23 (0.038)	-0.35 (0.054)	-0.32 (0.039)	-0.35 (0.039)	-0.35 (0.039)	-0.37 (0.038)	-0.41 (0.052)	-0.31 (0.053)
Week 8; n=77,70,73,75,147,74,143,142,134,145,77,74	-0.42 (0.059)	-0.30 (0.062)	-0.36 (0.061)	-0.45 (0.060)	-0.30 (0.043)	-0.44 (0.60)	-0.39 (0.043)	-0.41 (0.044)	-0.45 (0.045)	-0.46 (0.043)	-0.53 (0.059)	-0.43 (0.060)
Week 12;n=75,69,73,73,144,73,138,138,133,144,75,73	-0.48 (0.064)	-0.35 (0.067)	-0.44 (0.065)	-0.42 (0.065)	-0.33 (0.046)	-0.49 (0.065)	-0.43 (0.047)	-0.54 (0.047)	-0.50 (0.048)	-0.54 (0.046)	-0.61 (0.064)	-0.49 (0.065)
EOT; n=80,76,77,77,150,76,146,147,141,150,78,80	-0.46 (0.063)	-0.33 (0.064)	-0.41 (0.064)	-0.45 (0.064)	-0.33 (0.064)	-0.47 (0.064)	-0.42 (0.046)	-0.50 (0.046)	-0.48 (0.047)	-0.55 (0.046)	-0.59 (0.063)	-0.47 (0.063)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for change from Baseline to End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95% -0.30 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.079
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95% -0.22 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.065
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95% -0.30 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.065
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95% -0.29 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.066
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95% -0.35 to -0.10
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.065
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95% -0.41 to -0.11
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.078
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.070
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95% -0.29 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.077
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95% -0.05 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.090
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -0.12 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.089
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95% -0.16 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.089
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.086
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95% -0.02 to 0.29
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.077
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95% -0.19 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.090
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95% -0.11 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.078
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.20 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.078
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95% -0.18 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.078
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95% -0.25 to 0.06
	Parameter Dispersion	Type: Standard Deviation Value: 0.077
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95% -0.30 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.089
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95% -0.18 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.088
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline to Each Visit in Mean Number of Pads Used Per 24 Hours
Description	The average number of times a participant recorded a new pad used per day during the 3-day micturition diary period.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants who had at least one use of pad at baseline, and including participants with available data at Baseline and each post-baseline visit (indicated by "n"). LOCF was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Week 2; n=33,33,34,31,74,23,62,55,62,62,45,30	-0.81 (0.212)	-0.87 (0.212)	-0.88 (0.209)	-1.31 (0.219)	-0.92 (0.142)	-0.91 (0.255)	-0.86 (0.155)	-0.96 (0.164)	-0.89 (0.155)	-1.02 (0.155)	-1.13 (0.182)	-1.31 (0.223)
Week 4; n=32,31,35,31,75,23,61,52,64,62,45,30	-0.76 (0.224)	-0.93 (0.228)	-0.70 (0.214)	-1.62 (0.228)	-1.26 (0.147)	-1.23 (0.265)	-0.94 (0.162)	-1.09 (0.176)	-1.24 (0.159)	-1.30 (0.161)	-1.35 (0.189)	-1.36 (0.231)
Week 8; n=30,31,34,31,74,24,63,52,64,61,45,30	-0.97 (0.226)	-0.90 (0.223)	-1.11 (0.213)	-1.47 (0.223)	-1.25 (0.144)	-1.53 (0.253)	-1.10 (0.156)	-1.39 (0.172)	-1.29 (0.155)	-1.51 (0.159)	-1.37 (0.185)	-1.56 (0.227)
Week 12; n=30,31,34,29,72,23,60,52,63,62,45,31	-0.92 (0.246)	-0.97 (0.242)	-0.93 (0.231)	-1.35 (0.251)	-1.39 (0.159)	-1.75 (0.282)	-1.02 (0.174)	-1.44 (0.187)	-1.45 (0.170)	-1.63 (0.172)	-1.60 (0.201)	-1.60 (0.243)
EOT; n=33,34,35,32,76,24,63,56,64,65,46,32	-0.63 (0.244)	-1.04 (0.241)	-0.95 (0.237)	-1.44 (0.248)	-1.38 (0.161)	-1.73 (0.287)	-1.04 (0.177)	-1.38 (0.188)	-1.46 (0.176)	-1.63 (0.174)	-1.59 (0.207)	-1.63 (0.248)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for change from Baseline to End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95% -0.99 to 0.30
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.330
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95% -0.12 to 0.82
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.239
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95% -0.48 to 0.49
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.248
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95% -0.54 to 0.40
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.239
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95% -0.71 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.238
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95% -0.72 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.262
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95% -0.83 to 0.33
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.296
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95% -1.08 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.343
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95% -0.98 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.340
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.81
	Confidence Interval	(2-Sided) 95% -1.49 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.348
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) 95% -1.33 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.293
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95% -1.84 to -0.36
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.377
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95% -1.00 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.301
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) 95% -1.35 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.308
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95% -1.41 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.301
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) 95% -1.59 to -0.41
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.300
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95% -1.59 to -0.33
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.320
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) 95% -1.68 to -0.31
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.348
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline to Each 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 participant urinated (excluding incontinence only episodes) during sleeping time per day was derived from the 3-day micturition diary.
Time Frame	Baseline and Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants who had at least one nocturia episode at baseline, and including participants with available data at Baseline and each post-baseline visit (indicated by "n"). LOCF was used for the End of Treatment (EOT) analysis.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Week 2; n=78,69,75,72,144,71,142,138,133,138,74,73	-0.33 (0.115)	-0.37 (0.123)	-0.60 (0.118)	-0.38 (0.120)	-0.30 (0.085)	-0.45 (0.121)	-0.43 (0.086)	-0.51 (0.087)	-0.49 (0.088)	-0.61 (0.087)	-0.43 (0.119)	-0.53 (0.119)
Week 4; n=77,69,74,74,143,71,138,135,134,141,74,71	-0.50 (0.116)	-0.60 (0.123)	-0.71 (0.118)	-0.55 (0.118)	-0.47 (0.085)	-0.74 (0.121)	-0.59 (0.087)	-0.54 (0.088)	-0.69 (0.088)	-0.80 (0.086)	-0.67 (0.119)	-0.75 (0.121)
Week 8; n=75,67,73,73,143,72,140,135,130,142,74,70	-0.64 (0.126)	-0.65 (0.133)	-0.68 (0.127)	-0.80 (0.127)	-0.65 (0.091)	-1.01 (0.128)	-0.76 (0.092)	-0.79 (0.094)	-0.76 (0.095)	-0.98 (0.091)	-0.81 (0.127)	-0.91 (0.130)
Week 12;n=73,66,73,71,140,71,135,131,130,141,72,69	-0.79 (0.146)	-0.69 (0.154)	-0.84 (0.146)	-0.59 (0.148)	-0.70 (0.106)	-0.99 (0.148)	-0.75 (0.108)	-0.81 (0.109)	-0.80 (0.110)	-1.05 (0.105)	-0.98 (0.147)	-1.03 (0.150)
EOT; n=78,73,76,75,146,74,143,140,137,147,75,76	-0.74 (0.140)	-0.69 (0.145)	-0.82 (0.142)	-0.68 (0.143)	-0.69 (0.102)	-0.95 (0.144)	-0.73 (0.104)	-0.77 (0.105)	-0.77 (0.106)	-1.04 (0.102)	-0.94 (0.143)	-0.96 (0.142)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for change from Baseline to End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95% -0.60 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.177
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.33 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.146
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95% -0.37 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.146
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.60
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95% -0.37 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.147
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95% -0.63 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.145
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95% -0.60 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.176
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95% -0.61 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.175
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -0.35 to 0.44
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.201
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95% -0.48 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.199
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95% -0.33 to 0.45
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.200
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95% -0.30 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.81
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95% -0.60 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.201
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95% -0.34 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.174
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.38 to 0.30
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.175
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.38 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.175
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.080
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95% -0.64 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.173
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95% -0.60 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.200
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95% -0.62 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.199
	Estimation Comments

15. Secondary Outcome

Title	Change From Baseline to End of Treatment 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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full Analysis Set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	78	73	76	75	147	73	141	143	136	144	76	78
Least Squares Mean (Standard Error) [units on a scale]	-1.4 (0.14)	-1.4 (0.14)	-1.5 (0.14)	-1.5 (0.14)	-1.3 (0.10)	-1.5 (0.14)	-1.4 (0.10)	-1.7 (0.10)	-1.7 (0.10)	-1.8 (0.10)	-1.8 (0.14)	-1.6 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	Statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model for all pairwise comparisons includes the 2 main factors mirabegron dose and solifenacin succinate dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95% -0.5 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95% -0.3 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.14
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95% -0.6 to -0.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.14
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95% -0.7 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.14
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95% -0.7 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.14
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95% -0.8 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95% -0.6 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95% -0.4 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.20
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95% -0.5 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.19
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95% -0.5 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.19
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95% -0.3 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95% -0.5 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.20
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95% -0.3 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.084
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95% -0.6 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95% -0.7 to -0.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95% -0.7 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.17
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95% -0.8 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.19
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95% -0.6 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.19
	Estimation Comments

16. Secondary Outcome

Title	Percentage of Participants With Improvement in 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 1-point improvement (decrease) from Baseline in PPBC score.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	78	73	76	75	147	73	141	143	136	144	76	78
Number [percentage of participants]	69.2 85.4%	76.7 99.6%	78.9 101.2%	68.0 86.1%	72.8 46.7%	84.9 108.8%	74.5 50%	83.2 55.8%	77.9 54.1%	82.6 54%	82.9 102.3%	75.6 93.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The logistic regression model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.040
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.26
	Confidence Interval	(2-Sided) 95% 1.04 to 4.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95% 0.63 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.050
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.82
	Confidence Interval	(2-Sided) 95% 1.00 to 3.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95% 0.81 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.02
	Confidence Interval	(2-Sided) 95% 1.11 to 3.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.64
	Confidence Interval	(2-Sided) 95% 0.79 to 3.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% 0.57 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95% 0.58 to 2.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.67
	Confidence Interval	(2-Sided) 95% 0.77 to 3.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.41 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.55 to 1.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.36
	Confidence Interval	(2-Sided) 95% 1.01 to 5.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95% 0.60 to 2.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.070
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95% 0.95 to 3.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95% 0.77 to 2.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.034
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.11
	Confidence Interval	(2-Sided) 95% 1.06 to 4.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95% 0.76 to 3.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95% 0.55 to 2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Percentage of Participants With Major Improvement in 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'. Major improvement was defined as at least a 2-point improvement (decrease) from Baseline in PPBC score.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	78	73	76	75	147	73	141	143	136	144	76	78
Number [percentage of participants]	39.7 49%	42.5 55.2%	38.2 49%	44.0 55.7%	42.2 27.1%	46.6 59.7%	48.2 32.3%	52.4 35.2%	54.4 37.8%	54.9 35.9%	57.9 71.5%	50.0 61.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95% 0.64 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95% 0.82 to 2.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95% 0.91 to 2.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.81
	Confidence Interval	(2-Sided) 95% 1.10 to 2.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.87
	Confidence Interval	(2-Sided) 95% 1.15 to 3.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.72
	Confidence Interval	(2-Sided) 95% 0.95 to 3.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95% 0.77 to 2.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.49 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.46 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95% 0.59 to 2.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95% 0.55 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95% 0.59 to 2.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95% 0.73 to 2.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95% 0.82 to 2.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.80
	Confidence Interval	(2-Sided) 95% 0.99 to 3.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.87
	Confidence Interval	(2-Sided) 95% 1.04 to 3.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.72
	Confidence Interval	(2-Sided) 95% 0.87 to 3.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95% 0.70 to 2.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Percentage of Participants With Deterioration in 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'. Deterioration was defined as at least a 1 point increase from Baseline in PPBC score.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	78	73	76	75	147	73	141	143	136	144	76	78
Number [percentage of participants]	6.4 7.9%	4.1 5.3%	5.3 6.8%	4.0 5.1%	4.8 3.1%	2.7 3.5%	4.3 2.9%	2.8 1.9%	2.9 2%	1.4 0.9%	1.3 1.6%	6.4 7.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The logistic regression model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95% 0.06 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95% 0.21 to 2.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95% 0.13 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95% 0.10 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.082
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95% 0.04 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.36
	Confidence Interval	(2-Sided) 95% 0.04 to 3.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95% 0.42 to 5.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95% 0.19 to 5.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.24 to 4.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95% 0.12 to 3.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95% 0.28 to 3.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95% 0.06 to 2.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95% 0.20 to 3.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.46
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95% 0.12 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95% 0.10 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95% 0.04 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95% 0.04 to 3.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.64
	Confidence Interval	(2-Sided) 95% 0.39 to 6.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Change From Baseline to End of Treatment in Symptom Bother Score as Assessed by the Overactive Bladder Questionnaire (OAB-q)
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 participant on a scale from 1-6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from Baseline in symptom bother score indicates improvements.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	79	75	76	77	150	75	144	145	139	146	78	78
Least Squares Mean (Standard Error) [units on a scale]	-25.5 (1.96)	-27.1 (2.01)	-27.5 (2.00)	-29.8 (1.99)	-26.8 (1.42)	-29.9 (2.01)	-28.0 (1.45)	-31.7 (1.45)	-32.0 (1.48)	-33.5 (1.44)	-33.6 (1.97)	-31.4 (1.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	Statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model for all pairwise comparisons includes the 2 main factors mirabegron dose and solifenacin succinate dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95% -8.0 to 1.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.47
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95% -5.2 to 2.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.03
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95% -8.9 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.03
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.2
	Confidence Interval	(2-Sided) 95% -9.3 to -1.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.05
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) 95% -10.7 to -2.8
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.03
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.8
	Confidence Interval	(2-Sided) 95% -11.6 to -2.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.43
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.056
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95% -9.4 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.44
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95% -7.1 to 3.9
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.81
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95% -7.5 to 3.5
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.80
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.3
	Confidence Interval	(2-Sided) 95% -9.8 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.13
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95% -6.0 to 3.5
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.42
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95% -9.9 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.81
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95% -7.3 to 2.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.44
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95% -10.9 to -1.3
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.44
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95% -11.3 to -1.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.46
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-8.0
	Confidence Interval	(2-Sided) 95% -12.8 to -3.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.44
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-8.0
	Confidence Interval	(2-Sided) 95% -13.5 to -2.6
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.78
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) 95% -11.4 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.79
	Estimation Comments

20. Secondary Outcome

Title	Percentage of Participants With a Symptom Bother Response
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 participant on a scale from 1-6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. Symptom bother response is defined as improvement (decrease) of at least 10 points from Baseline.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	79	75	76	77	150	75	144	145	139	146	78	78
Number [percentage of participants]	73.4 90.6%	84.0 109.1%	78.9 101.2%	85.7 108.5%	81.3 52.1%	85.3 109.4%	82.6 55.4%	85.5 57.4%	85.6 59.4%	88.4 57.8%	88.5 109.3%	83.3 102.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons are for End of Treatment using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The logistic regression model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95% 0.63 to 3.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.55 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95% 0.63 to 2.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95% 0.70 to 2.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.66
	Confidence Interval	(2-Sided) 95% 0.83 to 3.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95% 0.67 to 3.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.42 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.75
	Confidence Interval	(2-Sided) 95% 0.75 to 4.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95% 0.56 to 2.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.97
	Confidence Interval	(2-Sided) 95% 0.83 to 4.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.57
	Confidence Interval	(2-Sided) 95% 0.78 to 3.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.070
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.24
	Confidence Interval	(2-Sided) 95% 0.94 to 5.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.64
	Confidence Interval	(2-Sided) 95% 0.81 to 3.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.084
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95% 0.92 to 3.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.043
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.14
	Confidence Interval	(2-Sided) 95% 1.02 to 4.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.61
	Confidence Interval	(2-Sided) 95% 1.22 to 5.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.43
	Confidence Interval	(2-Sided) 95% 0.99 to 5.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95% 0.63 to 3.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Change From Baseline to End of Treatment 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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	79	75	76	77	150	75	144	145	139	146	78	78
Least Squares Mean (Standard Error) [units on a scale]	24.5 (2.03)	22.5 (2.08)	25.8 (2.07)	27.7 (2.05)	23.7 (1.47)	26.6 (2.08)	25.5 (1.50)	28.5 (1.50)	29.2 (1.53)	30.1 (1.49)	30.3 (2.04)	28.9 (2.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	Statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model for all pairwise comparisons includes the 2 main factors mirabegron dose and solifenacin succinate dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95% -2.1 to 7.9
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.55
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95% -2.3 to 6.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.10
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Differrence
	Estimated Value	4.8
	Confidence Interval	(2-Sided) 95% 0.7 to 8.9
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.10
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.5
	Confidence Interval	(2-Sided) 95% 1.3 to 9.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.12
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.4
	Confidence Interval	(2-Sided) 95% 2.3 to 10.5
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.09
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 95% 1.7 to 11.6
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.52
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95% 0.3 to 10.2
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.52
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95% -7.7 to 3.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.90
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95% -4.4 to 7.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.89
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95% -2.4 to 8.9
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.88
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95% -5.7 to 4.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.51
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95% -3.6 to 7.8
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.91
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95% -3.9 to 6.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.52
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95% -0.9 to 9.0
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.52
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.7
	Confidence Interval	(2-Sided) 95% -0.2 to 9.7
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.54
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.6
	Confidence Interval	(2-Sided) 95% 0.7 to 10.6
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.52
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95% 0.2 to 11.5
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.88
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95% -1.2 to 10.1
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.88
	Estimation Comments

22. Secondary Outcome

Title	Percentage of Participants With a Health-related Quality of Life Total Score Response
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. HRQL response is defined as improvement (decrease) of at least 10 points from Baseline.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	79	75	76	77	150	75	144	145	139	146	78	78
Number [percentage of participants]	67.1 82.8%	57.3 74.4%	71.1 91.2%	74.0 93.7%	72.7 46.6%	74.7 95.8%	72.9 48.9%	78.6 52.8%	77.0 53.5%	84.2 55%	79.5 98.1%	82.1 101.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	All statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The logistic regression model includes the 2 main factors mirabegron dose and solifenacin dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.52 to 2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95% 0.58 to 1.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95% 0.70 to 2.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95% 0.79 to 2.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.21
	Confidence Interval	(2-Sided) 95% 1.19 to 4.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95% 0.70 to 2.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95% 0.72 to 3.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.064
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95% 0.24 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95% 0.59 to 2.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95% 0.59 to 2.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95% 0.58 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.72
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95% 0.53 to 2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% 0.58 to 2.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95% 0.71 to 2.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.57
	Confidence Interval	(2-Sided) 95% 0.80 to 3.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.45
	Confidence Interval	(2-Sided) 95% 1.22 to 4.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95% 0.72 to 3.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.67
	Confidence Interval	(2-Sided) 95% 0.74 to 3.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline 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 valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems in walking about; I have some problems in walking about; I am confined to bed. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of patients in that category.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
No problem → No problem	60 74.1%	58 75.3%	63 80.8%	59 74.7%	118 75.6%	54 69.2%	94 63.1%	113 75.8%	102 70.8%	120 78.4%	59 72.8%	56 69.1%
No problem → Some problems	6 7.4%	1 1.3%	4 5.1%	4 5.1%	6 3.8%	4 5.1%	9 6%	5 3.4%	9 6.3%	1 0.7%	0 0%	5 6.2%
No problem → Confined to bed	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
No problem → Missing data	1 1.2%	1 1.3%	1 1.3%	0 0%	0 0%	1 1.3%	1 0.7%	1 0.7%	1 0.7%	1 0.7%	0 0%	2 2.5%
Some problems → No problems	5 6.2%	6 7.8%	6 7.7%	4 5.1%	11 7.1%	8 10.3%	21 14.1%	15 10.1%	13 9%	14 9.2%	11 13.6%	8 9.9%
Some problems → Some problems	8 9.9%	10 13%	3 3.8%	10 12.7%	15 9.6%	9 11.5%	20 13.4%	12 8.1%	15 10.4%	11 7.2%	8 9.9%	9 11.1%
Some problems → Confined to bed	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Some problems → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	1 0.7%	0 0%	0 0%
Confined → No problems	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Confined → Some problems	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Confined → Confined to bed	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Confined → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → No problem	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	2 1.3%	0 0%	0 0%
Missing data → Some problems	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%	0 0%
Missing data → Confined to bed	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

24. Secondary Outcome

Title	Change From Baseline 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 valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no problems with self-care; I have some problems washing or dressing myself; I am unable to wash or dress myself. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of patients in that category.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
No problem → No problem	76 93.8%	69 89.6%	73 93.6%	72 91.1%	138 88.5%	68 87.2%	128 85.9%	138 92.6%	130 90.3%	141 92.2%	74 91.4%	72 88.9%
No problem → Some problems	0 0%	1 1.3%	3 3.8%	2 2.5%	2 1.3%	2 2.6%	5 3.4%	2 1.3%	1 0.7%	1 0.7%	1 1.2%	0 0%
No problem → Unable	0 0%	0 0%	0 0%	0 0%	1 0.6%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
No problem → Missing data	1 1.2%	0 0%	1 1.3%	0 0%	0 0%	1 1.3%	1 0.7%	1 0.7%	2 1.4%	2 1.3%	0 0%	2 2.5%
Some problems → No problems	1 1.2%	4 5.2%	0 0%	1 1.3%	6 3.8%	3 3.8%	8 5.4%	3 2%	3 2.1%	2 1.3%	1 1.2%	2 2.5%
Some problems → Some problems	2 2.5%	1 1.3%	0 0%	2 2.5%	3 1.9%	1 1.3%	3 2%	2 1.3%	4 2.8%	2 1.3%	2 2.5%	4 4.9%
Some problems → Unable	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%
Some problems → Missing data	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unable → No problems	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unable → Some problems	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unable → Unable	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unable → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → No problem	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	2 1.3%	0 0%	0 0%
Missing data → Some problems	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%	0 0%
Missing data → Unable	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

25. Secondary Outcome

Title	Change From Baseline 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 End of Treatment health status and reports the number of patients in that category.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
No problem → No problem	62 76.5%	52 67.5%	58 74.4%	60 75.9%	115 73.7%	57 73.1%	89 59.7%	110 73.8%	106 73.6%	109 71.2%	57 70.4%	48 59.3%
No problem → Some problems	2 2.5%	2 2.6%	3 3.8%	2 2.5%	3 1.9%	4 5.1%	8 5.4%	3 2%	9 6.3%	4 2.6%	1 1.2%	5 6.2%
No problem → Unable	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.2%
No problem → Missing data	0 0%	0 0%	1 1.3%	0 0%	0 0%	1 1.3%	1 0.7%	1 0.7%	1 0.7%	2 1.3%	0 0%	2 2.5%
Some problems → No problems	11 13.6%	11 14.3%	8 10.3%	11 13.9%	16 10.3%	7 9%	29 19.5%	24 16.1%	12 8.3%	21 13.7%	14 17.3%	14 17.3%
Some problems → Some problems	4 4.9%	10 13%	6 7.7%	4 5.1%	13 8.3%	6 7.7%	18 12.1%	8 5.4%	11 7.6%	12 7.8%	4 4.9%	8 9.9%
Some problems → Unable	0 0%	0 0%	0 0%	0 0%	2 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.2%	0 0%
Some problems → Missing data	1 1.2%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%
Unable → No problems	0 0%	0 0%	0 0%	0 0%	1 0.6%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%
Unable → Some problems	0 0%	0 0%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.2%	2 2.5%
Unable → Unable	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unable → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → No problem	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	2 1.3%	0 0%	0 0%
Missing data → Some problems	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%	0 0%
Missing data → Unable	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

26. Secondary Outcome

Title	Change From Baseline 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 valuing health status. Participants were asked to indicate which of the following statements best describes their health state: I have no pain or discomfort; I have moderate pain or discomfort; I have extreme pain or discomfort. In the table below, each row title lists Baseline health status first followed by End of Treatment health status and reports the number of participants in that category.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
No pain → No pain	38 46.9%	33 42.9%	40 51.3%	38 48.1%	70 44.9%	35 44.9%	67 45%	61 40.9%	66 45.8%	73 47.7%	39 48.1%	32 39.5%
No pain → Moderate pain	9 11.1%	12 15.6%	6 7.7%	4 5.1%	15 9.6%	3 3.8%	6 4%	11 7.4%	14 9.7%	7 4.6%	8 9.9%	6 7.4%
No pain → Extreme pain	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	1 0.7%	0 0%	0 0%	0 0%	0 0%	0 0%
No pain → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%	1 0.7%	1 0.7%	0 0%	1 0.7%	0 0%	2 2.5%
Moderate pain → No pain	12 14.8%	14 18.2%	10 12.8%	12 15.2%	24 15.4%	13 16.7%	24 16.1%	34 22.8%	28 19.4%	36 23.5%	14 17.3%	20 24.7%
Moderate pain → Moderate pain	16 19.8%	15 19.5%	19 24.4%	19 24.1%	37 23.7%	18 23.1%	37 24.8%	33 22.1%	27 18.8%	25 16.3%	12 14.8%	18 22.2%
Moderate pain → Extreme pain	1 1.2%	1 1.3%	0 0%	1 1.3%	0 0%	0 0%	4 2.7%	1 0.7%	0 0%	0 0%	1 1.2%	2 2.5%
Moderate pain → Missing data	1 1.2%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 1.4%	1 0.7%	0 0%	0 0%
Extreme pain → No pain	1 1.2%	0 0%	0 0%	1 1.3%	1 0.6%	2 2.6%	3 2%	1 0.7%	1 0.7%	1 0.7%	0 0%	0 0%
Extreme pain → Moderate pain	2 2.5%	0 0%	0 0%	1 1.3%	1 0.6%	0 0%	2 1.3%	2 1.3%	2 1.4%	4 2.6%	3 3.7%	0 0%
Extreme pain → Extreme pain	0 0%	0 0%	1 1.3%	1 1.3%	2 1.3%	3 3.8%	0 0%	2 1.3%	1 0.7%	0 0%	1 1.2%	0 0%
Extreme pain → Missing data	0 0%	1 1.3%	1 1.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → No pain	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 1.3%	0 0%	0 0%
Missing data → Moderate pain	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	1 0.7%	0 0%	0 0%	0 0%	0 0%
Missing data → Extreme pain	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

27. Secondary Outcome

Title	Change From Baseline 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 End of Treatment health status and reports the number of patients in that category.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
No anxiety → No anxiety	41 50.6%	38 49.4%	39 50%	42 53.2%	76 48.7%	36 46.2%	81 54.4%	78 52.3%	76 52.8%	80 52.3%	44 54.3%	36 44.4%
No anxiety → Moderate anxiety	5 6.2%	8 10.4%	7 9%	4 5.1%	11 7.1%	6 7.7%	7 4.7%	5 3.4%	9 6.3%	3 2%	5 6.2%	6 7.4%
No anxiety → Extreme anxiety	1 1.2%	0 0%	0 0%	0 0%	1 0.6%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%	0 0%
No anxiety → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	1 0.7%	1 0.7%	1 0.7%	0 0%	2 2.5%
Moderate anxiety → No anxiety	17 21%	9 11.7%	15 19.2%	21 26.6%	24 15.4%	19 24.4%	25 16.8%	35 23.5%	28 19.4%	33 21.6%	15 18.5%	14 17.3%
Moderate anxiety → Moderate anxiety	13 16%	18 23.4%	14 17.9%	9 11.4%	33 21.2%	12 15.4%	21 14.1%	22 14.8%	19 13.2%	26 17%	8 9.9%	19 23.5%
Moderate anxiety → Extreme anxiety	0 0%	0 0%	1 1.3%	0 0%	2 1.3%	1 1.3%	1 0.7%	0 0%	1 0.7%	1 0.7%	0 0%	1 1.2%
Moderate anxiety → Missing data	0 0%	1 1.3%	1 1.3%	0 0%	0 0%	1 1.3%	0 0%	0 0%	1 0.7%	1 0.7%	0 0%	0 0%
Extreme anxiety → No anxiety	0 0%	0 0%	0 0%	0 0%	2 1.3%	0 0%	1 0.7%	2 1.3%	2 1.4%	2 1.3%	3 3.7%	2 2.5%
Extreme anxiety → Moderate anxiety	2 2.5%	1 1.3%	0 0%	0 0%	0 0%	1 1.3%	7 4.7%	1 0.7%	4 2.8%	1 0.7%	1 1.2%	0 0%
Extreme anxiety → Extreme anxiety	0 0%	1 1.3%	0 0%	1 1.3%	1 0.6%	0 0%	1 0.7%	1 0.7%	0 0%	0 0%	2 2.5%	0 0%
Extreme anxiety → Missing data	1 1.2%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → No anxiety	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	2 1.3%	0 0%	0 0%
Missing data → Moderate anxiety	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Missing data → Extreme anxiety	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	0 0%	0 0%
Missing data → Missing data	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

28. Secondary Outcome

Title	Change From Baseline to End of Treatment in 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 Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	79	75	76	77	150	75	144	145	139	146	78	78
Mean (Standard Deviation) [units on a scale]	13.1 (21.11)	5.8 (19.38)	14.3 (22.38)	11.1 (19.26)	11.9 (21.33)	13.3 (21.81)	11.6 (21.94)	12.5 (19.95)	11.8 (18.91)	15.9 (20.94)	15.3 (24.17)	11.1 (23.18)

29. Secondary Outcome

Title	Change From Baseline to End of Treatment in Work Productivity and Activity Impairment (WPAI)
Description	This 6-item assessment measures productivity losses during the past 7 days and includes measures on work time missed due to health, impairment while working due to health (the participant's assessment of the degree to which health affected their productivity while working), overall work impairment due to health (takes into account both hours missed due to health and the participant's assessment of the degree to which health affected their productivity while working) and activity impairment due to health (the degree in which health problems affected their ability to do regular daily activities). Scores for each measure are expressed from 0 to 100 with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicates improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used.

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	80	76	77	77	150	76	146	147	141	150	78	80
Percent work time missed	-2.44 (10.580)	0.53 (3.031)	-0.24 (1.988)	-2.85 (11.205)	-1.29 (12.606)	-0.28 (2.737)	-0.55 (12.816)	-0.83 (17.199)	-0.84 (5.330)	-1.65 (4.654)	0.79 (6.757)	-1.12 (11.025)
Percent impairment while working	-7.50 (24.539)	-16.13 (24.314)	-10.00 (22.220)	-16.67 (25.207)	-17.33 (22.689)	-10.00 (17.728)	-8.43 (27.523)	-17.72 (26.187)	-13.85 (27.664)	-13.39 (24.515)	-18.00 (29.642)	-9.29 (26.377)
Percent overall work impairment	-9.50 (24.090)	-16.32 (24.653)	-9.91 (21.464)	-17.88 (28.134)	-17.26 (25.196)	-9.95 (17.988)	-8.59 (29.521)	-17.16 (27.695)	-14.00 (27.384)	-14.18 (25.092)	-17.69 (29.323)	-10.32 (27.580)
Percent activity impairment	-9.62 (26.989)	-14.52 (27.439)	-13.95 (26.386)	-13.73 (27.052)	-14.38 (24.182)	-17.12 (27.813)	-14.11 (31.398)	-25.31 (26.158)	-17.43 (29.008)	-20.42 (27.094)	-19.34 (27.439)	-19.74 (30.021)

30. Secondary Outcome

Title	Change From Baseline to End of Treatment in Treatment Satisfaction on 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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
Full analysis set participants with available Baseline and post-baseline data; LOCF imputation was used

Arm/Group Title	Placebo	Mirabegron 25 mg	Mirabegron 50 mg	Solifenacin 2.5 mg	Solifenacin 5 mg	Solifenacin 10 mg	Solifenacin 2.5 mg + Mirabegron 25 mg	Solifenacin 2.5 mg + Mirabegron 50 mg	Solifenacin 5 mg + Mirabegron 25 mg	Solifenacin 5 mg + Mirabegron 50 mg	Solifenacin 10 mg + Mirabegron 25 mg	Solifenacin 10 mg + Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.	Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.	Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
Measure Participants	78	73	76	75	147	73	141	143	136	144	76	78
Least Squares Mean (Standard Error) [units on a scale]	2.44 (0.298)	2.61 (0.307)	3.17 (0.301)	3.10 (0.303)	2.78 (0.217)	2.96 (0.307)	2.96 (0.221)	3.24 (0.220)	3.47 (0.225)	3.24 (0.219)	3.51 (0.301)	3.72 (0.297)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg
	Comments	Statistical comparisons were made using 2-sided tests at the 0.05 significance level. No adjustment for multiple testing was performed. The ANCOVA model for all pairwise comparisons includes the 2 main factors mirabegron dose and solifenacin succinate dose and their interaction, sex, age group and geographic region as fixed factors and baseline measurement as a covariate. LS Mean Differences were calculated by subtracting Solifenacin 5 mg/Placebo from the comparison treatment group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95% -0.56 to 0.92
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.376
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95% -0.43 to 0.79
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.310
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95% -0.15 to 1.06
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.308
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95% 0.08 to 1.30
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.313
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95% -0.14 to 1.07
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.308
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.049
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95% 0.00 to 1.46
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.371
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.22 to 1.66
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.368
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95% -0.67 to 1.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.428
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.084
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95% -0.10 to 1.56
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.423
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95% -0.18 to 1.49
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.425
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95% -0.39 to 1.06
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.369
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95% -0.32 to 1.36
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.428
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95% -0.21 to 1.25
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.371
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 2.5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.032
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95% 0.07 to 1.52
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.371
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95% 0.30 to 1.76
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.373
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 5 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% 0.07 to 1.52
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.369
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 25 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95% 0.24 to 1.90
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.423
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Solifenacin 10 mg + Mirabegron 50 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95% 0.45 to 2.10
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.421
	Estimation Comments

Adverse Events

	Placebo		Mirabegron 25 mg		Mirabegron 50 mg		Solifenacin 2.5 mg		Solifenacin 5 mg		Solifenacin 10 mg		Solifenacin 2.5 mg and Mirabegron 25 mg		Solifenacin 2.5 mg and Mirabegron 50 mg		Solifenacin 5 mg and Mirabegron 25 mg		Solifenacin 5 mg and Mirabegron 50 mg		Solifenacin 10 mg and Mirabegron 25 mg		Solifenacin 10 mg and Mirabegron 50 mg
Time Frame	Adverse events summarized for the Safety Analysis Set (SAF) were reported after the first dose of double-blind study drug and no more than 30 days after the last dose of double-blind study drug.
Adverse Event Reporting Description	The SAF included all patients randomized to a double-blind treatment who took at least 1 dose of study drug.One participant randomized to the Mirabegron 25 mg arm received treatment with Solifenacin 5 mg + Mirabegron 50 mg in error and is counted in that arm for safety analysis set analyses.

Arm/Group Title	Placebo		Mirabegron 25 mg		Mirabegron 50 mg		Solifenacin 2.5 mg		Solifenacin 5 mg		Solifenacin 10 mg		Solifenacin 2.5 mg and Mirabegron 25 mg		Solifenacin 2.5 mg and Mirabegron 50 mg		Solifenacin 5 mg and Mirabegron 25 mg		Solifenacin 5 mg and Mirabegron 50 mg		Solifenacin 10 mg and Mirabegron 25 mg		Solifenacin 10 mg and Mirabegron 50 mg
Arm/Group Description	Participants received matching placebo tablets orally once a day for 12 weeks.		Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.		Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 5 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 10 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks.		Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Mirabegron 25 mg		Mirabegron 50 mg		Solifenacin 2.5 mg		Solifenacin 5 mg		Solifenacin 10 mg		Solifenacin 2.5 mg and Mirabegron 25 mg		Solifenacin 2.5 mg and Mirabegron 50 mg		Solifenacin 5 mg and Mirabegron 25 mg		Solifenacin 5 mg and Mirabegron 50 mg		Solifenacin 10 mg and Mirabegron 25 mg		Solifenacin 10 mg and Mirabegron 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/81 (0%)		0/77 (0%)		2/78 (2.6%)		1/79 (1.3%)		0/156 (0%)		1/78 (1.3%)		3/149 (2%)		2/149 (1.3%)		2/144 (1.4%)		2/153 (1.3%)		1/81 (1.2%)		1/81 (1.2%)
Ear and labyrinth disorders
Vertigo	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		1/153 (0.7%)		0/81 (0%)		0/81 (0%)
Gastrointestinal disorders
Dysphagia	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		1/149 (0.7%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Inguinal Hernia	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		1/149 (0.7%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
General disorders
Fibrosis	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		1/153 (0.7%)		0/81 (0%)		0/81 (0%)
Infections and infestations
Gastroenteritis	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		1/149 (0.7%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Pyelonephritis	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		1/144 (0.7%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Injury, poisoning and procedural complications
Foreign body trauma	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		1/81 (1.2%)		0/81 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/81 (0%)		0/77 (0%)		0/78 (0%)		1/79 (1.3%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Intervertebral disc protrusion	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		1/153 (0.7%)		0/81 (0%)		0/81 (0%)
Musculoskeletal pain	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		1/149 (0.7%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Nervous system disorders
Neuralgia	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		1/144 (0.7%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Paraesthesia	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		1/153 (0.7%)		0/81 (0%)		0/81 (0%)
Trigeminal nerve disorder	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		1/144 (0.7%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/81 (0%)		0/77 (0%)		1/78 (1.3%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Psychiatric disorders
Confusional state	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		1/78 (1.3%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Renal and urinary disorders
Urinary retention	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		1/149 (0.7%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Reproductive system and breast disorders
Pelvic pain	0/81 (0%)		0/77 (0%)		1/78 (1.3%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		0/81 (0%)
Surgical and medical procedures
Abortion induced	0/81 (0%)		0/77 (0%)		0/78 (0%)		0/79 (0%)		0/156 (0%)		0/78 (0%)		0/149 (0%)		0/149 (0%)		0/144 (0%)		0/153 (0%)		0/81 (0%)		1/81 (1.2%)
Other (Not Including Serious) Adverse Events
	Placebo		Mirabegron 25 mg		Mirabegron 50 mg		Solifenacin 2.5 mg		Solifenacin 5 mg		Solifenacin 10 mg		Solifenacin 2.5 mg and Mirabegron 25 mg		Solifenacin 2.5 mg and Mirabegron 50 mg		Solifenacin 5 mg and Mirabegron 25 mg		Solifenacin 5 mg and Mirabegron 50 mg		Solifenacin 10 mg and Mirabegron 25 mg		Solifenacin 10 mg and Mirabegron 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/81 (19.8%)		16/77 (20.8%)		21/78 (26.9%)		19/79 (24.1%)		48/156 (30.8%)		33/78 (42.3%)		36/149 (24.2%)		34/149 (22.8%)		40/144 (27.8%)		39/153 (25.5%)		30/81 (37%)		35/81 (43.2%)
Gastrointestinal disorders
Dry mouth	3/81 (3.7%)		2/77 (2.6%)		4/78 (5.1%)		6/79 (7.6%)		18/156 (11.5%)		23/78 (29.5%)		19/149 (12.8%)		13/149 (8.7%)		21/144 (14.6%)		20/153 (13.1%)		16/81 (19.8%)		14/81 (17.3%)
Constipation	0/81 (0%)		0/77 (0%)		3/78 (3.8%)		1/79 (1.3%)		3/156 (1.9%)		4/78 (5.1%)		7/149 (4.7%)		6/149 (4%)		4/144 (2.8%)		2/153 (1.3%)		6/81 (7.4%)		8/81 (9.9%)
Infections and infestations
Nasopharyngitis	2/81 (2.5%)		5/77 (6.5%)		5/78 (6.4%)		5/79 (6.3%)		6/156 (3.8%)		2/78 (2.6%)		4/149 (2.7%)		6/149 (4%)		7/144 (4.9%)		6/153 (3.9%)		6/81 (7.4%)		6/81 (7.4%)
Escherichia urinary tract infection	2/81 (2.5%)		1/77 (1.3%)		2/78 (2.6%)		1/79 (1.3%)		6/156 (3.8%)		5/78 (6.4%)		3/149 (2%)		2/149 (1.3%)		3/144 (2.1%)		4/153 (2.6%)		3/81 (3.7%)		1/81 (1.2%)
Urinary tract infection	3/81 (3.7%)		1/77 (1.3%)		2/78 (2.6%)		1/79 (1.3%)		4/156 (2.6%)		5/78 (6.4%)		1/149 (0.7%)		2/149 (1.3%)		2/144 (1.4%)		3/153 (2%)		0/81 (0%)		3/81 (3.7%)
Vascular disorders
Hypertension	7/81 (8.6%)		9/77 (11.7%)		11/78 (14.1%)		8/79 (10.1%)		18/156 (11.5%)		5/78 (6.4%)		11/149 (7.4%)		11/149 (7.4%)		11/144 (7.6%)		9/153 (5.9%)		7/81 (8.6%)		11/81 (13.6%)

Limitations/Caveats

Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.

More Information

Certain Agreements

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 90 days prior to publication for review and comment.

Results Point of Contact

Name/Title	Medical Director
Organization	Astellas Pharma Europe, B.V.
Phone
Email	Astellas.resultsdisclosure@astellas.com

Responsible Party:

Astellas Pharma Europe B.V.

ClinicalTrials.gov Identifier:

NCT01340027

Other Study ID Numbers:

178-CL-100
2010-020601-32

First Posted:

Apr 21, 2011

Last Update Posted:

Dec 27, 2019

Last Verified:

Dec 1, 2019