SYNERGY II: A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder

• Sponsor: Astellas Pharma Europe B.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02045862
• Collaborator: (none)
• Enrollment: 1,829
• Locations: 251
• Arms: 3
• Actual Duration (Months): 29.8
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to examine how well the combination of two medicines (solifenacin succinate and mirabegron) worked compared to each medicine alone in the treatment of bladder problems, and how safe they were for long term use.

Condition or Disease	Intervention/Treatment	Phase
Urinary Bladder Overactive; Overactive Bladder; Urgency Incontinence; Urinary Bladder Diseases\Urologic Diseases	Drug: Solifenacin succinate; Drug: Mirabegron; Drug: Placebo to match solifenacin; Drug: Placebo to match mirabegron	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1829 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel-Group, Active-Controlled, Multi-center Study to Evaluate the Long-Term Safety and Efficacy of Combination of Solifenacin Succinate With Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in Subjects With Overactive Bladder
• Actual Study Start Date: Mar 17, 2014
• Actual Primary Completion Date: Sep 8, 2016
• Actual Study Completion Date: Sep 8, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Mirabegron 50 mg Participants received mirabegron 50 mg once a day for 52 weeks.	Drug: Mirabegron; Participants received mirabegron 50 mg orally once a day at the same time each day.; Other Names: Myrbetriq YM178 Betmiga Betanis ; Drug: Placebo to match solifenacin; Participants received placebo to match solifenacin 5 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.
Active Comparator: Solifenacin 5 mg Participants received solifenacin 5 mg once a day for 52 weeks.	Drug: Solifenacin succinate; Participants received solifenacin 5 mg orally once a day at the same time each day.; Other Names: Vesicare Vesitrim YM905 Vesikur ; Drug: Placebo to match mirabegron; Participants received placebo to match mirabegron 50 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.
Experimental: Solifenacin 5 mg + Mirabegron 50 mg Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.	Drug: Solifenacin succinate; Participants received solifenacin 5 mg orally once a day at the same time each day.; Other Names: Vesicare Vesitrim YM905 Vesikur ; Drug: Mirabegron; Participants received mirabegron 50 mg orally once a day at the same time each day.; Other Names: Myrbetriq YM178 Betmiga Betanis

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 56 weeks)]

   A TEAE was defined as an adverse event (AE) observed after taking the first dose of double-blind treatment until 14 days after taking the last dose of double-blind treatment for non-serious AEs and until 30 days after taking the last dose of double-blind treatment for serious adverse events (SAEs). This included abnormal laboratory tests, vital signs or electrocardiogram data that were defined as AEs if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant in the investigator's opinion. The severity of each AE was defined according to the following: Mild (No disruption of normal daily activities); Moderate (Affected normal daily activities) and Severe (Inability to perform daily activities).

2. Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours [Baseline and Week 52]

   An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and week 52 clinic visits.

3. Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours [Baseline and Week 52]

   A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7-days before the baseline and week 52 clinic visits.

Secondary Outcome Measures

1. Change From Baseline to EoT in Mean Volume Voided Per Micturition [Baseline and Week 52]

   The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period.

2. Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score [Baseline and Week 52]

   The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

3. Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS) [Baseline and Week 52]

   The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.

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

   An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and prior to each visit.

5. Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit [Months 1, 3, 6, 9, 12]

   An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.

6. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit [Baseline and Months 1, 3, 6, 9, 12]

   An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.

7. Number of Incontinence-Free Days During the 7-Day Micturition Diary Period Prior to Each Visit [Months 1, 3, 6, 9, 12]

   The number of incontinence-free days was the number of valid diary days during the 7-day micturition diary period prior to each visit with no incontinence episodes recorded.

8. Number of Incontinence-Free Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit [Months 1, 3, 6, 9, 12]

   The number of incontinence-free days with < 8 micturitions per day was the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded and with < 8 micturitions per day.

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

   An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit.

10. Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit [Months 1, 3, 6, 9, 12]

    An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceeded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.

11. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit [Baseline and Months 1, 3, 6, 9, 12]

    An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.

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

    A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7-days before the baseline and prior to each visit.

13. Number of Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT) [Months 1, 3, 6, 9, 12]

    The number of days with < 8 micturitions was the number of valid diary days during the 7-day micturition diary period with with less than 8 micturitions per day.

14. Change From Baseline to EoT in Corrected Micturition Frequency [Baseline and Month 12]

    Corrected micturition frequency was defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline. Corrected micturition frequency was calculated as the baseline mean volume voided per micturition multiplied by the baseline mean number of micturitions per 24 hours divided by the mean volume voided per micturition at EoT.

15. Change From Baseline to Months 3, 6 and 12 in Mean Volume Voided Per Micturition [Baseline and Months 3, 6, 12]

    The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period prior to each visit.

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

    Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode recorded by the participant in the micturition diary for 7 days prior to each visit as 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 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.

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

    A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The mean number of nocturia episodes was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit."

18. Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit [Months 1, 3, 6, 9, 12]

    A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit.

19. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes During the 7-Day Micturition Diary Period Prior to Each Visit [Baseline and Months 1, 3, 6, 9, 12]

    A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit

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

    The mean number of pads used per 24 hours was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit.

21. Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit [Months 1, 3, 6, 9, 12]

    The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.

22. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit [Baseline and Months 1, 3, 6, 9, 12]

    The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.

23. Change From Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

24. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQoL): Total Score [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

25. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Coping [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

26. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Concern [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

27. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Sleep [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consisted of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each time was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

28. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQL Subscale Score: Social [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

29. Change From Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of TS-VAS [Baseline and Months 1, 3, 6, 9, 12]

    The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.

30. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition (PPBC) [Baseline and Months 1, 3, 6, 9, 12]

    The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.

31. Percentage of Participants in Each Category of Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT [Month 12]

    The PGIC is a 2-part questionnaire, assessing both the change in the patient's overall condition and change in bladder condition since the start of the study (from very much worse to very much improved).

32. Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT [Month 12]

    The PGIC is a 2-part questionnaire, assessing both the change in the patient's overall condition and change in bladder condition since the start of the study (from very much worse to very much improved).

33. Number of Participants With Change From Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility [Baseline and 12 Months]

    The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

34. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care [Baseline and Month 12]

    The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

35. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities [Baseline and Month 12]

    The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

36. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort [Baseline and Month 12]

    The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

37. Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression [Baseline and Month 12]

    The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

38. Change From Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed [Baseline and Months 6,12]

    The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.

39. Change From Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working [Baseline and Months 6, 12]

    The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.

40. Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment [Baseline and Months 6, 12]

    The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes arre expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.

41. Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment [Baseline and Months 6, 12]

    The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.

42. Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT [Months 1, 3, 6, 9, 12]

    An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the last 3 days of the 7-day micturition diary is reported.

43. Percentage of Participants With ≥ 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

44. Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

45. Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit.

46. Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT [Months 1, 3, 6, 9, 12]

    An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the 7-day micturition diary is reported.

47. Percentage of Participants With Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    The percentage of participants with micturition frequency normalization was defined as participants who had ≥ 8 micturitions/24 hours at baseline and < 8 micturitions/24 hours postbaseline at months 1, 3, 6, 9, 12 and EoT.

48. Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.

49. Percentage of Participants With Major (≥ 2 Points) Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.

50. Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q Symptom Bother Scale) at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

51. Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

52. Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.

53. Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q Symptom Bother Scale and ≥1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The symptom bother portion of the OAB-q consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.

54. Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q HRQL Total Score and ≥ 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT [Baseline and Months 1, 3, 6, 9, 12]

    The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The HRQoL portion of the OAB-q consists of 25 HRQoL items comprising 4 HRQoL subscales, each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.

55. Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume [Baseline and Months 1, 3, 6, 9, 12]

    PVR volume was assessed by ultrasonography or a bladder scanner.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Main Inclusion at Screening (Visit 1):

• Subject had completed study 178-CL-101 or study 905-EC-012 (This inclusion criterion would no longer apply once the recruitment for study 178-CL-101 and study 905-EC-012 had been completed. In that case the subject had to have symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months);

• Subject was willing and able to complete the micturition diary and questionnaires correctly 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;

Main Inclusion at Randomization (Visit 2):

• Subject had a micturition frequency of on average ≥ 8 times per 24-hour period during the last 7 days of the micturition diary period (incontinence episode should not be counted as a micturition).

• Subject had experienced at least 3 incontinence episodes during the last 7 days of the micturition diary period.

• Subject had experienced on average at least 1 urgency episode (grade 3 or 4 on Patient Perception of Intensity of Urgency Scale [PPIUS]) per 24-hour period during the 7-day micturition diary period.

Exclusion Criteria:

Main Exclusion at Screening (Visit 1):

• Subject had clinically significant bladder outflow obstruction at risk of urinary retention;

• Subject had significant PVR volume (> 150 mL);

• Subject had significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor;

• Subject has an indwelling catheter or practices intermittent self-catheterization;

• Subject had evidence of a UTI (urine culture containing > 100,000 cfu/mL), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;

• Subject had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;

Main Exclusion at Randomization (Visit 2):

• Subject had evidence of a urinary tract infection (UTI) (urine culture containing > 100,000 cfu/mL) as assessed in the Screening visit (V1) samples. The subject could be rescreened after successful treatment of the UTI (confirmed by a dipstick negative for nitrite).

• Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site US10049	Mobile	Alabama	United States	36608
2	Site US10112	Mobile	Alabama	United States	36608
3	Site US10104	Chandler	Arizona	United States	85224
4	Site US10021	Phoenix	Arizona	United States	85051
5	Site US10122	Anaheim	California	United States	92801
6	Site US10082	Hawaiian Gardens	California	United States	90716
7	Site US10132	Los Angeles	California	United States	90017
8	Site US10133	Los Angeles	California	United States	90036
9	Site US10149	Paramount	California	United States	90723
10	Site US10003	San Diego	California	United States	92120
11	Site US10106	Tarzana	California	United States	91356
12	Site US10595	Valley Village	California	United States	91607
13	Site US10053	Wheat Ridge	Colorado	United States	80033
14	Site US10060	Bradenton	Florida	United States	34208
15	Site US10097	Hialeah	Florida	United States	33012
16	Site US10148	Hialeah	Florida	United States	33016
17	Site US10153	Hialeah	Florida	United States	33016
18	Site US10091	Jupiter	Florida	United States	33458
19	Site US10150	New Port Richey	Florida	United States	34652
20	Site US10124	Orlando	Florida	United States	32803
21	Site US10134	Orlando	Florida	United States	32806
22	Site US10009	Pembroke Pines	Florida	United States	33027
23	Site US10554	Plantation	Florida	United States	33317
24	Site US10037	Alpharetta	Georgia	United States	30005
25	Site US10127	Roswell	Georgia	United States	30076
26	Site US10120	Sandy Springs	Georgia	United States	30328
27	Site US10078	Wichita	Kansas	United States	67205
28	Site US10088	Lake Charles	Louisiana	United States	70601
29	Site US10025	Shreveport	Louisiana	United States	71106
30	Site US10558	Hanover	Maryland	United States	21076
31	Site US10282	Boston	Massachusetts	United States	02131
32	Site US10114	Watertown	Massachusetts	United States	02472
33	Site US10110	Billings	Montana	United States	59102
34	Site US10154	Missoula	Montana	United States	59801
35	Site US10553	Lincoln	Nebraska	United States	68510
36	Site US10002	Englewood	New Jersey	United States	07631
37	Site US10047	Lawrenceville	New Jersey	United States	08648
38	Site US10011	Albuquerque	New Mexico	United States	87102
39	Site US10015	Albuquerque	New Mexico	United States	87109
40	Site US10026	Garden City	New York	United States	11530
41	Site US10040	Kingston	New York	United States	12401
42	Site US10168	New York	New York	United States	10065
43	Site US10126	Newburgh	New York	United States	12550
44	Site US10028	Poughkeepsie	New York	United States	12601
45	Site US10076	Concord	North Carolina	United States	28025
46	Site US10129	Raleigh	North Carolina	United States	27609
47	Site US10062	Winston-Salem	North Carolina	United States	27103
48	Site US10050	Cleveland	Ohio	United States	44122
49	Site US10067	Wadsworth	Ohio	United States	44281
50	Site US10109	Oklahoma City	Oklahoma	United States	73112
51	Site US10541	Medford	Oregon	United States	97504
52	Site US10008	Bala-Cynwyd	Pennsylvania	United States	19004
53	Site US10017	Philadelphia	Pennsylvania	United States	19114
54	Site US10167	Pittsburgh	Pennsylvania	United States	15213
55	Site US10250	Pittsburgh	Pennsylvania	United States	15236
56	Site US10248	Pittsburgh	Pennsylvania	United States	15243
57	Site US10063	Uniontown	Pennsylvania	United States	15401
58	Site US10012	West Reading	Pennsylvania	United States	19611
59	Site US10166	Charleston	South Carolina	United States	29425
60	Site US10079	Mount Pleasant	South Carolina	United States	29464
61	Site US10023	Simpsonville	South Carolina	United States	29681
62	Site US10101	Summerville	South Carolina	United States	29485
63	Site US10006	Kingsport	Tennessee	United States	37660
64	Site US10065	Corpus Christi	Texas	United States	78414
65	Site US10085	Houston	Texas	United States	77058
66	Site US10219	Houston	Texas	United States	77094
67	Site US10093	Houston	Texas	United States	77099
68	Site US10090	Hurst	Texas	United States	76054
69	Site US10105	San Antonio	Texas	United States	78229
70	Site US10111	San Antonio	Texas	United States	78229
71	Site US10083	Virginia Beach	Virginia	United States	23462
72	Site US10013	Burien	Washington	United States	98166
73	Site US10004	Mountlake Terrace	Washington	United States	98043
74	Site US10155	Seattle	Washington	United States	98105
75	Site US10135	Walla Walla	Washington	United States	99362
76	Site AU61005	Broadmeadow	New South Wales	Australia	2292
77	Site AU61007	Randwick	New South Wales	Australia	2031
78	Site AU61021	Randwick	New South Wales	Australia	2031
79	Site AU61011	Wollongong	New South Wales	Australia	2522
80	Site AU61022	Brisbane	Queensland	Australia	4152
81	Site AU61010	Nambour	Queensland	Australia	4560
82	Site AU61019	Sherwood	Queensland	Australia	4075
83	Site AU61015	Daw Park	South Australia	Australia	5041
84	Site AU61025	Footscray	Victoria	Australia	3011
85	Site AU61002	Parkville	Victoria	Australia	3052
86	Site AU61004	Perth	Western Australia	Australia	6009
87	Site BE32004	Gent		Belgium	9000
88	Site BE32014	Roeselare		Belgium	8800
89	Site BE32012	Sint-Truiden		Belgium	3800
90	Site BG35908	Plovdiv		Bulgaria	4003
91	Site BG35902	Ruse		Bulgaria	7000
92	Site BG35905	Sofia		Bulgaria	1431
93	Site BG35903	Sofia		Bulgaria	1606
94	Site CA15035	Edmonton	Alberta	Canada	T5G 0B7
95	Site CA15033	Vancouver	British Columbia	Canada	V5Z 4E1
96	Site CA15008	Saint John	New Brunswick	Canada	E2L 3J8
97	Site CA15001	Barrie	Ontario	Canada	L4M 7G1
98	Site CA15006	Brampton	Ontario	Canada	L6T 4S5
99	Site CA15003	Brantford	Ontario	Canada	N3S 6T6
100	Site CA15007	Kitchener	Ontario	Canada	N2N 2B9
101	Site CA15013	Toronto	Ontario	Canada	M4N 3M5
102	Site CA15004	Toronto	Ontario	Canada	M4S 1Y2
103	Site CA15026	Drummondville	Quebec	Canada	J2B 7T1
104	Site CA15039	Levis	Quebec	Canada	G6W 5M6
105	Site CA15020	Montreal	Quebec	Canada	H4N 3C5
106	Site CA15027	Sherbrooke	Quebec	Canada	J1H 1Z1
107	Site CA15040	Montreal		Canada	H2R 1V6
108	Site CA15025	Quebec		Canada	G1S 2L6
109	Site CZ42015	Brno		Czechia	602 00
110	Site CZ42003	Hradec Kralove		Czechia	500 02
111	Site CZ42001	Hradec Kralove		Czechia	50005
112	Site CZ42010	Olomouc		Czechia	772 00
113	Site CZ42014	Ostrava		Czechia	700 30
114	Site CZ42005	Plzen		Czechia	32600
115	Site CZ42008	Praha 2		Czechia	12808
116	Site CZ42007	Praha 4		Czechia	140 00
117	Site CZ42013	Sternberk		Czechia	78501
118	Site CZ42009	Uherske Hradiste		Czechia	686 08
119	Site CZ42006	Usti nad Labem		Czechia	40001
120	Site DK45013	Aarhus		Denmark	8200
121	Site EE37201	Parnu		Estonia	80010
122	Site FI35801	Kouvola		Finland	45200
123	Site DE49034	Munich	Bavaria	Germany	81377
124	Site DE49031	Bergisch Gladbach	Northwest	Germany	51427
125	Site DE49032	Duisburg	NRW	Germany	47179
126	Site DE49003	Lutherstadt Eisleben	Sachsen Anhalt	Germany	06295
127	Site DE49013	Leipzig	Sachsen	Germany	04105
128	Site DE49008	Bad Ems		Germany	56130
129	Site DE49002	Duisburg		Germany	47051
130	Site DE49010	Ganderkesee		Germany	27777
131	Site DE49011	Halle (Saale)		Germany	06132
132	Site DE49001	Neustadt I. Sachsen		Germany	01844
133	Site DE49026	Rostock		Germany	18107
134	Site DE49014	Sangerhausen		Germany	06526
135	Site HU36007	Kecskemet	Bacs-Kiskun Megye	Hungary	6000
136	Site HU36005	Pecs	Baranya Megye	Hungary	7621
137	Site HU36003	Csongrad	Csongrad Megye	Hungary	6640
138	Site HU36001	Szentes	Csongrad Megye	Hungary	6600
139	Site HU36013	Sopron	Gyor-Moson Sopron	Hungary	9400
140	Site HU36012	Veszprem	Veszprem Megye	Hungary	8200
141	Site IT39022	Ancona		Italy	60126
142	Site IT39007	Avellino		Italy	83100
143	Site IT39001	Latina		Italy	04100
144	Site IT39020	Milano		Italy	20100
145	Site KR82004	Suwon-si	Gyeonggi-do	Korea, Republic of	443-721
146	Site KR82014	Bucheon-Si	Gyunggido	Korea, Republic of	420-767
147	Site KR82012	Seoul	Gyunggido	Korea, Republic of	143-729
148	Site KR82010	Jeonju-si	Jeollabuk-do South Korea	Korea, Republic of	561-712
149	Site KR82006	Busan		Korea, Republic of	602-715
150	Site KR82016	Busan		Korea, Republic of	602-739
151	Site KR82005	Daegu		Korea, Republic of	705-717
152	Site KR82029	Daegu		Korea, Republic of	705-718
153	Site KR82019	Daejeon		Korea, Republic of	301-721
154	Site KR82023	Incheon		Korea, Republic of	405760
155	Site KR82003	Seoul		Korea, Republic of	05505
156	Site KR82021	Seoul		Korea, Republic of	100-380
157	Site KR82020	Seoul		Korea, Republic of	110-744
158	Site KR82030	Seoul		Korea, Republic of	120-752
159	Site KR82013	Seoul		Korea, Republic of	134-701
160	Site KR82017	Seoul		Korea, Republic of	134-872
161	Site KR82002	Seoul		Korea, Republic of	135-710
162	Site KR82008	Seoul		Korea, Republic of	135-720
163	Site KR82015	Seoul		Korea, Republic of	136-075
164	Site KR82001	Seoul		Korea, Republic of	137-701
165	Site LV37102	Liepaja		Latvia	LV-3401
166	Site LV37103	Olaine		Latvia	LV-2114
167	Site LV37105	Riga		Latvia	LV-1002
168	Site LT37008	Kaunas		Lithuania	47144
169	Site LT37004	Kaunas		Lithuania	50009
170	Site LT37011	Kaunas		Lithuania	LT49449
171	Site LT37012	Klaipeda		Lithuania	LT-92288
172	Site LT37010	Vilnius		Lithuania	10207
173	Site LT37003	Vilnius		Lithuania	LT-01118
174	Site LT37007	Vilnius		Lithuania	LT-08661
175	Site LT37009	Vilnius		Lithuania	LT-09108
176	Site MY60002	Petaling Jaya		Malaysia	47500
177	Site MX52003	Mexico City	DF	Mexico	06700
178	Site NL31006	Enschede	NL	Netherlands	7513ER
179	Site NL31002	Amsterdam		Netherlands	1105 AZ
180	Site NL31005	Nijmegen		Netherlands	6532 SZ
181	Site NL31010	Sneek		Netherlands	8601 ZK
182	Site NZ64001	Christchurch	Canterbury	New Zealand	8013
183	Site NZ64002	Nelson		New Zealand	7010
184	Site NZ64003	Tauranga		New Zealand	3140
185	Site NZ64006	Whangarei		New Zealand	0112
186	Site NO47007	Alesund		Norway	6003
187	Site NO47006	Hamar		Norway	2317
188	Site NO47008	Lierskogen		Norway	3420
189	Site PL48018	Bialystok		Poland	15-351
190	Site PL48013	Chorzow		Poland	41-500
191	Site PL48014	Gdynia		Poland	81-384
192	Site PL48004	Lodz		Poland	90-302
193	Site PL48010	Lublin		Poland	20-632
194	Site PL48011	Myslowice		Poland	41-400
195	Site PL48016	Opole		Poland	45-086
196	Site PL48005	Piaseczno		Poland	05-500
197	Site PL48012	Warsaw		Poland	00-909
198	Site PL48003	Warszawa		Poland	02-507
199	Site PL48001	Warszawa		Poland	02-929
200	Site PL48019	Wrocław		Poland	50-088
201	Site RO40014	Cluj-Napoca	Cluj	Romania	400046
202	Site RO40004	Bucuresti		Romania	042122
203	Site RO40001	Bucuresti		Romania	50659
204	Site RO40005	Bucuresti		Romania	50659
205	Site RO40010	Sibiu		Romania	550245
206	Site RO40002	Timisoara		Romania	300736
207	Site RU70015	Kazan		Russian Federation	420097
208	Site RU70023	Penza		Russian Federation	440026
209	Site RU70019	Saint Petersburg		Russian Federation	194354
210	Site RU70002	Saint Petersburg		Russian Federation	197089
211	Site RU70022	Saint Petersburg		Russian Federation	198103
212	Site RU70014	St. Petersburg		Russian Federation	199178
213	Site RU70018	Ufa		Russian Federation	450096
214	Site SG65002	Singapore		Singapore	169608
215	Site SG65003	Singapore		Singapore	229899
216	Site SK42105	Bratislava		Slovakia	82101
217	Site SK42107	Kosice		Slovakia	04001
218	Site SK42101	Kosice		Slovakia	04013
219	Site SK42103	Nitra		Slovakia	949 01
220	Site SK42108	Poprad		Slovakia	05801
221	Site SK42104	Prešov		Slovakia	080 01
222	Site SK42102	Trencin		Slovakia	91101
223	Site SK42106	Trencin		Slovakia	91101
224	Site SI38604	Murska Sobota		Slovenia	9000
225	Site ZA27001	Centurion	Gauteng	South Africa	0157
226	Site ZA27002	Roodepoort	Gauteng	South Africa	1709
227	Site ZA27006	Durban	Kwa Zulu Natal	South Africa	4001
228	Site ZA27013	Meyerspark	Pretoria	South Africa	0184
229	Site ZA27007	Paarl	Western Cape	South Africa	7646
230	Site ES34004	Madrid		Spain	28031
231	Site ES34015	Madrid		Spain	28044
232	Site ES34009	Madrid		Spain	28046
233	Site ES34002	Valencia		Spain	46026
234	Site SE46007	Boras		Sweden	506 30
235	Site SE46005	Malmo		Sweden	211 52
236	Site SE46016	Stockholm		Sweden	111 57
237	Site SE46012	Stockholm		Sweden	141 86
238	Site SE46003	Stockholm		Sweden	182 88
239	Site SE46009	Uppsala		Sweden	753 19
240	Site TH66008	Bangkok		Thailand	10400
241	Site TH66009	Khon Kaen		Thailand	40002
242	Site UA38002	Cherenigiv		Ukraine	14034
243	Site UA38015	Chernivtsi		Ukraine	58002
244	Site UA38013	Dnepropetrovsk		Ukraine	49005
245	Site UA38007	Kiev		Ukraine	02232
246	Site UA38003	Kyiv		Ukraine	02660
247	Site UA38010	Kyiv		Ukraine	04053
248	Site UA38008	Zaporizhzhya		Ukraine	69600
249	Site GB44001	Sheffield	South Yorkshire	United Kingdom	S10 2JF
250	Site GB44006	Plymouth		United Kingdom	PL6 8DH
251	Site GB44009	Watford		United Kingdom	WD25 7NL

Sponsors and Collaborators

• Astellas Pharma Europe B.V.

Investigators

• Study Director: Medical Director, Astellas Pharma Europe B.V.

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: NCT02045862
• Other Study ID Numbers: 178-CL-102; 2012-005736-29
• First Posted: Jan 27, 2014
• Last Update Posted: Sep 13, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Astellas Pharma Europe B.V.: Solifenacin Succinate; Mirabegron; Urinary Incontinence; Combination Therapy; Urgency; Nocturia; Overactive Bladder
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Urologic Diseases; Urinary Bladder Diseases; Solifenacin Succinate; Mirabegron

Study Results

Participant Flow

Recruitment Details	Participants who had symptoms of "wet" overactive bladder (OAB) (urgency, urinary frequency and urgency incontinence) for ≥ 3 months were enrolled in 251 centers globally. A majority of the participants were recruited from participants who enrolled and completed studies 178-CL-101 (NCT01972841) or 905-EC-012 (NCT01908829).
Pre-assignment Detail	A total of 2084 participants were screened, 2063 participants received placebo run-in treatment and 1829 participants were randomized into 1 of 3 treatment arms in a 1:1:4 ratio in the 52-week double-blind treatment period. Randomization was stratified by sex, age group (< 65 years, ≥ 65 years) and geographic region.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Period Title: Overall Study
STARTED	306	305	1218
Treated	306	303	1210
COMPLETED	267	265	1092
NOT COMPLETED	39	40	126

Baseline Characteristics

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg	Total
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.	Total of all reporting groups
Overall Participants	306	305	1218	1829
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (12.7)	59.0 (13.3)	58.3 (13.0)	58.5 (13.0)
Sex: Female, Male (Count of Participants)
Female	243 79.4%	245 80.3%	973 79.9%	1461 79.9%
Male	63 20.6%	60 19.7%	245 20.1%	368 20.1%
Race/Ethnicity, Customized (Count of Participants)
White	266 86.9%	265 86.9%	1066 87.5%	1597 87.3%
Black or African American	5 1.6%	4 1.3%	27 2.2%	36 2%
Asian	31 10.1%	33 10.8%	119 9.8%	183 10%
Other	4 1.3%	3 1%	6 0.5%	13 0.7%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	15 4.9%	15 4.9%	54 4.4%	84 4.6%
Not Hispanic or Latino	291 95.1%	290 95.1%	1164 95.6%	1745 95.4%
Mean Number of Incontinence Episodes per 24 Hours (incontinence episodes/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [incontinence episodes/24 hours]	3.15 (3.56)	3.10 (3.58)	3.04 (3.17)	3.07 (3.31)
Mean Number of Micturitions per 24 Hours (micturitions/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micturitions/24 hours]	10.51 (2.41)	10.76 (2.83)	10.55 (2.73)	10.58 (2.70)
Mean Volume Voided per Micturition (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	161.00 (60.16)	160.70 (58.49)	159.29 (58.40)	159.82 (58.69)
Number of Incontinence Episodes per Week (incontinence episodes/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [incontinence episodes/week]	21.8 (24.8)	21.6 (25.0)	20.9 (21.9)	21.2 (22.9)
Mean Number of Urgency Incontinence Episodes per 24 Hours (urgency incontinence episodes/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [urgency incontinence episodes/24 hours]	2.86 (3.29)	2.91 (3.49)	2.74 (2.78)	2.79 (3.00)
Number of Urgency Incontinence Episodes per Week (urgency incontinence episodes/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [urgency incontinence episodes/week]	19.8 (22.8)	20.2 (24.5)	18.9 (19.1)	19.3 (20.7)
Mean Number of Urgency Episodes (Grade 3 or 4) per 24 Hours (urgency episodes/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [urgency episodes/24 hours]	6.34 (4.16)	6.63 (4.08)	6.53 (3.69)	6.51 (3.84)
Mean Number of Nocturia Episodes per 24 Hours (nocturia episodes/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nocturia episodes/24 hours]	1.48 (0.95)	1.58 (0.94)	1.49 (0.94)	1.51 (0.94)
Number of Nocturia Episodes per Week (nocturia episodes/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nocturia episodes/week]	10.3 (6.6)	11.0 (6.6)	10.4 (6.5)	10.4 (6.5)
Mean Number of Pads Used per 24 Hours (pads/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pads/24 hours]	2.51 (3.76)	2.77 (3.15)	2.58 (2.59)	2.60 (2.91)
Number of Pads Used per Week (pads/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pads/week]	17.3 (26.1)	19.2 (22.0)	17.7 (17.6)	17.9 (20.0)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	A TEAE was defined as an adverse event (AE) observed after taking the first dose of double-blind treatment until 14 days after taking the last dose of double-blind treatment for non-serious AEs and until 30 days after taking the last dose of double-blind treatment for serious adverse events (SAEs). This included abnormal laboratory tests, vital signs or electrocardiogram data that were defined as AEs if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant in the investigator's opinion. The severity of each AE was defined according to the following: Mild (No disruption of normal daily activities); Moderate (Affected normal daily activities) and Severe (Inability to perform daily activities).
Time Frame	From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 56 weeks)

Outcome Measure Data

Analysis Population Description

The analysis population was the safety analysis set (SAF), which consisted of all participants who received ≥ 1 dose of double-blind study drug and excluded participants from one site due to protocol noncompliance.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	305	303	1206
Any TEAEs	126 41.2%	134 43.9%	596 48.9%
Mild TEAEs	61 19.9%	69 22.6%	306 25.1%
Moderate TEAEs	52 17%	58 19%	238 19.5%
Severe TEAEs	13 4.2%	7 2.3%	52 4.3%
Drug-related TEAEs	35 11.4%	42 13.8%	200 16.4%
Serious TEAEs	8 2.6%	8 2.6%	51 4.2%
Drug-related Serious TEAEs	1 0.3%	0 0%	0 0%
TEAEs Leading to Discontuation of Study Drug	7 2.3%	5 1.6%	25 2.1%
Drug-related TEAEs Leading to Discont. of Drug	4 1.3%	4 1.3%	17 1.4%
TEAEs Leading to Death	0 0%	0 0%	1 0.1%

2. Primary Outcome

Title	Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and week 52 clinic visits.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

FAS population; Last observation carried forward (LOCF) was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	301	297	1184
Least Squares Mean (Standard Error) [incontinence episodes]	-1.58 (0.11)	-1.90 (0.11)	-2.03 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The 2-sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.69 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	The 2-sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

3. Primary Outcome

Title	Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours
Description	A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7-days before the baseline and week 52 clinic visits.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

FAS population; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	301	297	1184
Least Squares Mean (Standard Error) [micturitions]	-2.10 (0.13)	-2.16 (0.13)	-2.58 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The 2-sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the ANCOVA model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.77 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	The 2-sided P value was for pairwise comparisons between the combination therapy group and the corresponding monotherapy group from the ANCOVA model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.71 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to EoT in Mean Volume Voided Per Micturition
Description	The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

FAS population with baseline and at least one post-baseline measurement; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	289	293	1162
Least Squares Mean (Standard Error) [mL]	21.83 (3.12)	24.90 (3.10)	37.67 (1.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	15.84
	Confidence Interval	(2-Sided) 95%; 8.99 to 22.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.49
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	12.77
	Confidence Interval	(2-Sided) 95%; 5.98 to 19.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.47
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

FAS population with baseline and at least one post-baseline measurement; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	290	294	1163
Least Squares Mean (Standard Error) [units on a scale]	-21.96 (1.14)	-24.91 (1.13)	-29.51 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.55
	Confidence Interval	(2-Sided) 95%; -10.05 to -5.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-4.60
	Confidence Interval	(2-Sided) 95%; -7.09 to -2.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.27
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)
Description	The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

FAS population with baseline and at least one post-baseline measurement; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	289	294	1163
Least Squares Mean (Standard Error) [units on a scale]	2.19 (0.12)	2.15 (0.12)	2.73 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg: Difference of the adjusted mean (i.e., least squares mean) was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.32 to 0.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes Per 24 Hours
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	-0.97 (0.10)	-1.29 (0.11)	-1.45 (0.05)
Month 3	-1.31 (0.11)	-1.71 (0.11)	-1.78 (0.05)
Month 6	-1.42 (0.11)	-1.78 (0.11)	-1.93 (0.05)
Month 9	-1.53 (0.11)	-1.90 (0.11)	-2.00 (0.06)
Month 12	-1.67 (0.11)	-1.92 (0.11)	-2.06 (0.06)

8. Secondary Outcome

Title	Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	14.88 (1.52)	12.41 (1.22)	10.80 (0.58)
Month 3	12.23 (1.12)	9.23 (1.02)	8.33 (0.52)
Month 6	10.62 (1.08)	8.18 (1.01)	7.28 (0.48)
Month 9	10.53 (1.19)	7.28 (0.91)	6.74 (0.45)
Month 12	9.09 (1.10)	7.06 (0.94)	6.10 (0.46)
EoT	10.32 (1.08)	8.09 (0.94)	6.85 (0.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio of number of incontinence episodes during the EoT 7-day diary between the combination therapy group and the mirabegron monotherapy group was calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of incontinence episodes divided by number of valid diary days) at baseline included as a covariate and number of valid diary day at EoT as the offset variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Effects Poisson-Negative Binomial
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.54 to 0.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio of number of incontinence episodes during the EoT 7-day diary between the combination therapy group and the solifenacin monotherapy group was calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of incontinence episodes divided by number of valid diary days) at baseline included as a covariate and number of valid diary day at EoT as the offset variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Mixed Effects Poisson-Negative Binomial
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.61 to 0.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	-6.77 (0.73)	-9.17 (0.73)	-10.31 (0.36)
Month 3	-9.21 (0.76)	-12.05 (0.75)	-12.55 (0.38)
Month 6	-10.36 (0.76)	-12.50 (0.75)	-13.49 (0.37)
Month 9	-10.62 (0.76)	-13.51 (0.77)	-14.06 (0.38)
Month 12	-11.84 (0.77)	-13.47 (0.77)	-14.43 (0.38)
EoT	-11.17 (0.75)	-13.37 (0.75)	-14.29 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The two-sided p-value is for pairwise comparisons between the combination therapy group and the mirabegron monotherapy group from stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.12
	Confidence Interval	(2-Sided) 95%; -4.76 to -1.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.83
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The two-sided p-value is for pairwise comparisons between the combination therapy group and the solifenacin monotherapy group from stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95%; -2.57 to 0.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.84
	Estimation Comments

10. Secondary Outcome

Title	Number of Incontinence-Free Days During the 7-Day Micturition Diary Period Prior to Each Visit
Description	The number of incontinence-free days was the number of valid diary days during the 7-day micturition diary period prior to each visit with no incontinence episodes recorded.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with with data available at each time point; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	2.73 (0.15)	3.35 (0.17)	3.46 (0.08)
Month 3	3.30 (0.17)	3.98 (0.17)	4.17 (0.08)
Month 6	3.64 (0.17)	4.08 (0.17)	4.44 (0.08)
Month 9	3.97 (0.18)	4.33 (0.17)	4.56 (0.08)
Month 12	4.23 (0.18)	4.5 (0.18)	4.81 (0.08)
EoT	3.98 (0.17)	4.29 (0.16)	4.64 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio vs. Mirabegron 50 mg (EoT): Odds ratio was from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours as a covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Overdispersed Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.60
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio vs. Solifenacin 5 mg (EoT): Odds ratio was from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Overdispersed Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Number of Incontinence-Free Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit
Description	The number of incontinence-free days with < 8 micturitions per day was the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded and with < 8 micturitions per day.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	1.03 (0.10)	1.01 (0.10)	1.33 (0.06)
Month 3	1.24 (0.12)	1.48 (0.13)	1.91 (0.07)
Month 6	1.56 (0.14)	1.66 (0.14)	2.13 (0.08)
Month 9	1.56 (0.14)	1.64 (0.14)	2.20 (0.08)
Month 12	1.87 (0.15)	1.92 (0.15)	2.54 (0.08)
EoT	1.75 (0.14)	1.90 (0.14)	2.43 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio vs. Mirabegron 50 mg (EoT): Odds ratio was from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours and baseline mean number of micturitions per 24 hours as a covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Overdispersed Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio vs. Solifenacin 5 mg (EoT): Odds ratio was from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and log transformed baseline mean number of incontinence episodes per 24 hours and baseline mean number of micturitions per 24 hours as a covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Overdispersed Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.14 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours
Description	An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	297	1187
Month 1	-0.93 (0.10)	-1.25 (0.10)	-1.43 (0.05)
Month 3	-1.30 (0.10)	-1.64 (0.10)	-1.71 (0.05)
Month 6	-1.40 (0.10)	-1.67 (0.10)	-1.86 (0.05)
Month 9	-1.60 (0.11)	-1.78 (0.11)	-1.92 (0.05)
Month 12	-1.60 (0.10)	-1.82 (0.10)	-1.98 (0.05)
EoT	-1.51 (0.10)	-1.81 (0.10)	-1.94 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The two-sided p-value is for pairwise comparisons between the combination therapy group and the mirabegron monotherapy group from stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	The two-sided p-value is for pairwise comparisons between the combination therapy group and the solifenacin monotherapy group from stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

13. Secondary Outcome

Title	Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit
Description	An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceeded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	297	1187
Month 1	13.14 (1.42)	11.21 (1.19)	8.99 (0.47)
Month 3	10.37 (1.00)	8.12 (0.98)	6.95 (0.44)
Month 6	8.97 (0.95)	7.31 (0.96)	5.88 (0.41)
Month 9	8.08 (1.01)	6.51 (0.89)	5.47 (0.40)
Month 12	7.73 (1.00)	6.06 (0.85)	4.88 (0.38)
EoT	8.86 (0.98)	7.04 (0.86)	5.57 (0.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio of number of incontinence episodes during the EoT 7-day diary between the combination therapy group and the mirabegron monotherapy group was calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥65 years), geographic region and previous study history as factors, log(number of urgency incontinence episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary days at EoT as the offset variable
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.48 to 0.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio of number of incontinence episodes during the EoT 7-day diary between the combination therapy group and the solifenacin monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of urgency incontinence episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary day at EoT as the offset variable
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit
Description	An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 urgency incontinence episode at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	-6.45 (0.69)	-8.77 (0.69)	-10.1 (0.34)
Month 3	-9.06 (0.72)	-11.48 (0.71)	-11.99 (0.36)
Month 6	-10.09 (0.72)	-11.71 (0.71)	-13.0 (0.35)
Month 9	-11.1 (0.72)	-12.6 (0.73)	-13.44 (0.36)
Month 12	-11.27 (0.71)	-12.8 (0.71)	-13.8 (0.35)
EoT	-10.61 (0.7)	12.66 (0.7)	-13.59 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The two-sided p-value is for pairwise comparisons between the combination therapy group and the mirabegron monotherapy group from stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.98
	Confidence Interval	(2-Sided) 95%; -4.51 to -1.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.78
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	The two-sided p-value is for pairwise comparisons between the combination therapy group and the solifenacin monotherapy group from stratified rank ANCOVA.
	Method	Stratified Rank ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Stratified Rank ANCOVA
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95%; -2.47 to 0.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.78
	Estimation Comments

15. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions Per 24 Hours
Description	A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7-days before the baseline and prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	-1.09 (0.12)	-1.36 (0.12)	-1.64 (0.06)
Month 3	-1.63 (0.13)	-1.87 (0.12)	2.16 (0.06)
Month 6	-1.85 (0.13)	-2.04 (0.13)	-2.39 (0.06)
Month 9	-2.03 (0.13)	-2.03 (0.13)	-2.42 (0.06)
Month 12	-2.20 (0.13)	-2.13 (0.14)	-2.64 (0.07)

16. Secondary Outcome

Title	Number of Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)
Description	The number of days with < 8 micturitions was the number of valid diary days during the 7-day micturition diary period with with less than 8 micturitions per day.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	1.90 (0.13)	1.60 (0.12)	2.08 (0.07)
Month 3	2.07 (0.14)	2.14 (0.14)	2.66 (0.08)
Month 6	2.35 (0.15)	2.34 (0.15)	2.87 (0.08)
Month 9	2.38 (0.16)	2.33 (0.15)	2.93 (0.08)
Month 12	2.61 (0.16)	2.58 (0.16)	3.17 (0.08)
EoT	2.52 (0.15)	2.58 (0.15)	3.10 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio vs. Mirabegron 50 mg (EoT): Odds ratio was from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Overdispersed Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.14 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio vs. Solifenacin 5 mg (EoT): Odds ratio was from a overdispersed binomial regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Overdispersed Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; 1.09 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Change From Baseline to EoT in Corrected Micturition Frequency
Description	Corrected micturition frequency was defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline. Corrected micturition frequency was calculated as the baseline mean volume voided per micturition multiplied by the baseline mean number of micturitions per 24 hours divided by the mean volume voided per micturition at EoT.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

FAS population; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	301	297	1184
Least Squares Mean (Standard Error) [micturitions]	-0.72 (0.17)	-1.11 (0.17)	-1.51 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.16 to -0.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline mean number of micturitions per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.77 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

18. Secondary Outcome

Title	Change From Baseline to Months 3, 6 and 12 in Mean Volume Voided Per Micturition
Description	The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period prior to each visit.
Time Frame	Baseline and Months 3, 6, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 3	15.34 (2.96)	23.71 (2.92)	34.89 (1.45)
Month 6	20.87 (3.21)	27.08 (3.19)	38.56 (1.57)
Month 12	21.85 (3.42)	24.05 (3.37)	38.72 (1.67)

19. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours
Description	Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode recorded by the participant in the micturition diary for 7 days prior to each visit as 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 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 Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Participants with ≥ 1 urgency episode at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	-1.93 (0.17)	-2.31 (0.17)	-2.68 (0.09)
Month 3	-2.68 (0.17)	-3.02 (0.17)	-3.36 (0.08)
Month 6	-2.93 (0.17)	-3.17 (0.17)	-3.72 (0.08)
Month 9	-3.40 (0.18)	-3.55 (0.18)	-3.87 (0.09)
Month 12	-3.40 (0.17)	-3.56 (0.17)	-3.95 (0.09)
EoT	-3.11 (0.17)	-3.45 (0.17)	-3.84 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 95%; -1.10 to -0.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.76 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

20. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours
Description	A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The mean number of nocturia episodes was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit."
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	262	252	1027
Month 1	-0.20 (0.04)	-0.22 (0.04)	-0.34 (0.02)
Month 3	-0.34 (0.04)	-0.38 (0.04)	-0.46 (0.02)
Month 6	-0.41 (0.05)	-0.39 (0.05)	-0.49 (0.02)
Month 9	-0.42 (0.05)	-0.44 (0.05)	-0.50 (0.02)
Month 12	-0.46 (0.05)	-0.44 (0.05)	-0.56 (0.02)
EoT	-0.45 (0.04)	-0.45 (0.04)	-0.55 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

21. Secondary Outcome

Title	Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit
Description	A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	262	252	1027
Month 1	8.76 (0.41)	9.23 (0.44)	8.00 (0.20)
Month 3	7.93 (0.39)	7.92 (0.40)	7.17 (0.19)
Month 6	7.12 (0.35)	7.86 (0.43)	6.96 (0.20)
Month 9	7.40 (0.38)	7.48 (0.41)	6.84 (0.20)
Month 12	6.88 (0.38)	7.39 (0.44)	6.33 (0.19)
EoT	7.13 (0.37)	7.47 (0.42)	6.51 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio of number of nocturia episodes during the EoT 7-day diary between the combination therapy group and the mirabegron monotherapy group was calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of nocturia episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary days as the offset variable
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.067
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.06
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio of number of nocturia episodes during the EoT 7-day diary between the combination therapy group and the solifenacin monotherapy group was calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of nocturia episodes divided by number of valid diary days) included as a covariate and post baseline number of valid diary day as the offset variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.131
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.92
	Confidence Interval	() 95%; 0.82 to 1.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.06
	Estimation Comments

22. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes During the 7-Day Micturition Diary Period Prior to Each Visit
Description	A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 nocturia episode at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	262	252	1027
Month 1	-1.56 (0.29)	-1.58 (0.29)	-2.39 (0.15)
Month 3	-2.45 (0.29)	-2.78 (0.30)	-3.26 (0.15)
Month 6	-3.08 (0.33)	-2.81 (0.33)	-3.44 (0.16)
Month 9	-2.91 (0.32)	-3.13 (0.32)	-3.55 (0.16)
Month 12	-3.29 (0.32)	-3.08 (0.33)	-3.97 (0.16)
EoT	-3.24 (0.31)	-3.20 (0.32)	-3.90 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.34 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean was calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 95%; -1.39 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used Per 24 Hours
Description	The mean number of pads used per 24 hours was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 pads used at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	201	193	771
Month 1	-0.67 (0.10)	-0.96 (0.11)	-1.25 (0.05)
Month 3	-1.12 (0.11)	-1.30 (0.11)	-1.49 (0.06)
Month 6	-1.30 (0.12)	-1.24 (0.12)	-1.59 (0.06)
Month 9	-1.38 (0.12)	-1.31 (0.13)	-1.65 (0.06)
Month 12	-1.35 (0.12)	-1.37 (0.13)	-1.67 (0.06)
EoT	-1.23 (0.12)	-1.38 (0.12)	-1.66 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.69 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.55 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

24. Secondary Outcome

Title	Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit
Description	The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 pad used at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	201	193	771
Month 1	12.67 (1.98)	12.55 (1.59)	8.75 (0.50)
Month 3	9.61 (1.12)	9.47 (1.28)	7.23 (0.5)
Month 6	7.99 (1.03)	9.16 (1.28)	6.51 (0.47)
Month 9	7.65 (1.08)	8.91 (1.28)	6.18 (0.46)
Month 12	7.60 (1.05)	8.09 (1.23)	5.70 (0.44)
EoT	9.09 (1.07)	8.54 (1.10)	6.33 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio vs. Mirabegron 50 mg (EoT): Rate ratio of number of pads during the EoT 7-day diary between the combination therapy group and the mirabegron monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of pads divided by number of valid diary days) included as a covariate and post baseline number of valid diary days as the offset variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Rate ratio vs. Solifenacin 5 mg (EoT): Rate ratio of number of pads during the EoT 7-day diary between the combination therapy group and the solifenacin monotherapy group is calculated from a negative binomial regression model incl. treatment group, sex, age group (< 65, ≥ 65 years), geographic region and previous study history as factors, log(number of pads divided by number of valid diary days) included as a covariate and post baseline number of valid diary days as the offset variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

25. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit
Description	The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with ≥ 1 pad used at baseline were included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	201	193	771
Month 1	-4.74 (0.71)	-6.72 (0.72)	-8.89 (0.36)
Month 3	-7.83 (0.77)	-9.21 (0.78)	10.47 (0.39)
Month 6	-9.09 (0.85)	-8.86 (0.85)	-11.12 (0.42)
Month 9	-9.59 (0.87)	-9.33 (0.89)	-11.44 (0.43)
Month 12	-9.39 (0.85)	-9.92 (0.87)	-11.66 (0.42)
EoT	-8.59 (0.82)	-9.89 (0.84)	-11.58 (0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.98
	Confidence Interval	(2-Sided) 95%; -4.78 to -1.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.92
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.68
	Confidence Interval	(2-Sided) 95%; -3.52 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.93
	Estimation Comments

26. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	-16.37 (1.08)	-20.82 (1.07)	-22.86 (0.54)
Month 3	-19.69 (1.08)	-23.13 (1.07)	-26.88 (0.53)
Month 6	-20.97 (1.14)	-24.27 (1.12)	-27.73 (0.55)
Month 9	-21.41 (1.15)	-25.82 (1.14)	-28.45 (0.56)
Month 12	-23.41 (1.19)	-25.38 (1.18)	-30.18 (0.58)

27. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQoL): Total Score
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	11.67 (0.92)	14.01 (0.91)	15.69 (0.45)
Month 3	15.25 (0.95)	16.41 (0.94)	19.26 (0.47)
Month 6	16.63 (1.02)	17.96 (1.00)	20.03 (0.49)
Month 9	16.69 (1.02)	18.53 (1.01)	20.75 (0.50)
Month 12	17.33 (1.04)	18.80 (1.03)	21.82 (0.51)
EoT	16.57 (1.00)	18.47 (0.99)	21.33 (0.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	4.76
	Confidence Interval	(2-Sided) 95%; 2.56 to 6.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.12
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	2.86
	Confidence Interval	(2-Sided) 95%; 0.68 to 5.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.11
	Estimation Comments

28. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Coping
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	13.05 (1.09)	15.40 (1.08)	17.58 (0.54)
Month 3	17.57 (1.14)	18.38 (1.13)	21.64 (0.56)
Month 6	19.68 (1.22)	20.53 (1.19)	22.73 (0.59)
Month 9	19.54 (1.21)	21.21 (1.20)	23.58 (0.59)
Month 12	19.47 (1.25)	21.90 (1.23)	24.86 (0.61)
EoT	18.54 (1.19)	21.13 (1.18)	24.14 (0.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	5.60
	Confidence Interval	(2-Sided) 95%; 2.99 to 8.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.33
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	3.01
	Confidence Interval	(2-Sided) 95%; 0.43 to 5.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.32
	Estimation Comments

29. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Concern
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	13.24 (1.03)	15.49 (1.02)	17.60 (0.51)
Month 3	16.37 (1.05)	17.64 (1.04)	21.23 (0.52)
Month 6	17.77 (1.10)	19.05 (1.07)	21.73 (0.53)
Month 9	18.15 (1.11)	19.74 (1.10)	22.30 (0.54)
Month 12	19.10 (1.12)	19.40 (1.10)	23.30 (0.54)
EoT	17.98 (1.08)	19.22 (1.07)	23.00 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	5.01
	Confidence Interval	(2-Sided) 95%; 2.65 to 7.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.21
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	3.78
	Confidence Interval	(2-Sided) 95%; 1.43 to 6.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.20
	Estimation Comments

30. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Sleep
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consisted of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each time was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	10.96 (1.08)	14.24 (1.07)	15.82 (0.54)
Month 3	14.09 (1.12)	16.71 (1.10)	19.75 (0.55)
Month 6	14.84 (1.22)	17.70 (1.19)	20.09 (0.59)
Month 9	14.86 (1.22)	17.73 (1.21)	21.15 (0.60)
Month 12	16.53 (1.29)	18.28 (1.27)	22.17 (0.63)
EoT	16.44 (1.22)	18.32 (1.21)	21.59 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	5.15
	Confidence Interval	(2-Sided) 95%; 2.47 to 7.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.36
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	3.27
	Confidence Interval	(2-Sided) 95%; 0.62 to 5.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.35
	Estimation Comments

31. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQL Subscale Score: Social
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	7.99 (0.84)	9.41 (0.83)	9.89 (0.42)
Month 3	11.14 (0.85)	11.19 (0.84)	12.22 (0.42)
Month 6	11.89 (0.89)	12.54 (0.87)	13.30 (0.43)
Month 9	11.92 (0.90)	13.33 (0.89)	13.64 (0.44)
Month 12	12.25 (0.90)	13.47 (0.89)	14.52 (0.44)
EoT	11.57 (0.87)	13.22 (0.87)	14.25 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	2.68
	Confidence Interval	(2-Sided) 95%; 0.77 to 4.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.98
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.287
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; -0.87 to 2.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.97
	Estimation Comments

32. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of TS-VAS
Description	The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	1.88 (0.12)	1.95 (0.12)	2.27 (0.06)
Month 3	2.10 (0.11)	2.06 (0.11)	2.57 (0.06)
Month 6	2.22 (0.12)	2.25 (0.12)	2.72 (0.06)
Month 9	2.24 (0.12)	2.28 (0.12)	2.74 (0.06)
Month 12	2.33 (0.12)	2.34 (0.12)	2.89 (0.06)

33. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition (PPBC)
Description	The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	-0.84 (0.07)	-0.89 (0.07)	-1.05 (0.03)
Month 3	-1.09 (0.07)	-1.08 (0.07)	-1.33 (0.03)
Month 6	-1.11 (0.07)	-1.18 (0.07)	-1.42 (0.04)
Month 9	-1.25 (0.07)	-1.31 (0.07)	-1.48 (0.04)
Month 12	-1.29 (0.08)	-1.36 (0.07)	-1.59 (0.04)
EoT	-1.22 (0.07)	-1.34 (0.07)	-1.54 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Mirabegron 50 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the mirabegron monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.47 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Difference vs. Solifenacin 5 mg (EoT): Difference of the adjusted mean is calculated by subtracting the adjusted mean of the solifenacin monotherapy group from the adjusted mean of the combination therapy group (solifenacin 5 mg + mirabegron 50 mg) based on the ANCOVA model with treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as fixed factors and baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.36 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

34. Secondary Outcome

Title	Percentage of Participants in Each Category of Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT
Description	The PGIC is a 2-part questionnaire, assessing both the change in the patient's overall condition and change in bladder condition since the start of the study (from very much worse to very much improved).
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

FAS population with data available. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 12: Very much improved	25.5 8.3%	23.4 7.7%	33.8 2.8%
Month 12: Much improved	30.5 10%	35.8 11.7%	34.0 2.8%
Month 12: Minimally improved	21.9 7.2%	19.7 6.5%	16.1 1.3%
Month 12: No change	5.0 1.6%	6.4 2.1%	4.5 0.4%
Month 12: Minimally worse	0.7 0.2%	0.7 0.2%	0.4 0%
Month 12: Much worse	1.0 0.3%	0.3 0.1%	0.1 0%
Month 12: Very much worse	0.3 0.1%	0.3 0.1%	0.5 0%
EoT: Very much improved	25.8 8.4%	24.4 8%	34.1 2.8%
EoT: Much improved	31.5 10.3%	37.1 12.2%	34.7 2.8%
EoT: Minimally improved	22.2 7.3%	20.4 6.7%	16.6 1.4%
EoT: No change	6.3 2.1%	7.0 2.3%	5.1 0.4%
EoT: Minimally worse	0.7 0.2%	0.7 0.2%	0.4 0%
EoT: Much worse	1.3 0.4%	0.7 0.2%	0.1 0%
EoT: Very much worse	0.3 0.1%	0.3 0.1%	0.5 0%

35. Secondary Outcome

Title	Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT
Description	The PGIC is a 2-part questionnaire, assessing both the change in the patient's overall condition and change in bladder condition since the start of the study (from very much worse to very much improved).
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

FAS population with data available. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 12: Very much improved	12.9 4.2%	14.7 4.8%	18.0 1.5%
Month 12: Much improved	23.8 7.8%	26.8 8.8%	28.7 2.4%
Month 12: Minimally improved	18.9 6.2%	17.1 5.6%	18.7 1.5%
Month 12: No change	24.2 7.9%	24.7 8.1%	20.7 1.7%
Month 12: Minimally worse	3.6 1.2%	2.7 0.9%	2.7 0.2%
Month 12: Much worse	0.7 0.2%	0 0%	0.4 0%
Month 12: Very much worse	0.7 0.2%	0.7 0.2%	0.3 0%
EoT: Very much improved	13.2 4.3%	15.1 5%	18.3 1.5%
EoT: Much improved	24.5 8%	27.8 9.1%	28.9 2.4%
EoT: Minimally improved	19.2 6.3%	18.1 5.9%	19.1 1.6%
EoT: No change	25.8 8.4%	25.8 8.5%	21.6 1.8%
EoT: Minimally worse	3.6 1.2%	3.0 1%	2.8 0.2%
EoT: Much worse	1.0 0.3%	0.3 0.1%	0.5 0%
EoT: Very much worse	0.7 0.2%	0.7 0.2%	0.3 0%

36. Secondary Outcome

Title	Number of Participants With Change From Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility
Description	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).
Time Frame	Baseline and 12 Months

Outcome Measure Data

Analysis Population Description

FAS population; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
No problems -> no problems	164 53.6%	164 53.8%	675 55.4%
No problems -> slight problems	15 4.9%	15 4.9%	56 4.6%
No problems -> moderate problems	10 3.3%	4 1.3%	26 2.1%
No problems -> severe problems	1 0.3%	1 0.3%	2 0.2%
No problems -> unable to walk about	1 0.3%	0 0%	0 0%
No problems -> no data	3 1%	0 0%	7 0.6%
Slight problems -> no problems	19 6.2%	24 7.9%	83 6.8%
Slight problems -> slight problems	18 5.9%	29 9.5%	87 7.1%
Slight problems -> moderate problems	4 1.3%	6 2%	26 2.1%
Slight problems -> severe problems	3 1%	1 0.3%	2 0.2%
Slight problems -> unable to walk about	0 0%	0 0%	0 0%
Slight problems -> no data	2 0.7%	1 0.3%	0 0%
Moderate problems -> no problems	14 4.6%	11 3.6%	38 3.1%
Moderate problems -> slight problems	13 4.2%	17 5.6%	47 3.9%
Moderate problems -> moderate problems	9 2.9%	5 1.6%	50 4.1%
Moderate problems -> severe problems	2 0.7%	4 1.3%	8 0.7%
Moderate problems -> unable to walk about	0 0%	0 0%	0 0%
Moderate problems -> no data	0 0%	0 0%	1 0.1%
Severe problems -> no problems	2 0.7%	4 1.3%	15 1.2%
Severe problems -> slight problems	2 0.7%	2 0.7%	13 1.1%
Severe problems -> moderate problems	6 2%	4 1.3%	16 1.3%
Severe problems -> severe problems	5 1.6%	3 1%	15 1.2%
Severe problems -> unable to walk about	1 0.3%	0 0%	2 0.2%
Severe problems -> no data	0 0%	0 0%	0 0%
Unable to walk about -> no problems	0 0%	0 0%	1 0.1%
Unable to walk about -> slight problems	0 0%	0 0%	1 0.1%
Unable to walk about -> moderate problems	0 0%	0 0%	0 0%
Unable to walk about -> severe problems	0 0%	0 0%	0 0%
Unable to walk about -> unable to walk about	0 0%	0 0%	0 0%
Unable to walk about -> no data	0 0%	0 0%	0 0%
No data -> no problems	4 1.3%	3 1%	19 1.6%
No data -> slight problems	4 1.3%	1 0.3%	3 0.2%
No data -> moderate problems	0 0%	0 0%	0 0%
No data -> severe problems	0 0%	0 0%	0 0%
No data -> unable to walk about	0 0%	0 0%	0 0%
No data -> no data	0 0%	0 0%	0 0%

37. Secondary Outcome

Title	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care
Description	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

FAS populaton; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
No problems -> no problems	223 72.9%	232 76.1%	906 74.4%
No problems -> slight problems	12 3.9%	9 3%	40 3.3%
No problems -> moderate problems	8 2.6%	0 0%	12 1%
No problems -> severe problems	0 0%	1 0.3%	2 0.2%
No problems -> unable to wash/dress myself	0 0%	0 0%	0 0%
No problems -> no data	5 1.6%	1 0.3%	7 0.6%
Slight problems -> no problems	16 5.2%	18 5.9%	64 5.3%
Slight problems -> slight problems	9 2.9%	14 4.6%	44 3.6%
Slight problems -> moderate problems	0 0%	4 1.3%	12 1%
Slight problems -> severe problems	0 0%	1 0.3%	1 0.1%
Slight problems -> unable to wash/dress myself	0 0%	0 0%	0 0%
Slight problems -> no data	0 0%	0 0%	1 0.1%
Moderate problems -> no problems	5 1.6%	4 1.3%	18 1.5%
Moderate problems -> slight problems	5 1.6%	6 2%	20 1.6%
Moderate problems -> moderate problems	5 1.6%	3 1%	21 1.7%
Moderate problems -> severe problems	0 0%	0 0%	2 0.2%
Moderate problems -> unable to wash/dress myself	0 0%	0 0%	0 0%
Moderate problems -> no data	0 0%	0 0%	0 0%
Severe problems -> no problems	0 0%	1 0.3%	8 0.7%
Severe problems -> slight problems	1 0.3%	0 0%	3 0.2%
Severe problems -> moderate problems	3 1%	1 0.3%	4 0.3%
Severe problems -> severe problems	1 0.3%	0 0%	5 0.4%
Severe problems -> unable to wash/dress myself	0 0%	0 0%	0 0%
Severe problems -> no data	0 0%	0 0%	0 0%
Unable to wash/dress myself -> no problems	0 0%	0 0%	0 0%
Unable to wash/dress myself -> slight problems	0 0%	0 0%	1 0.1%
Unable to wash/dress myself -> moderate problems	0 0%	0 0%	0 0%
Unable to wash/dress myself -> severe problems	0 0%	0 0%	0 0%
Unable to wash/dress myself -> unable to wash/dres	1 0.3%	0 0%	0 0%
Unable to wash/dress myself -> no data	0 0%	0 0%	0 0%
No data -> no problems	6 2%	3 1%	22 1.8%
No data -> slight problems	2 0.7%	1 0.3%	0 0%
No data -> moderate problems	0 0%	0 0%	0 0%
No data -> severe problems	0 0%	0 0%	0 0%
No data -> unable to wash/dress myself	0 0%	0 0%	0 0%
No data -> no data	0 0%	0 0%	0 0%

38. Secondary Outcome

Title	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities
Description	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

FAS population; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
No problems -> No problems	165 53.9%	160 52.5%	672 55.2%
No problems -> Slight problems	13 4.2%	16 5.2%	65 5.3%
No problems -> Moderate problems	8 2.6%	4 1.3%	15 1.2%
No problems -> Severe problems	1 0.3%	0 0%	1 0.1%
No problems -> unable to do usual activities	0 0%	0 0%	0 0%
No problems -> no data	4 1.3%	0 0%	7 0.6%
Slight problems -> no problems	27 8.8%	39 12.8%	131 10.8%
Slight problems -> slight problems	28 9.2%	33 10.8%	85 7%
Slight problems -> moderate problems	5 1.6%	6 2%	26 2.1%
Slight problems -> severe problems	2 0.7%	1 0.3%	1 0.1%
Slight problems ->unable to do usual activities	0 0%	0 0%	0 0%
Slight problems -> no data	1 0.3%	0 0%	0 0%
Moderate problems -> no problems	12 3.9%	12 3.9%	40 3.3%
Moderate problems -> slight problems	11 3.6%	9 3%	44 3.6%
Moderate problems -> moderate problems	7 2.3%	4 1.3%	43 3.5%
Moderate problems -> severe problems	2 0.7%	0 0%	2 0.2%
Moderate problems ->unable to do usual activities	0 0%	0 0%	0 0%
Moderate problems -> no data	0 0%	1 0.3%	1 0.1%
Severe problems -> no problems	2 0.7%	1 0.3%	10 0.8%
Severe problems -> slight problems	0 0%	2 0.7%	9 0.7%
Severe problems -> moderate problems	0 0%	6 2%	7 0.6%
Severe problems -> severe problems	4 1.3%	1 0.3%	6 0.5%
Severe problems -> unable to do usual activities	0 0%	0 0%	1 0.1%
Severe problems -> no data	0 0%	0 0%	0 0%
Unable to do usual activities -> no problems	0 0%	0 0%	0 0%
Unable to do usual activities -> slight problems	0 0%	0 0%	1 0.1%
Unable to do usual activities -> moderate problems	1 0.3%	0 0%	4 0.3%
Unable to do usual activities -> severe problems	0 0%	0 0%	0 0%
Unable to do usual activities -> unable to do	1 0.3%	0 0%	0 0%
Unable to do usual activities -> no data	0 0%	0 0%	0 0%
No data -> no problems	6 2%	2 0.7%	20 1.6%
No data -> slight problems	1 0.3%	2 0.7%	2 0.2%
No data -> moderate problems	1 0.3%	0 0%	0 0%
No data -> severe problems	0 0%	0 0%	0 0%
No data -> unable to do usual activities	0 0%	0 0%	0 0%
No data -> no data	0 0%	0 0%	0 0%

39. Secondary Outcome

Title	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort
Description	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

FAS population; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
No pain/discomfort -> no pain/discomfort	120 39.2%	119 39%	495 40.6%
No pain/discomfort -> slight pain/discomfort	21 6.9%	19 6.2%	70 5.7%
No pain/discomfort -> moderate pain/discomfort	7 2.3%	1 0.3%	20 1.6%
No pain/discomfort -> severe pain/discomfort	1 0.3%	0 0%	3 0.2%
No pain/discomfort -> extreme pain/discomfort	0 0%	0 0%	0 0%
No pain/discomfort -> no data	2 0.7%	1 0.3%	6 0.5%
Slight pain/discomfort -> no pain/discomfort	44 14.4%	37 12.1%	132 10.8%
Slight pain/discomfort -> slight pain/discomfort	24 7.8%	48 15.7%	152 12.5%
Slight pain/discomfort -> moderate pain/discomfort	11 3.6%	9 3%	26 2.1%
Slight pain/discomfort -> severe pain/discomfort	2 0.7%	1 0.3%	5 0.4%
Slight pain/discomfort -> extreme pain/discomfort	0 0%	0 0%	1 0.1%
Slight pain/discomfort -> no data	0 0%	0 0%	1 0.1%
Moderate pain/discomfort -> no pain/discomfort	9 2.9%	11 3.6%	49 4%
Moderate pain/discomfort -> slight pain/discomfort	19 6.2%	17 5.6%	78 6.4%
Moderate pain/discomfort -> moderate pain/discomf	16 5.2%	10 3.3%	65 5.3%
Moderate pain/discomfort -> severe pain/discomfort	2 0.7%	3 1%	8 0.7%
Moderate pain/discomfort -> extreme pain/discomf	0 0%	0 0%	1 0.1%
Moderate pain/discomfort -> no data	1 0.3%	0 0%	1 0.1%
Severe pain/discomfort -> no pain/discomfort	3 1%	6 2%	15 1.2%
Severe pain/discomfort -> slight pain/discomfort	2 0.7%	3 1%	9 0.7%
Severe pain/discomfort -> moderate pain/discomfort	5 1.6%	5 1.6%	13 1.1%
Severe pain/discomfort -> severe pain/discomfort	2 0.7%	3 1%	11 0.9%
Severe pain/discomfort -> extreme pain/discomfort	0 0%	0 0%	1 0.1%
Severe pain/discomfort -> no data	1 0.3%	0 0%	0 0%
Extreme pain/discomfort -> no pain/discomfort	0 0%	0 0%	0 0%
Extreme pain/discomfort -> slight pain/discomfort	0 0%	0 0%	3 0.2%
Extreme pain/discomfort -> moderate pain/discomf	1 0.3%	0 0%	2 0.2%
Extreme pain/discomfort -> severe pain/discomfort	0 0%	2 0.7%	2 0.2%
Extreme pain/discomfort -> extreme pain/discomfort	0 0%	0 0%	2 0.2%
Extreme pain/discomfort -> no data	1 0.3%	0 0%	0 0%
No data -> no pain/discomfort	5 1.6%	1 0.3%	11 0.9%
No data -> slight pain/discomfort	3 1%	3 1%	11 0.9%
No data -> moderate pain/discomfort	0 0%	0 0%	0 0%
No data -> extreme pain/discomfort	0 0%	0 0%	0 0%
No data -> severe pain/discomfort	0 0%	0 0%	0 0%
No data -> no data	0 0%	0 0%	0 0%

40. Secondary Outcome

Title	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression
Description	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

FAS population; LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Not anxious -> not anxious	137 44.8%	142 46.6%	588 48.3%
Not anxious -> slightly anxious	22 7.2%	18 5.9%	68 5.6%
Not anxious -> moderately anxious	4 1.3%	1 0.3%	7 0.6%
Not anxious -> severely anxious	1 0.3%	0 0%	1 0.1%
Not anxious -> extremely anxious	0 0%	0 0%	0 0%
Not anxious -> no data	3 1%	1 0.3%	5 0.4%
Slightly anxious -> not anxious	35 11.4%	43 14.1%	177 14.5%
Slightly anxious -> slightly anxious	30 9.8%	33 10.8%	106 8.7%
Slightly anxious -> moderately anxious	4 1.3%	8 2.6%	21 1.7%
Slightly anxious -> severely anxious	3 1%	1 0.3%	0 0%
Slightly anxious -> extremely anxious	0 0%	1 0.3%	1 0.1%
Slightly anxious -> no data	1 0.3%	0 0%	1 0.1%
Moderately anxious -> not anxious	15 4.9%	11 3.6%	37 3%
Moderately anxious -> slightly anxious	11 3.6%	14 4.6%	55 4.5%
Moderately anxious -> moderately anxious	12 3.9%	8 2.6%	35 2.9%
Moderately anxious -> severely anxious	1 0.3%	1 0.3%	5 0.4%
Moderately anxious -> extremely anxious	0 0%	0 0%	0 0%
Moderately anxious -> no data	0 0%	0 0%	1 0.1%
Severely anxious -> not anxious	2 0.7%	2 0.7%	10 0.8%
Severely anxious -> slightly anxious	3 1%	2 0.7%	14 1.1%
Severely anxious -> moderately anxious	5 1.6%	3 1%	13 1.1%
Severely anxious -> severely anxious	2 0.7%	1 0.3%	7 0.6%
Severely anxious -> extremely anxious	1 0.3%	0 0%	1 0.1%
Severely anxious -> no data	1 0.3%	0 0%	1 0.1%
Extremely anxious -> not anxious	0 0%	1 0.3%	4 0.3%
Extremely anxious -> slightly anxious	0 0%	2 0.7%	2 0.2%
Extremely anxious -> moderately anxious	1 0.3%	0 0%	8 0.7%
Extremely anxious -> severely anxious	0 0%	2 0.7%	2 0.2%
Extremely anxious -> extremely anxious	0 0%	0 0%	1 0.1%
Extremely anxious -> no data	0 0%	0 0%	0 0%
No data -> not anxious	6 2%	3 1%	14 1.1%
No data -> slightly anxious	1 0.3%	1 0.3%	7 0.6%
No data -> moderately anxious	1 0.3%	0 0%	0 0%
No data -> severely anxious	0 0%	0 0%	0 0%
No data -> extremely anxious	0 0%	0 0%	1 0.1%
No data -> no data	0 0%	0 0%	0 0%

41. Secondary Outcome

Title	Change From Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed
Description	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.
Time Frame	Baseline and Months 6,12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with both baseline and post-baseline values and who were employed during the study are included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	114	136	468
Month 6	-0.49 (17.12)	-0.59 (15.67)	-3.11 (20.68)
Month 12	0.39 (15.55)	-1.95 (18.51)	-3.74 (23.83)
EoT	-0.45 (18.51)	-1.30 (18.04)	-3.26 (22.88)

42. Secondary Outcome

Title	Change From Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working
Description	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.
Time Frame	Baseline and Months 6, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with both baseline and post-baseline values and who were employed during the study are included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	114	135	461
Month 6	-16.94 (24.10)	-12.97 (21.05)	-13.41 (24.37)
Month 12	-19.16 (23.38)	-14.72 (27.32)	-16.68 (24.16)
EoT	-17.81 (23.45)	-13.90 (27.18)	-15.63 (25.61)

43. Secondary Outcome

Title	Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment
Description	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes arre expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.
Time Frame	Baseline and Months 6, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with both baseline and post-baseline values and who were employed during the study are included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	114	135	461
Month 6	-16.33 (27.58)	-12.09 (22.26)	-13.99 (26.04)
Month 12	-17.83 (26.90)	-15.38 (27.97)	-17.27 (27.25)
EoT	-16.83 (27.63)	-14.16 (27.51)	-16.15 (28.51)

44. Secondary Outcome

Title	Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment
Description	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.
Time Frame	Baseline and Months 6, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. Only participants with both baseline and post-baseline values during the study are included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	292	285	1167
Month 6	-15.04 (27.08)	-16.25 (24.78)	-16.94 (28.49)
Month 12	-16.85 (27.57)	-14.12 (29.87)	-18.91 (29.26)
EoT	-16.02 (27.63)	-14.02 (30.29)	-18.75 (29.14)

45. Secondary Outcome

Title	Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the last 3 days of the 7-day micturition diary is reported.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	24.4 8%	39.9 13.1%	38.3 3.1%
Month 3	40.1 13.1%	44.8 14.7%	49.6 4.1%
Month 6	40.6 13.3%	50.5 16.6%	54.7 4.5%
Month 9	47.0 15.4%	54.4 17.8%	55.8 4.6%
Month 12	51.6 16.9%	55.5 18.2%	61.2 5%
EoT	47.8 15.6%	53.2 17.4%	58.8 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours during the last 3 days as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.65
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours during the last 3 days as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

46. Secondary Outcome

Title	Percentage of Participants With ≥ 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	63.7 20.8%	67.5 22.1%	72.8 6%
Month 3	69.1 22.6%	71.3 23.4%	81.8 6.7%
Month 6	70.4 23%	74.6 24.5%	80.5 6.6%
Month 9	70.1 22.9%	76.1 25%	82.9 6.8%
Month 12	72.8 23.8%	74.1 24.3%	84.4 6.9%
EoT	70.7 23.1%	72.4 23.7%	82.9 6.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OAB-q subscale as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.03
	Confidence Interval	(2-Sided) 95%; 1.49 to 2.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OAB-q subscale as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.87
	Confidence Interval	(2-Sided) 95%; 1.37 to 2.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

47. Secondary Outcome

Title	Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT
Description	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	46.6 15.2%	53.8 17.6%	57.0 4.7%
Month 3	53.6 17.5%	59.4 19.5%	64.6 5.3%
Month 6	56.9 18.6%	62.9 20.6%	66.1 5.4%
Month 9	57.1 18.7%	62.9 20.6%	67.7 5.6%
Month 12	58.4 19.1%	62.4 20.5%	69.0 5.7%
EoT	56.2 18.4%	61.6 20.2%	68.4 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OAB-q subscale as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.82
	Confidence Interval	(2-Sided) 95%; 1.36 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline OAB-q subscale as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

48. Secondary Outcome

Title	Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Months 1, 3, 6, 9, 12 and EoT
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	46.7 15.3%	55.2 18.1%	62.0 5.1%
Month 3	58.2 19%	67.0 22%	73.3 6%
Month 6	63.2 20.7%	71.8 23.5%	76.6 6.3%
Month 9	67.0 21.9%	73.6 24.1%	77.8 6.4%
Month 12	72.9 23.8%	75.4 24.7%	81.3 6.7%
EoT	69.1 22.6%	73.1 24%	79.5 6.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.80
	Confidence Interval	(2-Sided) 95%; 1.34 to 2.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio wa from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.06 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

49. Secondary Outcome

Title	Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the 7-day micturition diary is reported.
Time Frame	Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	17.2 5.6%	26.4 8.7%	27.9 2.3%
Month 3	27.0 8.8%	35.1 11.5%	40.0 3.3%
Month 6	32.3 10.6%	39.9 13.1%	44.7 3.7%
Month 9	37.1 12.1%	43.7 14.3%	46.9 3.9%
Month 12	41.9 13.7%	47.3 15.5%	52.5 4.3%
EoT	38.9 12.7%	45.1 14.8%	49.7 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.67
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.133
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

50. Secondary Outcome

Title	Percentage of Participants With Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT
Description	The percentage of participants with micturition frequency normalization was defined as participants who had ≥ 8 micturitions/24 hours at baseline and < 8 micturitions/24 hours postbaseline at months 1, 3, 6, 9, 12 and EoT.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS with data available at each time point. Participants with less < 8 micturitions per 24 hours at baseline were not included in the analysis. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	34.5 11.3%	29.3 9.6%	36.8 3%
Month 3	36.7 12%	36.6 12%	46.6 3.8%
Month 6	42.3 13.8%	43.4 14.2%	51.4 4.2%
Month 9	44.5 14.5%	41.9 13.7%	52.5 4.3%
Month 12	46.3 15.1%	44.7 14.7%	56.4 4.6%
EoT	46.0 15%	46.3 15.2%	55.9 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 1.18 to 2.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of micturitions per 24 hours as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; 1.12 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

51. Secondary Outcome

Title	Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT
Description	The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	53.0 17.3%	59.2 19.4%	64.1 5.3%
Month 3	61.9 20.2%	65.7 21.5%	72.5 6%
Month 6	64.6 21.1%	68.8 22.6%	73.8 6.1%
Month 9	65.5 21.4%	68.9 22.6%	75.1 6.2%
Month 12	69.7 22.8%	73.7 24.2%	76.9 6.3%
EoT	66.2 21.6%	71.4 23.4%	76.0 6.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.68
	Confidence Interval	(2-Sided) 95%; 1.24 to 2.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

52. Secondary Outcome

Title	Percentage of Participants With Major (≥ 2 Points) Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT
Description	The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	24.9 8.1%	28.2 9.2%	30.7 2.5%
Month 3	31.3 10.2%	33.9 11.1%	42.8 3.5%
Month 6	35.0 11.4%	38.2 12.5%	45.4 3.7%
Month 9	37.5 12.3%	40.9 13.4%	47.0 3.9%
Month 12	40.6 13.3%	40.4 13.2%	51.9 4.3%
EoT	38.3 12.5%	39.8 13%	50.3 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.69
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline PPBC as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.62
	Confidence Interval	(2-Sided) 95%; 1.22 to 2.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

53. Secondary Outcome

Title	Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q Symptom Bother Scale) at Months 1, 3, 6, 9, 12 and EoT
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	36.1 11.8%	46.6 15.3%	52.6 4.3%
Month 3	47.8 15.6%	55.5 18.2%	65.1 5.3%
Month 6	50.4 16.5%	56.9 18.7%	65.8 5.4%
Month 9	53.1 17.4%	61.9 20.3%	69.2 5.7%
Month 12	59.2 19.3%	60.9 20%	73.2 6%
EoT	55.7 18.2%	58.2 19.1%	70.8 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline OAB-q symptom bother scale as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.99
	Confidence Interval	(2-Sided) 95%; 1.50 to 2.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio is from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline OAB-q symptom bother scale as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95%; 1.35 to 2.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

54. Secondary Outcome

Title	Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	28.5 9.3%	36.6 12%	40.9 3.4%
Month 3	39.6 12.9%	43.8 14.4%	52.3 4.3%
Month 6	41.6 13.6%	47.9 15.7%	55.3 4.5%
Month 9	43.7 14.3%	51.2 16.8%	57.6 4.7%
Month 12	46.9 15.3%	50.4 16.5%	60.6 5%
EoT	44.3 14.5%	49.0 16.1%	59.2 4.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline OAB-q HRQL total score as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.93
	Confidence Interval	(2-Sided) 95%; 1.46 to 2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline OAB-q HRQL total score as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 1.20 to 2.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

55. Secondary Outcome

Title	Percentage of Participants Who Were Double Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT
Description	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	32.1 10.5%	37.1 12.2%	46.0 3.8%
Month 3	43.3 14.2%	47.7 15.6%	57.6 4.7%
Month 6	46.8 15.3%	52.1 17.1%	60.6 5%
Month 9	49.6 16.2%	53.2 17.4%	63.0 5.2%
Month 12	57.6 18.8%	60.1 19.7%	67.0 5.5%
EoT	52.9 17.3%	57.5 18.9%	65.1 5.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline PPBC as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.70
	Confidence Interval	(2-Sided) 95%; 1.28 to 2.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours and baseline PPBC as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 1.06 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

56. Secondary Outcome

Title	Percentage of Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q Symptom Bother Scale and ≥1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT
Description	The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The symptom bother portion of the OAB-q consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	29.9 9.8%	35.5 11.6%	42.8 3.5%
Month 3	38.9 12.7%	44.8 14.7%	54.1 4.4%
Month 6	42.4 13.9%	46.1 15.1%	55.9 4.6%
Month 9	46.5 15.2%	50.8 16.7%	59.2 4.9%
Month 12	51.4 16.8%	53.6 17.6%	63.7 5.2%
EoT	47.4 15.5%	51.4 16.9%	61.7 5.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours, baseline OAB-q symptom bother scale and baseline PPBC as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.86
	Confidence Interval	(2-Sided) 95%; 1.40 to 2.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours, baseline OAB-q symptom bother scale and baseline PPBC as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 95%; 1.19 to 2.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

57. Secondary Outcome

Title	Participants Who Were Triple Responders (≥ 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, ≥ 10 Points Improvement on OAB-q HRQL Total Score and ≥ 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT
Description	The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The HRQoL portion of the OAB-q consists of 25 HRQoL items comprising 4 HRQoL subscales, each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	302	299	1193
Month 1	25.2 8.2%	29.0 9.5%	35.5 2.9%
Month 3	33.3 10.9%	39.1 12.8%	45.9 3.8%
Month 6	36.8 12%	41.2 13.5%	49.6 4.1%
Month 9	39.0 12.7%	44.0 14.4%	51.3 4.2%
Month 12	44.1 14.4%	47.6 15.6%	54.6 4.5%
EoT	40.1 13.1%	45.2 14.8%	53.3 4.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours, baseline OAB-q HRQL total score and baseline PPBC as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 1.33 to 2.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Solifenacin 5 mg, Solifenacin 5 mg + Mirabegron 50 mg
	Comments	Odds ratio was from a logistic regression model including treatment group, sex, age group (< 65, ≥ 65 years), previous study history and geographic region as factors and baseline mean number of incontinence episodes per 24 hours, baseline OAB-q HRQL total score and baseline PPBC as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

58. Secondary Outcome

Title	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume
Description	PVR volume was assessed by ultrasonography or a bladder scanner.
Time Frame	Baseline and Months 1, 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

SAF population with data available at each time point. LOCF was used for EoT.

Arm/Group Title	Mirabegron 50 mg	Solifenacin 5 mg	Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.	Participants received solifenacin 5 mg once a day for 52 weeks.	Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Measure Participants	305	303	1206
Month 1	3.179 (27.491)	4.549 (33.973)	7.894 (38.369)
Month 3	4.686 (29.354)	3.233 (32.679)	7.033 (37.328)
Month 6	1.596 (29.399)	3.418 (31.864)	6.708 (35.881)
Month 9	3.074 (32.897)	3.436 (32.170)	8.229 (40.313)
Month 12	2.002 (32.453)	4.818 (33.764)	7.946 (38.118)
EoT	1.747 (32.400)	7.382 (42.916)	8.522 (39.501)

Adverse Events

Time Frame	From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 56 weeks)
Adverse Event Reporting Description	The total number of deaths data includes deaths reported after the abovementioned timeframe.
Arm/Group Title	Mirabegron 50 mg		Solifenacin 5 mg		Solifenacin 5 mg + Mirabegron 50 mg
Arm/Group Description	Participants received mirabegron 50 mg once a day for 52 weeks.		Participants received solifenacin 5 mg once a day for 52 weeks.		Participants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
All Cause Mortality
	Mirabegron 50 mg		Solifenacin 5 mg		Solifenacin 5 mg + Mirabegron 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/305 (0.3%)		0/303 (0%)		1/1206 (0.1%)
Serious Adverse Events
	Mirabegron 50 mg		Solifenacin 5 mg		Solifenacin 5 mg + Mirabegron 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/305 (2.6%)		8/303 (2.6%)		51/1206 (4.2%)
Cardiac disorders
Atrial fibrillation	1/305 (0.3%)		0/303 (0%)		2/1206 (0.2%)
Cardiac arrest	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Coronary artery occlusion	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Myocardial ischaemia	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Endocrine disorders
Hyperparathyroidism	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Eye disorders
Amaurosis fugax	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Gastrointestinal disorders
Abdominal pain	1/305 (0.3%)		0/303 (0%)		1/1206 (0.1%)
Abdominal pain upper	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Diverticulum intestinal	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Enterocele	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Gastrointestinal disorder	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Gastrooesophageal reflux disease	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Gastrooesophageal sphincter insufficiency	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Inguinal hernia	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Pancreatitis acute	0/305 (0%)		1/303 (0.3%)		1/1206 (0.1%)
Small intestinal obstruction	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
General disorders
Non-cardiac chest pain	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Pyrexia	1/305 (0.3%)		0/303 (0%)		0/1206 (0%)
Hepatobiliary disorders
Cholelithiasis	0/305 (0%)		0/303 (0%)		2/1206 (0.2%)
Infections and infestations
Appendicitis	1/305 (0.3%)		0/303 (0%)		2/1206 (0.2%)
Bronchitis	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Cellulitis	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Erysipelas	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Haematoma infection	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Meningitis aseptic	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Pneumonia	1/305 (0.3%)		0/303 (0%)		2/1206 (0.2%)
Superinfection bacterial	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Clavicle fracture	0/305 (0%)		0/303 (0%)		2/1206 (0.2%)
Femur fracture	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Hip fracture	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Humerus fracture	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Incisional hernia	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Meniscus injury	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Pelvic fracture	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Sternal fracture	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Subdural haematoma	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Investigations
Blood glucose increased	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Exostosis	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Lumbar spinal stenosis	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Osteitis	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Osteoarthritis	0/305 (0%)		0/303 (0%)		2/1206 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/305 (0%)		0/303 (0%)		3/1206 (0.2%)
Bladder cancer	1/305 (0.3%)		0/303 (0%)		0/1206 (0%)
Bowen's disease	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Breast cancer female	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Breast cancer recurrent	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Malignant melanoma	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Malignant melanoma in situ	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Metastatic uterine cancer	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Squamous cell carcinoma of skin	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Nervous system disorders
Carotid artery stenosis	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Dizziness	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Long thoracic nerve palsy	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Sciatica	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Psychiatric disorders
Delirium	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Reproductive system and breast disorders
Hysterocele	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Pelvic pain	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Uterine prolapse	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Vaginal haemorrhage	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/305 (0.3%)		0/303 (0%)		0/1206 (0%)
Pneumothorax	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Surgical and medical procedures
Appendicectomy	1/305 (0.3%)		0/303 (0%)		0/1206 (0%)
Cholecystectomy	0/305 (0%)		0/303 (0%)		2/1206 (0.2%)
Colon polypectomy	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Cystocele repair	1/305 (0.3%)		0/303 (0%)		0/1206 (0%)
Hysterectomy	1/305 (0.3%)		0/303 (0%)		0/1206 (0%)
Spinal fusion surgery	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Spinal operation	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Vascular disorders
Hypertension	0/305 (0%)		1/303 (0.3%)		0/1206 (0%)
Thrombosis	0/305 (0%)		0/303 (0%)		1/1206 (0.1%)
Other (Not Including Serious) Adverse Events
	Mirabegron 50 mg		Solifenacin 5 mg		Solifenacin 5 mg + Mirabegron 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/305 (8.9%)		33/303 (10.9%)		115/1206 (9.5%)
Gastrointestinal disorders
Dry mouth	12/305 (3.9%)		18/303 (5.9%)		74/1206 (6.1%)
Infections and infestations
Nasopharyngitis	16/305 (5.2%)		15/303 (5%)		43/1206 (3.6%)

Limitations/Caveats

Due to lack of data integrity, one site's data were not included in the efficacy and safety analysis, and another site's data for 5 patients were not included in the efficacy analysis.

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 prior to publication for review and comment as specified in the Investigator Agreement.