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

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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."

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

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).

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

PVR volume was assessed by ultrasonography or a bladder scanner.