Trial Outcomes & Findings for This Was a Multinational Study Comparing the Efficacy and Safety of Two Medicines , Solifenacin Succinate and Mirabegron Taken Together, or Separately, or a Mock Treatment (Placebo) in Subjects With Symptoms of Overactive Bladder (NCT NCT01972841)

Patients who had symptoms of "wet" overactive bladder (OAB) (urgency, urinary frequency and urgency incontinence) for ≥ 3 months were enrolled at 435 centers in 42 countries. Eligible participants went into a single-blind, 4-week placebo run-in period and completed a micturition diary the last 7 days prior to each study visit.

A total of 6991 participants were screened, 6275 participants received placebo run-in treatment and 3527 participants were randomized into 1 of 6 treatment arms in a 1:1:1:1:2:2 ratio in the 12-week double-blind treatment period. A total of 953 participants were also enrolled in an ambulatory blood pressure monitoring (ABPM) substudy.

Full analysis set (FAS) comprised all RAS patients who took ≥ 1 dose of double-blind treatment after randomization, reported ≥ 1 micturition in the baseline diary and ≥ 1 micturition postbaseline, reported ≥ 1 incontinence episode in the baseline diary and excluded participants from one site. Participants with available data were included.

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 per day on valid diary days during the 7-day micturition diary period.

A micturition was defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period.

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 was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consisted 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 indicates an improvement.

The TS-VAS was a visual analogue scale which asked 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 number of incontinence episodes was calculated as the total number of incontinence episodes on valid diary days recorded during the 7-day micturition diary period.

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.

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 number of times a participant recorded an urgency incontinence episode on valid diary days during the 7-day micturition diary period prior to each visit.

The mean number of urgency incontinence episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days during the 7-day micturition diary period prior to each visit.

An urgency episode was a complaint of a sudden, compelling desire to pass urine, which was difficult to defer; it was recorded when a micturition or incontinence episode was recorded and the severity of urinary urgency recorded was 3 (severe urgency) or 4 (urgency incontinence) according to the Patient Perception of Intensity of Urgency Scale (PPIUS). The mean number of urgency episodes per 24 hours was calculated from data recorded by the participant per day on valid diary days 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 went to bed with the intention to sleep until the time the patients got 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 on valid diary days during the 7-day micturition diary period prior to each visit.

The mean number of nocturia episodes per 24hr was calculated from data recorded by the participant per day on valid diary days 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 on valid diary days 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 per day on valid diary days 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 with no incontinence episodes recorded.

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

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.

The PPBC was 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 OAB-q was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion in the OAB-q (seen in this outcome measure) consisted 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 was a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion in the OAB-q (seen in this outcome measure) consisted of 25 HRQL items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction), scored 1-6. The total HRQoL 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 Coping score was calculated by adding 8 response 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 Concern score was calculated by adding 7 response 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 Sleep score was calculated by adding 5 response 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 Social score was calculated by adding 5 response 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 PGIC was 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 was 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 was 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 had 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

The EQ-5D questionnaire was 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 had 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

The EQ-5D questionnaire was 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 had 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

The EQ-5D questionnaire was 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 had 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

The EQ-5D questionnaire was 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 had 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).

The WPAI:SHP was 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 were expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.