A Phase 3 interventional study of Solifenacin succinate and Mirabegron in Urinary Bladder Overactive, Urinary Bladder Diseases\Urologic Diseases and Overactive Bladder, sponsored by Astellas Pharma Europe B.V.. Completed at 435 sites in 42 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-31.
Sponsored by Astellas Pharma Europe B.V. · Phase 3, Interventional, and Treatment
The purpose of this study was to examine how well two medicines (solifenacin succinate and mirabegron) combined work compared to each medicine alone in the treatment of bladder problems.
Exclusion Criteria:
Participants who received solifenacin 5 mg and mirabegron 25 mg once a day for 12 weeks.
Drug: Solifenacin succinate · Drug: Mirabegron · Drug: Placebo to match mirabegron
Participants who received solifenacin 5 mg and mirabegron 50 mg once a day for 12 weeks.
Drug: Solifenacin succinate · Drug: Mirabegron · Drug: Placebo to match mirabegron
Participants who received matching placebo once a day for 12 weeks.
Drug: Placebo to match solifenacin succinate · Drug: Placebo to match mirabegron
Participants who received solifenacin 5 mg once a day for 12 weeks.
Drug: Solifenacin succinate · Drug: Placebo to match mirabegron
Participants who received mirabegron 25 mg once a day for 12 weeks.
Drug: Mirabegron · Drug: Placebo to match solifenacin succinate · Drug: Placebo to match mirabegron
Participants who received mirabegron 50 mg once a day for 12 weeks.
Drug: Mirabegron · Drug: Placebo to match solifenacin succinate · Drug: Placebo to match mirabegron
Oral tablet
Also known as: Vesikur, Vesitrim, YM905, Vesicare
Oral tablet
Also known as: YM178, Betmiga, Betanis, Myrbetriq
Oral tablet
Oral tablet
Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours
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.
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours
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.
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to EoT in Mean Volume Voided Per Micturition
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 EoT (up to 12 weeks)
Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score
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.
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to EoT in Treatment Satisfaction-Visual Analogue Scale (TS-VAS)
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.
Time frame: Baseline and EoT (up to 12 weeks)
Number of Incontinence Episodes at Weeks 4, 8, 12 and EoT
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.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Incontinence Episodes
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8 and 12 in Mean Number of Incontinence Episodes Per 24 Hours
Time frame: Baseline and weeks 4, 8 and 12
Change From Baseline to Weeks 4, 8 and 12 in Mean Number of Micturitions Per 24 Hours
Time frame: Baseline and weeks 4, 8 and 12
Change From Baseline to Weeks 4, 8 and 12 in Mean Volume Voided Per Micturition
Time frame: Baseline and weeks 4, 8 and 12
Change From Baseline to EoT in Corrected Micturition Frequency
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.
Time frame: Baseline and Week 12
Number of Urgency Incontinence Episodes at Weeks 4, 8, 12 and EoT
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.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Urgency Incontinence Episodes
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours
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.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours
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.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Number of Nocturia Episodes at Weeks 4, 8, 12 and EoT
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.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Nocturia Episodes
Time frame: Baseline and weeks 4, 8, 12, and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours
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.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Number of Pads Used at Weeks 4, 8, 12 and EoT
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.
Time frame: Weeks 4, 8 and 12 (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Number of Pads Used
Time frame: Baseline and weeks 4, 8, 12 and EOT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Mean Number of Pads Used Per 24 Hours
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.
Time frame: Baseline and weeks 4, 8 and 12 (up to 12 weeks)
Number of Incontinence-Free Days at Weeks 4, 8, 12 and EoT
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.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Number of Days With < 8 Micturitions at Weeks 4, 8, 12 and EoT
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.
Time frame: Weeks 4, 8,12 and EoT (up to 12 weeks)
Number of Incontinence-Free Days With < 8 Micturitions at Weeks 4, 8, 12 and EoT
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: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Patient Perception of Bladder Condition Questionnaire (PPBC)
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.
Time frame: Baseline and weeks 4, 8, 12, EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8 and 12 in the OAB-q Symptom Bother Score
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.
Time frame: Baseline and weeks 4, 8 and 12
Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q Health-Related Quality of Life Questionnaire (HRQL) Total Score
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.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Coping
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.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Concern
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.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Sleep
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.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in OAB-q HRQL Subscale Score: Social
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.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Week 12 and EoT
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).
Time frame: Week 12 and EoT (up to 12 weeks)
PGIC Scale: Impression in General Health at Week 12 and EoT
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).
Time frame: Week 12 and EoT (up to 12 weeks)
Change From Baseline to EoT in European Quality of Life in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility
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).
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-Care
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).
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities
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).
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort
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).
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression
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).
Time frame: Baseline and EoT (up to 12 weeks)
Change From Baseline to Week 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed
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.
Time frame: Baseline and week 12 and EoT (up to 12 weeks)
Change From Baseline to Week 12 and EoT in WPAI:SHP Score: Percent Impairment While Working
Time frame: Baseline and week 12 and EoT (up to 12 weeks)
Change From Baseline to Week 12 and EoT in WPAI:SHP Score: Percent Overall Work Impairment
Time frame: Baseline and week 12 and EoT (up to 12 weeks)
Change From Baseline to Week 12 and EoT in WPAI:SHP Score: Percent Activity Impairment
Time frame: Baseline and week 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8 and 12 in TS-VAS
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.
Time frame: Baseline and week 4, 8 and 12
Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Weeks 4, 8, 12 and EoT
The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 3 days prior to weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants With ≥ 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Weeks 4, 8, 12 and EoT
The percentage of participants with ≥ 10 points improvement from baseline to each visit (weeks 4, 8, 12 and EoT).
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants With ≥ 10 Points Improvement From Baseline in HRQL Total Score at Weeks 4, 8, 12 and EoT
The percentage of participants with ≥ 10 points improvement from baseline to each visit (weeks 4, 8, 12 and EoT).
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Weeks 4, 8, 12 and EoT
The percentage of participants with ≥ 50% decrease from baseline in mean number of incontinence episodes per 24 hours at each time point (weeks 4, 8, 12 and EoT).
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants for Micturition Frequency Normalization at Weeks 4, 8, 12 and EoT
The percentage of participants with micturition frequency normalization was defined as any participant who had ≥ 8 micturitions/24 hours at baseline and \< 8 micturitions/24 h postbaseline at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8 , 12 and EoT (up to 12 weeks)
Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Weeks 4, 8, 12 and EoT
The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 7 days prior to weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants With ≥ 1 Point Improvement From Baseline in PPBC at Weeks 4, 8, 12 and EoT
The percentage of participants with ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants With Major (≥ 2 Points) Improvement From Baseline in PPBC at Weeks 4, 8, 12 and EoT
The percentage of participants with a major (≥ 2 points) improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
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 Weeks 4, 8, 12 and EoT
The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
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 Weeks 4, 8, 12 and EoT
The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q HRQL total score at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
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 Weeks 4, 8, 12 and EoT
The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants Who Were Triple Responders (50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, at Least 10 Points Improvement on OAB-q Symptom Bother Scale and at Least 1 Point Improvement on PPBC) at Weeks 4, 8, 12 and EoT
The percentage of participants considered as triple responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score, and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Percentage of Participants Who Were Triple Responders (50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, at Least 10 Points Improvement on OAB-q HRQL Total Score and at Least 1 Point Improvement on PPBC) at Weeks 4, 8, 12 and EoT
The percentage of participants considered as triple responders, defined as participants with 50% reduction in mean number of incontinence episodes per24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the HRQL total score, and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
Time frame: Weeks 4, 8, 12 and EoT (up to 12 weeks)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
A TEAE refered to an adverse event (AE; defined as any untoward medical occurrence in a participant administered a study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment) which started or worsened in the period from first double-blind medication intake until 14 days after the last double-blind medication intake. Serious TEAEs with a start date reported until 30 days after the last double-blind medication intake were also summarized as TEAEs, and also included serious TEAEs upgraded by the sponsor based on review of the sponsor's list of Always Serious terms if any upgrade was done. Drug-related TEAEs may be possible or probable, as assessed by the investigator, or records where relationship is missing.
Time frame: From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 16 weeks)
Change From Baseline to Weeks 4, 8, 12 and EoT in Postvoid Residual (PVR) Volume
PVR volume was assessed by ultrasonography or a bladder scanner.
Time frame: Baseline and weeks 4, 8, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in Mean 24-hours, Mean Daytime and Mean Nighttime Systolic Blood Pressure (SBP)
Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in Mean 24-h, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP)
Vital signs (blood pressure and pulse rate) were monitored using ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in Mean 24-h, Mean Daytime and Mean Nighttime Pulse Rate (PR)
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in Mean SBP in the Time to Maximum Concentration (Tmax) Window
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax (time to maximum concentration) window of mirabegron and solifenacin was from 4-6 hours postdose.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in Mean DBP in the Tmax Window
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in Mean PR in the Tmax Window
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Maximum 1-hour Change From Time-matched Baseline in SBP at Weeks 4, 12 and EoT
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. The maximum 1 hour change from time-matched baseline was calculated as the maximum difference between the post-baseline hourly means and the time-matched baseline hourly means.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Maximum 1-hour Change From Time-matched Baseline in DBP at Weeks 4, 12 and EoT
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose. The maximum 1 hour change from time-matched baseline was calculated as the maximum difference between the post-baseline hourly means and the time-matched baseline hourly means.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Maximum 1-hour Change From Time-matched Baseline in PR at Weeks 4, 12 and EoT
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose. The maximum 1 hour change from time-matched baseline was calculated as the maximum difference between the post-baseline hourly means and the time-matched baseline hourly means.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in SBP Peak/Trough Difference
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference was defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in DBP Peak/Trough Difference
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference was defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 12 and EoT in PR Peak/Trough Difference
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference was defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.
Time frame: Baseline and weeks 4, 12 and EoT (up to 12 weeks)
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.
| Milestone | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Started | 447 | 441 | 437 | 434 | 885 | 883 |
| Completed | 404 | 397 | 387 | 397 | 802 | 798 |
| Not completed | 43 | 44 | 50 | 37 | 83 | 85 |
| Withdrew: Randomized but never received treatment | 2 | 5 | 4 | 2 | 6 | 13 |
| Withdrew: Adverse event | 13 | 8 | 12 | 9 | 21 | 26 |
| Withdrew: Lack of efficacy | 1 | 0 | 0 | 2 | 4 | 1 |
| Withdrew: Lost to follow-up | 4 | 2 | 4 | 2 | 9 | 3 |
| Withdrew: Protocol violation | 2 | 2 | 3 | 5 | 9 | 4 |
| Withdrew: Withdrawal by participants | 21 | 27 | 23 | 16 | 33 | 34 |
| Withdrew: Miscellaneous | 0 | 0 | 4 | 1 | 0 | 4 |
| Withdrew: Did not have end of treatment page | 0 | 0 | 0 | 0 | 1 | 0 |
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.
| incontinence episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours | -1.34 ± 0.10 | -1.70 ± 0.10 | -1.76 ± 0.10 | -1.79 ± 0.10 | -2.04 ± 0.07 | -1.98 ± 0.07 |
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.
| micturitions | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours | -1.64 ± 0.12 | -2.00 ± 0.12 | -2.03 ± 0.12 | -2.20 ± 0.12 | -2.49 ± 0.08 | -2.59 ± 0.08 |
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.
| mL | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Change From Baseline to EoT in Mean Volume Voided Per Micturition | 8.44 ± 2.55 | 13.32 ± 2.57 | 21.99 ± 2.57 | 30.99 ± 2.56 | 34.84 ± 1.81 | 39.73 ± 1.81 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score | -19.45 ± 0.98 | -23.93 ± 0.99 | -26.14 ± 0.98 | -26.44 ± 0.98 | -31.06 ± 0.69 | -32.24 ± 0.70 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Change From Baseline to EoT in Treatment Satisfaction-Visual Analogue Scale (TS-VAS) | 1.42 ± 0.11 | 2.16 ± 0.11 | 2.18 ± 0.11 | 2.28 ± 0.11 | 2.53 ± 0.08 | 2.55 ± 0.08 |
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.
| incontinence episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 18.09 ± 1.17 | 15.65 ± 1.08 | 12.90 ± 1.06 | 15.31 ± 1.11 | 12.51 ± 0.67 | 11.44 ± 0.70 |
| Week 8 | 14.45 ± 1.12 | 12.84 ± 1.05 | 11.31 ± 1.09 | 12.19 ± 1.06 | 9.70 ± 0.65 | 9.33 ± 0.68 |
| Week 12 | 14.06 ± 1.17 | 10.60 ± 0.98 | 9.50 ± 0.98 | 11.25 ± 1.03 | 7.62 ± 0.57 | 8.21 ± 0.68 |
| End of treatment | 13.70 ± 1.08 | 11.19 ± 0.95 | 9.79 ± 0.94 | 11.21 ± 0.98 | 8.02 ± 0.55 | 8.18 ± 0.64 |
| incontinence episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -5.23 ± 0.66 | -7.59 ± 0.66 | -8.99 ± 0.67 | -8.92 ± 0.67 | -9.62 ± 0.47 | -10.51 ± 0.47 |
| Week 8 | -8.79 ± 0.71 | -10.57 ± 0.72 | -10.97 ± 0.72 | -11.89 ± 0.72 | -12.53 ± 0.50 | -12.78 ± 0.51 |
| Week 12 | -9.05 ± 0.72 | -12.33 ± 0.72 | -12.58 ± 0.72 | -12.75 ± 0.71 | -14.50 ± 0.51 | -13.94 ± 0.51 |
| End of treatment | -9.42 ± 0.68 | -11.93 ± 0.68 | -12.39 ± 0.68 | -12.65 ± 0.68 | -14.29 ± 0.48 | -13.98 ± 0.48 |
| incontinence episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.74 ± 0.10 | -1.07 ± 0.10 | -1.24 ± 0.10 | -1.24 ± 0.10 | -1.38 ± 0.07 | -1.50 ± 0.07 |
| Week 8 | -1.20 ± 0.10 | -1.51 ± 0.10 | -1.57 ± 0.10 | -1.66 ± 0.10 | -1.79 ± 0.07 | -1.84 ± 0.07 |
| Week 12 | -1.30 ± 0.11 | -1.76 ± 0.11 | -1.81 ± 0.11 | -1.80 ± 0.10 | -2.08 ± 0.07 | -1.98 ± 0.07 |
| micturitions | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -1.02 ± 0.11 | -1.46 ± 0.11 | -1.44 ± 0.11 | -1.39 ± 0.11 | -1.67 ± 0.08 | -1.91 ± 0.08 |
| Week 8 | -1.43 ± 0.11 | -1.95 ± 0.12 | -1.89 ± 0.12 | -1.84 ± 0.12 | -2.23 ± 0.08 | -2.42 ± 0.08 |
| Week 12 | -1.51 ± 0.12 | -2.01 ± 0.12 | -2.03 ± 0.12 | -2.22 ± 0.12 | -2.47 ± 0.08 | -2.60 ± 0.08 |
| mL | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 6.95 ± 2.13 | 10.08 ± 2.14 | 15.52 ± 2.14 | 24.23 ± 2.15 | 25.54 ± 1.51 | 28.99 ± 1.51 |
| Week 8 | 9.00 ± 2.48 | 10.96 ± 2.52 | 17.73 ± 2.53 | 27.55 ± 2.50 | 32.94 ± 1.78 | 36.51 ± 1.77 |
| Week 12 | 8.70 ± 2.70 | 12.88 ± 2.74 | 22.40 ± 2.73 | 31.89 ± 2.68 | 35.52 ± 1.90 | 41.28 ± 1.90 |
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.
| micturitions | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Change From Baseline to EoT in Corrected Micturition Frequency | 0.15 ± 0.24 | -0.17 ± 0.24 | -0.97 ± 0.24 | -1.28 ± 0.24 | -1.10 ± 0.17 | -1.52 ± 0.17 |
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.
| urgency incontinence episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 15.76 ± 1.10 | 13.36 ± 0.99 | 11.46 ± 1.00 | 13.19 ± 1.06 | 10.22 ± 0.58 | 9.33 ± 0.58 |
| Week 8 | 12.77 ± 1.07 | 10.65 ± 0.94 | 10.09 ± 1.02 | 10.41 ± 1.00 | 7.58 ± 0.53 | 7.31 ± 0.54 |
| Week 12 | 12.00 ± 1.09 | 8.84 ± 0.89 | 8.32 ± 0.94 | 9.29 ± 0.96 | 5.86 ± 0.46 | 6.27 ± 0.49 |
| End of treatment | 11.69 ± 1.00 | 9.37 ± 0.86 | 8.63 ± 0.89 | 9.29 ± 0.91 | 6.25 ± 0.45 | 6.15 ± 0.47 |
| urgency incontinence episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -5.49 ± 0.63 | -7.07 ± 0.63 | -8.39 ± 0.63 | -8.53 ± 0.63 | -9.44 ± 0.44 | -10.23 ± 0.44 |
| Week 8 | -8.30 ± 0.66 | -9.93 ± 0.67 | -10.07 ± 0.67 | -11.10 ± 0.67 | -12.18 ± 0.47 | -12.18 ± 0.47 |
| Week 12 | -8.96 ± 0.65 | -11.39 ± 0.66 | -11.66 ± 0.66 | -12.10 ± 0.65 | -13.87 ± 0.46 | -13.53 ± 0.46 |
| End of treatment | -9.26 ± 0.62 | -11.03 ± 0.62 | -11.44 ± 0.62 | -12.03 ± 0.62 | -13.64 ± 0.44 | -13.64 ± 0.44 |
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.
| urgency incontinence episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.78 ± 0.09 | -1.00 ± 0.09 | -1.15 ± 0.09 | -1.19 ± 0.09 | -1.35 ± 0.06 | -1.47 ± 0.06 |
| Week 8 | -1.15 ± 0.10 | -1.43 ± 0.10 | -1.44 ± 0.10 | -1.56 ± 0.10 | -1.74 ± 0.07 | -1.79 ± 0.07 |
| Week 12 | -1.29 ± 0.10 | -1.63 ± 0.10 | -1.67 ± 0.10 | -1.72 ± 0.10 | -1.99 ± 0.07 | -1.93 ± 0.07 |
| End of treatment | -1.33 ± 0.09 | -1.58 ± 0.09 | -1.62 ± 0.09 | -1.71 ± 0.09 | -1.95 ± 0.06 | -1.94 ± 0.06 |
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.
| urgency episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -1.34 ± 0.15 | -1.95 ± 0.14 | -1.91 ± 0.15 | -2.14 ± 0.15 | -2.42 ± 0.10 | -2.66 ± 0.10 |
| Week 8 | -1.85 ± 0.15 | -2.54 ± 0.15 | -2.43 ± 0.15 | -2.90 ± 0.15 | -3.13 ± 0.11 | -3.28 ± 0.11 |
| Week 12 | -2.05 ± 0.16 | -2.85 ± 0.16 | -2.70 ± 0.16 | -3.11 ± 0.16 | -3.45 ± 0.11 | -3.50 ± 0.11 |
| End of treatment | -2.06 ± 0.15 | -2.74 ± 0.15 | -2.63 ± 0.15 | -3.05 ± 0.15 | -3.38 ± 0.11 | -3.51 ± 0.11 |
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.
| nocturia episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 9.62 ± 0.43 | 8.46 ± 0.36 | 9.11 ± 0.47 | 9.22 ± 0.42 | 8.40 ± 0.25 | 8.09 ± 0.25 |
| Week 8 | 8.99 ± 0.44 | 8.07 ± 0.34 | 8.61 ± 0.45 | 8.37 ± 0.38 | 7.63 ± 0.25 | 7.11 ± 0.24 |
| Week 12 | 8.91 ± 0.43 | 7.99 ± 0.37 | 8.34 ± 0.48 | 8.17 ± 0.39 | 7.26 ± 0.24 | 6.67 ± 0.23 |
| End of treatment | 8.83 ± 0.42 | 7.79 ± 0.35 | 8.14 ± 0.45 | 8.12 ± 0.37 | 7.33 ± 0.24 | 6.67 ± 0.22 |
| nocturia episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -1.27 ± 0.27 | -2.25 ± 0.28 | -1.80 ± 0.27 | -1.79 ± 0.28 | -2.39 ± 0.19 | -2.50 ± 0.19 |
| Week 8 | -1.94 ± 0.27 | -2.70 ± 0.28 | -2.41 ± 0.28 | -2.60 ± 0.28 | -3.13 ± 0.20 | -3.48 ± 0.20 |
| Week 12 | -1.95 ± 0.29 | -2.77 ± 0.30 | -2.73 ± 0.29 | -2.89 ± 0.29 | -3.49 ± 0.21 | -3.96 ± 0.21 |
| End of treatment | -2.05 ± 0.27 | -2.91 ± 0.28 | -2.75 ± 0.28 | -2.81 ± 0.28 | -3.42 ± 0.20 | -3.96 ± 0.20 |
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.
| nocturia episodes | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.17 ± 0.04 | -0.31 ± 0.04 | -0.25 ± 0.04 | -0.24 ± 0.04 | -0.33 ± 0.03 | -0.35 ± 0.03 |
| Week 8 | -0.27 ± 0.04 | -0.37 ± 0.04 | -0.35 ± 0.04 | -0.36 ± 0.04 | -0.44 ± 0.03 | -0.50 ± 0.03 |
| Week 12 | -0.26 ± 0.04 | -0.38 ± 0.04 | -0.39 ± 0.04 | -0.41 ± 0.04 | -0.49 ± 0.03 | -0.56 ± 0.03 |
| End of treatmemt | -0.27 ± 0.04 | -0.40 ± 0.04 | -0.39 ± 0.04 | -0.39 ± 0.04 | -0.48 ± 0.03 | -0.56 ± 0.03 |
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.
| pads | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 15.62 ± 1.33 | 13.46 ± 1.24 | 10.05 ± 1.21 | 11.41 ± 1.23 | 9.71 ± 0.70 | 9.34 ± 0.68 |
| Week 8 | 12.75 ± 1.22 | 10.79 ± 1.05 | 9.53 ± 1.39 | 8.45 ± 1.03 | 8.07 ± 0.65 | 7.58 ± 0.62 |
| Week 12 | 12.62 ± 1.21 | 9.65 ± 1.00 | 8.44 ± 1.26 | 8.21 ± 0.95 | 6.60 ± 0.58 | 6.64 ± 0.61 |
| End of treatment | 12.29 ± 1.11 | 10.15 ± 0.97 | 8.16 ± 1.17 | 8.53 ± 0.94 | 7.04 ± 0.56 | 6.80 ± 0.59 |
| pads | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -3.69 ± 0.71 | -5.68 ± 0.71 | -7.83 ± 0.71 | -8.23 ± 0.70 | -7.61 ± 0.50 | -8.58 ± 0.50 |
| Week 8 | -6.24 ± 0.77 | -8.44 ± 0.77 | -8.43 ± 0.76 | -10.67 ± 0.76 | -9.49 ± 0.54 | -10.59 ± 0.54 |
| Week 12 | -6.29 ± 0.75 | -9.06 ± 0.75 | -9.41 ± 0.75 | -10.80 ± 0.73 | -10.66 ± 0.52 | -11.23 ± 0.53 |
| End of treatment | -6.60 ± 0.71 | -8.76 ± 0.71 | -9.80 ± 0.72 | -10.63 ± 0.70 | -10.67 ± 0.50 | -11.21 ± 0.50 |
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.
| pads | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.52 ± 0.10 | -0.81 ± 0.10 | -1.12 ± 0.10 | -1.19 ± 0.10 | -1.09 ± 0.07 | -1.23 ± 0.07 |
| Week 8 | -0.82 ± 0.11 | -1.20 ± 0.11 | -1.24 ± 0.11 | -1.53 ± 0.11 | -1.36 ± 0.08 | -1.51 ± 0.08 |
| Week 12 | -0.92 ± 0.11 | -1.30 ± 0.11 | -1.37 ± 0.11 | -1.56 ± 0.11 | -1.54 ± 0.08 | -1.59 ± 0.08 |
| End of treatment | -0.94 ± 0.10 | -1.26 ± 0.10 | -1.41 ± 0.10 | -1.53 ± 0.10 | -1.53 ± 0.07 | -1.58 ± 0.07 |
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.
| incontinence-free days | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 2.25 ± 0.13 | 2.48 ± 0.13 | 2.98 ± 0.13 | 2.74 ± 0.14 | 3.08 ± 0.10 | 3.37 ± 0.10 |
| Week 8 | 2.92 ± 0.14 | 3.17 ± 0.14 | 3.63 ± 0.15 | 3.31 ± 0.14 | 3.88 ± 0.10 | 4.01 ± 0.10 |
| Week 12 | 3.19 ± 0.15 | 3.69 ± 0.15 | 3.96 ± 0.15 | 3.68 ± 0.14 | 4.33 ± 0.10 | 4.25 ± 0.10 |
| End of treatment | 3.16 ± 0.14 | 3.51 ± 0.14 | 3.89 ± 0.14 | 3.61 ± 0.14 | 4.20 ± 0.10 | 4.23 ± 0.10 |
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.
| days | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 1.49 ± 0.10 | 1.74 ± 0.10 | 1.55 ± 0.10 | 1.86 ± 0.11 | 2.07 ± 0.08 | 2.11 ± 0.08 |
| Week 8 | 1.69 ± 0.10 | 2.08 ± 0.12 | 1.99 ± 0.11 | 2.22 ± 0.12 | 2.59 ± 0.09 | 2.70 ± 0.09 |
| Week 12 | 1.76 ± 0.11 | 2.31 ± 0.13 | 2.25 ± 0.12 | 2.49 ± 0.13 | 2.87 ± 0.09 | 2.95 ± 0.10 |
| End of treatment | 1.80 ± 0.11 | 2.28 ± 0.12 | 2.22 ± 0.12 | 2.49 ± 0.12 | 2.84 ± 0.09 | 2.92 ± 0.09 |
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.
| days | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 0.64 ± 0.07 | 0.84 ± 0.08 | 0.87 ± 0.08 | 0.91 ± 0.08 | 1.21 ± 0.07 | 1.32 ± 0.07 |
| Week 8 | 0.85 ± 0.08 | 1.20 ± 0.10 | 1.23 ± 0.10 | 1.31 ± 0.10 | 1.75 ± 0.08 | 1.89 ± 0.08 |
| Week 12 | 0.98 ± 0.09 | 1.47 ± 0.11 | 1.50 ± 0.11 | 1.60 ± 0.11 | 2.12 ± 0.09 | 2.15 ± 0.09 |
| End of treatment | 1.01 ± 0.08 | 1.40 ± 0.10 | 1.47 ± 0.10 | 1.59 ± 0.10 | 2.04 ± 0.08 | 2.12 ± 0.09 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.54 ± 0.06 | -0.72 ± 0.06 | -0.83 ± 0.06 | -0.81 ± 0.06 | -0.99 ± 0.04 | -1.07 ± 0.04 |
| Week 8 | -0.80 ± 0.06 | -1.07 ± 0.06 | -1.12 ± 0.06 | -1.18 ± 0.06 | -1.32 ± 0.04 | -1.48 ± 0.04 |
| Week 12 | -0.95 ± 0.06 | -1.23 ± 0.06 | -1.34 ± 0.06 | -1.32 ± 0.06 | -1.57 ± 0.04 | -1.72 ± 0.04 |
| End of treatment | -0.91 ± 0.06 | -1.18 ± 0.06 | -1.31 ± 0.06 | -1.27 ± 0.06 | -1.53 ± 0.04 | -1.66 ± 0.04 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -13.84 ± 0.92 | -17.05 ± 0.93 | -18.98 ± 0.93 | -19.53 ± 0.93 | -23.46 ± 0.65 | -25.19 ± 0.65 |
| Week 8 | -17.35 ± 0.98 | -22.79 ± 0.99 | -23.54 ± 0.98 | -24.69 ± 0.97 | -29.10 ± 0.69 | -30.04 ± 0.69 |
| Week 12 | -19.94 ± 1.01 | -24.44 ± 1.02 | -26.80 ± 1.02 | -26.72 ± 1.01 | -31.70 ± 0.72 | -33.15 ± 0.72 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 10.16 ± 0.83 | 13.54 ± 0.83 | 15.28 ± 0.83 | 14.78 ± 0.83 | 17.46 ± 0.58 | 17.95 ± 0.59 |
| Week 8 | 14.51 ± 0.88 | 17.95 ± 0.89 | 18.54 ± 0.88 | 18.57 ± 0.88 | 22.30 ± 0.62 | 22.45 ± 0.62 |
| Week 12 | 15.76 ± 0.92 | 19.59 ± 0.93 | 21.48 ± 0.92 | 20.54 ± 0.91 | 24.63 ± 0.65 | 24.93 ± 0.65 |
| End of treatment | 15.37 ± 0.88 | 18.94 ± 0.89 | 21.00 ± 0.89 | 20.15 ± 0.89 | 23.96 ± 0.63 | 24.30 ± 0.63 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 11.74 ± 0.99 | 14.87 ± 1.00 | 17.68 ± 1.00 | 16.52 ± 1.00 | 19.31 ± 0.70 | 20.36 ± 0.70 |
| Week 8 | 16.13 ± 1.04 | 20.64 ± 1.05 | 21.52 ± 1.04 | 21.69 ± 1.03 | 25.49 ± 0.74 | 25.85 ± 0.73 |
| Week 12 | 18.17 ± 1.09 | 22.04 ± 1.10 | 24.94 ± 1.10 | 23.67 ± 1.09 | 28.32 ± 0.77 | 29.03 ± 0.78 |
| End of treatment | 17.73 ± 1.05 | 21.28 ± 1.06 | 24.32 ± 1.05 | 23.25 ± 1.05 | 27.37 ± 0.74 | 28.12 ± 0.75 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 11.24 ± 0.95 | 15.89 ± 0.96 | 17.39 ± 0.95 | 17.18 ± 0.95 | 20.48 ± 0.67 | 21.09 ± 0.67 |
| Week 8 | 16.10 ± 0.99 | 20.63 ± 1.01 | 20.55 ± 1.00 | 20.96 ± 0.99 | 25.26 ± 0.71 | 25.65 ± 0.70 |
| Week 12 | 17.53 ± 1.03 | 22.37 ± 1.04 | 23.62 ± 1.04 | 23.19 ± 1.03 | 27.53 ± 0.73 | 28.24 ± 0.73 |
| End of treatment | 16.98 ± 1.00 | 21.55 ± 1.01 | 23.07 ± 1.00 | 22.65 ± 1.00 | 26.89 ± 0.71 | 27.47 ± 0.71 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 9.28 ± 0.95 | 12.70 ± 0.96 | 13.80 ± 0.96 | 13.08 ± 0.96 | 15.97 ± 0.68 | 16.66 ± 0.68 |
| Week 8 | 13.58 ± 1.03 | 16.39 ± 1.05 | 17.33 ± 1.03 | 16.43 ± 1.03 | 20.29 ± 0.73 | 20.49 ± 0.73 |
| Week 12 | 14.40 ± 1.05 | 18.04 ± 1.06 | 19.16 ± 1.06 | 18.35 ± 1.05 | 22.97 ± 0.74 | 22.76 ± 0.75 |
| End of treatment | 14.17 ± 1.01 | 17.51 ± 1.02 | 19.11 ± 1.02 | 17.97 ± 1.01 | 22.39 ± 0.72 | 22.39 ± 0.72 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 7.07 ± 0.78 | 9.04 ± 0.79 | 10.19 ± 0.78 | 9.89 ± 0.78 | 11.55 ± 0.55 | 11.25 ± 0.55 |
| Week 8 | 10.65 ± 0.82 | 11.50 ± 0.83 | 12.34 ± 0.82 | 12.02 ± 0.81 | 14.89 ± 0.58 | 14.73 ± 0.58 |
| Week 12 | 10.84 ± 0.83 | 13.43 ± 0.84 | 15.35 ± 0.84 | 13.74 ± 0.83 | 16.16 ± 0.59 | 16.08 ± 0.59 |
| End of treatment | 10.56 ± 0.81 | 13.04 ± 0.81 | 14.87 ± 0.81 | 13.57 ± 0.81 | 15.84 ± 0.57 | 15.82 ± 0.57 |
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).
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 12: Very much improved | 8.4 | 13.9 | 15.1 | 13.5 | 19.8 | 27.1 |
| Week 12: Much improved | 29.7 | 32.9 | 34.8 | 40.5 | 39.8 | 34.0 |
| Week 12: Minimally improved | 29.7 | 26.8 | 26.5 | 25.8 | 22.2 | 20.7 |
| Week 12: No change | 17.5 | 12.9 | 9.7 | 8.9 | 7.7 | 7.3 |
| Week 12: Minimally worse | 4.1 | 1.5 | 2.2 | 1.7 | 0.8 | 0.8 |
| Week 12: Much worse | 1.0 | 1.0 | 1.2 | 0.5 | 0.2 | 0 |
| Week 12: Very much worse | 0.5 | 0.5 | 0.7 | 0.5 | 0.2 | 0.5 |
| EoT: Very much improved | 8.4 | 13.9 | 15.1 | 13.5 | 20.0 | 27.1 |
| EoT: Much improved | 30.4 | 33.2 | 34.8 | 41.0 | 40.0 | 34.6 |
| EoT: Minimally improved | 29.9 | 26.8 | 27.0 | 26.3 | 22.6 | 21.3 |
| EoT: No change | 18.2 | 13.4 | 10.2 | 9.6 | 7.9 | 7.4 |
| EoT: Minimally worse | 4.1 | 1.5 | 2.2 | 1.7 | 0.8 | 0.8 |
| EoT: Much worse | 1.0 | 1.0 | 1.2 | 0.7 | 0.4 | 0 |
| EoT: Very much worse | 0.5 | 0.5 | 0.7 | 0.5 | 0.2 | 0.6 |
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).
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 12: Very much improved | 4.8 | 8.0 | 7.3 | 7.7 | 10.3 | 14.6 |
| Week 12: Much improved | 23.9 | 28.0 | 29.2 | 31.8 | 33.4 | 30.2 |
| Week 12: Minimally improved | 23.9 | 21.5 | 22.4 | 24.1 | 20.1 | 20.9 |
| Week 12: No change | 31.8 | 27.8 | 27.5 | 25.3 | 23.9 | 21.6 |
| Week 12: Minimally worse | 4.3 | 2.9 | 2.2 | 1.4 | 2.5 | 2.2 |
| Week 12: Much worse | 1.7 | 0.7 | 1.2 | 0.5 | 0.5 | 0.1 |
| Week 12: Very much worse | 0.2 | 0.5 | 0.5 | 0.5 | 0.2 | 0.6 |
| End of treatment: Very much improved | 4.8 | 8.0 | 7.3 | 7.7 | 10.3 | 14.6 |
| End of treatment: Much improved | 24.2 | 28.0 | 29.2 | 31.8 | 33.6 | 30.4 |
| End of treatment: Minimally improved | 24.4 | 21.5 | 22.9 | 24.1 | 20.2 | 21.3 |
| End of treatment:No change | 32.3 | 28.3 | 27.7 | 26.5 | 24.3 | 21.9 |
| End of treatment: Minimally worse | 4.3 | 2.9 | 2.4 | 1.9 | 2.8 | 2.7 |
| End of treatment: Much worse | 1.9 | 0.7 | 1.2 | 0.5 | 0.5 | 0.2 |
| End of treatment: Very much worse | 0.5 | 0.7 | 0.5 | 0.7 | 0.2 | 0.7 |
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).
| participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| No problems -> no problems | 204 | 239 | 225 | 227 | 449 | 452 |
| No problems -> slight problems | 16 | 20 | 25 | 22 | 41 | 38 |
| No problems -> moderate problems | 11 | 12 | 9 | 8 | 20 | 10 |
| No problems -> severe problems | 1 | 3 | 3 | 1 | 1 | 2 |
| No problems -> unable to walk about | 0 | 1 | 0 | 0 | 0 | 1 |
| No problems -> no data | 2 | 4 | 5 | 4 | 6 | 9 |
| Slight problems -> no problems | 33 | 35 | 35 | 30 | 76 | 60 |
| Slight problems -> slight problems | 27 | 20 | 24 | 19 | 40 | 49 |
| Slight problems -> moderate problems | 11 | 6 | 4 | 6 | 19 | 9 |
| Slight problems -> severe problems | 5 | 0 | 3 | 1 | 2 | 2 |
| Slight problems -> unable to walk about | 0 | 0 | 0 | 0 | 0 | 0 |
| Slight problems -> no data | 2 | 3 | 0 | 0 | 0 | 2 |
| Moderate problems -> no problems | 17 | 7 | 25 | 18 | 31 | 46 |
| Moderate problems -> slight problems | 18 | 10 | 10 | 22 | 24 | 25 |
| Moderate problems -> moderate problems | 21 | 12 | 10 | 13 | 33 | 35 |
| Moderate problems -> severe problems | 10 | 5 | 4 | 2 | 8 | 10 |
| Moderate problems -> unable to walk about | 0 | 0 | 0 | 1 | 1 | 1 |
| Moderate problems -> no data | 1 | 1 | 0 | 1 | 0 | 2 |
| Severe problems -> no problems | 3 | 5 | 9 | 7 | 12 | 17 |
| Severe problems -> slight problems | 6 | 7 | 3 | 4 | 13 | 8 |
| Severe problems -> moderate problems | 5 | 4 | 8 | 8 | 15 | 15 |
| Severe problems -> severe problems | 8 | 5 | 1 | 8 | 11 | 13 |
| Severe problems -> unable to walk about | 0 | 0 | 0 | 0 | 0 | 0 |
| Severe problems -> no data | 0 | 0 | 2 | 1 | 1 | 0 |
| Unable to walk about -> no problems | 0 | 0 | 0 | 2 | 2 | 0 |
| Unable to walk about -> slight problems | 1 | 0 | 0 | 0 | 0 | 0 |
| Unable to walk about -> moderate problems | 1 | 0 | 0 | 0 | 0 | 1 |
| Unable to walk about -> severe problems | 1 | 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 | 12 | 7 | 3 | 6 | 15 | 16 |
| No data -> slight problems | 1 | 0 | 1 | 2 | 4 | 2 |
| No data -> moderate problems | 0 | 3 | 1 | 0 | 0 | 2 |
| No data -> severe problems | 0 | 1 | 0 | 2 | 2 | 0 |
| No data -> unable to walk about | 0 | 0 | 0 | 0 | 0 | 0 |
| No data -> no data | 1 | 0 | 1 | 0 | 1 | 0 |
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).
| participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| No problems -> no problems | 311 | 324 | 336 | 319 | 652 | 647 |
| No problems -> slight problems | 21 | 17 | 9 | 20 | 22 | 26 |
| No problems -> moderate problems | 9 | 5 | 6 | 3 | 12 | 4 |
| No problems -> severe problems | 0 | 0 | 1 | 1 | 1 | 1 |
| No problems -> unable to wash/dress myself | 1 | 0 | 1 | 0 | 0 | 0 |
| No problems -> no data | 4 | 8 | 6 | 5 | 6 | 12 |
| Slight problems -> no problems | 17 | 13 | 16 | 25 | 35 | 33 |
| Slight problems -> slight problems | 10 | 10 | 12 | 12 | 22 | 26 |
| Slight problems -> moderate problems | 2 | 4 | 1 | 2 | 3 | 7 |
| Slight problems -> severe problems | 2 | 0 | 0 | 0 | 1 | 2 |
| Slight problems -> unable to wash/dress myself | 0 | 0 | 0 | 0 | 0 | 0 |
| Slight problems -> no data | 1 | 0 | 0 | 1 | 1 | 0 |
| Moderate problems -> no problems | 6 | 8 | 3 | 2 | 17 | 18 |
| Moderate problems -> slight problems | 3 | 1 | 8 | 3 | 9 | 7 |
| Moderate problems -> moderate problems | 9 | 1 | 2 | 6 | 8 | 9 |
| Moderate problems -> severe problems | 0 | 0 | 0 | 0 | 2 | 1 |
| Moderate problems -> unable to wash/dress myself | 0 | 0 | 0 | 0 | 0 | 0 |
| Moderate problems -> no data | 0 | 0 | 0 | 0 | 0 | 1 |
| Severe problems -> no problems | 2 | 2 | 2 | 1 | 3 | 4 |
| Severe problems -> slight problems | 1 | 0 | 0 | 3 | 3 | 3 |
| Severe problems -> moderate problems | 1 | 2 | 0 | 0 | 7 | 3 |
| Severe problems -> severe problems | 3 | 3 | 0 | 1 | 1 | 0 |
| Severe problems -> unable to wash/dress myself | 0 | 0 | 0 | 0 | 0 | 0 |
| Severe problems -> no data | 0 | 0 | 1 | 0 | 0 | 0 |
| Unable to wash/dress myself -> no problems | 0 | 1 | 1 | 0 | 0 | 3 |
| Unable to wash/dress myself -> slight problems | 0 | 0 | 0 | 0 | 0 | 0 |
| Unable to wash/dress myself -> moderate problems | 1 | 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 w/d | 0 | 0 | 0 | 1 | 0 | 0 |
| Unable to wash/dress myself -> no data | 0 | 0 | 0 | 0 | 0 | 0 |
| No data -> no problems | 13 | 8 | 3 | 8 | 20 | 18 |
| No data -> slight problems | 0 | 2 | 2 | 1 | 1 | 0 |
| No data -> moderate problems | 0 | 1 | 0 | 1 | 0 | 2 |
| 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 | 1 | 0 | 1 | 0 | 1 | 0 |
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).
| participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| No problems -> No problems | 196 | 228 | 219 | 223 | 434 | 451 |
| No problems -> Slight problems | 37 | 25 | 28 | 25 | 37 | 48 |
| No problems -> Moderate problems | 9 | 5 | 9 | 8 | 13 | 11 |
| No problems -> Severe problems | 2 | 0 | 1 | 0 | 1 | 1 |
| No problems -> unable to do usual activities | 0 | 0 | 0 | 0 | 1 | 1 |
| No problems -> no data | 2 | 5 | 4 | 3 | 5 | 8 |
| Slight problems -> no problems | 45 | 41 | 52 | 52 | 98 | 95 |
| Slight problems -> slight problems | 28 | 29 | 23 | 25 | 64 | 56 |
| Slight problems -> moderate problems | 15 | 9 | 3 | 8 | 18 | 12 |
| Slight problems -> severe problems | 2 | 0 | 2 | 0 | 2 | 3 |
| Slight problems ->unable to do usual activities | 0 | 0 | 0 | 0 | 0 | 0 |
| Slight problems -> no data | 2 | 2 | 0 | 3 | 2 | 4 |
| Moderate problems -> no problems | 14 | 13 | 15 | 13 | 44 | 26 |
| Moderate problems -> slight problems | 12 | 9 | 16 | 14 | 29 | 30 |
| Moderate problems -> moderate problems | 15 | 11 | 9 | 12 | 25 | 17 |
| Moderate problems -> severe problems | 1 | 3 | 0 | 1 | 3 | 3 |
| Moderate problems ->unable to do usual activities | 0 | 0 | 0 | 0 | 0 | 1 |
| Moderate problems -> no data | 1 | 1 | 2 | 0 | 0 | 1 |
| Severe problems -> no problems | 7 | 3 | 7 | 6 | 7 | 11 |
| Severe problems -> slight problems | 3 | 4 | 6 | 2 | 8 | 8 |
| Severe problems -> moderate problems | 6 | 7 | 5 | 6 | 9 | 7 |
| Severe problems -> severe problems | 4 | 1 | 1 | 3 | 2 | 9 |
| Severe problems -> unable to do usual activities | 0 | 1 | 0 | 0 | 0 | 0 |
| Severe problems -> no data | 0 | 0 | 1 | 0 | 0 | 0 |
| Unable to do usual activities -> no problems | 0 | 1 | 0 | 0 | 0 | 2 |
| Unable to do usual activities -> slight problems | 1 | 0 | 0 | 0 | 1 | 1 |
| Unable to do usual activities -> moderate problems | 2 | 1 | 1 | 0 | 1 | 1 |
| Unable to do usual activities -> severe problems | 0 | 0 | 1 | 0 | 0 | 0 |
| Unable to do usual activities -> unable to do usu. | 0 | 0 | 0 | 1 | 1 | 0 |
| Unable to do usual activities -> no data | 0 | 0 | 0 | 0 | 0 | 0 |
| No data -> no problems | 12 | 7 | 2 | 7 | 18 | 15 |
| No data -> slight problems | 1 | 2 | 3 | 1 | 1 | 3 |
| No data -> moderate problems | 0 | 2 | 0 | 2 | 2 | 2 |
| 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 | 1 | 0 | 1 | 0 | 1 | 0 |
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).
| participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| No pain/discomfort -> no pain/discomfort | 131 | 175 | 153 | 154 | 290 | 317 |
| No pain/discomfort -> slight pain/discomfort | 38 | 29 | 37 | 33 | 74 | 51 |
| No pain/discomfort -> moderate pain/discomfort | 10 | 9 | 17 | 13 | 19 | 20 |
| No pain/discomfort -> severe pain/discomfort | 0 | 0 | 3 | 3 | 3 | 1 |
| No pain/discomfort -> extreme pain/discomfort | 0 | 0 | 0 | 0 | 1 | 0 |
| No pain/discomfort -> no data | 2 | 3 | 4 | 2 | 3 | 8 |
| Slight pain/discomfort -> no pain/discomfort | 53 | 51 | 44 | 46 | 117 | 105 |
| Slight pain/discomfort -> slight pain/discomfort | 54 | 49 | 45 | 47 | 94 | 101 |
| Slight pain/discomfort -> moderate pain/discomfort | 12 | 11 | 14 | 18 | 15 | 19 |
| Slight pain/discomfort -> severe pain/discomfort | 3 | 0 | 2 | 0 | 6 | 3 |
| Slight pain/discomfort -> exteme pain/discomfort | 2 | 0 | 1 | 0 | 0 | 0 |
| Slight pain/discomfort -> no data | 2 | 5 | 2 | 2 | 2 | 4 |
| Moderate pain/discomfort -> no pain/discomfort | 20 | 14 | 24 | 23 | 45 | 46 |
| Moderate pain/discomfort -> slight pain/discomfort | 23 | 15 | 20 | 22 | 46 | 45 |
| Moderate pain/discomfort -> moderate pain/discomf | 31 | 13 | 16 | 15 | 34 | 40 |
| Moderate pain/discomfort -> severe pain/discomfort | 4 | 5 | 3 | 1 | 4 | 6 |
| Moderate pain/discomfort -> extreme pain/discomf | 0 | 0 | 0 | 0 | 1 | 0 |
| Moderate pain/discomfort -> no data | 1 | 0 | 0 | 1 | 1 | 1 |
| Severe pain/discomfort -> no pain/discomfort | 2 | 4 | 3 | 1 | 8 | 12 |
| Severe pain/discomfort -> slight pain/discomfort | 3 | 4 | 6 | 4 | 11 | 7 |
| Severe pain/discomfort -> moderate pain/discomfort | 8 | 4 | 6 | 11 | 15 | 11 |
| Severe pain/discomfort -> severe pain/discomfort | 4 | 3 | 1 | 4 | 7 | 8 |
| Severe pain/discomfort -> extreme pain/discomfort | 0 | 1 | 1 | 0 | 1 | 0 |
| Severe pain/discomfort -> no data | 0 | 0 | 1 | 0 | 1 | 0 |
| Extreme pain/discomfort -> no pain/discomfort | 0 | 0 | 0 | 0 | 1 | 0 |
| Extreme pain/discomfort -> slight pain/discomfort | 1 | 0 | 0 | 2 | 1 | 1 |
| Extreme pain/discomfort -> moderate pain/discom. | 0 | 2 | 1 | 0 | 1 | 1 |
| Extreme pain/discomfort -> severe pain/discomfort | 0 | 2 | 1 | 2 | 3 | 0 |
| Extreme pain/discomfort -> extreme pain/discomfort | 0 | 0 | 0 | 0 | 1 | 0 |
| Extreme pain/discomfort -> no data | 0 | 0 | 0 | 1 | 0 | 0 |
| No data -> no pain/discomfort | 11 | 5 | 3 | 6 | 14 | 14 |
| No data -> slight pain/discomfort | 2 | 2 | 2 | 2 | 6 | 3 |
| No data -> moderate pain/discomfort | 0 | 4 | 0 | 2 | 1 | 3 |
| No data -> severe pain/discomfort | 0 | 0 | 0 | 0 | 0 | 0 |
| No data -> extreme pain/discomfort | 0 | 0 | 0 | 0 | 0 | 0 |
| No data -> no data | 1 | 0 | 1 | 0 | 1 | 0 |
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).
| participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Not anxious -> not anxious | 157 | 176 | 187 | 166 | 360 | 370 |
| Not anxious -> slightly anxious | 42 | 27 | 25 | 29 | 45 | 50 |
| Not anxious -> moderately anxious | 7 | 6 | 6 | 8 | 13 | 11 |
| Not anxious -> severely anxious | 0 | 2 | 5 | 1 | 2 | 1 |
| Not anxious -> extremely anxious | 0 | 0 | 1 | 0 | 0 | 1 |
| Not anxious -> no data | 2 | 3 | 2 | 1 | 3 | 6 |
| Slightly anxious -> not anxious | 42 | 60 | 54 | 59 | 122 | 134 |
| Slightly anxious -> slightly anx | 49 | 40 | 45 | 40 | 79 | 65 |
| Slightly anxious -> moderately anxious | 17 | 16 | 12 | 17 | 18 | 16 |
| Slightly anxious -> severely anxious | 4 | 2 | 2 | 2 | 5 | 5 |
| Slightly anxious -> extremely anxious | 0 | 0 | 0 | 0 | 1 | 0 |
| Slightly anxious -> no data | 2 | 3 | 2 | 5 | 3 | 4 |
| Moderately anxious -> not anxious | 12 | 13 | 12 | 22 | 42 | 35 |
| Moderately anxious -> slightly anxious | 19 | 17 | 19 | 14 | 43 | 41 |
| Moderately anxious -> moderately anxious | 17 | 7 | 11 | 10 | 18 | 23 |
| Moderately anxious -> severely anxious | 2 | 3 | 0 | 1 | 8 | 7 |
| Moderately anxious -> extremely anxious | 0 | 1 | 0 | 0 | 1 | 1 |
| Moderately anxious -> no data | 1 | 1 | 2 | 0 | 1 | 3 |
| Severely anxious -> not anxious | 7 | 5 | 6 | 6 | 12 | 8 |
| Severely anxious -> slightly anxious | 3 | 3 | 4 | 5 | 11 | 6 |
| Severely anxious -> moderately anxious | 5 | 7 | 2 | 6 | 6 | 7 |
| Severely anxious -> severely anxious | 10 | 1 | 2 | 5 | 5 | 2 |
| Severely anxious -> extremely anxious | 1 | 0 | 0 | 1 | 0 | 3 |
| Severely anxious -> no data | 0 | 1 | 1 | 0 | 0 | 0 |
| Extremely anxious -> not anxious | 2 | 1 | 0 | 0 | 2 | 1 |
| Extremely anxious -> slightly anxious | 2 | 2 | 1 | 2 | 2 | 3 |
| Extremely anxious -> moderately anxious | 1 | 1 | 1 | 1 | 2 | 1 |
| Extremely anxious -> severely anxious | 0 | 1 | 1 | 3 | 0 | 1 |
| Extremely anxious -> extremely anxious | 0 | 0 | 2 | 1 | 1 | 2 |
| Extremely anxious -> no data | 0 | 0 | 0 | 0 | 0 | 0 |
| No data -> not anxious | 9 | 8 | 3 | 6 | 13 | 14 |
| No data -> slightly anxious | 4 | 1 | 2 | 2 | 6 | 3 |
| No data -> moderately anxious | 0 | 2 | 0 | 2 | 1 | 2 |
| No data -> severely anxious | 0 | 0 | 0 | 0 | 0 | 1 |
| No data -> extremely anxious | 0 | 0 | 0 | 0 | 1 | 0 |
| No data -> no data | 1 | 0 | 1 | 0 | 1 | 0 |
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.
| percentage of work time missed | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 12 | -2.98 ± 21.70 | -0.33 ± 22.03 | -1.72 ± 18.70 | -2.47 ± 14.13 | -2.06 ± 20.93 | -2.59 ± 19.65 |
| End of treatment | -2.96 ± 21.61 | -0.33 ± 22.03 | -1.71 ± 18.64 | -2.44 ± 14.03 | -1.48 ± 21.95 | -2.55 ± 19.54 |
| percentage of impairment while working | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 12 | -11.27 ± 25.36 | -14.96 ± 26.21 | -12.25 ± 25.06 | -10.85 ± 25.58 | -14.69 ± 26.99 | -13.07 ± 27.35 |
| End of treatment | -11.18 ± 25.28 | -14.96 ± 26.21 | -12.37 ± 25.01 | -10.98 ± 25.68 | -14.58 ± 26.92 | -12.87 ± 27.31 |
| percentage of overall work impairment | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 12 | -12.23 ± 25.66 | -15.70 ± 26.54 | -12.92 ± 26.71 | -12.31 ± 26.91 | -16.31 ± 29.06 | -13.97 ± 29.30 |
| End of treatment | -12.14 ± 25.58 | -15.70 ± 26.54 | -13.05 ± 26.65 | -12.42 ± 26.98 | -16.07 ± 29.12 | -13.76 ± 29.25 |
| percentage of activity impairment | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 12 | -11.49 ± 27.31 | -16.89 ± 27.57 | -14.99 ± 27.81 | -16.19 ± 29.16 | -19.60 ± 28.80 | -18.92 ± 29.47 |
| End of treatment | -11.55 ± 27.19 | -16.72 ± 27.82 | -15.05 ± 27.95 | -16.05 ± 28.95 | -19.45 ± 28.80 | -18.76 ± 29.33 |
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.
| units on a scale | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 1.14 ± 0.12 | 1.68 ± 0.12 | 1.77 ± 0.12 | 1.82 ± 0.12 | 2.06 ± 0.08 | 2.13 ± 0.08 |
| Week 8 | 1.50 ± 0.11 | 2.16 ± 0.12 | 2.09 ± 0.11 | 2.20 ± 0.11 | 2.48 ± 0.08 | 2.48 ± 0.08 |
| Week 12 | 1.47 ± 0.12 | 2.24 ± 0.12 | 2.23 ± 0.12 | 2.32 ± 0.12 | 2.58 ± 0.08 | 2.63 ± 0.08 |
The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 3 days prior to weeks 4, 8, 12 and EoT.
| percentage of particpants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 23.2 | 24.9 | 27.6 | 28.9 | 35.1 | 37.3 |
| Week 8 | 28.7 | 35.3 | 40.7 | 38.3 | 45.3 | 48.2 |
| Week 12 | 38.0 | 42.5 | 47.4 | 42.7 | 52.3 | 52.7 |
| End of treatment | 37.6 | 40.6 | 46.3 | 42.9 | 50.7 | 52.2 |
The percentage of participants with ≥ 10 points improvement from baseline to each visit (weeks 4, 8, 12 and EoT).
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 56.4 | 62.6 | 69.9 | 73.9 | 73.9 | 75.8 |
| Week 8 | 62.2 | 71.6 | 73.4 | 79.2 | 83.9 | 82.8 |
| Week 12 | 66.0 | 72.1 | 78.4 | 82.4 | 83.5 | 85.1 |
| End of treatment | 65.3 | 71.2 | 77.1 | 81.2 | 82.8 | 84.3 |
The percentage of participants with ≥ 10 points improvement from baseline to each visit (weeks 4, 8, 12 and EoT).
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 45.3 | 52.8 | 59.7 | 61.7 | 62.9 | 61.3 |
| Week 8 | 51.2 | 62.2 | 65.3 | 66.2 | 71.5 | 69.3 |
| Week 12 | 57.7 | 62.4 | 69.1 | 71.7 | 76.3 | 71.8 |
| End of treatment | 56.8 | 61.0 | 68.3 | 71.2 | 74.5 | 71.1 |
The percentage of participants with ≥ 50% decrease from baseline in mean number of incontinence episodes per 24 hours at each time point (weeks 4, 8, 12 and EoT).
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 41.1 | 45.3 | 56.7 | 53.2 | 57.2 | 60.6 |
| Week 8 | 54.9 | 61.8 | 63.7 | 65.3 | 69.8 | 70.6 |
| Week 12 | 58.6 | 66.4 | 70.2 | 71.0 | 75.9 | 76.1 |
| End of treatment | 59.5 | 64.5 | 69.0 | 70.5 | 74.5 | 75.7 |
The percentage of participants with micturition frequency normalization was defined as any participant who had ≥ 8 micturitions/24 hours at baseline and \< 8 micturitions/24 h postbaseline at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 24.1 | 30.8 | 25.4 | 31.1 | 36.0 | 37.7 |
| Week 8 | 28.7 | 37.9 | 34.5 | 37.0 | 45.3 | 49.0 |
| Week 12 | 29.7 | 42.3 | 40.7 | 44.9 | 50.8 | 53.1 |
| End of treatment | 31.1 | 42.1 | 40.1 | 45.0 | 51.3 | 52.6 |
The percentage of participants with zero incontinence episodes per 24 hours postbaseline in the last 7 days prior to weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 12.8 | 13.1 | 16.7 | 17.7 | 23.9 | 26.0 |
| Week 8 | 19.1 | 24.4 | 29.8 | 28.2 | 36.6 | 38.4 |
| Week 12 | 29.1 | 32.2 | 35.0 | 31.9 | 42.4 | 43.7 |
| End of treatment | 28.6 | 30.6 | 34.0 | 31.5 | 40.9 | 43.1 |
The percentage of participants with ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 48.9 | 52.8 | 60.3 | 58.1 | 63.1 | 62.7 |
| Week 8 | 56.4 | 65.3 | 69.7 | 72.7 | 71.6 | 75.4 |
| Week 12 | 59.8 | 66.9 | 73.8 | 74.1 | 76.6 | 80.0 |
| End of treaetment | 59.8 | 65.4 | 72.4 | 71.9 | 75.7 | 78.4 |
The percentage of participants with a major (≥ 2 points) improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 15.9 | 20.6 | 22.4 | 27.4 | 31.1 | 31.1 |
| Week 8 | 27.0 | 33.3 | 35.0 | 40.5 | 42.7 | 46.4 |
| Week 12 | 29.6 | 39.0 | 42.3 | 44.5 | 50.7 | 52.9 |
| End of treatment | 29.5 | 37.2 | 40.7 | 42.6 | 49.7 | 51.2 |
The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 28.6 | 34.8 | 45.7 | 44.9 | 47.8 | 52.3 |
| Week 8 | 39.8 | 50.0 | 51.5 | 56.5 | 63.1 | 63.5 |
| Week 12 | 45.0 | 55.7 | 59.4 | 63.1 | 66.7 | 69.5 |
| End of treatment | 45.2 | 54.0 | 58.2 | 62.6 | 65.2 | 68.2 |
The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and minimal important difference reached (improvement by ≥ 10 points) on the OAB-q HRQL total score at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 23.2 | 28.3 | 39.8 | 37.7 | 40.4 | 40.5 |
| Week 8 | 32.9 | 43.2 | 46.1 | 48.4 | 54.1 | 53.0 |
| Week 12 | 39.2 | 48.3 | 53.5 | 54.8 | 61.6 | 59.2 |
| End of treatment | 39.1 | 46.0 | 52.9 | 54.0 | 59.0 | 58.2 |
The percentage of participants considered as double responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 23.2 | 27.9 | 37.7 | 34.5 | 39.9 | 42.9 |
| Week 8 | 35.6 | 44.7 | 50.1 | 51.3 | 53.8 | 57.7 |
| Week 12 | 40.6 | 51.7 | 54.9 | 56.9 | 62.0 | 65.4 |
| End of treatment | 40.9 | 48.5 | 53.9 | 56.0 | 59.9 | 63.8 |
The percentage of participants considered as triple responders, defined as participants with 50% reduction in mean number of incontinence episodes per 24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the OAB-q Symptom Bother score, and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 17.8 | 24.0 | 33.6 | 31.4 | 37.5 | 40.2 |
| Week 8 | 29.7 | 41.3 | 43.2 | 47.8 | 51.6 | 54.7 |
| Week 12 | 35.8 | 47.7 | 49.6 | 54.5 | 58.2 | 62.0 |
| End of treatment | 36.1 | 45.0 | 48.4 | 53.3 | 56.3 | 60.3 |
The percentage of participants considered as triple responders, defined as participants with 50% reduction in mean number of incontinence episodes per24 hours compared to baseline, minimal important difference reached (improvement by ≥ 10 points) on the HRQL total score, and ≥ 1 point improvement from baseline in PPBC at weeks 4, 8, 12 and EoT.
| percentage of participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 15.2 | 20.6 | 30.0 | 28.6 | 32.7 | 33.4 |
| Week 8 | 24.9 | 36.9 | 38.9 | 43.0 | 46.3 | 46.8 |
| Week 12 | 33.3 | 42.0 | 45.6 | 49.9 | 54.5 | 54.2 |
| End of treatment | 33.3 | 39.1 | 44.8 | 49.2 | 51.6 | 52.8 |
A TEAE refered to an adverse event (AE; defined as any untoward medical occurrence in a participant administered a study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment) which started or worsened in the period from first double-blind medication intake until 14 days after the last double-blind medication intake. Serious TEAEs with a start date reported until 30 days after the last double-blind medication intake were also summarized as TEAEs, and also included serious TEAEs upgraded by the sponsor based on review of the sponsor's list of Always Serious terms if any upgrade was done. Drug-related TEAEs may be possible or probable, as assessed by the investigator, or records where relationship is missing.
| Participants | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Any TEAE | 145 | 135 | 147 | 149 | 345 | 314 |
| Drug-related TEAEs | 45 | 37 | 52 | 63 | 157 | 150 |
| Deaths | 0 | 0 | 0 | 0 | 0 | 0 |
| Serious TEAEs | 8 | 6 | 5 | 3 | 12 | 19 |
| Drug-related serious TEAEs | 0 | 1 | 1 | 0 | 2 | 3 |
| TEAEs leading to discontinuation | 9 | 7 | 10 | 7 | 20 | 22 |
| Drug-related TEAEs leading to discontinuation | 7 | 4 | 6 | 5 | 17 | 19 |
PVR volume was assessed by ultrasonography or a bladder scanner.
| mL | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.8 ± 29.9 | 1.6 ± 28.0 | -2.1 ± 29.7 | 5.8 ± 35.6 | 7.2 ± 47.7 | 10.6 ± 51.1 |
| Week 8 | -1.9 ± 28.6 | -0.4 ± 29.8 | -0.6 ± 34.4 | 5.4 ± 35.2 | 7.0 ± 37.4 | 9.9 ± 46.0 |
| Week 12 | -1.0 ± 29.9 | 1.0 ± 29.8 | 0.0 ± 30.1 | 4.7 ± 33.1 | 7.9 ± 44.4 | 9.6 ± 50.1 |
| End of treatment | -1.0 ± 29.4 | 0.7 ± 29.1 | -0.8 ± 30.0 | 4.8 ± 33.3 | 9.0 ± 55.0 | 11.0 ± 54.9 |
Vital signs (blood pressure and pulse rate) were monitored using an ambulatory blood pressure monitoring (ABPM) device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.
| mmHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4: 24-hour mean | -1.00 ± 1.22 | -2.04 ± 1.31 | 0.96 ± 1.30 | 1.03 ± 1.26 | -0.85 ± 0.90 | 0.31 ± 0.85 |
| Week 4: mean daytime | -1.55 ± 1.22 | -1.19 ± 1.33 | -0.67 ± 1.31 | -1.13 ± 1.34 | -1.63 ± 0.91 | -0.53 ± 0.85 |
| Week 4: mean nighttime | -0.51 ± 1.38 | -1.14 ± 1.46 | 1.42 ± 1.44 | 0.41 ± 1.47 | 1.14 ± 1.03 | 0.54 ± 0.98 |
| Week 12: 24-hour mean | -1.97 ± 1.37 | -2.70 ± 1.42 | -1.75 ± 1.41 | 0.40 ± 1.45 | -0.71 ± 1.02 | 0.40 ± 0.95 |
| Week 12: mean daytime | -2.22 ± 1.37 | -2.53 ± 1.46 | -2.14 ± 1.48 | -2.09 ± 1.50 | -0.39 ± 1.06 | -0.71 ± 1.02 |
| Week 12: mean nighttime | -1.03 ± 1.64 | -2.81 ± 1.77 | -0.77 ± 1.68 | 1.31 ± 1.76 | 0.11 ± 1.23 | 0.79 ± 1.17 |
| End of treatment: 24-hour mean | -1.73 ± 1.24 | -3.44 ± 1.29 | -1.14 ± 1.27 | 0.37 ± 1.25 | -0.52 ± 0.90 | -0.08 ± 0.85 |
| End of treatment: mean daytime | -2.01 ± 1.22 | -3.29 ± 1.31 | -1.92 ± 1.30 | -2.17 ± 1.30 | -0.68 ± 0.92 | -1.28 ± 0.87 |
| End of treatment: mean nighttime | -1.00 ± 1.47 | -3.48 ± 1.54 | -0.60 ± 1.52 | 1.42 ± 1.52 | 0.41 ± 1.09 | 0.91 ± 1.04 |
Vital signs (blood pressure and pulse rate) were monitored using ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.
| mmHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4: 24-hour mean | -0.70 ± 0.50 | -0.86 ± 0.54 | 0.22 ± 0.54 | 0.25 ± 0.52 | 0.03 ± 0.37 | 0.38 ± 0.35 |
| Week 4: mean daytime | -1.25 ± 0.53 | -0.36 ± 0.58 | -0.33 ± 0.57 | -0.77 ± 0.58 | -0.40 ± 0.40 | 0.07 ± 0.37 |
| Week 4: mean nighttime | -0.12 ± 0.59 | -0.97 ± 0.62 | 0.40 ± 0.62 | 0.48 ± 0.63 | 0.93 ± 0.44 | 0.47 ± 0.42 |
| Week 12: 24-hour mean | -0.80 ± 0.56 | -0.93 ± 0.58 | -0.19 ± 0.57 | 0.43 ± 0.59 | -0.37 ± 0.41 | 0.31 ± 0.39 |
| Week 12: mean daytime | -0.85 ± 0.60 | -0.54 ± 0.64 | -0.40 ± 0.65 | -0.33 ± 0.66 | -0.06 ± 0.46 | -0.18 ± 0.44 |
| Week 12: mean nighttime | -0.49 ± 0.66 | -1.39 ± 0.71 | -0.03 ± 0.68 | 0.92 ± 0.71 | 0.23 ± 0.49 | 0.49 ± 0.47 |
| End of treatment: 24-hour mean | -0.96 ± 0.51 | -1.41 ± 0.53 | -0.11 ± 0.52 | 0.05 ± 0.52 | -0.02 ± 0.37 | 0.25 ± 0.35 |
| End of treatment: mean daytime | -1.17 ± 0.53 | -0.98 ± 0.58 | -0.69 ± 0.57 | -0.79 ± 0.57 | -0.18 ± 0.40 | -0.36 ± 0.38 |
| End of treatment: mean nighttime | -0.41 ± 0.60 | -2.00 ± 0.63 | 0.08 ± 0.63 | 0.71 ± 0.63 | 0.56 ± 0.45 | 0.61 ± 0.43 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours.
| beats per minute (bpm) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4: 24-hour mean | -0.83 ± 0.63 | 1.14 ± 0.68 | 2.32 ± 0.67 | 0.36 ± 0.65 | 0.40 ± 0.46 | 0.69 ± 0.44 |
| Week 4: mean daytime | -0.70 ± 0.73 | 1.19 ± 0.79 | 3.52 ± 0.78 | 0.37 ± 0.80 | -0.05 ± 0.54 | 0.61 ± 0.51 |
| Week 4: mean nighttime | -0.72 ± 0.68 | 0.98 ± 0.71 | 1.77 ± 0.70 | 1.09 ± 0.72 | 0.86 ± 0.50 | 0.86 ± 0.48 |
| Week 12: 24-hour mean | 0.70 ± 0.72 | 0.38 ± 0.74 | 1.19 ± 0.74 | 0.12 ± 0.76 | 0.94 ± 0.53 | 1.44 ± 0.50 |
| Week 12: mean daytime | 0.89 ± 0.82 | 0.25 ± 0.88 | 2.12 ± 0.89 | -0.13 ± 0.90 | 0.84 ± 0.64 | 1.36 ± 0.61 |
| Week 12: mean nighttime | 0.34 ± 0.71 | 0.21 ± 0.77 | 0.19 ± 0.73 | 0.06 ± 0.76 | 0.76 ± 0.53 | 1.52 ± 0.51 |
| End of treatment: 24-hour mean | 0.41 ± 0.65 | 0.63 ± 0.68 | 1.67 ± 0.67 | 0.02 ± 0.66 | 0.85 ± 0.47 | 1.52 ± 0.45 |
| End of treatment: mean daytime | 0.45 ± 0.74 | 0.37 ± 0.80 | 2.64 ± 0.79 | -0.07 ± 0.79 | 0.32 ± 0.56 | 1.24 ± 0.53 |
| End of treatment: mean nighttime | 0.39 ± 0.66 | 0.82 ± 0.69 | 0.75 ± 0.68 | 0.45 ± 0.68 | 1.21 ± 0.49 | 1.64 ± 0.47 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax (time to maximum concentration) window of mirabegron and solifenacin was from 4-6 hours postdose.
| mmHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -2.71 ± 1.68 | 0.34 ± 1.86 | -1.03 ± 1.72 | -1.77 ± 1.74 | -1.55 ± 1.23 | -1.47 ± 1.17 |
| Week 12 | -4.86 ± 1.78 | -2.13 ± 1.95 | -1.64 ± 1.88 | -3.15 ± 1.96 | -0.26 ± 1.32 | 0.60 ± 1.32 |
| End of treatment | -4.40 ± 1.60 | -2.19 ± 1.68 | -1.94 ± 1.64 | -3.64 ± 1.65 | -0.61 ± 1.16 | -0.98 ± 1.12 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose.
| mmHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -1.24 ± 0.84 | 0.09 ± 0.93 | -0.65 ± 0.86 | -0.48 ± 0.87 | -0.22 ± 0.62 | -0.71 ± 0.58 |
| Week 12 | -1.74 ± 0.92 | -0.45 ± 1.00 | -0.31 ± 0.97 | -1.49 ± 1.01 | 0.48 ± 0.68 | -0.03 ± 0.68 |
| End of treatment | -1.85 ± 0.84 | -0.71 ± 0.88 | -0.71 ± 0.85 | -1.22 ± 0.86 | 0.44 ± 0.61 | -0.80 ± 0.59 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose.
| bpm | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 0.02 ± 1.08 | 2.39 ± 1.19 | 3.68 ± 1.10 | 0.47 ± 1.11 | -0.91 ± 0.79 | 0.67 ± 0.75 |
| Week 12 | 0.10 ± 1.10 | 1.22 ± 1.20 | 1.87 ± 1.16 | 0.37 ± 1.21 | 0.15 ± 0.81 | 1.39 ± 0.81 |
| End of treatment | -0.43 ± 1.05 | 0.82 ± 1.10 | 3.41 ± 1.07 | -1.25 ± 1.08 | 0.34 ± 0.76 | 1.25 ± 0.73 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. The maximum 1 hour change from time-matched baseline was calculated as the maximum difference between the post-baseline hourly means and the time-matched baseline hourly means.
| mmHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 34.05 ± 2.06 | 31.14 ± 2.20 | 38.20 ± 2.19 | 35.16 ± 2.11 | 32.88 ± 1.51 | 32.80 ± 1.43 |
| Week 12 | 33.21 ± 2.30 | 30.68 ± 2.38 | 32.88 ± 2.36 | 35.11 ± 2.42 | 33.53 ± 1.70 | 32.82 ± 1.59 |
| End of treatment | 34.98 ± 2.11 | 30.65 ± 2.20 | 33.53 ± 2.16 | 34.95 ± 2.14 | 34.70 ± 1.54 | 32.55 ± 1.45 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose. The maximum 1 hour change from time-matched baseline was calculated as the maximum difference between the post-baseline hourly means and the time-matched baseline hourly means.
| mmHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 18.78 ± 1.27 | 19.15 ± 1.36 | 20.41 ± 1.35 | 20.02 ± 1.31 | 20.74 ± 0.93 | 20.27 ± 0.88 |
| Week 12 | 19.68 ± 1.23 | 19.52 ± 1.28 | 20.41 ± 1.27 | 21.18 ± 1.30 | 19.26 ± 0.92 | 20.01 ± 0.85 |
| End of treatment | 20.29 ± 1.16 | 19.29 ± 1.22 | 20.71 ± 1.19 | 20.47 ± 1.18 | 20.29 ± 0.85 | 20.36 ± 0.80 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Tmax window of mirabegron and solifenacin was from 4-6 hours postdose. The maximum 1 hour change from time-matched baseline was calculated as the maximum difference between the post-baseline hourly means and the time-matched baseline hourly means.
| bpm | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 22.34 ± 1.35 | 23.86 ± 1.44 | 25.12 ± 1.43 | 24.28 ± 1.38 | 21.48 ± 0.99 | 21.80 ± 0.94 |
| Week 12 | 22.63 ± 1.42 | 23.54 ± 1.47 | 26.03 ± 1.46 | 23.52 ± 1.50 | 22.60 ± 1.05 | 24.08 ± 0.98 |
| End of treatment | 23.01 ± 1.31 | 24.12 ± 1.37 | 26.23 ± 1.34 | 23.33 ± 1.33 | 22.66 ± 0.96 | 24.14 ± 0.90 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference was defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.
| mmHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.71 ± 1.86 | 0.14 ± 1.99 | -0.69 ± 1.98 | 0.85 ± 1.91 | -1.61 ± 1.36 | 0.41 ± 1.29 |
| Week 12 | 1.18 ± 1.98 | -2.45 ± 2.05 | -4.55 ± 2.03 | -1.63 ± 2.08 | 0.68 ± 1.47 | 0.62 ± 1.37 |
| End of treatment | 1.15 ± 1.83 | -1.38 ± 1.91 | -2.30 ± 1.87 | -0.97 ± 1.85 | 0.25 ± 1.33 | 0.68 ± 1.26 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference was defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.
| nnHg | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | -0.76 ± 1.31 | -1.08 ± 1.40 | -0.20 ± 1.39 | -1.60 ± 1.34 | 0.39 ± 0.96 | -0.56 ± 0.91 |
| Week 12 | 0.53 ± 1.30 | 0.15 ± 1.34 | -1.90 ± 1.33 | -0.66 ± 1.36 | -1.24 ± 0.96 | 0.46 ± 0.90 |
| End of treatment | 0.87 ± 1.23 | 0.27 ± 1.28 | -0.96 ± 1.26 | -1.67 ± 1.24 | -0.98 ± 0.89 | 0.52 ± 0.85 |
Vital signs (blood pressure and pulse rate) were monitored using an ABPM device placed on the upper arm followed by intake of the double-blind study medication and worn for at least 24 hours. Peak/trough difference was defined as the difference between the highest 1-h to lowest 1-h average per participant per visit.
| bpm | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Week 4 | 1.16 ± 1.38 | 0.46 ± 1.48 | 1.54 ± 1.46 | 0.78 ± 1.41 | -0.68 ± 1.01 | -0.51 ± 0.96 |
| Week 12 | 3.35 ± 1.45 | -0.04 ± 1.50 | 1.15 ± 1.49 | 3.49 ± 1.53 | -0.53 ± 1.07 | 1.48 ± 1.00 |
| End of treatment | 2.48 ± 1.32 | 0.45 ± 1.37 | 1.14 ± 1.35 | 3.16 ± 1.33 | -0.02 ± 0.96 | 1.80 ± 0.91 |
Collected over From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 16 weeks).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/429 (0%) | 8/429 (1.9%) | 8/429 (1.9%) |
| Mirabegron 25 mg | 0/423 (0%) | 6/423 (1.4%) | 17/423 (4%) |
| Mirabegron 50 mg | 0/422 (0%) | 5/422 (1.2%) | 14/422 (3.3%) |
| Solifenacin 5 mg | 0/423 (0%) | 3/423 (0.7%) | 25/423 (5.9%) |
| Solifenacin 5 mg + Mirabegron 25 mg | 0/853 (0%) | 12/853 (1.4%) | 72/853 (8.4%) |
| Solifenacin 5 mg + Mirabegron 50 mg | 0/848 (0%) | 19/848 (2.2%) | 60/848 (7.1%) |
| Event | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| AppendicitisInfections and infestations | 0/429 | 0/423 | 1/422 | 0/423 | 0/853 | 1/848 |
| Grand mal convulsionNervous system disorders | 0/429 | 0/423 | 1/422 | 0/423 | 0/853 | 0/848 |
| Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/429 | 0/423 | 1/422 | 0/423 | 0/853 | 0/848 |
| Hypovolaemic shockVascular disorders | 0/429 | 0/423 | 1/422 | 0/423 | 0/853 | 0/848 |
| CholelithiasisHepatobiliary disorders | 0/429 | 0/423 | 1/422 | 0/423 | 0/853 | 0/848 |
| PyelonephritisInfections and infestations | 0/429 | 1/423 | 0/422 | 0/423 | 0/853 | 0/848 |
| Scrub typhusInfections and infestations | 0/429 | 0/423 | 0/422 | 1/423 | 0/853 | 0/848 |
| Septic shockInfections and infestations | 0/429 | 1/423 | 0/422 | 0/423 | 0/853 | 0/848 |
| Angina pectorisCardiac disorders | 0/429 | 1/423 | 0/422 | 0/423 | 0/853 | 0/848 |
| Lower limb fractureInjury, poisoning and procedural complications | 0/429 | 1/423 | 0/422 | 0/423 | 0/853 | 0/848 |
| Event | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg |
|---|---|---|---|---|---|---|
| Dry mouthGastrointestinal disorders | 8/429 | 17/423 | 14/422 | 25/423 | 72/853 | 60/848 |
Randomized analysis set (RAS), comprised all randomized patients.
| Age, Continuous(Year) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Mean | 57.46 ± 13.2 | 56.77 ± 13.46 | 56.69 ± 13.28 | 57.88 ± 12.92 | 56.94 ± 13.78 | 57.3 ± 13.46 | 57.16 ± 13.42 |
| Sex: Female, Male(Participants) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Female | 345 | 343 | 338 | 342 | 686 | 684 | 2738 |
| Male | 102 | 98 | 99 | 92 | 199 | 199 | 789 |
| Mean number of incontinence episodes/24 h(incontinence episodes) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Mean | 3.41 ± 3.37 | 3.42 ± 3.40 | 3.18 ± 3.47 | 3.58 ± 3.51 | 3.22 ± 3.17 | 3.16 ± 3.08 | 3.29 ± 3.29 |
| Mean number of micturitions/24 h(micturitions) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Mean | 10.97 ± 2.86 | 10.81 ± 2.63 | 11.19 ± 3.27 | 10.76 ± 2.47 | 10.73 ± 2.88 | 10.74 ± 2.36 | 10.84 ± 2.73 |
| Mean volume voided per micturition(mL) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Least squares mean | 157.94 ± 58.78 | 152.46 ± 60.96 | 155.31 ± 60.78 | 151.94 ± 59.29 | 159.32 ± 58.29 | 153.57 ± 59.67 | 155.43 ± 59.49 |
| Number of incontinence episodes/week(incontinence episodes) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Mean | 23.6 ± 23.6 | 23.5 ± 23.6 | 21.7 ± 23.8 | 24.8 ± 24.5 | 22.1 ± 21.7 | 21.7 ± 21.3 | 22.7 ± 22.7 |
| Mean number of urgency incontinence episodes/24 h(urgency incontinence episodes) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Mean | 3.14 ± 3.23 | 3.00 ± 3.09 | 2.89 ± 3.31 | 3.23 ± 3.34 | 2.85 ± 2.81 | 2.80 ± 2.64 | 2.94 ± 3.00 |
| Number of urgency incontinence episodes/week(urgency incontinence episodes) | Placebo | Mirabegron 25 mg | Mirabegron 50 mg | Solifenacin 5 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Mean | 21.7 ± 22.6 | 20.6 ± 21.4 | 19.8 ± 22.7 | 22.4 ± 23.3 | 19.5 ± 19.3 | 19.2 ± 18.2 | 20.3 ± 20.7 |
5 further baseline measures are reported on the registry.
Showing the first 100 of 435 sites across 42 countries.
Plan to share: Yes — Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Supporting information: Study protocol, Sap, Csr
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