Overactive Bladder (OAB)
Conditions
Keywords
Anticholinergic, Overactive Bladder (OAB), Mirabegron, YM178
Brief summary
The objective of the study was to evaluate the safety and efficacy of add-on therapy with anticholinergics in patients with OAB on mirabegron.
Detailed description
This was a multicenter, open-label study to evaluate the safety and efficacy of add-on therapy with antimuscarinics in patients with OAB treated with mirabegron. The total duration of the study period was 54 weeks in total, comprising a 2-week screening period and a 52-week treatment period. Patients who met the eligibility criteria for provisional enrollment received orally the study drug for the screening period (mirabegron 50 mg) once daily after breakfast for 2 weeks. Patients who met the eligibility criteria after the screening period were randomized to solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg or tolterodine 4 mg in a 1:1:1:1 ratio, and received orally mirabegron 50 mg and antimuscarinics for 52 weeks. At week 8 visit, the dose of all antimuscarinics except for tolterodine could be increased by 2-fold (solifenacin 10 mg, propiverine 40 mg or imidafenacin 0.4 mg) if a patient met the following criteria: (1) had no response to the study drugs; (2) was considered by the investigator to have no safety concerns; and (3) agreed to increase the dose. However, in the event of AEs after the dose was increased, it could be reduced to the level before the increase. A dose increase for a second time after dose reduction was not permitted.
Interventions
DRUGMirabegron tablet
orally administered at a dose of 1 tablet once daily after breakfast
DRUGSolifenacin tablet
orally administered at a dose of 1 tablet once daily after breakfast (could be increased to 2 tablets)
orally administered at a dose of 1 tablet once daily after breakfast (could be increased to 1 tablet twice daily after breakfast and after dinner)
DRUGImidafenacin tablet
orally administered at a dose of 1 tablet (0.1 mg tablet) twice daily after breakfast and after dinner (could be increased to 2 tablets twice daily after breakfast and after dinner)
DRUGTolterodine capsule
orally administered at a dose of 1 capsule once daily after breakfast (could not be increased)
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female: OAB outpatient who had been postmenopausal for at least 1 year * Male: OAB outpatient who had no wish to have children in the future * Patient had been under treatment with mirabegron at a stable dose of 50 mg once daily for at least 6 weeks before the start of the screening period * Patient capable of walking to the bathroom without assistance * Patient had a total Overactive Bladder Symptom Score (OABSS) of ≥3 points and a Question 3 score of ≥2 points
Exclusion criteria
* Patient had an established diagnosis of stress urinary incontinence (patient had no symptom other than stress urinary incontinence) * Patient had urinary tract infection (cystitis, prostatitis, etc.), urinary calculus (ureteric calculus, urethral calculus, bladder calculus, etc.), interstitial cystitis, or a history of recurrent urinary tract infection (at least 3 episodes within 24 weeks before the start of the screening period) * Patient had a residual urine volume of ≥100 mL at week -2 visit or patient with benign prostatic hyperplasia or lower urinary tract obstruction * Patient had uncontrolled hypertension (sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at week -2 visit) * Patient had a pulse rate of ≥110 bpm or \<50 bpm at week -2 visit * Patient had a contraindication to antimuscarinics (urinary retention; obstruction in thepylorus, duodenum, or intestine; paralytic ileus; gastric/intestinal atony; myasthenia gravis; and decreased gastrointestinal motility/tone, etc.) * Patient had glaucoma, ulcerative colitis, hyperthyroidism, dementia, cognitive dysfunction, parkinsonism symptoms, or clinically significant cerebrovascular disorder * Patient had serious heart disease (myocardial infarction, cardiac failure, uncontrolled angina pectoris, serious arrhythmia, use of pacemaker, etc.), liver disease, kidney disease, immunological disease, lung disease, etc. or patient had a history of malignant tumor (except for malignant tumor that had not been treated for at least 5 years before the start of the screening period with no risk of recurrence) * Patient had drug hypersensitivity to β-agonists or anticholinergics * Patient was under treatment with flecainide acetate or propafenone hydrochloride * Patient had long QT syndrome, patient was vulnerable to arrhythmia such as bradycardia or acute myocardial ischemia, patient had hypokalemia, and patient had ischemic heart disease such as angina pectoris * Patient had used any prohibited concomitant medication within 4 weeks before the start of the screening period * Patient was under catheterization or intermittent self-catheterization or patient had pelvic organ prolapse that affected the urinary tract function * Patient had received radiotherapy that affected the urinary tract function * Patient had received surgical therapy that may have affected the urinary tract function within 24 weeks before the start of the screening period * Patient had received nonpharmacological therapy for OAB such as electric stimulation therapy (interferential low frequency therapy, magnetic stimulation therapy, etc.), biofeedback therapy, bladder training, or pelvic floor muscle exercise within 2 weeks before the start of the screening period * Patient had or had a history of mood disorder, neurotic disorder, and schizophrenia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug up to week 52 | TEAEs were defined as AEs observed after the first administration of the study drugs for the treatment period. The investigator assessed the severity of AEs, including abnormal clinical laboratory values, electrocardiogram (ECG), vital signs, as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A drug-related TEAE was a TEAE with at least a possible relationship to the study drug as assessed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Normalization for OABSS Total Score | Week 52 (end of treatment) | Normalization for OABSS Total Score was defined as OABSS total score ≤ 2 or OABSS Question 3 score ≤ 1. |
| Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Baseline and week 12, 28 and 52 | The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Symptom Severity and the Health-related Quality of Life (HRQL). The Symptom Severity section included 6 questions. For each participant, the symptom severity score was derived as a sum of scores for Questions 1 to 6. The total score ranges from 6 to 36 with higher symptom severity score indicating greater symptom bother. OAB-q SF data obtained at week 0 visit were used as baseline. |
| Change From Baseline in OAB-q SF Total HRQL Score | Baseline and week 12, 28 and 52 | The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the HRQL. The HRQL section included 13 questions. For each participant, the total HRQL score was derived as a sum of scores for Questions 7 to 19. The total score ranges from 13 to 78 with higher total HRQL score indicating greater HRQL. OAB-q SF data obtained at week 0 visit were used as baseline. |
| Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Baseline and week 4, 8, 12, 16, 28, 40, 52 | Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean number of micturitions per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable urinated was indicated, divided by the number of days on which episodes were recorded. |
| Number for Participants Who Achieved Normalization of the Mean Number of Micturitions Per 24 Hours | Week 52 (end of treatment) | Normalization for the mean number of micturitions per 24 hours was defined as \< 8 micturitions per 24 hours. |
| Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Baseline and week 4, 8, 12, 16, 28, 40, 52 | Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urgency episode was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable urgency was indicated, divided by the number of days on which episodes were recorded. Only participants who had an urgency episode at baseline was included in the analysis. |
| Number for Participants Who Achieved Normalization of the Mean Number of Urgency Episodes Per 24 Hours | Week 52 (end of treatment) | Normalization for the mean number of urgency episodes per 24 hours was defined as no urgency episode per 24 hours. |
| Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Baseline and week 4, 8, 12, 16, 28 and 52 | The OABSS questionnaire was a questionnaire completed by participants with 4 questions regarding their OAB symptoms. For each participant, the OABSS total score was calculated from the sum total of the score of each question. The total score ranges from 0 to 15 with higher score indicating more symptoms. The OABSS data obtained at week 0 were used as baseline. |
| Number for Participants Who Achieved Normalization of the Mean Number of Incontinence Episodes Per 24 Hours | Week 52 (end of treatment) | Normalization for the mean number of incontinence episodes per 24 hours was defined as no incontinence episode per 24 hours. |
| Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Baseline and week 4, 8, 12, 16, 28, 40, 52 | Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urge incontinence episode was defined as any episode when both urgency and incontinence occurred concurrently. The mean number of incontinence episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable urgency and urinary incontinence' were indicated, divided by the number of days on which episodes were recorded. Only participants who had an urge incontinence episode at baseline was included in the analysis. |
| Change From Baseline in the Mean Volume Voided Per Micturition | Baseline and week 4, 8, 12, 16, 28, 40, 52 | Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean volume per micturition was calculated by taking the sum of the urinary volumes where the volume voided was \> 0 and where urinary incontinence was not indicated in the patient diary, divided by the number of micturitions where the volume voided was \> 0 and where urinary incontinence was not indicated. Only participants who had volume voided was \> 0 at baseline was included in the analysis. |
| Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Baseline and week 4, 8, 12, 16, 28, 40, 52 | Participants completed the patient diary (paper document) for 3 days immediately before each visit. A nocturia episode was defined as waking at night 1 or more times to void. Night time was defined as the period between bedtime and the wake-up time the following day (micturitions at the same time as the wake-up time were excluded). The mean number of nocturia episodes per night was calculated by taking the sum of nocturia episodes in the patient diary where the variable urinated was indicated during the night time, divided by the number of nights. Only participants who had a nocturia episode at baseline was included in the analysis. |
| Number of Participants Who Achieved Normalization of the Mean Number of Nocturia Episodes Per 24 Hours | Week 52 (end of treatment) | Normalization for the mean number of nocturia episodes per 24 hours was defined as no nocturia episode per 24 hours. |
| Change From Baseline in Postvoid Residual (PVR) Volume | Baseline and week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Measurement of PVR volume was made using either ultrasonography or urethral catheterization, provided that the same method was used for the same participant throughout the study. |
| Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Baseline and week 4, 8, 12, 16, 28, 40, 52 | Participants completed the patient diary (paper document) for 3 days immediately before each visit. 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 by taking the sum of all marked episodes in the patient diary where the variable urinary incontinence' was indicated, divided by the number of days on which episodes were recorded. Only participants who had an incontinence episode at baseline was included in the analysis. |
Countries
Japan
Participant flow
Recruitment details
Participants with overactive bladder (OAB) were enrolled in 60 sites in Japan.
Pre-assignment details
Prior to randomization, participants received 50 mg mirabegron orally once daily after breakfast for 2 weeks during a screening period.
Participants by arm
| Arm | Count |
|---|---|
| Mirabegron + Solifenacin Participants received mirabegron 50 mg and solifenacin 5 mg once daily after breakfast orally for 8 weeks. In the next 44 weeks, participants continued to receive mirabegron 50 mg, but received an increased dose of solifenacin 10 mg, if the treatment was not effective. | 166 |
| Mirabegron + Propiverine Participants received mirabegron 50 mg and propiverine 20 mg once daily after breakfast orally for 8 weeks. In the next 44 weeks, participants continued to receive mirabegron 50 mg, but received an increased dose of propiverine 40 mg, if the treatment was not effective. | 161 |
| Mirabegron + Imidafenacin Participants received mirabegron 50 mg and imidafenacin 0.2 mg once daily after breakfast orally for 8 weeks. In the next 44 weeks, participants continued to receive mirabegron 50 mg, but received an increased dose of imidafenacin 0.4 mg, if the treatment was not effective. | 161 |
| Mirabegron + Tolterodine Participants received mirabegron 50 mg and tolterodine 4 mg once daily after breakfast orally for 52 weeks. | 159 |
| Total | 647 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 26 | 25 | 21 | 24 |
| Overall Study | Electrocardiogram adviser's judgment | 1 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 |
| Overall Study | Miscellaneous | 2 | 0 | 5 | 2 |
| Overall Study | Protocol Deviation | 3 | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 6 | 6 | 8 |
Baseline characteristics
| Characteristic | Mirabegron + Solifenacin | Mirabegron + Propiverine | Mirabegron + Imidafenacin | Mirabegron + Tolterodine | Total |
|---|---|---|---|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 9.4 | 64.0 years STANDARD_DEVIATION 9.3 | 65.7 years STANDARD_DEVIATION 8.7 | 65.7 years STANDARD_DEVIATION 10 | 65.0 years STANDARD_DEVIATION 9.4 |
| Mean Number of Incontinence Episodes per 24 Hours | 1.62 incontinence episodes STANDARD_DEVIATION 1.62 | 1.59 incontinence episodes STANDARD_DEVIATION 1.83 | 1.47 incontinence episodes STANDARD_DEVIATION 1.35 | 1.55 incontinence episodes STANDARD_DEVIATION 1.76 | 1.56 incontinence episodes STANDARD_DEVIATION 1.64 |
| Mean Number of Micturitions per 24 Hours | 10.06 micturitions STANDARD_DEVIATION 2.59 | 10.37 micturitions STANDARD_DEVIATION 2.65 | 10.13 micturitions STANDARD_DEVIATION 2.92 | 10.20 micturitions STANDARD_DEVIATION 2.62 | 10.19 micturitions STANDARD_DEVIATION 2.69 |
| Mean Number of Nocturia Episodes per Night | 1.50 nocturia episodes STANDARD_DEVIATION 0.96 | 1.68 nocturia episodes STANDARD_DEVIATION 1.08 | 1.61 nocturia episodes STANDARD_DEVIATION 1.29 | 1.67 nocturia episodes STANDARD_DEVIATION 1.04 | 1.61 nocturia episodes STANDARD_DEVIATION 1.1 |
| Mean Number of Urge Incontinence Episodes per 24 Hours | 1.55 urge incontinence episodes STANDARD_DEVIATION 1.47 | 1.39 urge incontinence episodes STANDARD_DEVIATION 1.45 | 1.30 urge incontinence episodes STANDARD_DEVIATION 1.16 | 1.31 urge incontinence episodes STANDARD_DEVIATION 1.62 | 1.38 urge incontinence episodes STANDARD_DEVIATION 1.43 |
| Mean Number of Urgency Episodes per 24 Hours | 3.26 urgency episodes STANDARD_DEVIATION 2.46 | 3.12 urgency episodes STANDARD_DEVIATION 2.67 | 3.27 urgency episodes STANDARD_DEVIATION 2.2 | 3.15 urgency episodes STANDARD_DEVIATION 2.54 | 3.20 urgency episodes STANDARD_DEVIATION 2.47 |
| Mean Volume Voided per Micturition | 166.600 mL STANDARD_DEVIATION 50.404 | 170.064 mL STANDARD_DEVIATION 63.781 | 169.309 mL STANDARD_DEVIATION 50.324 | 167.542 mL STANDARD_DEVIATION 54.32 | 168.368 mL STANDARD_DEVIATION 54.839 |
| OAB-q SF Score: Total Health-Related Quality of Life (HRQOL) | 75.16 Units on a Scale STANDARD_DEVIATION 17.65 | 77.36 Units on a Scale STANDARD_DEVIATION 16.11 | 74.85 Units on a Scale STANDARD_DEVIATION 18.5 | 75.37 Units on a Scale STANDARD_DEVIATION 19.33 | 75.68 Units on a Scale STANDARD_DEVIATION 17.91 |
| Overactive Bladder questionnaire Short Form (OAB-q SF) Score: Symptom Severity | 32.81 Units on a Scale STANDARD_DEVIATION 20.78 | 32.36 Units on a Scale STANDARD_DEVIATION 21.23 | 32.92 Units on a Scale STANDARD_DEVIATION 19.45 | 34.23 Units on a Scale STANDARD_DEVIATION 22.6 | 33.08 Units on a Scale STANDARD_DEVIATION 21 |
| Overactive Bladder Symptom Score (OABSS) | 7.4 Units on a Scale STANDARD_DEVIATION 2.6 | 7.7 Units on a Scale STANDARD_DEVIATION 2.5 | 7.8 Units on a Scale STANDARD_DEVIATION 2.3 | 7.7 Units on a Scale STANDARD_DEVIATION 2.3 | 7.6 Units on a Scale STANDARD_DEVIATION 2.4 |
| Postvoid Residual (PVR) Volume | 11.02 mL STANDARD_DEVIATION 15.43 | 10.43 mL STANDARD_DEVIATION 17.07 | 9.74 mL STANDARD_DEVIATION 14.35 | 9.10 mL STANDARD_DEVIATION 14.41 | 10.08 mL STANDARD_DEVIATION 15.34 |
| Sex: Female, Male Female | 146 Participants | 144 Participants | 146 Participants | 134 Participants | 570 Participants |
| Sex: Female, Male Male | 20 Participants | 17 Participants | 15 Participants | 25 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 166 | 0 / 161 | 0 / 161 | 1 / 159 |
| other Total, other adverse events | 115 / 166 | 117 / 161 | 108 / 161 | 97 / 159 |
| serious Total, serious adverse events | 10 / 166 | 4 / 161 | 5 / 161 | 9 / 159 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as AEs observed after the first administration of the study drugs for the treatment period. The investigator assessed the severity of AEs, including abnormal clinical laboratory values, electrocardiogram (ECG), vital signs, as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A drug-related TEAE was a TEAE with at least a possible relationship to the study drug as assessed by the investigator.
Time frame: From first dose of study drug up to week 52
Population: SAF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 113 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 3 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to death | 0 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 10 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to withdrawal of treatment | 23 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 76 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related serious TEAEs | 0 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 131 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to withdrawal of treat. | 12 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to death | 0 Participants |
| Mirabegron + Solifenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 15 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to death | 0 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to death | 0 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 4 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 122 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to withdrawal of treatment | 19 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 0 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 135 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 81 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 13 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related serious TEAEs | 1 Participants |
| Mirabegron + Propiverine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to withdrawal of treat. | 17 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to withdrawal of treatment | 16 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 133 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 116 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 2 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 72 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to death | 0 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to death | 0 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 5 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related serious TEAEs | 0 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 15 Participants |
| Mirabegron + Imidafenacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to withdrawal of treat. | 10 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 74 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 120 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related serious TEAEs | 1 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 4 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 12 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to withdrawal of treat. | 8 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to withdrawal of treatment | 18 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to death | 0 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 104 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 9 Participants |
| Mirabegron + Tolterodine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to death | 1 Participants |
Secondary
Change From Baseline in OAB-q SF Total HRQL Score
The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the HRQL. The HRQL section included 13 questions. For each participant, the total HRQL score was derived as a sum of scores for Questions 7 to 19. The total score ranges from 13 to 78 with higher total HRQL score indicating greater HRQL. OAB-q SF data obtained at week 0 visit were used as baseline.
Time frame: Baseline and week 12, 28 and 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in OAB-q SF Total HRQL Score | Week 12 | 12.07 units on a scale | Standard Deviation 13.37 |
| Mirabegron + Solifenacin | Change From Baseline in OAB-q SF Total HRQL Score | Week 28 | 15.15 units on a scale | Standard Deviation 14.63 |
| Mirabegron + Solifenacin | Change From Baseline in OAB-q SF Total HRQL Score | Week 52 | 15.99 units on a scale | Standard Deviation 14.63 |
| Mirabegron + Solifenacin | Change From Baseline in OAB-q SF Total HRQL Score | End of treatment | 14.38 units on a scale | Standard Deviation 14.98 |
| Mirabegron + Propiverine | Change From Baseline in OAB-q SF Total HRQL Score | Week 28 | 13.05 units on a scale | Standard Deviation 14 |
| Mirabegron + Propiverine | Change From Baseline in OAB-q SF Total HRQL Score | Week 52 | 13.89 units on a scale | Standard Deviation 14.04 |
| Mirabegron + Propiverine | Change From Baseline in OAB-q SF Total HRQL Score | End of treatment | 12.46 units on a scale | Standard Deviation 13.89 |
| Mirabegron + Propiverine | Change From Baseline in OAB-q SF Total HRQL Score | Week 12 | 11.35 units on a scale | Standard Deviation 13.15 |
| Mirabegron + Imidafenacin | Change From Baseline in OAB-q SF Total HRQL Score | Week 52 | 14.67 units on a scale | Standard Deviation 16.88 |
| Mirabegron + Imidafenacin | Change From Baseline in OAB-q SF Total HRQL Score | Week 28 | 14.88 units on a scale | Standard Deviation 17.16 |
| Mirabegron + Imidafenacin | Change From Baseline in OAB-q SF Total HRQL Score | End of treatment | 13.99 units on a scale | Standard Deviation 16.72 |
| Mirabegron + Imidafenacin | Change From Baseline in OAB-q SF Total HRQL Score | Week 12 | 11.06 units on a scale | Standard Deviation 15.72 |
| Mirabegron + Tolterodine | Change From Baseline in OAB-q SF Total HRQL Score | End of treatment | 14.36 units on a scale | Standard Deviation 17.51 |
| Mirabegron + Tolterodine | Change From Baseline in OAB-q SF Total HRQL Score | Week 28 | 12.94 units on a scale | Standard Deviation 15.55 |
| Mirabegron + Tolterodine | Change From Baseline in OAB-q SF Total HRQL Score | Week 12 | 12.05 units on a scale | Standard Deviation 16 |
| Mirabegron + Tolterodine | Change From Baseline in OAB-q SF Total HRQL Score | Week 52 | 15.06 units on a scale | Standard Deviation 16.4 |
Secondary
Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score
The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Symptom Severity and the Health-related Quality of Life (HRQL). The Symptom Severity section included 6 questions. For each participant, the symptom severity score was derived as a sum of scores for Questions 1 to 6. The total score ranges from 6 to 36 with higher symptom severity score indicating greater symptom bother. OAB-q SF data obtained at week 0 visit were used as baseline.
Time frame: Baseline and week 12, 28 and 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 12 | -18.59 units on a scale | Standard Deviation 15.89 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 28 | -21.38 units on a scale | Standard Deviation 18.15 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 52 | -20.55 units on a scale | Standard Deviation 18.29 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | End of treatment | -18.92 units on a scale | Standard Deviation 18.42 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 28 | -21.40 units on a scale | Standard Deviation 19.18 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 52 | -20.68 units on a scale | Standard Deviation 19.33 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | End of treatment | -18.99 units on a scale | Standard Deviation 19.14 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 12 | -20.2 units on a scale | Standard Deviation 19.4 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 52 | -20.51 units on a scale | Standard Deviation 18.28 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 28 | -20.40 units on a scale | Standard Deviation 19.23 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | End of treatment | -18.89 units on a scale | Standard Deviation 18.11 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 12 | -17.15 units on a scale | Standard Deviation 17.37 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | End of treatment | -21.28 units on a scale | Standard Deviation 20.99 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 28 | -21.95 units on a scale | Standard Deviation 20.95 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 12 | -21.22 units on a scale | Standard Deviation 20.42 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score | Week 52 | -22.49 units on a scale | Standard Deviation 21.23 |
Secondary
Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score
The OABSS questionnaire was a questionnaire completed by participants with 4 questions regarding their OAB symptoms. For each participant, the OABSS total score was calculated from the sum total of the score of each question. The total score ranges from 0 to 15 with higher score indicating more symptoms. The OABSS data obtained at week 0 were used as baseline.
Time frame: Baseline and week 4, 8, 12, 16, 28 and 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 52 | -4.0 units on a scale | Standard Deviation 2.7 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | End of treatment | -3.9 units on a scale | Standard Deviation 2.7 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 12 | -4.0 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 8 | -3.5 units on a scale | Standard Deviation 2.5 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 4 | -2.9 units on a scale | Standard Deviation 2.5 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 28 | -4.0 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Solifenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 16 | -4.1 units on a scale | Standard Deviation 2.7 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 4 | -3.1 units on a scale | Standard Deviation 2.5 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | End of treatment | -4.1 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 28 | -4.4 units on a scale | Standard Deviation 2.9 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 8 | -3.7 units on a scale | Standard Deviation 2.5 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 16 | -4.4 units on a scale | Standard Deviation 2.7 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 12 | -4.2 units on a scale | Standard Deviation 2.8 |
| Mirabegron + Propiverine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 52 | -4.1 units on a scale | Standard Deviation 2.5 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | End of treatment | -3.9 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 4 | -2.4 units on a scale | Standard Deviation 2.3 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 8 | -3.1 units on a scale | Standard Deviation 2.3 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 12 | -3.4 units on a scale | Standard Deviation 2.2 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 16 | -3.8 units on a scale | Standard Deviation 2.3 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 28 | -3.9 units on a scale | Standard Deviation 2.8 |
| Mirabegron + Imidafenacin | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 52 | -4.1 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 16 | -4.4 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 12 | -4.0 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | End of treatment | -4.2 units on a scale | Standard Deviation 2.8 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 52 | -4.3 units on a scale | Standard Deviation 2.9 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 8 | -3.5 units on a scale | Standard Deviation 2.6 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 4 | -3.0 units on a scale | Standard Deviation 2.5 |
| Mirabegron + Tolterodine | Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score | Week 28 | -4.3 units on a scale | Standard Deviation 2.9 |
Secondary
Change From Baseline in Postvoid Residual (PVR) Volume
Measurement of PVR volume was made using either ultrasonography or urethral catheterization, provided that the same method was used for the same participant throughout the study.
Time frame: Baseline and week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: SAF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 36 | 4.11 mL | Standard Deviation 19.17 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 32 | 0.70 mL | Standard Deviation 16.9 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 20 | 2.32 mL | Standard Deviation 18.01 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | End of treatment | 8.17 mL | Standard Deviation 39.42 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 28 | 2.95 mL | Standard Deviation 19.97 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 24 | 4.99 mL | Standard Deviation 21.14 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 48 | 2.60 mL | Standard Deviation 16.3 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | 9.07 mL | Standard Deviation 23.79 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | 4.72 mL | Standard Deviation 19.47 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 52 | 3.56 mL | Standard Deviation 17.51 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 44 | 2.17 mL | Standard Deviation 16.4 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 40 | 6.03 mL | Standard Deviation 21.79 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 7.51 mL | Standard Deviation 22.06 |
| Mirabegron + Solifenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | 10.68 mL | Standard Deviation 34.38 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 44 | 1.03 mL | Standard Deviation 16.89 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | 9.99 mL | Standard Deviation 36.05 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | 3.23 mL | Standard Deviation 20.4 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | 3.67 mL | Standard Deviation 20.42 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 1.06 mL | Standard Deviation 18.74 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 20 | 3.53 mL | Standard Deviation 19.43 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 24 | 4.03 mL | Standard Deviation 22.38 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 28 | 3.87 mL | Standard Deviation 19.82 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 32 | 1.34 mL | Standard Deviation 17.28 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 36 | 0.66 mL | Standard Deviation 17.96 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 40 | 3.29 mL | Standard Deviation 23.24 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 48 | 0.71 mL | Standard Deviation 17.05 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 52 | 4.58 mL | Standard Deviation 22.19 |
| Mirabegron + Propiverine | Change From Baseline in Postvoid Residual (PVR) Volume | End of treatment | 6.83 mL | Standard Deviation 32.2 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 44 | 3.14 mL | Standard Deviation 21.56 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 52 | 2.84 mL | Standard Deviation 19.94 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | 5.77 mL | Standard Deviation 25.39 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 4.04 mL | Standard Deviation 20.69 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 48 | 2.22 mL | Standard Deviation 17.58 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | 6.81 mL | Standard Deviation 22.11 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 40 | 5.19 mL | Standard Deviation 23.09 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 32 | 2.19 mL | Standard Deviation 17.26 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 24 | 2.79 mL | Standard Deviation 16.06 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | 7.19 mL | Standard Deviation 27.66 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 20 | 2.97 mL | Standard Deviation 19.82 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | End of treatment | 4.52 mL | Standard Deviation 23.51 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 28 | 5.56 mL | Standard Deviation 23.9 |
| Mirabegron + Imidafenacin | Change From Baseline in Postvoid Residual (PVR) Volume | Week 36 | 2.18 mL | Standard Deviation 19.97 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 28 | 5.07 mL | Standard Deviation 29.92 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 32 | 3.11 mL | Standard Deviation 25.17 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 52 | 2.02 mL | Standard Deviation 24.67 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 36 | 3.12 mL | Standard Deviation 17.85 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | 6.04 mL | Standard Deviation 28.98 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 40 | 5.40 mL | Standard Deviation 35.27 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | 8.39 mL | Standard Deviation 29.58 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 44 | 0.50 mL | Standard Deviation 18.59 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | End of treatment | 5.94 mL | Standard Deviation 35.83 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 48 | 2.33 mL | Standard Deviation 26.9 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 20 | 4.68 mL | Standard Deviation 27.56 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | 8.21 mL | Standard Deviation 28.58 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 24 | 1.46 mL | Standard Deviation 17.97 |
| Mirabegron + Tolterodine | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 8.67 mL | Standard Deviation 49.49 |
Secondary
Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. 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 by taking the sum of all marked episodes in the patient diary where the variable urinary incontinence' was indicated, divided by the number of days on which episodes were recorded. Only participants who had an incontinence episode at baseline was included in the analysis.
Time frame: Baseline and week 4, 8, 12, 16, 28, 40, 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 4 | -1.13 incontinence episodes | Standard Deviation 1.4 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 8 | -1.16 incontinence episodes | Standard Deviation 1.44 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 12 | -1.27 incontinence episodes | Standard Deviation 1.44 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 16 | -1.23 incontinence episodes | Standard Deviation 1.42 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 28 | -1.31 incontinence episodes | Standard Deviation 1.53 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 40 | -1.23 incontinence episodes | Standard Deviation 1.53 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 52 | -1.31 incontinence episodes | Standard Deviation 1.49 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | End of treatment | -1.25 incontinence episodes | Standard Deviation 1.48 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 40 | -1.28 incontinence episodes | Standard Deviation 1.56 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 28 | -1.28 incontinence episodes | Standard Deviation 1.82 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 8 | -1.21 incontinence episodes | Standard Deviation 1.5 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | End of treatment | -1.18 incontinence episodes | Standard Deviation 1.59 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 52 | -1.29 incontinence episodes | Standard Deviation 1.71 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 16 | -1.32 incontinence episodes | Standard Deviation 1.74 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 12 | -1.34 incontinence episodes | Standard Deviation 1.66 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 4 | -1.06 incontinence episodes | Standard Deviation 1.5 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 52 | -1.02 incontinence episodes | Standard Deviation 1.08 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 12 | -0.86 incontinence episodes | Standard Deviation 1.06 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 16 | -0.97 incontinence episodes | Standard Deviation 1.02 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 28 | -0.99 incontinence episodes | Standard Deviation 1.21 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 40 | -0.96 incontinence episodes | Standard Deviation 0.99 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | End of treatment | -1.03 incontinence episodes | Standard Deviation 1.08 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 4 | -0.81 incontinence episodes | Standard Deviation 0.95 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 8 | -0.74 incontinence episodes | Standard Deviation 1.13 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 12 | -1.23 incontinence episodes | Standard Deviation 1.58 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 16 | -1.33 incontinence episodes | Standard Deviation 1.72 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 8 | -1.21 incontinence episodes | Standard Deviation 1.7 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 4 | -1.09 incontinence episodes | Standard Deviation 1.66 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 28 | -1.28 incontinence episodes | Standard Deviation 1.63 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | End of treatment | -1.15 incontinence episodes | Standard Deviation 1.52 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 52 | -1.18 incontinence episodes | Standard Deviation 1.64 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours | Week 40 | -1.07 incontinence episodes | Standard Deviation 1.52 |
Secondary
Change From Baseline in the Mean Number of Micturitions Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean number of micturitions per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable urinated was indicated, divided by the number of days on which episodes were recorded.
Time frame: Baseline and week 4, 8, 12, 16, 28, 40, 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 4 | -1.57 micturitions | Standard Deviation 1.52 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 8 | -1.85 micturitions | Standard Deviation 1.69 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 12 | -2.04 micturitions | Standard Deviation 1.74 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 16 | -2.33 micturitions | Standard Deviation 1.74 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 28 | -2.29 micturitions | Standard Deviation 2.05 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 40 | -2.12 micturitions | Standard Deviation 2.01 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 52 | -2.29 micturitions | Standard Deviation 2.01 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | End of treatment | -2.18 micturitions | Standard Deviation 1.96 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 40 | -1.97 micturitions | Standard Deviation 2.17 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 28 | -2.10 micturitions | Standard Deviation 2.16 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 8 | -1.89 micturitions | Standard Deviation 1.87 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | End of treatment | -1.89 micturitions | Standard Deviation 2.08 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 52 | -2.08 micturitions | Standard Deviation 2.11 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 16 | -2.21 micturitions | Standard Deviation 2.03 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 12 | -1.90 micturitions | Standard Deviation 1.96 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 4 | -1.44 micturitions | Standard Deviation 1.7 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 52 | -1.82 micturitions | Standard Deviation 2.16 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 12 | -1.74 micturitions | Standard Deviation 1.9 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 16 | -1.86 micturitions | Standard Deviation 2 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 28 | -1.97 micturitions | Standard Deviation 2.39 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 40 | -1.80 micturitions | Standard Deviation 2.14 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | End of treatment | -1.75 micturitions | Standard Deviation 2.09 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 4 | -1.23 micturitions | Standard Deviation 1.8 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 8 | -1.62 micturitions | Standard Deviation 1.95 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 12 | -2.18 micturitions | Standard Deviation 2.1 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 16 | -2.20 micturitions | Standard Deviation 2.07 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 8 | -1.72 micturitions | Standard Deviation 1.87 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 4 | -1.51 micturitions | Standard Deviation 1.84 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 28 | 2.33 micturitions | Standard Deviation 2.09 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | End of treatment | -1.91 micturitions | Standard Deviation 2.22 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 52 | -1.80 micturitions | Standard Deviation 2.1 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Micturitions Per 24 Hours | Week 40 | -1.92 micturitions | Standard Deviation 1.9 |
Secondary
Change From Baseline in the Mean Number of Nocturia Episodes Per Night
Participants completed the patient diary (paper document) for 3 days immediately before each visit. A nocturia episode was defined as waking at night 1 or more times to void. Night time was defined as the period between bedtime and the wake-up time the following day (micturitions at the same time as the wake-up time were excluded). The mean number of nocturia episodes per night was calculated by taking the sum of nocturia episodes in the patient diary where the variable urinated was indicated during the night time, divided by the number of nights. Only participants who had a nocturia episode at baseline was included in the analysis.
Time frame: Baseline and week 4, 8, 12, 16, 28, 40, 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 4 | -0.33 nocturia episodes | Standard Deviation 0.83 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 8 | -0.42 nocturia episodes | Standard Deviation 0.82 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 12 | -0.45 nocturia episodes | Standard Deviation 0.96 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 16 | -0.49 nocturia episodes | Standard Deviation 0.86 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 28 | -0.42 nocturia episodes | Standard Deviation 1 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 40 | -0.53 nocturia episodes | Standard Deviation 0.93 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 52 | -0.55 nocturia episodes | Standard Deviation 0.91 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | End of treatment | -0.47 nocturia episodes | Standard Deviation 0.91 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 40 | -0.45 nocturia episodes | Standard Deviation 0.83 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 28 | -0.39 nocturia episodes | Standard Deviation 0.93 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 8 | -0.37 nocturia episodes | Standard Deviation 0.8 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | End of treatment | -0.38 nocturia episodes | Standard Deviation 0.88 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 52 | -0.44 nocturia episodes | Standard Deviation 0.86 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 16 | -0.37 nocturia episodes | Standard Deviation 0.92 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 12 | -0.28 nocturia episodes | Standard Deviation 0.93 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 4 | -0.29 nocturia episodes | Standard Deviation 0.73 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 52 | -0.53 nocturia episodes | Standard Deviation 0.95 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 12 | -0.45 nocturia episodes | Standard Deviation 0.99 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 16 | -0.54 nocturia episodes | Standard Deviation 0.99 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 28 | -0.48 nocturia episodes | Standard Deviation 0.97 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 40 | -0.39 nocturia episodes | Standard Deviation 0.94 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | End of treatment | -0.48 nocturia episodes | Standard Deviation 0.93 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 4 | -0.32 nocturia episodes | Standard Deviation 1 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 8 | -0.42 nocturia episodes | Standard Deviation 0.92 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 12 | -0.47 nocturia episodes | Standard Deviation 0.81 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 16 | -0.50 nocturia episodes | Standard Deviation 0.94 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 8 | -0.44 nocturia episodes | Standard Deviation 0.85 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 4 | -0.49 nocturia episodes | Standard Deviation 0.83 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 28 | -0.54 nocturia episodes | Standard Deviation 0.81 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | End of treatment | -0.48 nocturia episodes | Standard Deviation 0.88 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 52 | -0.50 nocturia episodes | Standard Deviation 0.94 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Nocturia Episodes Per Night | Week 40 | -0.54 nocturia episodes | Standard Deviation 0.82 |
Secondary
Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urge incontinence episode was defined as any episode when both urgency and incontinence occurred concurrently. The mean number of incontinence episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable urgency and urinary incontinence' were indicated, divided by the number of days on which episodes were recorded. Only participants who had an urge incontinence episode at baseline was included in the analysis.
Time frame: Baseline and week 4, 8, 12, 16, 28, 40, 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 28 | -1.26 urge incontinence episodes | Standard Deviation 1.34 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 40 | -1.19 urge incontinence episodes | Standard Deviation 1.36 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -1.13 urge incontinence episodes | Standard Deviation 1.24 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | End of treatment | -1.20 urge incontinence episodes | Standard Deviation 1.32 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -1.20 urge incontinence episodes | Standard Deviation 1.27 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 52 | -1.23 urge incontinence episodes | Standard Deviation 1.32 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -1.15 urge incontinence episodes | Standard Deviation 1.31 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -1.17 urge incontinence episodes | Standard Deviation 1.24 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -1.25 urge incontinence episodes | Standard Deviation 1.39 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | End of treatment | -1.12 urge incontinence episodes | Standard Deviation 1.33 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -1.00 urge incontinence episodes | Standard Deviation 1.32 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 28 | -1.10 urge incontinence episodes | Standard Deviation 1.49 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -1.22 urge incontinence episodes | Standard Deviation 1.47 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 40 | -1.14 urge incontinence episodes | Standard Deviation 1.28 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -1.14 urge incontinence episodes | Standard Deviation 1.23 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 52 | -1.14 urge incontinence episodes | Standard Deviation 1.37 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -0.72 urge incontinence episodes | Standard Deviation 0.64 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -0.71 urge incontinence episodes | Standard Deviation 0.96 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 28 | -0.85 urge incontinence episodes | Standard Deviation 1.15 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -0.79 urge incontinence episodes | Standard Deviation 0.88 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 40 | -0.91 urge incontinence episodes | Standard Deviation 0.96 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -0.87 urge incontinence episodes | Standard Deviation 0.86 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 52 | -0.93 urge incontinence episodes | Standard Deviation 0.97 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | End of treatment | -0.91 urge incontinence episodes | Standard Deviation 0.93 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 52 | -1.15 urge incontinence episodes | Standard Deviation 1.68 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -1.22 urge incontinence episodes | Standard Deviation 1.64 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 28 | -1.18 urge incontinence episodes | Standard Deviation 1.63 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 40 | -1.07 urge incontinence episodes | Standard Deviation 1.65 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -1.13 urge incontinence episodes | Standard Deviation 1.6 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | End of treatment | -1.05 urge incontinence episodes | Standard Deviation 1.59 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -0.96 urge incontinence episodes | Standard Deviation 1.63 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -1.05 urge incontinence episodes | Standard Deviation 1.64 |
Secondary
Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urgency episode was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable urgency was indicated, divided by the number of days on which episodes were recorded. Only participants who had an urgency episode at baseline was included in the analysis.
Time frame: Baseline and week 4, 8, 12, 16, 28, 40, 52
Population: FAS participants with available data at each time point are included in the analysis.A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 4 | -1.53 urgency episodes | Standard Deviation 1.99 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 8 | -1.78 urgency episodes | Standard Deviation 2.13 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 12 | -2.06 urgency episodes | Standard Deviation 2.2 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 16 | -2.30 urgency episodes | Standard Deviation 2.22 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 28 | -2.28 urgency episodes | Standard Deviation 2.25 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 40 | -2.14 urgency episodes | Standard Deviation 2.33 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 52 | -2.04 urgency episodes | Standard Deviation 2.69 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | End of treatment | -2.03 urgency episodes | Standard Deviation 2.55 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 40 | -2.27 urgency episodes | Standard Deviation 2.64 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 28 | -2.26 urgency episodes | Standard Deviation 2.76 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 8 | -1.90 urgency episodes | Standard Deviation 2.2 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | End of treatment | -2.24 urgency episodes | Standard Deviation 2.41 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 52 | -2.33 urgency episodes | Standard Deviation 2.54 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 16 | -2.36 urgency episodes | Standard Deviation 2.56 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 12 | -2.18 urgency episodes | Standard Deviation 2.39 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 4 | -1.63 urgency episodes | Standard Deviation 2.2 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 52 | -2.15 urgency episodes | Standard Deviation 2.28 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 12 | -1.88 urgency episodes | Standard Deviation 1.78 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 16 | -2.01 urgency episodes | Standard Deviation 1.89 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 28 | -2.18 urgency episodes | Standard Deviation 2.1 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 40 | -2.14 urgency episodes | Standard Deviation 2.17 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | End of treatment | -2.04 urgency episodes | Standard Deviation 2.19 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 4 | -1.23 urgency episodes | Standard Deviation 1.62 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 8 | -1.50 urgency episodes | Standard Deviation 1.65 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 12 | -2.10 urgency episodes | Standard Deviation 2.23 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 16 | -2.26 urgency episodes | Standard Deviation 2.3 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 8 | -1.89 urgency episodes | Standard Deviation 2.24 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 4 | -1.49 urgency episodes | Standard Deviation 2.16 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 28 | -2.28 urgency episodes | Standard Deviation 2.39 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | End of treatment | -2.07 urgency episodes | Standard Deviation 2.23 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 52 | -2.26 urgency episodes | Standard Deviation 2.31 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours | Week 40 | -2.19 urgency episodes | Standard Deviation 2.42 |
Secondary
Change From Baseline in the Mean Volume Voided Per Micturition
Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean volume per micturition was calculated by taking the sum of the urinary volumes where the volume voided was \> 0 and where urinary incontinence was not indicated in the patient diary, divided by the number of micturitions where the volume voided was \> 0 and where urinary incontinence was not indicated. Only participants who had volume voided was \> 0 at baseline was included in the analysis.
Time frame: Baseline and week 4, 8, 12, 16, 28, 40, 52
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 4 | 30.677 mL | Standard Deviation 37.45 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 8 | 38.328 mL | Standard Deviation 41.753 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 12 | 39.452 mL | Standard Deviation 43.802 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 16 | 39.952 mL | Standard Deviation 46.871 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 28 | 36.025 mL | Standard Deviation 50.761 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 40 | 43.578 mL | Standard Deviation 51.692 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 52 | 41.744 mL | Standard Deviation 47.045 |
| Mirabegron + Solifenacin | Change From Baseline in the Mean Volume Voided Per Micturition | End of treatment | 40.004 mL | Standard Deviation 45.095 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 40 | 43.102 mL | Standard Deviation 52.13 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 28 | 41.887 mL | Standard Deviation 48.797 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 8 | 38.614 mL | Standard Deviation 43.03 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | End of treatment | 38.691 mL | Standard Deviation 46.429 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 52 | 40.599 mL | Standard Deviation 45.607 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 16 | 40.661 mL | Standard Deviation 48.257 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 12 | 41.433 mL | Standard Deviation 45.91 |
| Mirabegron + Propiverine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 4 | 30.111 mL | Standard Deviation 39.034 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 52 | 36.653 mL | Standard Deviation 46.041 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 12 | 27.072 mL | Standard Deviation 41.636 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 16 | 24.489 mL | Standard Deviation 41.184 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 28 | 29.873 mL | Standard Deviation 48.976 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 40 | 29.826 mL | Standard Deviation 44.442 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | End of treatment | 32.854 mL | Standard Deviation 44.481 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 4 | 20.062 mL | Standard Deviation 30.816 |
| Mirabegron + Imidafenacin | Change From Baseline in the Mean Volume Voided Per Micturition | Week 8 | 23.820 mL | Standard Deviation 35.972 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 12 | 36.598 mL | Standard Deviation 46.23 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 16 | 37.786 mL | Standard Deviation 44.837 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 8 | 35.351 mL | Standard Deviation 35.449 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 4 | 32.854 mL | Standard Deviation 41.598 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 28 | 34.823 mL | Standard Deviation 42.451 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | End of treatment | 40.683 mL | Standard Deviation 46.566 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 52 | 40.548 mL | Standard Deviation 48.033 |
| Mirabegron + Tolterodine | Change From Baseline in the Mean Volume Voided Per Micturition | Week 40 | 41.378 mL | Standard Deviation 43.053 |
Secondary
Number for Participants Who Achieved Normalization of the Mean Number of Incontinence Episodes Per 24 Hours
Normalization for the mean number of incontinence episodes per 24 hours was defined as no incontinence episode per 24 hours.
Time frame: Week 52 (end of treatment)
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirabegron + Solifenacin | Number for Participants Who Achieved Normalization of the Mean Number of Incontinence Episodes Per 24 Hours | 61 Participants |
| Mirabegron + Propiverine | Number for Participants Who Achieved Normalization of the Mean Number of Incontinence Episodes Per 24 Hours | 61 Participants |
| Mirabegron + Imidafenacin | Number for Participants Who Achieved Normalization of the Mean Number of Incontinence Episodes Per 24 Hours | 69 Participants |
| Mirabegron + Tolterodine | Number for Participants Who Achieved Normalization of the Mean Number of Incontinence Episodes Per 24 Hours | 71 Participants |
Secondary
Number for Participants Who Achieved Normalization of the Mean Number of Micturitions Per 24 Hours
Normalization for the mean number of micturitions per 24 hours was defined as \< 8 micturitions per 24 hours.
Time frame: Week 52 (end of treatment)
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirabegron + Solifenacin | Number for Participants Who Achieved Normalization of the Mean Number of Micturitions Per 24 Hours | 60 Participants |
| Mirabegron + Propiverine | Number for Participants Who Achieved Normalization of the Mean Number of Micturitions Per 24 Hours | 47 Participants |
| Mirabegron + Imidafenacin | Number for Participants Who Achieved Normalization of the Mean Number of Micturitions Per 24 Hours | 47 Participants |
| Mirabegron + Tolterodine | Number for Participants Who Achieved Normalization of the Mean Number of Micturitions Per 24 Hours | 51 Participants |
Secondary
Number for Participants Who Achieved Normalization of the Mean Number of Urgency Episodes Per 24 Hours
Normalization for the mean number of urgency episodes per 24 hours was defined as no urgency episode per 24 hours.
Time frame: Week 52 (end of treatment)
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirabegron + Solifenacin | Number for Participants Who Achieved Normalization of the Mean Number of Urgency Episodes Per 24 Hours | 70 Participants |
| Mirabegron + Propiverine | Number for Participants Who Achieved Normalization of the Mean Number of Urgency Episodes Per 24 Hours | 77 Participants |
| Mirabegron + Imidafenacin | Number for Participants Who Achieved Normalization of the Mean Number of Urgency Episodes Per 24 Hours | 64 Participants |
| Mirabegron + Tolterodine | Number for Participants Who Achieved Normalization of the Mean Number of Urgency Episodes Per 24 Hours | 76 Participants |
Secondary
Number of Participants Who Achieved Normalization for OABSS Total Score
Normalization for OABSS Total Score was defined as OABSS total score ≤ 2 or OABSS Question 3 score ≤ 1.
Time frame: Week 52 (end of treatment)
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirabegron + Solifenacin | Number of Participants Who Achieved Normalization for OABSS Total Score | 98 Participants |
| Mirabegron + Propiverine | Number of Participants Who Achieved Normalization for OABSS Total Score | 101 Participants |
| Mirabegron + Imidafenacin | Number of Participants Who Achieved Normalization for OABSS Total Score | 91 Participants |
| Mirabegron + Tolterodine | Number of Participants Who Achieved Normalization for OABSS Total Score | 96 Participants |
Secondary
Number of Participants Who Achieved Normalization of the Mean Number of Nocturia Episodes Per 24 Hours
Normalization for the mean number of nocturia episodes per 24 hours was defined as no nocturia episode per 24 hours.
Time frame: Week 52 (end of treatment)
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of treatment) was performed to ensure all participants with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of treatment analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirabegron + Solifenacin | Number of Participants Who Achieved Normalization of the Mean Number of Nocturia Episodes Per 24 Hours | 26 Participants |
| Mirabegron + Propiverine | Number of Participants Who Achieved Normalization of the Mean Number of Nocturia Episodes Per 24 Hours | 21 Participants |
| Mirabegron + Imidafenacin | Number of Participants Who Achieved Normalization of the Mean Number of Nocturia Episodes Per 24 Hours | 21 Participants |
| Mirabegron + Tolterodine | Number of Participants Who Achieved Normalization of the Mean Number of Nocturia Episodes Per 24 Hours | 14 Participants |