Overactive Bladder
Conditions
Keywords
mirabegron, solifenacin
Brief summary
The purpose of this study was to evaluate the safety and efficacy of mirabegron as add-on therapy in patients with OAB treated with solifenacin.
Detailed description
The total duration of the study was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting the eligibility criteria for provisional enrollment received the study drug for the screening period (solifenacin) at the same dose as that before the start of the study (2.5 or 5 mg), once daily after breakfast orally for 2 weeks. After the screening period, patients meeting the eligibility criteria for formal enrollment received the study drugs for the treatment period (solifenacin 2.5 or 5 mg and mirabegron 25 mg), once daily after breakfast orally for 16 weeks. Mirabegron dose could be increased to 50 mg at week 8 visit if the patients met all of the following criteria: (1) had an inadequate response to mirabegron at the dose of 25 mg; (2) was judged by the investigator or coinvestigator to have no safety concerns; and (3) agreed to increase the dose.
Interventions
DRUGmirabegron
oral
DRUGsolifenacin
oral
Sponsors
Astellas Pharma Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female: postmenopausal OAB outpatient * Male: OAB outpatient who did not wish to have children at all * Patient had been treated with solifenacin at a stable dose once daily for at least 4 weeks prior to the study * Patient had a total OAB symptom score (OABSS ) score of ≥3 points and a Question 3 score ≥2 points
Exclusion criteria
* Patient had a residual urine volume of ≥100 mL or a maximum flow rate \<5 mL/s, or patients with benign prostatic hyperplasia, or lower urinary tract obstruction * 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 malignant tumor (except for malignant tumor that has not been treated for at least 5 y before the start of the screening period with no risk of recurrence) * Patient had received surgical therapy that may affect the urinary tract function within 24 weeks before the start of the screening period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug up to weeks 16 | 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 8 and 16 | 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) Severity Score | Baseline and week 8, 16 | The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the Health-related Quality of Life (HRQL). The Severity Symptom 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 8, 16 | 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 Number of Micturitions Per 24 Hours | Baseline and week 4, 8, 12, 16 | 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 Number of Micturitions Per 24 Hours | Week 16 | Normalization for the mean number of micturitions per 24 hours was defined as \< 8 micturitions per 24 hours. |
| Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Baseline and week 4, 8, 12, 16 | 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. |
| Change From Baseline in OABSS Total Score | Baseline and week 8, 16 | 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. |
| Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Baseline and week 4, 8, 12, 16 | 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. |
| Number for Participants Who Achieved Normalization of the Number of Incontinence Episodes Per 24 Hours | Week 16 | 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 Number of Urge Incontinence Episodes Per 24 Hours | Baseline and week 4, 8, 12, 16 | 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 Volume Voided Per Micturition | Baseline and week 8, 16 | 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 Number of Nocturia Episodes Per Night | Baseline and week 4, 8, 12, 16 | 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. |
| Change From Baseline in Postvoid Residual (PVR) Volume | Baseline and week 4, 8, 12, 16 | 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. |
| Number for Participants Who Achieved Normalization of the Number of Urgency Episodes Per 24 Hours | Week 16 | Normalization for the mean number of urgency episodes per 24 hours was defined as no urgency episode per 24 hours. |
Countries
Japan
Participant flow
Recruitment details
Participants with overactive bladder (OAB) were enrolled in 29 sites in Japan.
Participants by arm
| Arm | Count |
|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg Participants received solifenacin 2.5 mg and mirabegron 25 mg once daily after breakfast orally for 16 weeks. | 35 |
| Solifenacin 2.5 mg + Mirabegron 50 mg Participants received solifenacin 2.5 mg and mirabegron 25 mg once daily after breakfast orally for 8 weeks. In the next 8 weeks, participants continued to receive solifenacin 2.5 mg, but received an increased dose of mirabegron 50 mg. | 37 |
| Solifenacin 5 mg + Mirabegron 25 mg Participants received solifenacin 5 mg and mirabegron 25 mg once daily after breakfast orally for 16 weeks. | 58 |
| Solifenacin 5 mg + Mirabegron 50 mg Participants received solifenacin 5 mg and mirabegron 25 mg once daily after breakfast orally for 8 weeks. In the next 8 weeks, participants continued to receive solifenacin 5 mg, but received an increased dose of mirabegron 50 mg. | 93 |
| Total | 223 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 | 0 |
| Overall Study | Need Further Examinations Due to Biopsy | 0 | 0 | 1 | 0 |
| Overall Study | Not Meeting the Eligibility Criteria | 1 | 0 | 3 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 3 | 1 |
| Overall Study | Show no Stable Solifenacin Intake | 0 | 0 | 1 | 0 |
| Overall Study | Untenable Due to Recurrent Cystitis | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Solifenacin 2.5 mg + Mirabegron 25 mg | Solifenacin 2.5 mg + Mirabegron 50 mg | Solifenacin 5 mg + Mirabegron 25 mg | Solifenacin 5 mg + Mirabegron 50 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65.6 Years STANDARD_DEVIATION 8.71 | 62.8 Years STANDARD_DEVIATION 10.27 | 66.9 Years STANDARD_DEVIATION 9.47 | 63.8 Years STANDARD_DEVIATION 10.34 | 64.7 Years STANDARD_DEVIATION 9.92 |
| Number of Incontinence Episodes per 24 Hours | 1.45 incontinence episodes STANDARD_DEVIATION 1.454 | 1.54 incontinence episodes STANDARD_DEVIATION 1.248 | 2.09 incontinence episodes STANDARD_DEVIATION 2.121 | 1.51 incontinence episodes STANDARD_DEVIATION 1.52 | 1.64 incontinence episodes STANDARD_DEVIATION 1.616 |
| Number of Micturitions per 24 Hours | 10.38 micturitions STANDARD_DEVIATION 2.128 | 11.12 micturitions STANDARD_DEVIATION 2.722 | 9.81 micturitions STANDARD_DEVIATION 1.918 | 10.15 micturitions STANDARD_DEVIATION 2.331 | 10.26 micturitions STANDARD_DEVIATION 2.302 |
| Number of Nocturia Episodes per Night | 1.79 nocturia episodes STANDARD_DEVIATION 1.075 | 1.55 nocturia episodes STANDARD_DEVIATION 0.783 | 1.85 nocturia episodes STANDARD_DEVIATION 1.006 | 1.72 nocturia episodes STANDARD_DEVIATION 1.084 | 1.74 nocturia episodes STANDARD_DEVIATION 1.018 |
| Number of Urge Incontinence Episodes per 24 Hours | 1.42 urge incontinence episodes STANDARD_DEVIATION 1.506 | 1.42 urge incontinence episodes STANDARD_DEVIATION 1.243 | 1.69 urge incontinence episodes STANDARD_DEVIATION 1.366 | 1.30 urge incontinence episodes STANDARD_DEVIATION 1.138 | 1.43 urge incontinence episodes STANDARD_DEVIATION 1.245 |
| Number of Urgency Episodes per 24 Hours | 2.86 urgency episodes STANDARD_DEVIATION 2.433 | 4.12 urgency episodes STANDARD_DEVIATION 2.586 | 2.86 urgency episodes STANDARD_DEVIATION 1.997 | 3.63 urgency episodes STANDARD_DEVIATION 2.846 | 3.42 urgency episodes STANDARD_DEVIATION 2.586 |
| OAB-q SF Score: Total Health-Related Quality of Life (HRQOL) | 73.71 Units on a Scale STANDARD_DEVIATION 18.662 | 70.31 Units on a Scale STANDARD_DEVIATION 18.873 | 75.10 Units on a Scale STANDARD_DEVIATION 17.708 | 76.06 Units on a Scale STANDARD_DEVIATION 19.341 | 74.49 Units on a Scale STANDARD_DEVIATION 18.743 |
| Overactive Bladder questionnaire Short Form (OAB-q SF) Score: Symptom Severity | 33.94 Units on a Scale STANDARD_DEVIATION 20.386 | 39.37 Units on a Scale STANDARD_DEVIATION 20.47 | 32.12 Units on a Scale STANDARD_DEVIATION 17.701 | 31.29 Units on a Scale STANDARD_DEVIATION 19.205 | 33.27 Units on a Scale STANDARD_DEVIATION 19.328 |
| Overactive Bladder Symptom Score (OABSS) | 7.1 Units on a Scale STANDARD_DEVIATION 2.31 | 8.5 Units on a Scale STANDARD_DEVIATION 2.36 | 7.5 Units on a Scale STANDARD_DEVIATION 2.67 | 8.1 Units on a Scale STANDARD_DEVIATION 2.45 | 7.8 Units on a Scale STANDARD_DEVIATION 2.49 |
| Postvoid Residual (PVR) Volume | 14.95 mL STANDARD_DEVIATION 23.214 | 10.51 mL STANDARD_DEVIATION 16.066 | 13.93 mL STANDARD_DEVIATION 17.188 | 12.11 mL STANDARD_DEVIATION 20.199 | 12.76 mL STANDARD_DEVIATION 19.273 |
| Sex: Female, Male Female | 30 Participants | 32 Participants | 45 Participants | 79 Participants | 186 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 13 Participants | 14 Participants | 37 Participants |
| Volume Voided per Micturition | 158.627 mL STANDARD_DEVIATION 47.0511 | 158.633 mL STANDARD_DEVIATION 43.6678 | 182.362 mL STANDARD_DEVIATION 56.3405 | 173.658 mL STANDARD_DEVIATION 47.5973 | 171.029 mL STANDARD_DEVIATION 49.7826 |
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 / 35 | 0 / 37 | 0 / 58 | 0 / 93 |
| other Total, other adverse events | 23 / 35 | 21 / 37 | 39 / 58 | 67 / 93 |
| serious Total, serious adverse events | 1 / 35 | 1 / 37 | 5 / 58 | 4 / 93 |
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 weeks 16
Population: SAF
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 1 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to PD | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related Serious TEAEs | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to permanent discontinuation (PD) | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 1 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 22 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 6 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 23 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 20 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to PD | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 6 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related Serious TEAEs | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to permanent discontinuation (PD) | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 1 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 21 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 0 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 1 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related Serious TEAEs | 1 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to PD | 2 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 1 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 1 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 12 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 5 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to permanent discontinuation (PD) | 3 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 42 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 40 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 4 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs leading to PD | 1 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Deaths | 0 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 28 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Mild | 67 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 69 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Severe | 0 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-related Serious TEAEs | 0 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Moderate | 2 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to permanent discontinuation (PD) | 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 8, 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 8 | 15.14 units on a scale | Standard Deviation 12.786 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 (LOCF) | 17.34 units on a scale | Standard Deviation 13.005 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 | 17.54 units on a scale | Standard Deviation 13.349 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 8 | 9.31 units on a scale | Standard Deviation 15.559 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 (LOCF) | 16.72 units on a scale | Standard Deviation 16.439 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 | 16.72 units on a scale | Standard Deviation 16.439 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 | 14.72 units on a scale | Standard Deviation 16.428 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 8 | 12.43 units on a scale | Standard Deviation 15.449 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 (LOCF) | 13.88 units on a scale | Standard Deviation 16.08 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 8 | 6.14 units on a scale | Standard Deviation 13.797 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 (LOCF) | 12.56 units on a scale | Standard Deviation 17.022 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in OAB-q SF Total HRQL Score | Week 16 | 12.72 units on a scale | Standard Deviation 17.17 |
Secondary
Change From Baseline in 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 8, 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in OABSS Total Score | Week 8 | -3.5 units on a scale | Standard Deviation 2.32 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in OABSS Total Score | Week 16 (LOCF) | -3.4 units on a scale | Standard Deviation 2.95 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in OABSS Total Score | Week 16 | -3.5 units on a scale | Standard Deviation 2.6 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in OABSS Total Score | Week 8 | -2.1 units on a scale | Standard Deviation 2.22 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in OABSS Total Score | Week 16 (LOCF) | -3.9 units on a scale | Standard Deviation 2.7 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in OABSS Total Score | Week 16 | -3.9 units on a scale | Standard Deviation 2.7 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in OABSS Total Score | Week 16 | -3.6 units on a scale | Standard Deviation 2.9 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in OABSS Total Score | Week 8 | -3.5 units on a scale | Standard Deviation 2.52 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in OABSS Total Score | Week 16 (LOCF) | -3.6 units on a scale | Standard Deviation 2.86 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in OABSS Total Score | Week 8 | -2.5 units on a scale | Standard Deviation 2.32 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in OABSS Total Score | Week 16 (LOCF) | -4.0 units on a scale | Standard Deviation 2.9 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in OABSS Total Score | Week 16 | -4.0 units on a scale | Standard Deviation 2.9 |
Secondary
Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score
The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the Health-related Quality of Life (HRQL). The Severity Symptom 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 8, 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 8 | -19.46 units on a scale | Standard Deviation 16.735 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 (LOCF) | -21.21 units on a scale | Standard Deviation 18.631 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 | -21.00 units on a scale | Standard Deviation 19.557 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 8 | -12.52 units on a scale | Standard Deviation 20.926 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 (LOCF) | -22.25 units on a scale | Standard Deviation 20.877 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 | -22.25 units on a scale | Standard Deviation 20.877 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 | -17.68 units on a scale | Standard Deviation 15.93 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 8 | -15.29 units on a scale | Standard Deviation 14.348 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 (LOCF) | -17.55 units on a scale | Standard Deviation 16.253 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 8 | -10.39 units on a scale | Standard Deviation 17.222 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 (LOCF) | -16.31 units on a scale | Standard Deviation 18.034 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score | Week 16 | -16.56 units on a scale | Standard Deviation 18.171 |
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
Population: SAF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 0.63 mL | Standard Deviation 24.102 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | -2.83 mL | Standard Deviation 19.442 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 (LOCF) | -0.42 mL | Standard Deviation 23.576 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | -2.53 mL | Standard Deviation 21.047 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | -4.95 mL | Standard Deviation 18.078 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | 5.29 mL | Standard Deviation 22.163 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 3.96 mL | Standard Deviation 14.897 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 (LOCF) | 3.96 mL | Standard Deviation 14.897 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | 5.07 mL | Standard Deviation 19.512 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | 5.88 mL | Standard Deviation 17.709 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | 6.51 mL | Standard Deviation 22.067 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | 13.78 mL | Standard Deviation 35.702 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | 11.05 mL | Standard Deviation 32.31 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 7.31 mL | Standard Deviation 22.754 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 (LOCF) | 8.00 mL | Standard Deviation 28.833 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 | 3.60 mL | Standard Deviation 24.223 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 8 | 1.87 mL | Standard Deviation 13.428 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 4 | 4.36 mL | Standard Deviation 20.797 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 12 | 1.17 mL | Standard Deviation 17.997 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in Postvoid Residual (PVR) Volume | Week 16 (LOCF) | 3.17 mL | Standard Deviation 24.144 |
Secondary
Change From Baseline in the 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
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 | -1.22 incontinence episodes | Standard Deviation 1.076 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 8 | -1.06 incontinence episodes | Standard Deviation 0.983 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -1.07 incontinence episodes | Standard Deviation 1.064 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 12 | -1.31 incontinence episodes | Standard Deviation 1.236 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 4 | -0.85 incontinence episodes | Standard Deviation 0.675 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 12 | -1.04 incontinence episodes | Standard Deviation 1.177 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 | -1.08 incontinence episodes | Standard Deviation 1.168 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -1.08 incontinence episodes | Standard Deviation 1.168 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 8 | -0.73 incontinence episodes | Standard Deviation 0.842 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 4 | -0.55 incontinence episodes | Standard Deviation 0.787 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 12 | -1.03 incontinence episodes | Standard Deviation 1.238 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 4 | -1.12 incontinence episodes | Standard Deviation 1.141 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 8 | -1.26 incontinence episodes | Standard Deviation 1.453 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 | -1.32 incontinence episodes | Standard Deviation 1.517 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -1.32 incontinence episodes | Standard Deviation 1.505 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 | -1.08 incontinence episodes | Standard Deviation 1.068 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 8 | -0.76 incontinence episodes | Standard Deviation 1.273 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 4 | -0.64 incontinence episodes | Standard Deviation 1.032 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 12 | -0.93 incontinence episodes | Standard Deviation 1.248 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -1.06 incontinence episodes | Standard Deviation 1.055 |
Secondary
Change From Baseline in the 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
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 | -2.06 micturitions | Standard Deviation 1.677 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 8 | -1.69 micturitions | Standard Deviation 1.69 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 (LOCF) | -1.89 micturitions | Standard Deviation 1.789 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 12 | -1.98 micturitions | Standard Deviation 1.667 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 4 | -0.34 micturitions | Standard Deviation 1.576 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 12 | -2.40 micturitions | Standard Deviation 1.997 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 | -2.36 micturitions | Standard Deviation 2.106 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 (LOCF) | -2.36 micturitions | Standard Deviation 2.106 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 8 | -1.31 micturitions | Standard Deviation 1.862 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 4 | -0.98 micturitions | Standard Deviation 1.977 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 12 | -1.50 micturitions | Standard Deviation 1.85 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 4 | -1.33 micturitions | Standard Deviation 1.604 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 8 | -1.74 micturitions | Standard Deviation 1.586 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 | -1.90 micturitions | Standard Deviation 1.92 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 (LOCF) | -1.94 micturitions | Standard Deviation 1.792 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 | -2.13 micturitions | Standard Deviation 2.118 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 8 | -1.32 micturitions | Standard Deviation 1.656 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 4 | -1.02 micturitions | Standard Deviation 1.666 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 12 | -1.75 micturitions | Standard Deviation 2.136 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Micturitions Per 24 Hours | Week 16 (LOCF) | -2.12 micturitions | Standard Deviation 2.094 |
Secondary
Change From Baseline in the 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
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 | -0.38 nocturia episodes | Standard Deviation 0.881 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 8 | -0.38 nocturia episodes | Standard Deviation 0.681 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 (LOCF) | -0.43 nocturia episodes | Standard Deviation 0.847 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 12 | -0.35 nocturia episodes | Standard Deviation 0.704 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 4 | 0.17 nocturia episodes | — |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 12 | -0.48 nocturia episodes | Standard Deviation 0.796 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 | -0.31 nocturia episodes | Standard Deviation 0.674 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 (LOCF) | -0.31 nocturia episodes | Standard Deviation 0.674 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 8 | -0.21 nocturia episodes | Standard Deviation 0.688 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 4 | -0.07 nocturia episodes | Standard Deviation 0.787 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 12 | -0.29 nocturia episodes | Standard Deviation 0.829 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 4 | -0.45 nocturia episodes | Standard Deviation 0.709 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 8 | -0.37 nocturia episodes | Standard Deviation 0.682 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 | -0.44 nocturia episodes | Standard Deviation 0.813 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 (LOCF) | -0.44 nocturia episodes | Standard Deviation 0.812 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 | -0.61 nocturia episodes | Standard Deviation 0.992 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 8 | -0.44 nocturia episodes | Standard Deviation 0.825 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 4 | -0.27 nocturia episodes | Standard Deviation 0.738 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 12 | -0.58 nocturia episodes | Standard Deviation 0.916 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Nocturia Episodes Per Night | Week 16 (LOCF) | -0.60 nocturia episodes | Standard Deviation 0.982 |
Secondary
Change From Baseline in the 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
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -1.07 urge incontinence episodes | Standard Deviation 0.94 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -1.17 urge incontinence episodes | Standard Deviation 1.045 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -0.97 urge incontinence episodes | Standard Deviation 0.948 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -1.30 urge incontinence episodes | Standard Deviation 1.252 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -0.87 urge incontinence episodes | Standard Deviation 0.689 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -0.94 urge incontinence episodes | Standard Deviation 1.115 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -1.00 urge incontinence episodes | Standard Deviation 1.089 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -1.00 urge incontinence episodes | Standard Deviation 1.089 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -0.65 urge incontinence episodes | Standard Deviation 0.793 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -0.50 urge incontinence episodes | Standard Deviation 0.756 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -0.84 urge incontinence episodes | Standard Deviation 0.996 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -0.77 urge incontinence episodes | Standard Deviation 1.22 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -1.07 urge incontinence episodes | Standard Deviation 1.068 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -1.11 urge incontinence episodes | Standard Deviation 1.089 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -1.04 urge incontinence episodes | Standard Deviation 1.412 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 | -0.96 urge incontinence episodes | Standard Deviation 1.04 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 8 | -0.72 urge incontinence episodes | Standard Deviation 1.208 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 4 | -0.82 urge incontinence episodes | Standard Deviation 1.055 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 12 | -0.91 urge incontinence episodes | Standard Deviation 1.16 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours | Week 16 (LOCF) | -0.94 urge incontinence episodes | Standard Deviation 1.027 |
Secondary
Change From Baseline in the 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
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 | -1.77 urgency episodes | Standard Deviation 1.253 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 8 | -1.77 urgency episodes | Standard Deviation 0.969 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 (LOCF) | -1.57 urgency episodes | Standard Deviation 1.382 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 12 | -1.95 urgency episodes | Standard Deviation 1.279 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 4 | -1.15 urgency episodes | Standard Deviation 1.843 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 12 | -2.55 urgency episodes | Standard Deviation 2.162 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 | -2.59 urgency episodes | Standard Deviation 2.201 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 (LOCF) | -2.59 urgency episodes | Standard Deviation 2.201 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 8 | -1.49 urgency episodes | Standard Deviation 1.897 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 4 | -1.26 urgency episodes | Standard Deviation 1.927 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 12 | -1.89 urgency episodes | Standard Deviation 1.674 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 4 | -1.45 urgency episodes | Standard Deviation 1.79 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 8 | -1.76 urgency episodes | Standard Deviation 1.49 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 | -1.93 urgency episodes | Standard Deviation 1.759 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 (LOCF) | -1.93 urgency episodes | Standard Deviation 1.877 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 | -2.06 urgency episodes | Standard Deviation 2.419 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 8 | -1.37 urgency episodes | Standard Deviation 2.189 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 4 | -1.43 urgency episodes | Standard Deviation 2.057 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 12 | -1.88 urgency episodes | Standard Deviation 2.576 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Number of Urgency Episodes Per 24 Hours | Week 16 (LOCF) | -2.02 urgency episodes | Standard Deviation 2.392 |
Secondary
Change From Baseline in the 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 8, 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Volume Voided Per Micturition | Week 8 | 22.120 mL | Standard Deviation 26.222 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Volume Voided Per Micturition | Week 16 (LOCF) | 29.865 mL | Standard Deviation 32.54 |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Change From Baseline in the Volume Voided Per Micturition | Week16 | 28.532 mL | Standard Deviation 32.2243 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Volume Voided Per Micturition | Week 8 | 19.380 mL | Standard Deviation 31.5492 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Volume Voided Per Micturition | Week 16 (LOCF) | 33.031 mL | Standard Deviation 38.2492 |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Change From Baseline in the Volume Voided Per Micturition | Week16 | 33.031 mL | Standard Deviation 38.2492 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Volume Voided Per Micturition | Week16 | 35.780 mL | Standard Deviation 33.8236 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Volume Voided Per Micturition | Week 8 | 33.781 mL | Standard Deviation 32.6029 |
| Solifenacin 5 mg + Mirabegron 25 mg | Change From Baseline in the Volume Voided Per Micturition | Week 16 (LOCF) | 34.118 mL | Standard Deviation 32.679 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Volume Voided Per Micturition | Week 8 | 24.821 mL | Standard Deviation 35.8941 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Volume Voided Per Micturition | Week 16 (LOCF) | 36.957 mL | Standard Deviation 43.6344 |
| Solifenacin 5 mg + Mirabegron 50 mg | Change From Baseline in the Volume Voided Per Micturition | Week16 | 36.921 mL | Standard Deviation 43.8896 |
Secondary
Number for Participants Who Achieved Normalization of the 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 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number for Participants Who Achieved Normalization of the Number of Incontinence Episodes Per 24 Hours | 10 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number for Participants Who Achieved Normalization of the Number of Incontinence Episodes Per 24 Hours | 21 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number for Participants Who Achieved Normalization of the Number of Incontinence Episodes Per 24 Hours | 19 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number for Participants Who Achieved Normalization of the Number of Incontinence Episodes Per 24 Hours | 46 Participants |
Secondary
Number for Participants Who Achieved Normalization of the 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 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number for Participants Who Achieved Normalization of the Number of Micturitions Per 24 Hours | 10 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number for Participants Who Achieved Normalization of the Number of Micturitions Per 24 Hours | 17 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number for Participants Who Achieved Normalization of the Number of Micturitions Per 24 Hours | 23 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number for Participants Who Achieved Normalization of the Number of Micturitions Per 24 Hours | 40 Participants |
Secondary
Number for Participants Who Achieved Normalization of the 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 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number for Participants Who Achieved Normalization of the Number of Urgency Episodes Per 24 Hours | 16 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number for Participants Who Achieved Normalization of the Number of Urgency Episodes Per 24 Hours | 13 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number for Participants Who Achieved Normalization of the Number of Urgency Episodes Per 24 Hours | 31 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number for Participants Who Achieved Normalization of the Number of Urgency Episodes Per 24 Hours | 38 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 8 and 16
Population: FAS participants with available data at each time point are included in the analysis. A last visit analysis (at the end of study) was performed to ensure all patients with postbaseline data were included in the analyses. Last observation carried forward (LOCF) imputation was used for the end of study analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 8 | 19 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 (LOCF) | 19 Participants |
| Solifenacin 2.5 mg + Mirabegron 25 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 | 18 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 8 | 8 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 (LOCF) | 16 Participants |
| Solifenacin 2.5 mg + Mirabegron 50 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 | 16 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 | 27 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 8 | 28 Participants |
| Solifenacin 5 mg + Mirabegron 25 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 (LOCF) | 29 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 8 | 26 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 (LOCF) | 49 Participants |
| Solifenacin 5 mg + Mirabegron 50 mg | Number of Participants Who Achieved Normalization for OABSS Total Score | Week 16 | 48 Participants |