A Study to Evaluate the Efficacy and Safety of Mirabegron Compared to Solifenacin in Patients With Overactive Bladder Who Were Previously Treated With Another Medicine But Were Not Satisfied With That Treatment.

Study Overview
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Brief Summary
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The purpose of the study was to assess the efficacy, safety and tolerability of mirabegron 50 mg versus (vs) solifenacin 5 mg in the treatment of patients with OAB who were dissatisfied with their treatment due to lack of efficacy.

Official Title
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A Double-Blind, Randomized, Parallel Group, Multi-Centre Study to Evaluate the Efficacy and Safety of Mirabegron Compared to Solifenacin in Subjects With Overactive Bladder (OAB) Treated With Antimuscarinics and Dissatisfied Due to Lack of Efficacy

Conditions
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Urologic Diseases, Urinary Bladder, Overactive, Urinary Bladder Diseases

Intervention / Treatment
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* Drug: Mirabegron
* Drug: Solifenacin succinate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is willing and able to complete the micturition diary and questionnaires correctly Subject has symptoms of OAB (urinary frequency and urgency with or without urgency incontinence) for at least 3 months Subject is currently or has previously received at least one antimuscarinic agent intended to treat their OAB. The last antimuscarinic must have been taken for at least 4 weeks and taken within 6 months prior to the Screening Visit Exclusion Criteria: Female subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential is sexually active and not practicing a highly reliable method of birth control Subject has neurogenic bladder Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator (for female subjects confirmed by a cough provocation test) Subject has an indwelling catheter or practices intermittent self-catheterization Subject has diabetic neuropathy Subject has evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis, toxic megacolon, myasthenia gravis or any other medical condition which makes the use of anticholinergics contraindicated The subject is currently receiving or has a history of treatment with intravesical botulinum toxin (cosmetic use is acceptable) or resiniferatoxin within 9 months prior to screening Subject receives non-drug treatment including electro-stimulation therapy (with the exception of a bladder training program or pelvic floor exercises which started more than 30 days prior to screening) Subject has moderate to severe hepatic impairment Subject has severe renal impairment or end stage renal disease Subject has severe uncontrolled hypertension Subject has a clinically significant abnormal electrocardiogram (ECG) or has a known history of QT prolongation or currently taking medication known to prolong the QT interval Subject has a known or suspected hypersensitivity to solifenacin, mirabegron or any of the inactive ingredients Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening Subject has been treated with an experimental device within 30 days or received an experimental agent within the longer of 30 days or five half-lives Subject is using prohibited medications which cannot be stopped safely at the Screening Visit. Subject is excluded if using restricted medications not meeting protocol-specified criteria Subject's last antimuscarinic treatment was solifenacin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mirabegron 50 mg<br>Participants who received mirabegron 50 mg once daily for 12 weeks. | Drug: Mirabegron<br>* oral tablet<br>* Other names: Betmiga;|
| Active Comparator: Solifenacin 5 mg<br>Participants who received solifenacin 5 mg once daily for 12 weeks. | Drug: Solifenacin succinate<br>* oral tablet<br>* Other names: Vesitrim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Final Visit in the Mean Number of Micturitions Per 24 Hours | A micturition is any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period. | Baseline and final visit (up to Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting at Least One Treatment-emergent Adverse Event of Dry Mouth, Constipation or Blurred Vision During Double-blind Treatment Period | A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE; defined as any untoward medical occurrence in a patient administered a study drug) that started or worsened in the period from the first double-blind medication intake until 30 days after the last double-blind medication intake. The following TEAEs were selected for inclusion in the analysis: Dry mouth (aptyalism, dry mouth, dry throat), constipation (constipation), blurred vision (vision blurred, myopia, refraction disorder, accommodation disorder). | From first dose of study drug up to 30 days after last dose of study drug (up to 16 weeks) | 
| Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Micturitions Per 24 Hours |  | Baseline and Week 4, Week 8, Week 12 | 
| Number of Incontinence Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit | An incontinence episode is any involuntary leakage of urine. The total number of incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit. | Week 4, Week 8, Week 12 | 
| Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | An incontinence episode is any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period. | Baseline and Week 4, Week 8, Week 12 | 
| Number of Urgency Incontinence Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit | An urgency incontinence episode is any involuntary leakage of urine accompanied by or immediately proceeded by urgency. The total number of urgency incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit. | Week 4, Week 8, Week 12 | 
| Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours | An urgency incontinence episode is any involuntary leakage of urine accompanied by or immediately proceeded by urgency. The mean number of urgency incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period. | Baseline and Week 4, Week 8, Week 12 | 
| Change From Baseline to 4, 8 and 12 Weeks of Treatment and at the Final Visit in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours | An urgency episode is a sudden compelling desire to pass urine immediately followed by an incontinent event or the patient having to rush to the toilet and make it in time; severity recorded as 3 (severe urgency) or 4 (urgency incontinence) on the Patient Perception of the Intensity of Urgency Scale (PPIUS) validated scale. The mean number of urgency episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period. | Baseline and Week 4, Week 8, Week 12 | 
| Change From Baseline to 4, 8 and 12 Weeks of Treatment and at the Final Visit in Mean Level of Urgency | Urgency level was rated by the participant during the 3-day micturition diary period using the PPIUS 5-point categorical scale: 0. No urgency; 1. Mild urgency; 2. Moderate urgency; 3. Severe urgency; 4. Urgency incontinence. | Baseline and Week 4, Week 8, Week 12 | 
| Number of Pads Used at 4, 8 and 12 Weeks of Treatment and at the Final Visit | The total number of pads per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit. | Week 4, Week 8, Week 12 | 
| Change From Baseline in Mean Number of Pads Used Per 24 Hours After 4, 8 and 12 Weeks of Treatment | The mean number of pads per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period. | Baseline and Week 4, Week 8 , Week 12 | 
| Number of Nocturia Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit | A nocturia episode is defined as waking at night ≥1 times to void (i.e., any voiding associated with sleep disturbance between the time the patient goes to bed with the intention to sleep until the time the patient gets up in the morning with the intention to stay awake). The total number of nocturia episodes were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit. | Week 4, Week 8, Week 12 | 
| Change From Baseline in Mean Number of Nocturia Episodes Per 24 Hours After 4, 8 and 12 Weeks of Treatment | A nocturia episode is defined as waking at night ≥1 times to void (i.e., any voiding associated with sleep disturbance between the time the patient goes to bed with the intention to sleep until the time the patient gets up in the morning with the intention to stay awake). The mean number of nocturia episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period. | Baseline and Week 4, Week 8, Week 12 | 
| Percentage of Participants With Normalization of Micturitions at Weeks 4, 8, 12 and Final Visit | A responder is defined as a participant who has ≥8 micturitions at baseline and has <8 micturitions per 24 hours during the treatment period at each specified visit, where change from baseline is <0. | Week 4, Week 8, Week 12 | 
| Percentage of Participants With 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and Final Visit | A responder is defined as a participant with at least 50% decrease from baseline in mean number of incontinence episodes per 24 hours during the treatment period at specified visit. | Week 4, Week 8, Week 12 | 
| Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and Final Visit | A responder is defined as a participant who reported incontinence episodes at baseline and reported no incontinence episodes during the treatment period at specified visit. | Week 4, Week 8, Week 12 | 
| Change From Baseline to Week 4 in Mobility Scores as Assessed by the European Quality of Life 5-Dimensions (EQ-5D-5L) Questionnaire | The European Quality of Life 5-Dimensions Questionnaire (EQ-5D-5L) is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 4 | 
| Change From Baseline to Week 4 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 4 | 
| Change From Baseline to Week 4 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 4 | 
| Change From Baseline to Week 4 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 4 | 
| Change From Baseline to Week 4 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 4 | 
| Change From Baseline to Week 8 in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 8 | 
| Change From Baseline to Week 8 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 8 | 
| Change From Baseline to Week 8 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 8 | 
| Change From Baseline to Week 8 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 8 | 
| Change From Baseline to Week 8 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 8 | 
| Change From Baseline to Week 12 in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and Week 12 | 
| Change From Baseline to Final Visit in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and final visit (up to Week 12) | 
| Change From Baseline to Final Visit in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and final visit (up to Week 12) | 
| Change From Baseline to Final Visit in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and final visit (up to Week 12) | 
| Change From Baseline to Final Visit in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and final visit (up to Week 12) | 
| Change From Baseline to Final Visit in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire | The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform [extreme problems]). | Baseline and final visit (up to Week 12) | 
| Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Symptom Bother Score as Assessed by the Overactive Bladder Questionnaire (OAB-q) | The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, scored from 1 to 6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicates an improvement. | Baseline and Week 4, Week 8, Week 12 | 
| Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Total Health-Related Quality of Life (HRQoL) Score as Assessed by the OAB-q | The OAB-q is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: coping, concern, sleep, social interaction). The total score is calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement. | Baseline and Week 4, Week 8, Week 12 | 
| Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Patient Perception of Bladder Condition (PPBC) | The Patient Perception of Bladder Condition (PPBC) questionnaire is a single-item questionnare used to assess participants' perceptions and impressions of their bladder condition. Participants assessed their bladder condition using a 6-point categorical scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. | Baseline and Week 4, Week 8, Week 12 | 
| Change From Baseline to Week 12 and the Final Visit in the Patient's Assessment of Treatment Satisfaction (TS)-Visual Analog Scale (VAS) | The Treatment Satisfaction (TS)-Visual Analogue Scale (VAS) was a self-rated scale with the participant answering the question Are you satisfied with your treatment? and placing a vertical mark on a line from 0 (No, not at all) to 10 (Yes, completely). | Baseline and Week 12 | 
| Change From Baseline to Week 12 and the Final Visit in the Patient's Assessment of Treatment Satisfaction Questionnaire-Likert Scale | The Treatment Satisfaction (TS)-Likert Scale was a self-rated scale with the participant answering the question How satisfied were you with your treatment? with on a scale from 1 (extremely dissatisfied) to 7 (extremely satisfied). | Baseline and Week 12 | 
| Percentage of Participants With Improvement in Symptom Bother Score as Assessed by the OAB-q: ≥ 10 Points Improvement in OAB-q at Week 12 and Final Visit | A responder is defined as a participant with ≥10 points improvement in symptom bother from baseline. | Baseline to Week 12 | 
| Percentage of Participants With Improvement in HRQoL Scales as Assessed by the OAB-q: ≥10 Points Improvement in OAB-q at Week 12 and Final Visit | A responder is defined as a participant with >=10 points improvement in the total HRQL score from baseline. | Baseline to Week 12 | 
| Percentage of Participants With Improvement of Treatment Satisfaction Questionnaire - Likert Scale: ≥1, ≥2, ≥3, ≥4, ≥5, and 6-point Improvement From Baseline to Week 12 | A responder is defined as a participant with ≥1, ≥2, ≥3, ≥4, ≥5 or 6-point improvement from baseline in TS-Likert scale. | Baseline to Week 12 | 
| Percentage of Participants With Improvement in Treatment Satisfaction Questionnaire - Likert Scale: ≥1, ≥2, ≥3, ≥4, ≥5, and 6-point Improvement From Baseline to Final Visit | A responder is defined as a participant with >=1 or >=2 or >=3 or >=4 or >=5 or 6-point improvement from baseline in TS-Likert scale. | Baseline to final visit (up to Week 12) | 
| Percentage of Participants With Improvement in PPBC: ≥1 Point Improvement at Week 12 and Final Visit | A responder is defined as a participant with ≥1 point improvement in PPBC from baseline. | Baseline to Week 12 | 
| Percentage of Participants With Major Improvement in PPBC: ≥2 Point Improvement at Week 12 and Final Visit | A responder is defined as a participant with ≥2 point improvement in PPBC from baseline. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vesitrim, Frequency, Urgency, Urgency incontinence, Urinary incontinence, Overactive Bladder (OAB), Micturition, Mirabegron, YM178, Vesicare, Solifenacin