A Study of Mirabegron (YM178) in Men With Lower Urinary Tract Symptoms (LUTS) and Bladder Outlet Obstruction (BOO)

Study Overview
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Brief Summary
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This study examined the safety, tolerability, and efficacy of mirabegron (YM178) compared to placebo.

Official Title
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A Phase 2, Randomized, Double-blind, Parallel Group, Placebo Controlled, Multi-center Study to Evaluate the Urodynamics and Safety of YM178 in Male Subjects With Lower Urinary Tract Symptoms (LUTS) and Bladder Outlet Obstruction (BOO)

Conditions
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Lower Urinary Tract Symptoms, Bladder Outlet Obstruction

Intervention / Treatment
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* Drug: Mirabegron
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men 45 years of age or older Documented bladder outlet obstruction Exclusion Criteria: History of urinary retention Symptomatic and recurrent urinary tract infection (UTI)

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Male

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received matching mirabegron placebo tablets orally once daily for 12 weeks. | Drug: Placebo<br>* oral<br>|
| Experimental: Mirabegron 50 mg<br>Participants received 50 mg mirabegron tablets orally once daily for 12 weeks. | Drug: Mirabegron<br>* oral<br>* Other names: Myrbetriq;|
| Experimental: Mirabegron 100 mg<br>Participants received 100 mg mirabegron tablets orally once daily for 12 weeks. | Drug: Mirabegron<br>* oral<br>* Other names: Myrbetriq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | Maximum urinary flow rate (Qmax) was measured by the Investigator using cystometry and was sent to an independent central reading center for review and interpretation. Least squares means (LSM) were derived from an analysis of covariance (ANCOVA) model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) | Detrusor pressure at maximum urinary flow rate (PdetQmax) was measured by the Investigator using cystometry and was sent to an independent central reading center for review and interpretation. Least squares means (LSM) were derived from an analysis of covariance (ANCOVA) model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Treatment in Bladder Contractile Index (BCI) | The Bladder Contractile Index (BCI) is a value used to measure the degree of contractility. BCI was calculated using the following formula: BCI = pdetQmax + 5Qmax. Strong contractility is a BCI > 150, normal contractility is a BCI of 100-150 and weak contractility is a BCI of < 100. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Week 12 | 
| Change From Baseline to End of Treatment in Bladder Voiding Efficiency (BVE) | Bladder Voiding Efficiency (BVE) is a product of bladder contractility against the urethral resistance and is measured according to the degree of bladder emptying. BVE is expressed as a percentage and is calculated using the formula: Bladder Voiding efficiency = (Voided volume x 100)/maximum cystometric capacity. A higher number indicates a higher voiding efficiency. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Week 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Healthy micturitions (urinations) result in complete emptying of the bladder. Post Void Residual (PVR) is the volume of urine retained after voiding and was assessed using abdominal ultrasound. An increasing PVR over time is an indicator of abnormal bladder function or detrusor decompensation. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug. | From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks). | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | The IPSS is a validated global questionnaire used to assess the degree of bother from benign prostatic hyperplasia symptoms and is based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | The IPSS is a validated global questionnaire used to assess the degree of bother from benign prostatic hyperplasia symptoms based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The voiding score is the sum of the responses to 4 questions relating to urination (incomplete emptying, intermittency, weak stream and straining) and ranges from 0 to 20 (asymptomatic to very symptomatic). Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | The IPSS is a validated global questionnaire used to assess the degree of bother from benign prostatic hyperplasia symptoms based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The storage symptom score is the sum of the responses to 3 questions relating to storage symptoms (frequency, urgency and nocturia) and ranges from 0 to 15 (asymptomatic to very symptomatic). Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | The patient perception of bladder condition (PPBC) asks participants to assess their bladder condition using a 6-point validated Likert scale which ranges from 1 (does not cause me any problems at all) to 6 (causes me many severe problems). Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | A micturition is any voluntary urination, excluding episodes of incontinence only. The mean number of micturitions per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Urgency Episodes With Urgency Severity ≥ 3 Per 24 Hours | For each micturition and/or incontinence episode in the 3 days preceding the clinic visit, participants rated the degree of associated urgency (the sudden compelling desire to pass urine, which is difficult to defer) according to the following scale: 0: No Urgency, felt no need to empty my bladder but did so for another reason; 1: Mild Urgency, could postpone passing water for as long as necessary; 2: Moderate Urgency, could postpone passing water for a short while; 3: Severe Urgency, could not postpone passing water; 4: Urge Incontinence, leaked before reaching the toilet. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | The mean number of incontinence episodes (the involuntary leakage of urine) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | The mean volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 1, 4, 8 and 12 | 
| Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Male Lower Urinary Tract Symptom (ICIQ MLUTS) Total Symptom Score | Male lower urinary tract symptoms were assessed by the ICIQ MaleLUTS questionnaire which consists of 13 questions each on a 0-4 scale (larger scores correspond to worse conditions). The total symptom score ranges from 0 to 52. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 4, 8 and 12 | 
| Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Male Lower Urinary Tract Symptom (ICIQ MLUTS) Total Bother Score | The degree to which urinary symptoms bothered participants was assessed by the ICIQ MaleLUTS questionnaire which consists of 13 symptom bother questions each on a 0-10 scale (larger scores correspond to worse outcomes). The total bother score ranges from 0 to 130. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 4, 8 and 12 | 
| Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Lower Urinary Tract Symptom Quality of Life (ICIQ-LUTSqol) Symptom Score | Quality of life was assessed by the ICIQ-LUTSqol questionnaire which consists of 19 questions each on a 1-4 scale (larger scores correspond to less quality of life). The total symptom score ranges from 19 - 76. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 4, 8 and 12 | 
| Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Lower Urinary Tract Symptom Quality of Life (ICIQ-LUTSqol) Overall Symptom Interference of Life Score | Participants were asked to rate how much their urinary symptoms interfered overall with their everyday life on a scale from 0 (not at all) to 10 (a great deal). Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate. | Baseline and Weeks 4, 8 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta-3 Receptor Agonist, YM178, Men, Lower Urinary Tract Symptoms, Bladder Outlet Obstruction