Bladder Outlet Obstruction, Lower Urinary Tract Symptoms
Conditions
Keywords
Beta-3 Receptor Agonist, YM178, Men, Lower Urinary Tract Symptoms, Bladder Outlet Obstruction
Brief summary
This study examined the safety, tolerability, and efficacy of mirabegron (YM178) compared to placebo.
Interventions
DRUGMirabegron
oral
DRUGPlacebo
oral
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) | Baseline and Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks). | 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. |
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Change From Baseline to End of Treatment in Bladder Contractile Index (BCI) | Baseline and Week 12 | 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. |
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| 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 | Baseline and Weeks 4, 8 and 12 | 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. |
| 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 | Baseline and Weeks 4, 8 and 12 | 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. |
| 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 | Baseline and Weeks 4, 8 and 12 | 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. |
| 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 | Baseline and Weeks 4, 8 and 12 | 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. |
| 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 | Baseline and Weeks 1, 4, 8 and 12 | 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. |
| Change From Baseline to End of Treatment in Bladder Voiding Efficiency (BVE) | Baseline and Week 12 | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching mirabegron placebo tablets orally once daily for 12 weeks. | 65 |
| Mirabegron 50 mg Participants received 50 mg mirabegron tablets orally once daily for 12 weeks. | 70 |
| Mirabegron 100 mg Participants received 100 mg mirabegron tablets orally once daily for 12 weeks. | 65 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 |
| Overall Study | Non-compliant with study procedures | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Mirabegron 50 mg | Mirabegron 100 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 8.43 | 64.1 years STANDARD_DEVIATION 8.82 | 62.6 years STANDARD_DEVIATION 9.92 | 62.7 years STANDARD_DEVIATION 9.1 |
| Race/Ethnicity, Customized American Indian or Alaskan native | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 3 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized Black or African American | 6 participants | 6 participants | 4 participants | 16 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White | 56 participants | 60 participants | 59 participants | 175 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 65 Participants | 70 Participants | 65 Participants | 200 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 65 | 4 / 70 | 2 / 65 |
| serious Total, serious adverse events | 0 / 65 | 0 / 70 | 0 / 65 |
Outcome results
Primary
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.
Time frame: Baseline and Week 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at Baseline \& 1 or both at any postbaseline on-treatment visit. Data include the last on-treatment assessment for patients who did not complete the Week 12 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) | 2.92 cmH2O | Standard Error 2.906 |
| Mirabegron 50 mg | Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) | -3.03 cmH2O | Standard Error 2.872 |
| Mirabegron 100 mg | Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) | 1.53 cmH2O | Standard Error 3.086 |
Comparison: The study was designed to show non-inferiority of mirabegron compared to placebo for both primary outcome measures. The comparison between mirabegron 50 mg and placebo was conducted first. If non-inferiority was demonstrated in this comparison, mirabegron 100 mg was compared to placebo. However, if the first comparison did not demonstrate non-inferiority, no further comparison was made. This procedure maintained the overall type I error of one-sided 2.5%.95% CI: [-13.98, 2.09]ANCOVA
Comparison: The study was designed to show non-inferiority of mirabegron compared to placebo for both primary outcome measures. The comparison between mirabegron 50 mg and placebo was conducted first. If non-inferiority was demonstrated in this comparison, mirabegron 100 mg was compared to placebo. However, if the first comparison did not demonstrate non-inferiority, no further comparison was made. This procedure maintained the overall type I error of one-sided 2.5%.95% CI: [-9.73, 6.96]ANCOVA
Primary
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.
Time frame: Baseline and Week 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at Baseline \& 1 or both at any postbaseline on-treatment visit. Data include the last on-treatment assessment for patients who did not complete the Week 12 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | -0.33 mL/sec | Standard Error 0.37 |
| Mirabegron 50 mg | Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | 0.07 mL/sec | Standard Error 0.366 |
| Mirabegron 100 mg | Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | 0.30 mL/sec | Standard Error 0.388 |
Comparison: The study was designed to show non-inferiority of mirabegron compared to placebo for both primary outcome measures. The comparison between mirabegron 50 mg and placebo was conducted first. If non-inferiority was demonstrated in this comparison, mirabegron 100 mg was compared to placebo. However, if the first comparison did not demonstrate non-inferiority, no further comparison was made. This procedure maintained the overall type I error of one-sided 2.5%.95% CI: [-0.63, 1.42]ANCOVA
Comparison: The study was designed to show non-inferiority of mirabegron compared to placebo for both primary outcome measures. The comparison between mirabegron 50 mg and placebo was conducted first. If non-inferiority was demonstrated in this comparison, mirabegron 100 mg was compared to placebo. However, if the first comparison did not demonstrate non-inferiority, no further comparison was made. This procedure maintained the overall type I error of one-sided 2.5%.95% CI: [-0.43, 1.68]ANCOVA
Secondary
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.
Time frame: Baseline and Week 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at Baseline \& 1 or both at any postbaseline on-treatment visit. Data include the last on-treatment assessment for patients who did not complete the Week 12 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Bladder Contractile Index (BCI) | 1.25 Scores on a scale | Standard Error 3.363 |
| Mirabegron 50 mg | Change From Baseline to End of Treatment in Bladder Contractile Index (BCI) | -2.60 Scores on a scale | Standard Error 3.324 |
| Mirabegron 100 mg | Change From Baseline to End of Treatment in Bladder Contractile Index (BCI) | 2.51 Scores on a scale | Standard Error 3.567 |
Secondary
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.
Time frame: Baseline and Week 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at Baseline \& 1 or both at any postbaseline on-treatment visit. Data include the last on-treatment assessment for patients who did not complete the Week 12 visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Bladder Voiding Efficiency (BVE) | -3.01 Percent voiding efficiency | Standard Error 3.163 |
| Mirabegron 50 mg | Change From Baseline to End of Treatment in Bladder Voiding Efficiency (BVE) | -5.49 Percent voiding efficiency | Standard Error 3.093 |
| Mirabegron 100 mg | Change From Baseline to End of Treatment in Bladder Voiding Efficiency (BVE) | 2.06 Percent voiding efficiency | Standard Error 3.277 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 12 [N=59; 61; 52] | -2.2 scores on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 8 [N=62; 63; 57] | -2.1 scores on a scale | Standard Error 0.33 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 1 [N=63; 63; 57] | -0.7 scores on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 4 [N=63; 62; 58] | -1.7 scores on a scale | Standard Error 0.31 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at EOT [N=63; 64; 58] | -2.2 scores on a scale | Standard Error 0.34 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 8 [N=62; 63; 57] | -3.2 scores on a scale | Standard Error 0.32 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 1 [N=63; 63; 57] | -1.4 scores on a scale | Standard Error 0.25 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 4 [N=63; 62; 58] | -2.6 scores on a scale | Standard Error 0.31 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 12 [N=59; 61; 52] | -3.4 scores on a scale | Standard Error 0.35 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at EOT [N=63; 64; 58] | -3.3 scores on a scale | Standard Error 0.34 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at EOT [N=63; 64; 58] | -2.5 scores on a scale | Standard Error 0.36 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 12 [N=59; 61; 52] | -2.5 scores on a scale | Standard Error 0.39 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 1 [N=63; 63; 57] | -1.0 scores on a scale | Standard Error 0.26 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 8 [N=62; 63; 57] | -2.6 scores on a scale | Standard Error 0.35 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score | Change from Baseline at Week 4 [N=63; 62; 58] | -2.3 scores on a scale | Standard Error 0.33 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 1 [N=63; 63; 57] | -1.7 scores on a scale | Standard Error 0.47 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 12 [N=58; 61; 52] | -5.2 scores on a scale | Standard Error 0.83 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 8 [N=62; 63; 56] | -5.0 scores on a scale | Standard Error 0.68 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at EOT [N=63; 64; 58] | -5.0 scores on a scale | Standard Error 0.78 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 4 [N=63; 62; 58] | -4.0 scores on a scale | Standard Error 0.62 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at EOT [N=63; 64; 58] | -6.2 scores on a scale | Standard Error 0.77 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 1 [N=63; 63; 57] | -2.4 scores on a scale | Standard Error 0.47 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 4 [N=63; 62; 58] | -5.2 scores on a scale | Standard Error 0.62 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 8 [N=62; 63; 56] | -6.3 scores on a scale | Standard Error 0.68 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 12 [N=58; 61; 52] | -6.3 scores on a scale | Standard Error 0.81 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 4 [N=63; 62; 58] | -4.4 scores on a scale | Standard Error 0.66 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at EOT [N=63; 64; 58] | -4.8 scores on a scale | Standard Error 0.83 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 12 [N=58; 61; 52] | -4.8 scores on a scale | Standard Error 0.89 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 1 [N=63; 63; 57] | -1.6 scores on a scale | Standard Error 0.5 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score | Change from Baseline at Week 8 [N=62; 63; 56] | -5.3 scores on a scale | Standard Error 0.73 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 12 [N=58; 61; 52] | -3.0 scores on a scale | Standard Error 0.55 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 8 [N=62; 63; 56] | -3.0 scores on a scale | Standard Error 0.44 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 1 [N=63; 63; 57] | -0.9 scores on a scale | Standard Error 0.33 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 4 [N=63; 62; 58] | -2.3 scores on a scale | Standard Error 0.41 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at EOT [N=63; 64; 58] | -2.8 scores on a scale | Standard Error 0.52 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 8 [N=62; 63; 56] | -3.1 scores on a scale | Standard Error 0.43 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 1 [N=63; 63; 57] | -1.0 scores on a scale | Standard Error 0.33 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 4 [N=63; 62; 58] | -2.5 scores on a scale | Standard Error 0.41 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 12 [N=58; 61; 52] | -2.9 scores on a scale | Standard Error 0.53 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at EOT [N=63; 64; 58] | -2.9 scores on a scale | Standard Error 0.51 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at EOT [N=63; 64; 58] | -2.4 scores on a scale | Standard Error 0.54 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 12 [N=58; 61; 52] | -2.3 scores on a scale | Standard Error 0.58 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 1 [N=63; 63; 57] | -0.5 scores on a scale | Standard Error 0.35 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 8 [N=62; 63; 56] | -2.7 scores on a scale | Standard Error 0.47 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score | Change from Baseline at Week 4 [N=63; 62; 58] | -2.1 scores on a scale | Standard Error 0.43 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at Baseline \& 1 or both at any postbaseline on-treatment visit. The analysis only includes patients with \>0 incontinence episodes at baseline. End of treatment (EOT) includes patients who didn't complete Week 12.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 12 [N=9; 17; 13] | -0.98 Incontinence episodes | Standard Error 0.528 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 8 [N=9; 17; 13] | -0.77 Incontinence episodes | Standard Error 0.558 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 1 [N=9; 18; 13] | -1.16 Incontinence episodes | Standard Error 0.561 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 4 [N=9; 18; 13 | -0.99 Incontinence episodes | Standard Error 0.638 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at EOT [N=9; 18; 13] | -0.96 Incontinence episodes | Standard Error 0.516 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 8 [N=9; 17; 13] | -0.70 Incontinence episodes | Standard Error 0.396 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 1 [N=9; 18; 13] | -0.18 Incontinence episodes | Standard Error 0.386 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 4 [N=9; 18; 13 | -0.42 Incontinence episodes | Standard Error 0.439 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 12 [N=9; 17; 13] | -0.91 Incontinence episodes | Standard Error 0.374 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at EOT [N=9; 18; 13] | -0.89 Incontinence episodes | Standard Error 0.355 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at EOT [N=9; 18; 13] | -1.98 Incontinence episodes | Standard Error 0.474 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 12 [N=9; 17; 13] | -2.03 Incontinence episodes | Standard Error 0.485 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 1 [N=9; 18; 13] | -0.97 Incontinence episodes | Standard Error 0.516 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 8 [N=9; 17; 13] | -2.31 Incontinence episodes | Standard Error 0.513 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Change from Baseline at Week 4 [N=9; 18; 13 | -1.60 Incontinence episodes | Standard Error 0.586 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 1 [N=63; 64; 57] | -0.15 micturitions | Standard Error 0.295 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 12 [N=62; 63; 54] | -0.27 micturitions | Standard Error 0.322 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 8 [N=62; 63; 57] | -0.61 micturitions | Standard Error 0.337 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at EOT [N=63; 64; 58] | -0.31 micturitions | Standard Error 0.317 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 4 [N=63; 64; 58] | -0.36 micturitions | Standard Error 0.333 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at EOT [N=63; 64; 58] | -1.35 micturitions | Standard Error 0.313 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 1 [N=63; 64; 57] | -0.58 micturitions | Standard Error 0.291 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 4 [N=63; 64; 58] | -0.90 micturitions | Standard Error 0.328 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 8 [N=62; 63; 57] | -1.32 micturitions | Standard Error 0.333 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 12 [N=62; 63; 54] | -1.33 micturitions | Standard Error 0.318 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 4 [N=63; 64; 58] | -1.36 micturitions | Standard Error 0.347 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at EOT [N=63; 64; 58] | -1.37 micturitions | Standard Error 0.331 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 12 [N=62; 63; 54] | -1.23 micturitions | Standard Error 0.348 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 1 [N=63; 64; 57] | -0.48 micturitions | Standard Error 0.311 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours | Change from Baseline at Week 8 [N=62; 63; 57] | -1.41 micturitions | Standard Error 0.352 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Change from Baseline at Week 12 [N=62; 63; 54] | -0.33 Urgency episodes | Standard Error 0.295 |
| Placebo | 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 | Change from Baseline at Week 8 [N=62; 63; 57] | -0.35 Urgency episodes | Standard Error 0.288 |
| Placebo | 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 | Change from Baseline at Week 1 [N=63; 64; 57] | 0.09 Urgency episodes | Standard Error 0.256 |
| Placebo | 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 | Change from Baseline at Week 4 [N=63; 64; 58] | -0.11 Urgency episodes | Standard Error 0.284 |
| Placebo | 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 | Change from Baseline at EOT [N=63; 64; 58] | -0.33 Urgency episodes | Standard Error 0.29 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 8 [N=62; 63; 57] | -1.43 Urgency episodes | Standard Error 0.285 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 1 [N=63; 64; 57] | -0.81 Urgency episodes | Standard Error 0.253 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 4 [N=63; 64; 58] | -1.13 Urgency episodes | Standard Error 0.281 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 12 [N=62; 63; 54] | -1.65 Urgency episodes | Standard Error 0.292 |
| Mirabegron 50 mg | 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 | Change from Baseline at EOT [N=63; 64; 58] | -1.60 Urgency episodes | Standard Error 0.287 |
| Mirabegron 100 mg | 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 | Change from Baseline at EOT [N=63; 64; 58] | -0.93 Urgency episodes | Standard Error 0.304 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 12 [N=62; 63; 54] | -0.90 Urgency episodes | Standard Error 0.32 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 1 [N=63; 64; 57] | -0.60 Urgency episodes | Standard Error 0.271 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 8 [N=62; 63; 57] | -0.98 Urgency episodes | Standard Error 0.302 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 4 [N=63; 64; 58] | -0.95 Urgency episodes | Standard Error 0.298 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 12 [N=62; 63; 54] | 4.49 mL | Standard Error 4.61 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 8 [N=62; 63; 57] | 4.53 mL | Standard Error 4.93 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 1 [N=63; 64; 57] | 2.75 mL | Standard Error 4.58 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 4 [N=63; 64; 58] | 10.25 mL | Standard Error 4.779 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at EOT [N=63; 64; 58] | 5.40 mL | Standard Error 4.608 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 8 [N=62; 63; 57] | 14.52 mL | Standard Error 4.859 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 1 [N=63; 64; 57] | 6.71 mL | Standard Error 4.508 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 4 [N=63; 64; 58] | 12.55 mL | Standard Error 4.705 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 12 [N=62; 63; 54] | 16.62 mL | Standard Error 4.549 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at EOT [N=63; 64; 58] | 15.82 mL | Standard Error 4.537 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at EOT [N=63; 64; 58] | 15.80 mL | Standard Error 4.823 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 12 [N=62; 63; 54] | 16.20 mL | Standard Error 5 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 1 [N=63; 64; 57] | 10.38 mL | Standard Error 4.833 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 8 [N=62; 63; 57] | 22.83 mL | Standard Error 5.163 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition | Change from Baseline at Week 4 [N=63; 64; 58] | 18.31 mL | Standard Error 5.001 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 12 [N=60; 61; 53] | -0.6 scores on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 8 [N=62; 63; 57] | -0.5 scores on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 1 [N=63; 63; 57] | -0.2 scores on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 4 [N=63; 62; 58] | -0.3 scores on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at EOT [N=63; 64; 58] | -0.6 scores on a scale | Standard Error 0.13 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 8 [N=62; 63; 57] | -0.7 scores on a scale | Standard Error 0.12 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 1 [N=63; 63; 57] | -0.3 scores on a scale | Standard Error 0.09 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 4 [N=63; 62; 58] | -0.5 scores on a scale | Standard Error 0.11 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 12 [N=60; 61; 53] | -0.9 scores on a scale | Standard Error 0.13 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at EOT [N=63; 64; 58] | -0.9 scores on a scale | Standard Error 0.13 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at EOT [N=63; 64; 58] | -0.8 scores on a scale | Standard Error 0.13 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 12 [N=60; 61; 53] | -0.9 scores on a scale | Standard Error 0.14 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 1 [N=63; 63; 57] | -0.6 scores on a scale | Standard Error 0.1 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 8 [N=62; 63; 57] | -0.9 scores on a scale | Standard Error 0.12 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) | Change from Baseline at Week 4 [N=63; 62; 58] | -0.6 scores on a scale | Standard Error 0.12 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4, 8 and 12
Population: The Safety Analysis set included all participants who received at least one dose of study drug. End of treatment (EOT) analysis includes the last assessment for patients who did not complete the Week 12 visit; N indicates the number of patients included at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 12 [N=59; 63; 57] | 4.65 mL | Standard Error 11.598 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 8 [N=62; 67; 61] | -9.92 mL | Standard Error 6.922 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 1 [N=63; 66; 63] | -8.10 mL | Standard Error 6.512 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 4 [N=63; 67; 63] | 1.08 mL | Standard Error 6.734 |
| Placebo | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at EOT [N=64; 70; 65] | 0.55 mL | Standard Error 10.702 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 8 [N=62; 67; 61] | 5.11 mL | Standard Error 6.621 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 1 [N=63; 66; 63] | -2.93 mL | Standard Error 6.316 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 4 [N=63; 67; 63] | -1.03 mL | Standard Error 6.506 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 12 [N=59; 63; 57] | 21.13 mL | Standard Error 11.235 |
| Mirabegron 50 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at EOT [N=64; 70; 65] | 17.89 mL | Standard Error 10.19 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at EOT [N=64; 70; 65] | 30.77 mL | Standard Error 10.598 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 12 [N=59; 63; 57] | 33.22 mL | Standard Error 11.822 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 1 [N=63; 66; 63] | 0.51 mL | Standard Error 6.48 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 8 [N=62; 67; 61] | -3.71 mL | Standard Error 6.972 |
| Mirabegron 100 mg | Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) | Change from Baseline at Week 4 [N=63; 67; 63] | 8.63 mL | Standard Error 6.702 |
Secondary
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.
Time frame: Baseline and Weeks 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Change from Baseline at Week 4 [N=61; 62; 58] | -0.4 scores on a scale | Standard Error 0.26 |
| Placebo | 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 | Change from Baseline at Week 8 [N=60; 63; 57] | -0.9 scores on a scale | Standard Error 0.27 |
| Placebo | 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 | Change from Baseline at Week 12 [N=59; 61; 53] | -1.1 scores on a scale | Standard Error 0.3 |
| Placebo | 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 | Change from Baseline at EOT [N=62; 63; 58] | -1.1 scores on a scale | Standard Error 0.29 |
| Mirabegron 50 mg | 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 | Change from Baseline at EOT [N=62; 63; 58] | -2.0 scores on a scale | Standard Error 0.28 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 4 [N=61; 62; 58] | -1.2 scores on a scale | Standard Error 0.26 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 12 [N=59; 61; 53] | -2.1 scores on a scale | Standard Error 0.29 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 8 [N=60; 63; 57] | -1.7 scores on a scale | Standard Error 0.26 |
| Mirabegron 100 mg | 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 | Change from Baseline at EOT [N=62; 63; 58] | -1.9 scores on a scale | Standard Error 0.3 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 8 [N=60; 63; 57] | -1.7 scores on a scale | Standard Error 0.28 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 12 [N=59; 61; 53] | -1.9 scores on a scale | Standard Error 0.32 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 4 [N=61; 62; 58] | -1.0 scores on a scale | Standard Error 0.27 |
Secondary
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.
Time frame: Baseline and Weeks 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Change from Baseline at Week 4 [N=41; 37; 33] | -3.2 scores on a scale | Standard Error 0.97 |
| Placebo | 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 | Change from Baseline at Week 8 [N=39; 36; 31] | -4.8 scores on a scale | Standard Error 1.03 |
| Placebo | 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 | Change from Baseline at Week 12 [N=40; 30;26] | -4.7 scores on a scale | Standard Error 1.11 |
| Placebo | 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 | Change from Baseline at EOT [N=47; 40; 36] | -4.8 scores on a scale | Standard Error 0.95 |
| Mirabegron 50 mg | 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 | Change from Baseline at EOT [N=47; 40; 36] | -6.9 scores on a scale | Standard Error 1.03 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 4 [N=41; 37; 33] | -4.1 scores on a scale | Standard Error 1.03 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 12 [N=40; 30;26] | -6.9 scores on a scale | Standard Error 1.29 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 8 [N=39; 36; 31] | -6.4 scores on a scale | Standard Error 1.06 |
| Mirabegron 100 mg | 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 | Change from Baseline at EOT [N=47; 40; 36] | -5.0 scores on a scale | Standard Error 1.11 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 8 [N=39; 36; 31] | -5.7 scores on a scale | Standard Error 1.18 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 12 [N=40; 30;26] | -5.7 scores on a scale | Standard Error 1.47 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 4 [N=41; 37; 33] | -3.1 scores on a scale | Standard Error 1.13 |
Secondary
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.
Time frame: Baseline and Weeks 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Change from Baseline at Week 4 [N=58; 53; 56] | -7.5 scores on a scale | Standard Error 2.71 |
| Placebo | 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 | Change from Baseline at Week 8 [N=57; 57; 53] | -11.6 scores on a scale | Standard Error 2.77 |
| Placebo | 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 | Change from Baseline at Week 12 [N=54; 53; 51] | -15.1 scores on a scale | Standard Error 3.32 |
| Placebo | 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 | Change from Baseline at EOT [N=60; 57; 58] | -14.0 scores on a scale | Standard Error 3.15 |
| Mirabegron 50 mg | 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 | Change from Baseline at EOT [N=60; 57; 58] | -20.1 scores on a scale | Standard Error 3.21 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 4 [N=58; 53; 56] | -13.6 scores on a scale | Standard Error 2.82 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 12 [N=54; 53; 51] | -19.3 scores on a scale | Standard Error 3.35 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 8 [N=57; 57; 53] | -21.9 scores on a scale | Standard Error 2.76 |
| Mirabegron 100 mg | 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 | Change from Baseline at EOT [N=60; 57; 58] | -18.6 scores on a scale | Standard Error 3.2 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 8 [N=57; 57; 53] | -19.3 scores on a scale | Standard Error 2.86 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 12 [N=54; 53; 51] | -17.4 scores on a scale | Standard Error 3.44 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 4 [N=58; 53; 56] | -10.0 scores on a scale | Standard Error 2.75 |
Secondary
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.
Time frame: Baseline and Weeks 4, 8 and 12
Population: The Full Analysis Set included all patients who received at least 1 dose of double-blind study drug \& had both Qmax \& PdetQmax measurements at baseline \& 1 or both at any postbaseline on-treatment visit. End of treatment (EOT) includes the last on-treatment assessment for patients who didn't complete Week 12; N is the number of patients included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Change from Baseline at Week 4 [N=60; 60; 58] | -2.8 scores on a scale | Standard Error 0.61 |
| Placebo | 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 | Change from Baseline at Week 8 [N=61; 61; 56] | -3.9 scores on a scale | Standard Error 0.65 |
| Placebo | 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 | Change from Baseline at Week 12 [N=58; 60; 53] | -4.2 scores on a scale | Standard Error 0.76 |
| Placebo | 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 | Change from Baseline at EOT [N=62; 61; 58] | -3.9 scores on a scale | Standard Error 0.73 |
| Mirabegron 50 mg | 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 | Change from Baseline at EOT [N=62; 61; 58] | -4.8 scores on a scale | Standard Error 0.73 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 4 [N=60; 60; 58] | -4.0 scores on a scale | Standard Error 0.61 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 12 [N=58; 60; 53] | -4.9 scores on a scale | Standard Error 0.74 |
| Mirabegron 50 mg | 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 | Change from Baseline at Week 8 [N=61; 61; 56] | -5.1 scores on a scale | Standard Error 0.65 |
| Mirabegron 100 mg | 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 | Change from Baseline at EOT [N=62; 61; 58] | -5.5 scores on a scale | Standard Error 0.75 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 8 [N=61; 61; 56] | -4.9 scores on a scale | Standard Error 0.68 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 12 [N=58; 60; 53] | -5.4 scores on a scale | Standard Error 0.8 |
| Mirabegron 100 mg | 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 | Change from Baseline at Week 4 [N=60; 60; 58] | -3.5 scores on a scale | Standard Error 0.63 |
Secondary
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.
Time frame: From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks).
Population: The Safety Analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Adverse events | 28 participants |
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Mild intensity adverse events | 17 participants |
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Moderate intensity adverse events | 7 participants |
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Severe intensity adverse events | 4 participants |
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Drug-related adverse events | 8 participants |
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Serious adverse events | 0 participants |
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | AEs leading to study drug discontinuation | 2 participants |
| Placebo | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Deaths | 0 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Moderate intensity adverse events | 10 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | AEs leading to study drug discontinuation | 1 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Severe intensity adverse events | 2 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Drug-related adverse events | 5 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Serious adverse events | 0 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Adverse events | 28 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Mild intensity adverse events | 16 participants |
| Mirabegron 50 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Deaths | 0 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Moderate intensity adverse events | 14 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Mild intensity adverse events | 20 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Adverse events | 34 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Severe intensity adverse events | 0 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | AEs leading to study drug discontinuation | 2 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Serious adverse events | 0 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Drug-related adverse events | 11 participants |
| Mirabegron 100 mg | Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests | Deaths | 0 participants |