Trial Outcomes & Findings for A Study of Mirabegron (YM178) in Men With Lower Urinary Tract Symptoms (LUTS) and Bladder Outlet Obstruction (BOO) (NCT NCT00410514)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

200 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2014-04-04

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Overall Study STARTED	65	70	65
Overall Study Safety Analysis Set (SAF)	65	70	65
Overall Study Full Analysis Set (FAS)	63	64	58
Overall Study COMPLETED	63	67	58
Overall Study NOT COMPLETED	2	3	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Overall Study Adverse Event	2	2	2
Overall Study Protocol Violation	0	1	1
Overall Study Lost to Follow-up	0	0	2
Overall Study Non-compliant with study procedures	0	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=65 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=70 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=65 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.	Total n=200 Participants Total of all reporting groups
Age, Continuous	61.2 years STANDARD_DEVIATION 8.43 • n=5 Participants	64.1 years STANDARD_DEVIATION 8.82 • n=7 Participants	62.6 years STANDARD_DEVIATION 9.92 • n=5 Participants	62.7 years STANDARD_DEVIATION 9.10 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	70 Participants n=7 Participants	65 Participants n=5 Participants	200 Participants n=4 Participants
Race/Ethnicity, Customized White	56 participants n=5 Participants	60 participants n=7 Participants	59 participants n=5 Participants	175 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	6 participants n=5 Participants	6 participants n=7 Participants	4 participants n=5 Participants	16 participants n=4 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	6 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaskan native	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax)	-0.33 mL/sec Standard Error 0.370	0.07 mL/sec Standard Error 0.366	0.30 mL/sec Standard Error 0.388

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=57 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax)	2.92 cmH2O Standard Error 2.906	-3.03 cmH2O Standard Error 2.872	1.53 cmH2O Standard Error 3.086

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=57 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Change From Baseline to End of Treatment in Bladder Contractile Index (BCI)	1.25 Scores on a scale Standard Error 3.363	-2.60 Scores on a scale Standard Error 3.324	2.51 Scores on a scale Standard Error 3.567

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Change From Baseline to End of Treatment in Bladder Voiding Efficiency (BVE)	-3.01 Percent voiding efficiency Standard Error 3.163	-5.49 Percent voiding efficiency Standard Error 3.093	2.06 Percent voiding efficiency Standard Error 3.277

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=70 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=65 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-2.93 mL Standard Error 6.316	0.51 mL Standard Error 6.480
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	-1.03 mL Standard Error 6.506	8.63 mL Standard Error 6.702
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	5.11 mL Standard Error 6.621	-3.71 mL Standard Error 6.972
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	21.13 mL Standard Error 11.235	33.22 mL Standard Error 11.822
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	17.89 mL Standard Error 10.190	30.77 mL Standard Error 10.598

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=70 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=65 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests Serious adverse events	0 participants	0 participants	0 participants
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests AEs leading to study drug discontinuation	2 participants	1 participants	2 participants
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests Deaths	0 participants	0 participants	0 participants
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests Adverse events	28 participants	28 participants	34 participants
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests Mild intensity adverse events	17 participants	16 participants	20 participants
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests Moderate intensity adverse events	7 participants	10 participants	14 participants
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests Severe intensity adverse events	4 participants	2 participants	0 participants
Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests Drug-related adverse events	8 participants	5 participants	11 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-2.4 scores on a scale Standard Error 0.47	-1.6 scores on a scale Standard Error 0.50
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	-5.2 scores on a scale Standard Error 0.62	-4.4 scores on a scale Standard Error 0.66
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	-6.3 scores on a scale Standard Error 0.68	-5.3 scores on a scale Standard Error 0.73
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	-6.3 scores on a scale Standard Error 0.81	-4.8 scores on a scale Standard Error 0.89
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	-6.2 scores on a scale Standard Error 0.77	-4.8 scores on a scale Standard Error 0.83

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-1.0 scores on a scale Standard Error 0.33	-0.5 scores on a scale Standard Error 0.35
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	-2.5 scores on a scale Standard Error 0.41	-2.1 scores on a scale Standard Error 0.43
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	-3.1 scores on a scale Standard Error 0.43	-2.7 scores on a scale Standard Error 0.47
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	-2.9 scores on a scale Standard Error 0.53	-2.3 scores on a scale Standard Error 0.58
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	-2.9 scores on a scale Standard Error 0.51	-2.4 scores on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-1.4 scores on a scale Standard Error 0.25	-1.0 scores on a scale Standard Error 0.26
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	-2.6 scores on a scale Standard Error 0.31	-2.3 scores on a scale Standard Error 0.33
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	-3.2 scores on a scale Standard Error 0.32	-2.6 scores on a scale Standard Error 0.35
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	-3.4 scores on a scale Standard Error 0.35	-2.5 scores on a scale Standard Error 0.39
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	-3.3 scores on a scale Standard Error 0.34	-2.5 scores on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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 0.10	-0.3 scores on a scale Standard Error 0.09	-0.6 scores on a scale Standard Error 0.10
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	-0.5 scores on a scale Standard Error 0.11	-0.6 scores on a scale Standard Error 0.12
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	-0.7 scores on a scale Standard Error 0.12	-0.9 scores on a scale Standard Error 0.12
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	-0.9 scores on a scale Standard Error 0.13	-0.9 scores on a scale Standard Error 0.14
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	-0.9 scores on a scale Standard Error 0.13	-0.8 scores on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-0.58 micturitions Standard Error 0.291	-0.48 micturitions Standard Error 0.311
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	-0.90 micturitions Standard Error 0.328	-1.36 micturitions Standard Error 0.347
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	-1.32 micturitions Standard Error 0.333	-1.41 micturitions Standard Error 0.352
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	-1.33 micturitions Standard Error 0.318	-1.23 micturitions Standard Error 0.348
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	-1.35 micturitions Standard Error 0.313	-1.37 micturitions Standard Error 0.331

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-0.81 Urgency episodes Standard Error 0.253	-0.60 Urgency episodes Standard Error 0.271
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	-1.13 Urgency episodes Standard Error 0.281	-0.95 Urgency episodes Standard Error 0.298
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	-1.43 Urgency episodes Standard Error 0.285	-0.98 Urgency episodes Standard Error 0.302
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	-1.65 Urgency episodes Standard Error 0.292	-0.90 Urgency episodes Standard Error 0.320
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 0.290	-1.60 Urgency episodes Standard Error 0.287	-0.93 Urgency episodes Standard Error 0.304

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-0.18 Incontinence episodes Standard Error 0.386	-0.97 Incontinence episodes Standard Error 0.516
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	-0.42 Incontinence episodes Standard Error 0.439	-1.60 Incontinence episodes Standard Error 0.586
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	-0.70 Incontinence episodes Standard Error 0.396	-2.31 Incontinence episodes Standard Error 0.513
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	-0.91 Incontinence episodes Standard Error 0.374	-2.03 Incontinence episodes Standard Error 0.485
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	-0.89 Incontinence episodes Standard Error 0.355	-1.98 Incontinence episodes Standard Error 0.474

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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 4.580	6.71 mL Standard Error 4.508	10.38 mL Standard Error 4.833
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	12.55 mL Standard Error 4.705	18.31 mL Standard Error 5.001
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 4.930	14.52 mL Standard Error 4.859	22.83 mL Standard Error 5.163
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 4.610	16.62 mL Standard Error 4.549	16.20 mL Standard Error 5.000
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	15.82 mL Standard Error 4.537	15.80 mL Standard Error 4.823

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-4.0 scores on a scale Standard Error 0.61	-3.5 scores on a scale Standard Error 0.63
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	-5.1 scores on a scale Standard Error 0.65	-4.9 scores on a scale Standard Error 0.68
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	-4.9 scores on a scale Standard Error 0.74	-5.4 scores on a scale Standard Error 0.80
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	-4.8 scores on a scale Standard Error 0.73	-5.5 scores on a scale Standard Error 0.75

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-13.6 scores on a scale Standard Error 2.82	-10.0 scores on a scale Standard Error 2.75
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	-21.9 scores on a scale Standard Error 2.76	-19.3 scores on a scale Standard Error 2.86
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	-19.3 scores on a scale Standard Error 3.35	-17.4 scores on a scale Standard Error 3.44
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	-20.1 scores on a scale Standard Error 3.21	-18.6 scores on a scale Standard Error 3.20

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-4.1 scores on a scale Standard Error 1.03	-3.1 scores on a scale Standard Error 1.13
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	-6.4 scores on a scale Standard Error 1.06	-5.7 scores on a scale Standard Error 1.18
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	-6.9 scores on a scale Standard Error 1.29	-5.7 scores on a scale Standard Error 1.47
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	-6.9 scores on a scale Standard Error 1.03	-5.0 scores on a scale Standard Error 1.11

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=64 Participants Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=58 Participants Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
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	-1.2 scores on a scale Standard Error 0.26	-1.0 scores on a scale Standard Error 0.27
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	-1.7 scores on a scale Standard Error 0.26	-1.7 scores on a scale Standard Error 0.28
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 0.30	-2.1 scores on a scale Standard Error 0.29	-1.9 scores on a scale Standard Error 0.32
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	-2.0 scores on a scale Standard Error 0.28	-1.9 scores on a scale Standard Error 0.30

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Mirabegron 50 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Mirabegron 100 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=65 participants at risk Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.	Mirabegron 50 mg n=70 participants at risk Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.	Mirabegron 100 mg n=65 participants at risk Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Infections and infestations Nasopharyngitis	1.5% 1/65 • From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks).	5.7% 4/70 • From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks).	3.1% 2/65 • From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks).

Additional Information

Associate Medical Director, Medical Sciences

Astellas Pharma Global Development, Inc. (APGD)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER