Study to Evaluate the Efficacy, Safety, and Tolerability... | NCT02216214

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.	Drug: Placebo
Mirabegron	Experimental	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.	Drug: Mirabegron

Name	Type	Description	Arm Group Labels	Other Names
Mirabegron	Drug	oral tablet	Mirabegron	YM178 Myrbetriq

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to End of Treatment (EOT) in Mean Number of Micturitions Per 24 Hours	A micturition was defined as any voluntary act of passing urine (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated as the average number of times a participant urinated per day during the 3-day micturition diary period.	Baseline and EOT (up to 12 weeks)
Change From Baseline to EOT in Mean Number of Incontinence Episodes Per 24 Hours	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated as the average number of times a participant recorded an incontinence episode per day during the 3-day micturition diary period.	Baseline and EOT (up to 12 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to EOT in Mean Volume Voided Per Micturition	The mean volume voided per micturition during 3 days of the 3-day micturition diary period.	Baseline and EOT (up to 12 weeks)
Change From Baseline to EOT in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score

Eligibility Module

Eligibility Criteria

Inclusion Criteria assessed at Visit 1 (Screening):

Subject is willing and able to complete the micturition diary and questionnaires correctly.
Subject has symptoms of wet overactive bladder (OAB) (urinary frequency and urgency with incontinence) for greater than or equal to 3 months prior to Screening.
Subject agrees not to participate in another interventional study from the time of screening until the final study visit.

Inclusion Criteria assessed after placebo run-in period at Visit 3 (Baseline):

Subject continues to meet all inclusion criteria of Visit 1.
Subjects must experience at least one incontinence episode in the placebo run-in period based on the 3-day micturition diary.
Subject must experience at least 3 episodes of urgency (grade 3 or 4) based on the 3-day micturition diary.
Subject must experience an average of greater than or equal to 8 micturitions/day based on the 3-day micturition diary.

Exclusion Criteria assessed at Visit 1 (Screening):

Subject has ongoing symptoms suggestive of bladder outlet obstruction (BOO) or history of BOO that is currently not well controlled.
Subject has Post-Void Residual Volume (PVR) greater than 150 mL.
Subject has neurogenic bladder or neurological dysfunction or injury which could affect the lower urinary tract or nerve supply.
Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the Investigator (for female subjects confirmed by a cough provocation test). Subjects with a history of stress incontinence that is currently treated (e.g. remote history of surgery for stress incontinence) may be included as long as they pass cough provocation test.
Subject has an indwelling catheter or practices intermittent self-catheterization.
Subject has evidence of Urinary Tract Infection (UTI). Urine culture and sensitivity will be performed for positive leukocytes, or nitrites, or turbidity, or at the investigator's discretion and will be confirmed with a culture greater than 100,000 cfu/mL. If a subject has a UTI at Screening (Visit 1), the subject can be rescreened after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture).
Subject has a chronic inflammatory condition such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs (i.e., within the confines of the pelvis including the bladder and rectum in both sexes and the uterus, ovaries, and fallopian tubes in females; organs of the lower gastrointestinal tract are not necessarily considered pelvic organs as the distal ascending colon, the full transverse colon and proximal portion of the descending colon are in the abdomen).
Subject resides in a nursing home.
Subject is likely to enter a hospital or nursing home due to medical instability within the next 6 months in the opinion of the Investigator.
Subject has received intravesical injection in the past 12 months with botulinum toxin, resiniferatoxin, or capsaicin.
Subject has received electro-stimulation therapy for OAB (e.g. sacral nerve stimulation or Percutaneous Tibial Nerve Stimulation [PTNS]).
Subject began or has changed a bladder training program or pelvic floor exercises less than 30 days prior to Screening.
Subject has moderate or severe hepatic impairment defined as Child-Pugh Class B or C.
Subject has severe renal impairment defined as estimated creatinine clearance less than 29 mL/min determined by Estimated Glomerular Filtration Rate (eGFR, Cockroft-Gault, or MDRD formulae). A subject with end stage renal disease or undergoing dialysis is also not a candidate for the study.
Subject has severe uncontrolled hypertension, which is defined as a sitting systolic blood pressure greater than or equal to 180 mmHg and/or diastolic blood pressure greater than or equal to 110 mmHg.
Subject has evidence of QT prolongation on electrocardiogram (ECG) defined as QTc greater than 450 msec for males, QTc greater than 470 msec for females or a known history of QT prolongation.
Subject has a clinically significant ECG abnormality, as determined by the Investigator.
Subject has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2x upper limit of normal (ULN), or γ-GT greater than 3x ULN and considered clinically significant by the Investigator.
Subject has a hypersensitivity to any components of mirabegron, other β-AR agonists, or any of the inactive ingredients.
Subject has any clinically significant condition, which in the opinion of the Investigator makes the subject unsuitable for study participation.
Subject has been treated with an experimental device within 28 days or received an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Screening.
Subject has a concurrent malignancy or history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
Subject with current history of alcohol and/or drug abuse.
Subject is using prohibited medications which cannot be stopped safely during the period.
Subject has stopped, started or changed the dose of a restricted medication within the last 30 days prior to Screening.
Subject is involved in the conduct of the study as an employee of the Astellas group, third party associated with the study, or the study site team.
Subject has previously received mirabegron.

Exclusion Criteria assessed after placebo run-in period at Visit 3 (Baseline):

Subject fulfills any exclusion criteria of Visit 1 (subject does not need to repeat screening assessments [PVR, cough provocation test, chemistry/hematology/urinalysis]).
Subject was non-compliant during 2-week placebo run-in period, defined as taking less than 80% or greater than 120% of study medication.
Subject has any systolic blood pressure measurement > 180 mmHg or diastolic blood pressure measurement > 110 in the 3-day diary or during the baseline visit.

Name	Affiliation	Role
Medical Director	Astellas Pharma Global Development, Inc., Medical Affairs, Americas	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Site US00066		Huntsville	Alabama	35801	United States
Site US00148

PubMed Identifier	Type	Citation	Retractions
32725584	Derived	Herschorn S, Staskin D, Schermer CR, Kristy RM, Wagg A. Safety and Tolerability Results from the PILLAR Study: A Phase IV, Double-Blind, Randomized, Placebo-Controlled Study of Mirabegron in Patients >/= 65 years with Overactive Bladder-Wet. Drugs Aging. 2020 Sep;37(9):665-676. doi: 10.1007/s40266-020-00783-w.
32183741	Derived

Label	URL
Link to results on Astellas Clinical Study Results website	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 10, 2015	Nov 19, 2018

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-1.7± 0.2 OG001-2.3± 0.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Difference vs. Mirabegron: Differences of adjusted change from baseline values as well as the 95% CIs were generated from the ANCOVA model with treatment group, sex, age group (<75, >=75 years) and country as fixed factors and baseline value as a covariate.	ANCOVA		<0.001	P-value compares the Mirabegron group to the placebo group.	Least Squares Mean (LSM) Mean Difference	-0.7	Standard Error of the Mean	0.2	2-Sided	95	-1.05	-0.33					Superiority

Primary

Change From Baseline to EOT in Mean Number of Incontinence Episodes Per 24 Hours

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated as the average number of times a participant recorded an incontinence episode per day during the 3-day micturition diary period.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

incontinence episodes/24 hours

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Mean Volume Voided Per Micturition

The mean volume voided per micturition during 3 days of the 3-day micturition diary period.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score

The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 questions, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in OAB-q: Health Related Quality of Life (HRQL) Total Score

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Patient Perception of Bladder Condition (PPBC)

The PPBC is a validated, global assessment tool using a 6-point Likert scale that asks participants to rate their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. A higher score indicated a worse perception of bladder condition.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours

Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode with a severity of grade 3 or 4, assessed by participants based on the PPIUS, where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The mean number of urgency episodes (grade 3 and/or 4) per 24 hours was calculated as the average number of times a participant recorded an urgency episode (grade 3 and/or 4) with or without incontinence per day during the 3-day micturition diary period.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

urgency episodes/24 hours

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron

Secondary

Change From Baseline to EOT in Mean Number of Urgency Incontinence Episodes Per 24 Hours

An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency episodes was calculated as the average number of times a participant recorded an urgency incontinence episode per day during the 3-day micturition diary period.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

urgency incontinence episodes/24 hours

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From to EOT in Mean Number of Nocturia Episodes Per 24 Hours

A nocturia episode was defined as waking at night one or more time to void (i.e., any voiding associated with sleep disturbance between the date/time the participant goes to bed with the intention to sleep until the date/time the participant gets up in the morning with the intention to stay awake). A night time episode of incontinence only is not considered a nocturia episode. The mean number of nocturia episodes per 24 hours was calculated as the average number of times a participant recorded a nocturia episode per day during the 3-day micturition diary period.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

nocturia episodes/24 hours

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Barthel Index of Daily Living Score

The Barthel Index consists of 10 items that measure a person's daily functioning; specifically the activities of daily living and mobility. The total possible score ranges from 0 to 20, with lower scores indicating increased disability.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Vulnerable Elder Survey-13 (VES-13) Score

The VES-13 is a simple function-based tool for screening community-dwelling populations to identify older persons at risk for health deterioration. The VES-13 considers age, self-related health, limitation in physical function, and functional disabilities. The total possible score ranges from 0 to 10, with higher scores indicating increased disability.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in PPIUS

The PPIUS is a 5-point categorical scale used by participants to rate the degree of associated urgency for each micturition and/or incontinence episode they experienced. categories include: 0 - No urgency, I felt no need to empty my bladder, but did so for other reasons; 1 - Mild urgency, I could postpone voiding as long as necessary, without fear of wetting myself; 2 - Moderate urgency, I could postpone voiding for a short while, without fear of wetting myself; 3 - Severe urgency, I could not postpone voiding, but had to rush to the toilet in order not to wet myself; 4 - Urge incontinence, I leaked before arriving at the toilet. Scores were recorded in the micturition diary.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in OAB-q HRQL Subscale Scores

The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The Coping score has 8 items, the Concern score has 7 items, the Sleep and Social score has 5 items each. Each subscale score was calculated by adding each score's items and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Treatment Satisfaction Visual Analog Scale (TS-VAS)

The TS-VAS is a visual analog scale that asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) to 100 (Yes, completely).

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in University of Alabama, Birmingham - Life Space Assessment (UAB-LSA)

The UAB-LSA measures mobility in terms of the spatial extent of a person's life. Life space is defined based upon the distance a person routinely travels to perform activities over this time frame. The UAB-LSA includes determining how far and how often the person leaves his or her place of residence and the degree of independence the person has. Each level of life space represents a distance further from the room where one sleeps: 0 - Mobility limited to the room where one sleeps; 1 - Mobility limited to within one's dwelling; 2 - Mobility limited to the space just proximal to one's personal living space (for instance, a porch, patio, or yard just outside the home or hallway outside of an apartment); 3 - Mobility limited to one's neighborhood; 4 - Mobility limited to one's town; 5 - Mobility outside one's town. The total scores ranges from 0-120, where a higher score indicates greater mobility.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline in Number of Incontinence Episodes Reported During 3-Day Diary Prior to Each Visit

An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes were calculated as the total number of the incontinence episodes recorded during the 3-day micturition diary period.

The analysis population was the FAS-I. Participants with available data at all time points are included in the analysis. LOCF was used for EOT.

Posted

Mean

Standard Error

incontinence episodes

Baseline and Weeks 4, 8 and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline in Number of Pads During 3-Day Diary Prior to Each Visit

The number of pads were calculated as the number of times a participant records a new pad used during the 3-day micturition diary period. No data were collected for the number of pads used due to a failure in the programming of the diary used for data collection.

The analysis population was the FAS-I.

Posted

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Percentage of Participants Who Achieved Micturition Frequency Normalization

Participants who achieved micturition frequency normalization were defined as participants who had at least 8 micturitions per 24 hours at baseline and less than 8 micturitions per 24 hours post-baseline.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. Non-responder imputation (NRI) was used for EOT.

Posted

Number

percentage of participants

End of treatment (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours

An incontinence episode was defined as the complaint of any involuntary leakage of urine. Participants with 50% reduction in mean number of incontinence episodes per 24 hours were defined as participants with at least 50% decrease from baseline in mean number of incontinence episodes per 24 hours during the treatment period at each visit.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. NRI was used for EOT.

Posted

Number

percentage of participants

End of treatment (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Percentage of Participants With Zero Incontinence Episodes Per 24 Hours

An incontinence episode was defined as the complaint of any involuntary leakage of urine. Participants with zero incontinence episodes per 24 hours were defined as participants who had no incontinence episodes per 24 hours during the treatment period at each visit.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. NRI was used for EOT.

Posted

Number

percentage of participants

End of treatment (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Percentage of Participants With ≥ 10-Point Improvement From Baseline in OAB-q HRQL Subscales

The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The Coping score has 8 items, the Concern score has 7 items, the Sleep and Social score has 5 items each. Each subscale score was calculated by adding each score's items and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. Participants with ≥ 10-point improvement from baseline in OAB-q HRQL subscales were defined as participants with at least 10-point improvement from baseline in OAB-q Subscales at each visit.

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. NRI was used for EOT.

Posted

Number

percentage of participants

End of treatment (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron

Secondary

Percentage of Participants With ≥ 1-Point Improvement From Baseline in PPBC

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. NRI was used for EOT.

Posted

Number

percentage of participants

End of treatment (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron

Secondary

Percentage of Participants Major (≥ 2-Point) Improvement From Baseline in PPBC

The analysis population was the FAS-I. Participants with available data at baseline and EOT are included in the analysis. NRI was used for EOT.

Posted

Number

percentage of participants

End of treatment (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron

Secondary

Number of Participants With Adverse Events (AEs)

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. AEs were considered as serious if resulted in in death, was life-threatening resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly or birth defect, required inpatient hospitalization or led to prolongation of hospitalization and other medically important events.

The analysis population was the SAF.

Posted

Count of Participants

Participants

From first dose of study drug up to 30 days after last dose of study drug (up to 13 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline to EOT in Montreal Cognitive Assessment (MoCA) Score

The MoCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points, with lower scores indicating worse cognitive function.

The analysis population was the SAF. Participants with available data at baseline and EOT are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Secondary

Change From Baseline in Post-void Residual Volume (PVR)

PVR was assessed by ultrasonography or bladder scan.

The analysis population was the SAF. Participants with available data are included in the analysis. LOCF was used for EOT.

Posted

Least Squares Mean

Standard Deviation

Baseline and EOT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
OG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Units

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Angina pectoris	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Diverticulum	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Flatulence	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Asthenia	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Chest pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Chills	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Oedema peripheral	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Allergy to arthropod bite	Immune system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Arthritis infective	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0011 events1 affected445 at risk
Cellulitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0011 events1 affected445 at risk
Pneumonia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected442 at risk EG0010 events0 affected445 at risk
Soft tissue infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Scapula fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Tonsil cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected442 at risk EG0011 events1 affected445 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected442 at risk EG0010 events0 affected445 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk
Knee operation	Surgical and medical procedures	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected442 at risk EG0011 events1 affected445 at risk

ID	Term
D053201	Urinary Bladder, Overactive
D014549	Urinary Incontinence

ID	Term
D001745	Urinary Bladder Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D059411	Lower Urinary Tract Symptoms
D020924	Urological Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D014555	Urination Disorders

ID	Title	Description
BG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
BG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.	0	442	12	442	12	442
EG001	Mirabegron	Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.	0	445	15	445	23	445