A Phase 4 Study to Evaluate the Efficacy, Safety, and Tol... | NCT02656173

Status Module

Name	Class
Astellas Pharma Singapore Pte. Ltd.	INDUSTRY

Label	Type	Description	Intervention Names
Mirabegron 50 mg	Experimental	Participants who received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks	Drug: Mirabegron Drug: Tamsulosin
Placebo	Experimental	Participants who received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.	Drug: Placebo Drug: Tamsulosin

Name	Type	Description	Arm Group Labels	Other Names
Mirabegron	Drug	Oral tablet	Mirabegron 50 mg	YM178

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 micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by participants on a 3-day micturition diary before each visit.	Baseline and EoT (up to 12 weeks)
Change From Baseline to Weeks 4, 8, 12 in Mean Number of Micturitions Per 24 Hours	A micturition was defined as any voluntary micturition (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by participants on a 3-day micturition diary before each visit.	Baseline and week 4, 8 and 12

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to EoT in Mean Number of Urgency Episodes Per 24 Hours	An urgency episode was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes per 24 hours was calculated from data recorded by participants on a 3-day micturition diary before each visit.	Baseline and EoT (up to 12 weeks)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

at Visit 1 (Screening):

Patient had been under treatment with tamsulosin 0.2mg for at least 4 weeks before the start of the Screening period.
Patient with a history of an average of at least 2 episodes of urgency per 24 hours and an average of 8 or more micturitions per 24 hours during the last 3 days before the start of the Screening period (verified by interview).
Patient who had no wish to have children in the future (Unique to Japan).
Male subjects and their female spouses/partners who were of childbearing potential must be using highly effective contraception consisting of two forms of birth control (at least one of which must be a barrier method), starting at Screening, continuing throughout the study period, and for 28 days after the final study drug administration.
Subject must not donate sperm, starting at Screening, continuing throughout the study period, and for 28 days after the final study drug administration.
Patient was willing and able to complete the micturition diary and questionnaires correctly.
Subject agreed not to participate in another interventional study while receiving treatment in this study.

at Visit 2 (Baseline):

Subject with an average of at least 2 episodes of urgency per 24 hours and an average of 8 or more micturitions per 24 hours based on a 3-day micturition diary from the Screening period.

Exclusion Criteria:

at Visit 1 (Screening):

Patient with suspected symptoms of OAB, with onset only transient (e.g., drug-induced, psychogenic).
Patient with PVR urine volume >100 mL or Q max <5 mL/sec.
Patient with prostate-specific antigen (PSA) ≥4 ng/mL.
Patient with neurogenic bladder (e.g., spinal-cord lesions or other damage that will clearly affect urination; multiple sclerosis; Parkinson's disease) or a history of surgery that caused damage to the pelvic plexus.
Patient with urethral stricture or bladder-neck stenosis.
Patient with diabetic neuropathy complications.
Patient who had undergone a surgical procedure, previous pelvic radiation therapy, or hyperthermia therapy that may affect urinary tract function.
Patient with significant stress incontinence or postsurgical prostate incontinence, as determined by the Investigator.
Patient with an indwelling catheter or practices intermittent self-catheterization.
Patient with 3 or more episodes of recurrent urinary tract infection (UTI) within the last 6 months.
Patient with a UTI; prostatitis; chronic inflammation, such as interstitial cystitis; urinary calculus; or previous or current malignant disease of the pelvic organs.
Patient with a concurrent malignancy or history of any malignancy (within the past 5 years), except for non-metastatic basal-cell or squamous-cell carcinoma of the skin that had been treated successfully.
Patient with serious heart disease, liver disease, kidney disease, immunological disease, lung disease.
Patient who had received intravesical injection within the last 12 months with botulinum toxin, resiniferatoxin, or capsaicin.
Patient who had received electrostimulation therapy for OAB.
Patient who had received a bladder training program or pelvic floor exercises <28 days prior to the start of the Screening period.
Patient with postural hypotension or syncope, hypokalemia, or closed-angle glaucoma.
Patient with evidence of QT prolongation on electrocardiogram (ECG), defined as QTcF >450 msec.
Patient with severe uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) >180 mmHg and/or diastolic blood pressure (DBP) >110 mmHg.
Patient with a clinically significant ECG abnormality, as determined by the Investigator.
Patient who had severe renal impairment, defined as an estimated glomerular filtration rate of <29 mL/min/1.73m2; end-stage renal disease; or is undergoing dialysis.
Patient with aspartate transaminase (AST) or alanine transaminase (ALT) >2 times the upper limit of normal (ULN), or gamma-glutamyl transferase (γ-GT) >3 times the ULN and considered clinically significant by the Investigator.
Patient with moderate or severe hepatic impairment, defined as Child-Pugh Class B or C.
Patient with hypersensitivity to any of the components of mirabegron, other beta-adrenergic receptor (β-AR) agonists, or any of the inactive ingredients.
Patient with ongoing alcohol and/or drug abuse.
Patient with or a history of mood disorder, neurotic disorder, or schizophrenia.
Patient with dementia, cognitive dysfunction, or clinically significant cerebrovascular disorder.
Patient who had been treated with an experimental device <84 days or received an investigational agent <84 days prior to the start of the Screening period.
Patient had used any prohibited concomitant medication <28 days (but, <1 year for 5α-reductase inhibitors) before the start of the Screening period.
Patient with any clinically significant condition, which in the opinion of the Investigator, made the subject unsuitable for study participation.
Patient who was involved in the conduct of the study as an employee of the Astellas group, a third party associated with the study, or the study site team.

at Visit 2 (Baseline):

Subject fulfills any exclusion criteria of Visit 1 at Visit 2.
Subject was noncompliant during the 4 week tamsulosin Screening period, defined as taking less than 80% or greater than 120% of prescribed dose of study medication.
Subject had an average total daily urine volume >3000 mL, as recorded in the 3-day micturition diary.

Name	Affiliation	Role
Medical Director	Astellas Pharma Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Site JP81046		Aichi			Japan
Site JP81009

PubMed Identifier	Type	Citation	Retractions
33245533	Derived	Kakizaki H, Lee KS, Katou D, Yamamoto O, Sumarsono B, Uno S, Yamaguchi O. Mirabegron Add-On Therapy to Tamsulosin in Men with Overactive Bladder: Post Hoc Analyses of Efficacy from the MATCH Study. Adv Ther. 2021 Jan;38(1):739-757. doi: 10.1007/s12325-020-01517-5. Epub 2020 Nov 27.

Label	URL
Link to results on the 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 matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
FG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

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	May 10, 2016	Jul 3, 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

year

Title

Denominators

Categories

Title	Measurements
	OG000-0.90± 1.91 OG001-1.35± 1.81

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	Analysis of Covariance (ANCOVA) was used for analysis, including treatment group and region as fixed factors and baseline as a covariate.	ANCOVA		<0.001		least square mean difference	-0.52			2-Sided	95	-0.82	-0.21					Superiority

Primary

Change From Baseline to Weeks 4, 8, 12 in Mean Number of Micturitions Per 24 Hours

FAS.

Posted

Mean

Standard Deviation

micturitions

Baseline and week 4, 8 and 12

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Secondary

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

An urgency episode was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes per 24 hours was calculated from data recorded by participants on a 3-day micturition diary before each visit.

FAS who had at least 1 urgency episode at baseline. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

urgency episodes

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Secondary

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

An urgency incontinence episode was defined as any episode when both urgency and incontinence occurred concurrently. The mean number of urgency incontinence episodes per 24 hours was calculated from data recorded by participants on a 3-day micturition diary before each visit.

FAS who had at least 1 urgency incontinence episode at baseline. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

urgency incontinence episodes

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants

Secondary

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 from data recorded by participants on a 3-day micturition diary before each visit.

FAS who had at least 1 incontinence episode at baseline. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

incontinence episodes

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to EoT in Mean Number of Nocturia Episodes

A nocturia episode was defined as a micturition episode initiated between night time. Night time was defined as the period between sleep onset time and the wake-up time the following day (micturitions at the same time as the wake-up time were excluded). The mean number of nocturia episodes per 24 hours was calculated from data recorded by participants on a 3-day micturition diary before each visit.

FAS who had at least 1 nocturia episode at baseline. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

nocturia episodes

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants

Secondary

Change From Baseline to EoT in Mean Volume Voided Per Micturition

The mean volume voided per micturition was calculated from data recorded by participants on a 3-day micturition diary before each visit.

FAS who had volume voided as > 0. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to EoT in Total Overactive Bladder Symptom Score (OABSS)

The OABSS is a 4-item questionnaire that assesses urinary frequency. Total score was the sum total of the score of each item (ranges: 0-15). Negative change means improvement.

FAS. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

units on a scale

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to EoT in OABSS Subscale Scores

Each OABSS subscale score was based on each question in the questionnaire: Daytime Frequency ("How many times do you typically urinate from waking in the morning until sleeping at night?" where scores range from 0-2), Nighttime Frequency ("How many times do you typically wake up to urinate from sleeping at night until waking in the morning?" where scores range from 0-3), Urgency ("How often do you have a sudden desire to urinate, which is difficult to defer?" where scores range from 0-5), Urgency Incontinence ("How often do you leak urine because you cannot defer the sudden desire to urinate?" where scores range from 0-5). A higher score is indicative of worse condition and a negative change from baseline indicates an improvement.

FAS. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

units on a scale

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Secondary

Change From Baseline to EoT in Total International Prostate Symptom Score (IPSS)

The IPSS included an 7-item questionnaire that assesses urinary frequency and incomplete voiding along with a QoL assessment. Total IPSS score was the sum total of the score (range: 0-35) of each item (Questions 1-7). Negative change means improvement.

FAS. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

units on a scale

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to EoT in IPSS Subscale Scores

IPSS subscale scores was calculated by following each formula. Storage subscale was derived as sum of scores for questions 2, 4, and 7 (range: 1-15). Voiding subscale-1 was derived as sum of scores for questions 3, 5, and 6 (range: 1-15). Voiding subscale-2 was derived as sum of voiding subscale-1 and the score for question 1 (range: 1-20). Individual scores and IPSS Quality of Life (QoL) score was the score of each item (range: 1-6) (Questions 1-7 and QoL item). A higher score is indicative of worse condition and a negative change from baseline indicates an improvement.

FAS. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

units on a scale

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts

Secondary

Change From Baseline to EoT in Symptom Bother as Assessed by the Overactive Bladder Questionnaire (OAB-q)

The OAB-q was a 33-item questionnaire, which consisted of an 8-item symptom bother scale and 25 health-related QoL items that form 4 subscales (coping, concern, sleep, and social interaction) and a total health-related QoL score.

Symptom Bother was derived as sum of scores for questions 1-8 (range: 0-100). Higher Symptom Bother is indicative of greater symptom bother.

FAS. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

units on a scale

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants

Secondary

Change From Baseline to EoT in Total Health-Related QoL (HRQoL) Scores as Assessed by the OAB-q

Total HRQL score was derived as sum of HRQL subscale scores (range: 25-150). Higher total HRQL score is indicative of better HRQL.

FAS. EoT value was defined as last post-baseline assessment during the double-blind study period for which the efficacy data are available.

Posted

Mean

Standard Deviation

units on a scale

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events

Treatment-emergent adverse events (TEAE) was defined as an adverse event (AE) with onset during the double-blind treatment period or an AE with onset during the screening period with worsening severity during the double-blind treatment period. The investigator assessed the severity of AEs as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A drug-related TEAE was a TEAE with at least a possible relationship to the study drug as assessed by the investigator. Serious TEAE was an AE considered serious.

Safety Analysis Set (SAF) consisted of all participants who received at least 1 dose of double-blind study drug.

Posted

Count of Participants

Participants

From first dose of study drug up to Week 12

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants

Secondary

Change From Baseline to EoT in Postvoid Residual (PVR) Volume

PVR was measured by ultrasonography.

SAF. EoT value was defined as last post-baseline assessment during the double-blind study period for which the safety data are available.

Posted

Mean

Standard Deviation

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to EoT in Maximum Urine Flow Rate (Qmax)

Urine flow rate was volume voided per micturition (voided volume) divided by time for the micturition (flow time).

SAF. EoT value was defined as last post-baseline assessment during the double-blind study period for which the safety data are available.

Posted

Mean

Standard Deviation

Baseline and EoT (up to 12 weeks)

ID	Title	Description
OG000	Placebo	Patients received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
OG001	Mirabegron 50mg	Patients received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina unstable	Cardiac disorders	MedDRA v18.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0011 events1 affected282 at risk
Cataract	Eye disorders	MedDRA v18.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected282 at risk
Macular fibrosis	Eye disorders	MedDRA v18.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected282 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA v18.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0011 events1 affected282 at risk
Oesophagitis chemical	Injury, poisoning and procedural complications	MedDRA v18.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected282 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Systematic Assessment	EG0001 events1 affected284 at risk EG0010 events0 affected282 at risk
Hypergammaglobulinaemia benign monoclonal	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected282 at risk
Glomerulonephritis	Renal and urinary disorders	MedDRA v18.1	Systematic Assessment	EG0000 events0 affected284 at risk EG0011 events1 affected282 at risk

ID	Term
D053201	Urinary Bladder, Overactive
D011470	Prostatic Hyperplasia

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
D011469	Prostatic Diseases
D005832	Genital Diseases, Male
D000091662	Genital Diseases

ID	Term
D000096926	Benzenesulfonamides
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D013450	Sulfones
D013457	Sulfur Compounds

ID	Title	Description
BG000	Placebo	Participants received matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.
BG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.
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 matching placebo once a day along with tamsulosin 0.2 mg for 12 weeks.	0	284	3	284	17	284
EG001	Mirabegron 50mg	Participants received mirabegron 50 mg once a day along with tamsulosin 0.2 mg for 12 weeks.	0	282	6	282	18	282