A Phase 4 Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Male Subjects With Overactive Bladder (OAB) Symptoms, While Taking the Alpha Blocker for Benign Prostatic Hypertrophy (BPH)

A Phase 4, Double-blind, Randomized, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Mirabegron in Japanese and Korean Male Patients With Overactive Bladder Under Treatment With the α-Blocker Tamsulosin for Benign Prostatic Hyperplasia

The primary objective of the study was to investigate the efficacy of mirabegron versus placebo in male patients with OAB symptoms while taking the alpha blocker, tamsulosin, for BPH.

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.