Clinical trial NCT02656173: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Overactive Bladder
Keywords: Tamsulosin
Overactive bladder
Benign prostatic hypertrophy
Mirabegron
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Singapore Pte. Ltd.
First posted: 2016-01-14
Enrollment: 568
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Change From Baseline to End of Treatment (EoT) in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to Weeks 4, 8, 12 in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and week 4, 8 and 12
Secondary outcomes:
measure: Change From Baseline to EoT in Mean Number of Urgency Episodes Per 24 Hours
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Mean Number of Nocturia Episodes
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Mean Volume Voided Per Micturition
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Total Overactive Bladder Symptom Score (OABSS)
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in OABSS Subscale Scores
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Total International Prostate Symptom Score (IPSS)
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in IPSS Subscale Scores
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Symptom Bother as Assessed by the Overactive Bladder Questionnaire (OAB-q)
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Total Health-Related QoL (HRQoL) Scores as Assessed by the OAB-q
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study drug up to Week 12
measure: Change From Baseline to EoT in Postvoid Residual (PVR) Volume
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline to EoT in Maximum Urine Flow Rate (Qmax)
timeFrame: Baseline and EoT (up to 12 weeks)
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP81046
city: Chiba
country: Japan
facility: Site JP81009
city: Chiba
country: Japan
facility: Site JP81045
city: Fukuoka
country: Japan
facility: Site JP81041
city: Fukuoka
country: Japan
facility: Site JP81042
city: Fukuoka
country: Japan
facility: Site JP81043
city: Fukuoka
country: Japan
facility: Site JP81044
city: Fukuoka
country: Japan
facility: Site JP81048
city: Gunma
country: Japan
facility: Site JP81004
city: Gunma
country: Japan
facility: Site JP81005
city: Hokkaido
country: Japan
facility: Site JP81001
city: Hokkaido
country: Japan
facility: Site JP81002
city: Hokkaido
country: Japan
facility: Site JP81003
city: Hyogo
country: Japan
facility: Site JP81038
city: Hyogo
country: Japan
facility: Site JP81039
city: Hyogo
country: Japan
facility: Site JP81040
city: Kanagawa
country: Japan
facility: Site JP81024
city: Kanagawa
country: Japan
facility: Site JP81056
city: Kochi
country: Japan
facility: Site JP81051
city: Kochi
country: Japan
facility: Site JP81052
city: Kumamoto
country: Japan
facility: Site JP81047
city: Osaka
country: Japan
facility: Site JP81025
city: Osaka
country: Japan
facility: Site JP81026
city: Osaka
country: Japan
facility: Site JP81027
city: Osaka
country: Japan
facility: Site JP81028
city: Osaka
country: Japan
facility: Site JP81029
city: Osaka
country: Japan
facility: Site JP81030
city: Osaka
country: Japan
facility: Site JP81031
city: Osaka
country: Japan
facility: Site JP81032
city: Osaka
country: Japan
facility: Site JP81033
city: Osaka
country: Japan
facility: Site JP81034
city: Osaka
country: Japan
facility: Site JP81035
city: Osaka
country: Japan
facility: Site JP81036
city: Osaka
country: Japan
facility: Site JP81037
city: Osaka
country: Japan
facility: Site JP81053
city: Osaka
country: Japan
facility: Site JP81054
city: Saitama
country: Japan
facility: Site JP81006
city: Saitama
country: Japan
facility: Site JP81007
city: Saitama
country: Japan
facility: Site JP81008
city: Shizuoka
country: Japan
facility: Site JP81050
city: Tokyo
country: Japan
facility: Site JP81010
city: Tokyo
country: Japan
facility: Site JP81011
city: Tokyo
country: Japan
facility: Site JP81012
city: Tokyo
country: Japan
facility: Site JP81013
city: Tokyo
country: Japan
facility: Site JP81014
city: Tokyo
country: Japan
facility: Site JP81015
city: Tokyo
country: Japan
facility: Site JP81016
city: Tokyo
country: Japan
facility: Site JP81017
city: Tokyo
country: Japan
facility: Site JP81018
city: Tokyo
country: Japan
facility: Site JP81019
city: Tokyo
country: Japan
facility: Site JP81020
city: Tokyo
country: Japan
facility: Site JP81021
city: Tokyo
country: Japan
facility: Site JP81022
city: Seoul
country: Korea, Republic of
facility: Site KR00001
city: Seoul
country: Korea, Republic of
facility: Site KR00002
city: Seoul
country: Korea, Republic of
facility: Site KR00003
city: Seoul
country: Korea, Republic of
facility: Site KR00004
city: Seoul
country: Korea, Republic of
facility: Site KR00005
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.