A Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Men With OAB Symptoms While Taking Tamsulosin Hydrochloride for Lower Urinary Tract Symptoms (LUTS) Due to Benign Prostatic Hyperplasia (BPH)
Condition: Benign Prostatic Hyperplasia; Overactive Bladder
MeSH terms: Urinary Bladder, Overactive; Prostatic Hyperplasia; Hyperplasia; Lower Urinary Tract Symptoms
Intervention: Mirabegron; Placebo; Tamsulosin Hydrochloride
Intervention description: Participants received initial dose of 25 mg of mirabegron (oral tablet) which was increased to 50 mg after 4 weeks.; Participants received initial dose of 25 mg of matching placebo (oral tablet) which was increased to 50 mg after 4 weeks.; Participants received once daily treatment with tamsulosin hydrochloride 0.4 mg (oral tablet) throughout the study.
Intervention MeSH terms: Tamsulosin; Mirabegron
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 715.0
Sex: Male
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Myrbetriq; Lower Urinary Tract Symptoms; Benign Prostatic Hyperplasia; Overactive Bladder; Betmiga; Mirabegron; Tamsulosin Hydrochloride

Summary:

      The purpose of the study was to assess the efficacy, safety, and tolerability of mirabegron
      versus placebo in men with overactive bladder (OAB) symptoms while taking tamsulosin
      hydrochloride for lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia
      (BPH).
    

Eligibility criteria:

        Inclusion Criteria assessed at Visit 1 (Screening):

          -  Men ≥40 years of age with history of overactive bladder (OAB) symptoms (frequency of
             ≥8 micturitions per day and urgency episodes of ≥2 per day) while taking tamsulosin
             hydrochloride for at least 2 months to treat LUTS due to BPH.

          -  Subject has symptoms of OAB (urinary frequency and urgency with or without
             incontinence) for ≥3 months prior to Screening.

          -  Subject has an International Prostate Symptom Score (IPSS) score ≥8.

          -  Subject has Prostate-Specific Antigen (PSA) <4 ng/mL or ≥4 but < 10 ng/mL with a
             prostate biopsy that is negative for cancer in the past 2 years.

          -  Subject is willing and able to complete the 3-day diary (including urine volumes,
             vital signs measurements), and Quality of Life questionnaires.

          -  Subject and the subject's spouses/partners who are of childbearing potential must be
             using a highly effective birth control, which includes established use of oral,
             injected or implanted hormonal methods of contraception, placement of an intrauterine
             device (IUD) or intrauterine system (IUS). Birth control must be practiced from
             Screening and continue throughout the study and for 30 days after the final study drug
             administration. In addition, sperm donation will not be allowed throughout the study
             and for 30 days after the final study drug administration.

          -  Subject agrees not to participate in another interventional study while on treatment.

        Inclusion Criteria assessed at Visit 2 (Baseline) based on the 3-day diary:

          -  Subject continues to meet all inclusion criteria of Visit 1 (Screening).

          -  Subject must experience an average of 8 or more micturitions per day over the 3-day
             diary period.

          -  Subject must experience an average of 2 episodes of urgency per day (grade 3 or 4)
             over the 3-diary period

        Exclusion Criteria assessed at Visit 1 (Screening):

          -  Subject has post-void residual volume (PVR) >200 mL.

          -  Subject has maximum urinary flow (Qmax) <5.0 mL/second with a minimum voided volume of
             125 mL.

          -  Subject has hematuria >3 rbc/hpf that has not been fully evaluated.

          -  Subject has evidence of Urinary Tract Infection (UTI). Urine culture and sensitivity
             will be performed for positive leukocytes, nitrites, or turbidity 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 may be rescreened after successful treatment of the
             UTI (confirmed by a laboratory result of negative urine culture).

          -  Subject has neurogenic bladder (spinal cord injury, multiple sclerosis, Parkinson's,
             etc.).

          -  Subject has diabetic neuropathy.

          -  Previous open, robotic or minimally invasive prostate surgery (including transurethral
             procedures). Planned (scheduled) pelvic or prostate surgery during the study period.

          -  Planned (scheduled) cataract surgery.

          -  Subject with significant stress incontinence

          -  Subject with clinically significant bladder outlet obstruction.

          -  Subject has an indwelling catheter or practices intermittent self-catheterization.

          -  Subject has experienced 3 or more episodes of recurrent urinary tract infection within
             the last 12 months.

          -  Subject has a symptomatic urinary tract infection, prostatitis, chronic inflammation
             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, prostate and rectum; organs of the lower
             gastrointestinal tract are not necessarily considered pelvic organs such as the distal
             ascending colon, the full transverse colon and proximal portion of the descending
             colon are in the abdomen).

          -  Subject has received intravesical injection in the past 12 months with botulinum
             toxin, resiniferatoxin, or capsaicin.

          -  Subject has ever 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 postural hypotension or syncope or postural orthostatic tachycardia.

          -  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/1.73 m2 as determined by hospital laboratory calculation of eGFR. A
             subject with End Stage Renal Disease (ESRD) 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 ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg.

          -  Subject has baseline resting pulse rate <60 BPM or >90 BPM.

          -  Subject has evidence of QT prolongation on Screening (Visit 1) or Baseline (Visit 2)
             electrocardiogram (ECG) defined as QTcF >450 msec.

          -  Subject has any clinically significant ECG abnormality.

          -  Subject has AST or ALT >2x upper limit of normal (ULN), or γ-GT >3x ULN and considered
             clinically significant.

          -  Subject has a hypersensitivity to any components of mirabegron, tamsulosin
             hydrochloride, or any of the inactive ingredients.

          -  Subject has a history of angioedema.

          -  Subject has any clinical significant condition which 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 has ongoing alcohol and/or drug abuse.

          -  Subject is using prohibited medications within 30 days prior to Screening (Visit 1)
             through Follow-Up Phone Call (Visit 6).

          -  Subject has stopped, started or changed the dose of a restricted medication within the
             30 days prior to Screening (Visit 1) through Follow-Up Phone Call (Visit 6)

          -  Subject has participated in an interventional trial within 30 days prior to Screening
             (Visit 1).

          -  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 in the 6 months prior to Screening (Visit
             1).

        Exclusion Criteria assessed at Visit 2 (Baseline):

          -  Subject was non-compliant during the 4-week tamsulosin hydrochloride run-in period,
             defined as taking less than 80% or greater than 120% of study medication.

          -  Subject had an average total daily urine volume >3000 mL as recorded in the 3-day
             diary.