Study to Assess the Efficacy and Safety of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder
Condition: Urinary Bladder, Overactive
MeSH terms: Urinary Bladder, Overactive
Intervention: Mirabegron; Tolterodine; Placebo to Mirabegron; Placebo to Tolterodine
Intervention description: Tablets; Capsules; Matching mirabegron placebo tablets.; Matching tolterodine placebo capsules.
Intervention MeSH terms: Mirabegron; Tolterodine Tartrate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2336.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Micturition; Urinary incontinence; Urinary urge incontinence; Overactive bladder (OAB); Urgency; YM178; Frequency

Summary:

      The study is intended to test efficacy, safety and tolerability of two doses of Mirabegron
      against placebo and compare the efficacy and safety with active comparator in patients with
      symptoms of overactive bladder.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject is willing and able to complete the micturition diary and questionnaires
             correctly

          -  Subject has symptoms of overactive bladder (urinary frequency and urgency with or
             without urge incontinence) for ≥ 3 months

          -  Subject experiences frequency of micturition on average ≥ 8 times per 24-hour period
             during the 3-day micturition diary period

          -  Subject must experience at least 3 episodes of urgency (grade 3 or 4) with or without
             incontinence, during the 3-day micturition diary period

        Exclusion Criteria:

          -  Subject is breastfeeding, pregnant, intends to become pregnant during the study, or of
             childbearing potential, sexually active and not practicing a highly reliable method of
             birth control

          -  Subject has significant stress incontinence or mixed stress/urge incontinence where
             stress is the predominant factor

          -  Subject has an indwelling catheter or practices intermittent self-catheterization

          -  Subject has diabetic neuropathy

          -  Subject has evidence of a symptomatic urinary tract infection, chronic inflammation
             such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or
             previous or current malignant disease of the pelvic organs

          -  Subject receives non-drug treatment including electro-stimulation therapy

          -  Subject has severe hypertension

          -  Subject has a known or suspected hypersensitivity to tolterodine, other
             anticholinergics, YM178, other beta-adrenoreceptor (ß-AR) agonists, or lactose or any
             of the other inactive ingredients

          -  Subject has been treated with any investigational drug or device within 30 days (90
             days in the UK)

          -  Subject had an average total daily urine volume > 3000 mL as recorded in the 3-day
             micturition diary period

          -  Subject has serum creatinine >150 umol/L, aspartate aminotransferase (AST) and/or
             alanine aminotransferase (ALT) > 2x upper limit of normal range (ULN), or gamma
             glutamyl transferase (γ-GT) > 3x ULN

          -  Subject has a clinically significant abnormal electrocardiogram (ECG)