Study to Test the Long Term Safety and Efficacy 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; Extended release 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: 2792.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Frequency; Overactive Bladder; Urgency; Urinary urge incontinence; Urinary incontinence; Micturition

Summary:

      The study is intended to test the safety, tolerability, efficacy of two doses of long term
      once daily (qd) treatment of Mirabegron in patients with symptoms of overactive bladder and
      secondly to compare these with active comparator.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient is willing and able to complete the micturition diary and questionnaires
             correctly

          -  Patient has symptoms of overactive bladder for ≥ 3 months

          -  Patient experiences frequency of micturition on average ≥ 8 times per 24-hour period
             during the 3-day micturition diary period

          -  Patient 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:

          -  Patient 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

          -  Patient has significant stress incontinence or mixed stress/urge incontinence where
             stress is the predominant factor

          -  Patient has an indwelling catheter or practices intermittent self-catheterization

          -  Patient has diabetic neuropathy

          -  Patient 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

          -  Patient receives non-drug treatment including electro-stimulation therapy

          -  Patient has severe hypertension

          -  Patient 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

          -  Patient has been treated with any investigational drug or device within 30 days (90
             days in the UK for all clinical studies except 178-CL-046)

          -  Patient had an average total daily urine volume > 3000 mL as recorded in the 3-day
             micturition diary period

          -  Patient has serum creatinine >150 umol/L, aspartate aminotransferase (AST) and/or
             alanine aminotransferase (ALT) > 2x upper limit of normal range (ULN), or
             gamma-glutamyl transpeptidase (γ-GT) > 3x ULN

          -  Patient has a clinically significant abnormal electrocardiogram (ECG)