A Study to Evaluate Tolerability and Participants Preference Between Mirabegron and Tolterodine Extended Release (ER) in Participants With Overactive Bladder (OAB)
Condition: Overactive Bladder (OAB)
MeSH terms: Urinary Bladder, Overactive
Intervention: Mirabegron; Tolterodine ER
Intervention description: Oral; Oral
Intervention MeSH terms: Mirabegron; Tolterodine Tartrate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 376.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Overactive bladder (OAB); tolterodine ER; mirabegron

Summary:

      The purpose of this study was to assess tolerability of mirabegron compared to tolterodine ER
      in the treatment of participants with symptoms of Overactive Bladder (OAB) as well as the
      impact of treatment on micturition frequency and incontinence episodes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is willing and able to complete the micturition diary and questionnaires
             correctly.

          -  Participant has symptoms of OAB (urinary frequency and urgency with or without
             incontinence) for greater than or equal to 3 months prior to Screening.

          -  Participant must be treatment-naïve to pharmaceutical agents for OAB.

          -  Female participant must not donate ova starting at Screening and throughout the study
             period, and for 30 days after the final study drug administration.

          -  Male participant must not donate sperm starting at Screening and throughout the study
             period and for at least 30 days after final study drug administration.

          -  Participant agrees not to participate in another interventional study from the time of
             screening until the final study visit.

          -  Inclusion Criteria assessed at Visit 2 (Week 0) based on the 3-day micturition diary:

               -  Participant continues to meet all inclusion criteria of Visit 1.

               -  Participant must experience at least 3 episodes of urgency (grade 3 or 4) during
                  the 3 day micturition diary.

               -  Participant must experience an average of greater than or equal to 8
                  micturitions/day on the 3 day micturition diary

        Exclusion Criteria:

          -  Female participant who is lactating or is intending to breastfeed during the study
             period and for 30 days after the final study visit.

          -  The participant has clinically significant bladder outlet obstruction (BOO) posing a
             risk of urinary retention.

          -  Participant has significant stress incontinence or mixed stress/urgency incontinence
             where stress is the predominant factor.

          -  Participant has evidence of Urinary Tract Infection (UTI) (urine culture greater than
             100,000 cfu/mL) as assessed at Screening (Visit 1). The participant can be rescreened
             after successful treatment of the UTI (confirmed by a laboratory result of negative
             urine culture).

          -  Participant has a neurological cause for detrusor overactivity (e.g., neurogenic
             bladder, diabetic neuropathy or systemic or central neurological disease such as
             multiple sclerosis and Parkinson's disease).

          -  Participant has an indwelling catheter or practices intermittent self-catheterization.

          -  Participant has a chronic inflammatory condition 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 and rectum in both sexes and the uterus, ovaries, and fallopian tubes in
             females); or of the lower gastrointestinal tract.

          -  Participant has uncontrolled narrow angle glaucoma, urinary or gastric retention,
             severe colitis ulcerosa, toxic megacolon, myasthenia gravis, polio or any other
             medical condition which makes the use of anticholinergics contraindicated.

          -  Participant has received intravesical injection in the past 12 months with botulinum
             toxin, resiniferatoxin, or capsaicin.

          -  Participant has received invasive treatment including electro-stimulation therapy.

          -  Participant is receiving a bladder training program or pelvic floor exercises which
             started or has changed less than 30 days prior to Screening.

          -  Participant has hepatic impairment defined as Child-Pugh Class A, B or C.

          -  Participant has severe renal impairment defined as creatinine clearance less than 30
             mL/min. A participant with End Stage Renal Disease or undergoing dialysis is also not
             a candidate for the study.

          -  Participant has severe uncontrolled hypertension, which is defined as a sitting
             systolic blood pressure greater than or equal 180 mmHg and/or diastolic blood pressure
             greater than or equal 110 mmHg.

          -  Participant has evidence of QT prolongation on electrocardiogram (ECG) defined as QTcF
             greater than 450 msec for males, QTcF greater than 470 msec for females or a known
             history of QT prolongation.

          -  Participant has a serum creatinine greater than 150 µmol/L, or aspartate
             aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2x upper limit
             of normal (ULN), or γ-GT greater than 3x ULN and considered clinically significant.

          -  Participant has a hypersensitivity to any components of Myrbetriq (mirabegron), other
             β-AR agonists, tolterodine or other antimuscarinic agents, or any of the inactive
             ingredients.

          -  Participant has been treated with an experimental device within 30 days or received an
             investigational agent within 30 days prior to Screening.

          -  Participant 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.

          -  Participant with current history of alcohol and/or drug abuse.

          -  Participant 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.

          -  Exclusion Criteria assessed at Visit 2 (Week 0):

               -  Participant fulfills any exclusion criteria at Visit 1.