A Study to Examine the Safety and Efficacy of a New Drug in Patients With Symptoms of Overactive Bladder (OAB)
Condition: Overactive Bladder
MeSH terms: Urinary Bladder, Overactive
Intervention: vibegron; Vibegron placebo; Tolterodine Tartrate ER; Tolterodine placebo
Intervention description: single daily oral dose of vibegron 75 mg for 12 weeks; placebo to match vibegron (experimental drug); single daily oral dose of tolterodine tartrate ER 4 mg for 12 weeks; placebo to match tolterodine (active comparator)
Intervention MeSH terms: Tolterodine Tartrate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1530.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Beta-3 adrenergic receptor (β3-AR) agonists; Incontinence; OAB; Vibegron; Urge urinary incontinence; Urinary bladder, overactive; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Agents

Summary:

      This study is designed to evaluate the safety, tolerability, and efficacy of vibegron
      administered once daily in patients with OAB.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Has a history of OAB for at least 3 months prior to the Screening Visit.

          2. Meets either the OAB Wet or OAB Dry criteria.

        Exclusion Criteria:

        Urology Medical History

          1. Patient had an average total daily urine volume > 3000 mL in the past 6 months or
             during the 14-day Run-in Period.

          2. Has lower urinary tract pathology that could, in the opinion of the Investigator, be
             responsible for urgency, frequency, or incontinence.

          3. Has a history of surgery to correct stress urinary incontinence, pelvic organ
             prolapse, or procedural treatments for BPH within 6 months of Screening.

          4. Has current history or evidence of Stage 2 or greater pelvic organ prolapse (prolapse
             extends beyond the hymenal ring).

          5. Patient is currently using a pessary for the treatment of pelvic organ prolapse.

          6. Has a known history of elevated post-void residual volume defined as greater than 150
             mL.

          7. Has undergone bladder training or electrostimulation within 28 days prior to Screening
             or plans to initiate either during the study.

          8. Has an active or recurrent (> 3 episodes per year) urinary tract infection by clinical
             symptoms or pre-defined laboratory criteria.

          9. Has a requirement for an indwelling catheter or intermittent catheterization.

         10. Has received an intradetrusor injection of botulinum toxin within 9 months prior to
             Screening.

         11. Has uncontrolled hyperglycemia (defined as fasting blood glucose > 150 mg/dL or 8.33
             mmol/L and/or non-fasting blood glucose > 200 mg/dL or 11.1 mmol/L) or, if in the
             opinion of the Investigator, is uncontrolled.

         12. Has evidence of diabetes insipidus.

         13. Is pregnant, breast-feeding, or is planning to conceive within the projected duration
             of the study.

         14. Has a concurrent malignancy or history of any malignancy within 5 years prior to
             signing informed consent, except for adequately treated basal cell or squamous cell
             skin cancer or in situ cervical cancer.

         15. Has uncontrolled hypertension (systolic blood pressure of ≥ 180 mmHg and/or diastolic
             blood pressure of ≥ 100 mmHg) or has a resting heart rate (by pulse) > 100 beats per
             minute.

         16. Has narrow angle glaucoma (primary open angle glaucoma is not excluded).

         17. Has a history of cerebral vascular accident, transient ischemic attack, unstable
             angina, myocardial infarction, coronary artery interventions (e.g., coronary artery
             bypass grafting or percutaneous coronary interventions [e.g., angioplasty, stent
             insertion]), or neurovascular interventions (e.g., carotid artery stenting) within 6
             months prior to the Screening Visit. Has a known history of liver disease.

         18. Has a history of injury, surgery, or neurodegenerative diseases (e.g., multiple
             sclerosis, Parkinson's) that could affect the lower urinary tract or its nerve supply.

         19. Has hematuria, including microscopic hematuria according to pre-defined criteria.

         20. Has clinically significant electrocardiogram (ECG) abnormality.

         21. Has alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit
             of normal (ULN), or bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if
             secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome).

         22. Has an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2.

         23. Has an allergy, intolerance, or a history of a significant clinical or laboratory
             adverse experience associated with any of the active or inactive components of the
             vibegron formulation or tolterodine formulation.

         24. Is currently participating or has participated in a study with an investigational
             compound or device within 28 days prior to signing informed consent, or has
             participated in any previous study with vibegron.