Mirabegron in Parkinson Disease and Impaired Cognition
Condition: Parkinson Disease; Overactive Bladder; Impaired Cognition
MeSH terms: Parkinson Disease; Urinary Bladder, Overactive; Cognitive Dysfunction
Intervention: mirabegron; Placebo
Intervention MeSH terms: Mirabegron
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 7.0
Sex: All
Minimum age: 25 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: mirabegron

Summary:

      There is a high prevalence of OAB symptoms among patients with Parkinson's disease and a lack
      of pharmacotherapies with an acceptable side effect profile. Specifically, available
      anticholinergic medications have a high risk of cognitive side-effects, which preclude their
      use in PD patients with CI. PD can also cause a number of non-motor symptoms that are likely
      to be adversely affected by the currently available anticholinergic agents. Mirabegron is the
      first pharmacologic treatment which may not exacerbate CI, constipation, orthostatic
      hypotension (OH), somnolence, and dry mouth in PD.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          1. Aged 25-80 at screening. Subjects older than 80 will be allowed at the discretion of
             the PI.

          2. Ambulatory (defined as able to ambulate at least 10 meters, with or without
             assistance).

          3. Clinical Diagnosis of PD based on the United Kingdom Brain Bank diagnostic criteria
             for PD.

          4. At baseline visit (Visit 2) patients must have:

               -  At least 8 micturitions per 24 hours and

               -  At least 3 urgency episodes per 3-day diary.

          5. A MoCA score between 19 and 28 (inclusive) at screening. For those on cognitive
             enhancers (donepezil, rivastigmine, memantine, galantamine) a MoCA score between 19
             and 29 (inclusive) at screening.

          6. Provide informed consent to participate in the study and understand that they may
             withdraw their consent at any time without prejudice to their future medical care.

          7. Be cognitively capable, in the opinion of investigator, to understand and provide such
             informed consent.

          8. Be cognitively capable to complete the required questionnaires and assessments, OR
             have a care partner who is willing and capable to assist them in the completion of
             these tasks.

          9. Be on a stable regimen of antiparkinson's medications at least 30 days prior to
             screening, and be expected to remain on a stable dose for the duration of the study.

         10. If taking cognitive enhancers (donepezil, rivastigmine, memantine, galantamine), must
             be on stable dose at least 30 days prior to screening, and be expected to remain on a
             stable dose for the duration of the study.

        EXCLUSION CRITERIA:

          1. Known or suspected alcohol or substance abuse in the preceding 12 months.

          2. Women who are pregnant or breastfeeding.

          3. Women of childbearing potential (WOCP) who are not using at least one method of
             contraception.

          4. Patients with severe renal impairment (CLcr ≤ 29 mL/min, or eGFR ≤ 29 mL/min/1.73 m2),
             or moderate or severe hepatic impairment (Child-Pugh classes B or C).

          5. Patients with bladder outlet obstruction (BOO) that, in the opinion of the study
             urologist, would expose them to risk of urinary retention during treatment with
             mirabegron.

          6. Patients treated with drugs metabolized by the CYP2D6 pathway.

          7. Patients with supine systolic blood pressure (SBP) ≥ 180 mm Hg, or diastolic blood
             pressure (DBP) ≥ 110 mm Hg.

          8. Clinically significant, uncontrolled cardiac arrhythmia, unstable angina, congestive
             heart failure (NYHA Class 3 or 4), or history of myocardial infarction in the
             preceding 2 years.

          9. History of cancer in the preceding 2 years other than successfully treated,
             non-metastatic, squamous cell or basal cell carcinoma, or cervical cancer in situ.

         10. Any major urological procedure in the preceding 90 days.

         11. Any major surgical procedure in the preceding 30 days.

         12. Previously treated with mirabegron within 60 days prior to the baseline visit (Visit
             2), or previously having failed treatment with mirabegron regardless of duration and
             timing of treatment.

         13. Current or previous, within the 60 days preceding the baseline visit (Visit 2),
             treatment with antimuscarinic agents for OAB symptoms; and, willingness to not use
             antimuscarinic agents for the duration of the study.

         14. Currently receiving any other investigational drug or having received an
             investigational drug within the 60 days preceding the baseline visit (Visit 2).

         15. Any condition or laboratory test result, which, in the opinion of the Investigator or
             the Study Urologist, might result in an increased risk to the patient, or would affect
             their participation in the study.

         16. Any patient who, in the opinion of the Investigator, is not a good candidate for the
             study or will not be able to follow study procedures.