Mirabegron in Parkinson Disease and Impaired Cognition

NCT02536976 | Completed Phase 4 Results DMC

• 1 other identifier: 04412-15-A
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Parkinson Disease; Overactive Bladder; Impaired Cognition

Keywords

mirabegron

Outcome Measures

Primary Outcomes (1)

• Change in Montreal Cognitive Assessment Total Score

  Change in Montreal Cognitive Assessment Total Score between week 2 and week 14. The Montreal Cognitive Assessment is a screening tool for global cognitive function with a total score ranging from 0 to 30 units on a scale, with higher score indicating better cognitive global function. Normal range is 26 thru 30.

  From Week 2 to Week 14

Secondary Outcomes (2)

• Change in Overactive Bladder Questionnaire Subscale Scores

  From Week 2 to Week 14

• Change in Unified Parkinson's Disease Rating Scale

  From Week 2 to Week 14

Study Arms (2)

Active treatment

EXPERIMENTAL

mirabegron

Drug: mirabegron

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

mirabegron DRUG

Also known as: Myrbetriq

Active treatment

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 25-80 at screening. Subjects older than 80 will be allowed at the discretion of the PI.
• Ambulatory (defined as able to ambulate at least 10 meters, with or without assistance).
• Clinical Diagnosis of PD based on the United Kingdom Brain Bank diagnostic criteria for PD.
• 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.
• 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.
• 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.
• Be cognitively capable, in the opinion of investigator, to understand and provide such informed consent.
• 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.
• 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.
• 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.

You may not qualify if:

• Known or suspected alcohol or substance abuse in the preceding 12 months.
• Women who are pregnant or breastfeeding.
• Women of childbearing potential (WOCP) who are not using at least one method of contraception.
• 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).
• 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.
• Patients treated with drugs metabolized by the CYP2D6 pathway.
• Patients with supine systolic blood pressure (SBP) ≥ 180 mm Hg, or diastolic blood pressure (DBP) ≥ 110 mm Hg.
• 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.
• 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.
• Any major urological procedure in the preceding 90 days.
• Any major surgical procedure in the preceding 30 days.
• 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.
• 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.
• Currently receiving any other investigational drug or having received an investigational drug within the 60 days preceding the baseline visit (Visit 2).
• 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.

Sponsors & Collaborators

• HealthPartners Institute: lead

Study Sites (1)

Struthers Parkinson's Center

Golden Valley, Minnesota, 55427, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Urinary Bladder, Overactive; Cognition Disorders

Interventions

mirabegron

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

Study closed before reaching target enrollment. Due to the small number of participants enrolled no statistical analysis was performed, therefore no conclusions can be obtained.

Results Point of Contact

• Title: Dr. Sotirios Parashos
• Organization: Struthers Parkinson's Center

sotirios.parashos@parknicolet.com

001-952-993-5495

Study Officials

• Sotirios A Parashos, MD, PhD

  Struthers Parkinson's Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2015
• First Posted: September 1, 2015
• Study Start: December 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: May 8, 2019
• Results First Posted: May 8, 2019

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)