A Study of E2027 in Participants With Dementia With Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD) With or Without Amyloid Copathology

NCT ID: NCT04764669

Last Updated: 2022-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-25
• Study Completion Date: 2022-01-27

Brief Summary

The purpose of study is to demonstrate the pharmacodynamic (PD) effects of E2027 on cerebrospinal fluid (CSF) cyclic guanosine monophosphate (cGMP) in participants with DLB and PDD with and without amyloid copathology after 9 weeks of treatment.

Conditions

Lewy Body Disease; Parkinson Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DLB Without Amyloid Copathology

Participants with DLB (without amyloid copathology) will receive E2027 50 milligram (mg) capsules, orally, once daily up to 12 weeks.

Group Type: EXPERIMENTAL

E2027

Intervention Type: DRUG

Oral hypromellose capsules.

DLB With Amyloid Copathology

Participants with DLB (with amyloid copathology) will receive E2027 50 mg capsules, orally, once daily up to 12 weeks.

Group Type: EXPERIMENTAL

E2027

Intervention Type: DRUG

Oral hypromellose capsules.

PDD Without Amyloid Copathology

Participants with PDD (without amyloid copathology) will receive E2027 50 mg capsules, orally, once daily up to 12 weeks.

Group Type: EXPERIMENTAL

E2027

Intervention Type: DRUG

Oral hypromellose capsules.

PDD With Amyloid Copathology

Participants with PDD (with amyloid copathology) will receive E2027 50 mg capsules, orally, once daily up to 12 weeks.

Group Type: EXPERIMENTAL

E2027

Intervention Type: DRUG

Oral hypromellose capsules.

Interventions

E2027

Oral hypromellose capsules.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female, age 50 to 85 years, inclusive at time of consent

2. Meet criteria for probable DLB (as defined by the 4th report of the DLB Consortium) or meet criteria for probable PDD (as defined by the task force of the Movement Disorder Society).

3. Mini-mental state examination (MMSE) greater than (>) 14 and less than (<) 26 at Screening Visit

4. For DLB participants, have experienced visual hallucinations since onset of their DLB

5. If receiving acetylcholinesterase inhibitors (AChEIs), must have been on a stable dose for at least 12 weeks before Screening Visit, with no plans for dose adjustment during the study. Treatment naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs from Screening to the end of the study.

6. If receiving memantine, must have been on a stable dose for at least 12 weeks before Screening Visit, with no plans for dose adjustment during the study. Treatment naive participants can be entered into the study but there should be no plans to initiate treatment with memantine from Screening to the end of the study.

7. If receiving Parkinson's disease medications, must have been on a stable dose for at least 4 weeks before Screening Visit, with no plans for dose adjustment during the study.

8. Must have an identified caregiver or informant who is willing and able to provide follow up information on the participant throughout the course of the study.

9. Provide written informed consent.

Exclusion Criteria

1. Any neurological condition that may be contributing to cognitive impairment above and beyond those caused by the participant's DLB or PDD, including any comorbidities detected by clinical assessment or magnetic resonance imaging (MRI) (identification of amyloid copathology is not exclusionary)

2. History of transient ischemic attacks or stroke within 12 months of Screening

3. Modified Hachinski Ischemic Scale >4

4. Parkinsonian (extrapyramidal) features with Hoehn and Yahr Scale (HYS) stage 4 or higher

5. Any major psychiatric diagnosis, including schizophrenia, bipolar disorder and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition

6. Geriatric Depression Scale (GDS) score >8

7. Severe visual or hearing impairment that may interfere with the participant study assessments including cognitive testing

8. Any contraindications to lumbar puncture

9. History of deep brain stimulation or other neurosurgical procedure for Parkinson's disease

10. Has thyroid stimulating hormone (TSH) above normal range

11. Abnormally low serum vitamin B12 levels (< the lower limit of normal [LLN]) for the testing laboratory

12. Contraindications to MRI scanning

13. Evidence of other clinically significant lesions that suggest a dementia diagnosis other than DLB or PDD on brain MRI at Screening

14. Other significant pathological findings on brain MRI at Screening

15. Hypersensitivity to E2027 or any of the excipients

16. A prolonged corrected QT interval calculated using Fridericia's formula (QTcF) as demonstrated by triplicate ECG at the Screening or Baseline Visit (that is, mean value >450 millisecond [msec])

17. Had symptomatic orthostatic hypotension or symptomatic orthostatic tachycardia which resulted in hospitalization or urgent medical review in hospital in the past 12 months before Screening

18. Any other clinically significant abnormalities in vital signs, ECG and laboratory values that in the opinion of the investigator, require further investigation or treatment or that may interfere with study procedures or safety

19. Malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma of the skin, or localized prostate cancer in male participants). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before Screening need not be excluded.

20. Has a "yes" answer to C-SSRS suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening

21. Known or suspected history of drug or alcohol dependency or abuse within 2 years before Screening, current use of recreational drugs or a positive urine drug test at Screening.

22. Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator may affect the participant's safety or interfere with the study assessments

23. Taking any of the prohibited medications or not meeting the requirements regarding stable doses of permitted medications

24. Participation in a clinical study involving any investigational drug/device for DLB or PDD within 6 months before Screening or any other investigational drug/device in the 8 weeks or 5 half-lives (whichever is longer) of the study medication before Screening unless it can be documented that the participant was in a placebo treatment arm

25. Planned surgery which requires general, spinal or epidural anesthesia that will take place during the study.

26. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 98 days after study drug discontinuation. No sperm donation is allowed during the study period and for 98 days after study drug discontinuation.

27. Females who are breastfeeding or pregnant at Screening or Baseline

28. Females of childbearing potential who:

• Within 28 days before study entry, did not use a highly effective method of contraception
• Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Banner Sun Health Research Institute

Sun City, Arizona, United States

JEM Research Institute

Atlantis, Florida, United States

Elias Research Associates (Allied Biomedical Research Institute)

Miami, Florida, United States

Napa Research

Pompano Beach, Florida, United States

University of South Florida, Department of Psychiatry and Behavioral Neurosciences

Tampa, Florida, United States

Alzheimer's Research and Treatment Center

Wellington, Florida, United States

University of Kentucky, Dept of Neurology, Sanders Brown Center on Aging

Lexington, Kentucky, United States

Advanced Memory Research Institute of NJPC

Toms River, New Jersey, United States

Neurological Associates of Albany, PC

Albany, New York, United States

Columbia University Medical Center

New York, New York, United States

Neurology Diagnostics, Inc.

Dayton, Ohio, United States

Cleveland Clinic, Lou Ruvo Center for Brain Health at Lakewood Hospital

Lakewood, Ohio, United States

Summit Research Network (Oregon) Inc.

Portland, Oregon, United States

Toronto Memory Program

Toronto, , Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

E2027-A001-203

Identifier Type: -

Identifier Source: org_study_id