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

Sponsor
Eisai Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04764669
Collaborator
(none)
34
14
4
11
2.4
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
34 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label Study To Evaluate the Pharmacodynamic Effects, Efficacy, Safety, and Tolerability of E2027 in Subjects With Dementia With Lewy Bodies or Parkinson's Disease Dementia With or Without Amyloid Copathology
Actual Study Start Date :
Feb 25, 2021
Actual Primary Completion Date :
Dec 8, 2021
Actual Study Completion Date :
Jan 27, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: DLB Without Amyloid Copathology

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

Drug: E2027
Oral hypromellose capsules.

Experimental: DLB With Amyloid Copathology

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

Drug: E2027
Oral hypromellose capsules.

Experimental: PDD Without Amyloid Copathology

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

Drug: E2027
Oral hypromellose capsules.

Experimental: PDD With Amyloid Copathology

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

Drug: E2027
Oral hypromellose capsules.

Outcome Measures

Primary Outcome Measures

  1. Percentage Change From Baseline in CSF cGMP at 9 Weeks of Treatment [Baseline; Week 9]

Secondary Outcome Measures

  1. Percentage of Participants With Adverse Events (AEs) Including Severe AEs, Serious AEs, AEs Resulting in Study Discontinuation [Up to Day 112]

    AEs will be graded on a 3-point scale (mild, moderate, severe). Severe AEs will be defined as those AEs that are incapacitating, with inability to work or to perform normal daily activity. A serious AEs will be defined as any untoward medical occurrence that at any dose results in death or life-threatening AE or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.

  2. Percentage of Participants With Orthostatic Hypotension and Orthostatic Tachycardia [Up to Day 112]

  3. Percentage of Participants With Markedly Abnormal Laboratory Values and Shift from Baseline in Laboratory Values [Up to Day 112]

  4. Percentage of Participants With Abnormal Electrocardiogram (ECG) Parameters and ECG Findings [Up to Day 112]

  5. Percentage of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) [Up to Day 112]

    The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories) is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. C-SSRS assess whether participant experience any of the following: completed suicide; suicide attempt (response of "yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). Here, number of participants with positive response ("yes") to suicidal behavior or/and ideation, any non-suicidal self-injurious behavior will be reported.

  6. Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale part III: Motor Examination (UPDRS-III) [Baseline, Day 84 and Day 112]

    The UPDRS scale evaluates extrapyramidal features in motor function in Parkinson's disease. It contains 33 items in 18 categories: (1) speech, (2) facial expression, (3) rigidity, (4) finger tapping, (5) hand movements, (6) supinational and pronation movements of hands, (7) toe tapping, (8) leg agility, (9) arising from chair, (10) gait, (11) freezing of gait, (12) postural stability, (13) posture, (14) body bradykinesia, (15) postural tremor of hands, (16) kinetic tremor of hands, (17) rest tremor amplitude and (18) constancy of rest tremor. Each item is scored 0 (normal) to 4 (severe), giving a total score range 0 to 132. The higher score indicates the worse motor function.

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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])

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

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

  8. 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

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

  10. 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.

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

  12. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Banner Sun Health Research Institute Sun City Arizona United States 85351
2 JEM Research Institute Atlantis Florida United States 33462
3 Elias Research Associates (Allied Biomedical Research Institute) Miami Florida United States 33155
4 Napa Research Pompano Beach Florida United States 33064
5 University of South Florida, Department of Psychiatry and Behavioral Neurosciences Tampa Florida United States 33613
6 Alzheimer's Research and Treatment Center Wellington Florida United States 33414
7 University of Kentucky, Dept of Neurology, Sanders Brown Center on Aging Lexington Kentucky United States 40536
8 Advanced Memory Research Institute of NJPC Toms River New Jersey United States 08755
9 Neurological Associates of Albany, PC Albany New York United States 12208
10 Columbia University Medical Center New York New York United States 10032
11 Neurology Diagnostics, Inc. Dayton Ohio United States 45459
12 Cleveland Clinic, Lou Ruvo Center for Brain Health at Lakewood Hospital Lakewood Ohio United States 44107
13 Summit Research Network (Oregon) Inc. Portland Oregon United States 97210
14 Toronto Memory Program Toronto Canada M3B 2S7

Sponsors and Collaborators

  • Eisai Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT04764669
Other Study ID Numbers:
  • E2027-A001-203
First Posted:
Feb 21, 2021
Last Update Posted:
Feb 7, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Eisai Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 7, 2022