Clinical trial NCT04764669: A Study of E2027 in Participants With Dementia With Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD) With or Without Amyloid Copathology
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lewy Body Disease
Parkinson Disease
Keywords: E2027
Amyloid Copathology
Parkinson's Disease Dementia
Dementia With Lewy Bodies
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 34
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9
timeFrame: Baseline, Week 9
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Treatment Emergent Orthostatic Hypotension
timeFrame: Week 3, Week 6, Week 9, Week 12 and Week 16
measure: Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Markedly Abnormal Laboratory Values
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings
timeFrame: From first dose of study drug up to Week 16
measure: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: From first dose of study drug up to Week 16
measure: Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)
timeFrame: Baseline, Week 12 and Week 16
Other outcomes:
Locations:
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Miami
country: United States
facility: Elias Research Associates (Allied Biomedical Research Institute)
state: Florida
city: Pompano Beach
country: United States
facility: Napa Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida, Department of Psychiatry and Behavioral Neurosciences
state: Florida
city: Wellington
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Lexington
country: United States
facility: University of Kentucky, Dept of Neurology, Sanders Brown Center on Aging
state: Kentucky
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJPC
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany, PC
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Dayton
country: United States
facility: Neurology Diagnostics, Inc.
state: Ohio
city: Lakewood
country: United States
facility: Cleveland Clinic, Lou Ruvo Center for Brain Health at Lakewood Hospital
state: Ohio
city: Portland
country: United States
facility: Summit Research Network (Oregon) Inc.
state: Oregon
city: Toronto
country: Canada
facility: Toronto Memory Program
Study officials:
References: