NCT04764669

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Feb 2021

Shorter than P25 for phase_2

Geographic Reach
2 countries

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 19, 2021

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 21, 2021

Completed
4 days until next milestone

Study Start

First participant enrolled

February 25, 2021

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 8, 2021

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2022

Completed
8 months until next milestone

Results Posted

Study results publicly available

September 26, 2022

Completed
Last Updated

September 26, 2022

Status Verified

August 1, 2022

Enrollment Period

10 months

First QC Date

February 19, 2021

Results QC Date

August 30, 2022

Last Update Submit

August 30, 2022

Conditions

Lewy Body DiseaseParkinson Disease

Keywords

E2027Amyloid CopathologyParkinson's Disease DementiaDementia With Lewy Bodies

Outcome Measures

Primary Outcomes (1)

  • Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9

    cGMP was measured in CSF samples using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantitative at 0.500 nanogram per milliliter (ng/ml). Evaluation of cGMP following dosing of E2027 was based on relative percent change from baseline.

    Baseline, Week 9

Secondary Outcomes (7)

  • Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation

    From first dose of study drug up to Week 16

  • Number of Participants With Treatment Emergent Orthostatic Hypotension

    Week 3, Week 6, Week 9, Week 12 and Week 16

  • Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia

    From first dose of study drug up to Week 16

  • Number of Participants With Markedly Abnormal Laboratory Values

    From first dose of study drug up to Week 16

  • Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings

    From first dose of study drug up to Week 16

  • +2 more secondary outcomes

Study Arms (4)

DLB Without Amyloid Copathology

EXPERIMENTAL

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

Drug: E2027

DLB With Amyloid Copathology

EXPERIMENTAL

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

Drug: E2027

PDD Without Amyloid Copathology

EXPERIMENTAL

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

Drug: E2027

PDD With Amyloid Copathology

EXPERIMENTAL

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

Drug: E2027

Interventions

E2027DRUG

Oral hypromellose capsules.

DLB With Amyloid CopathologyDLB Without Amyloid CopathologyPDD With Amyloid CopathologyPDD Without Amyloid Copathology

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female, age 50 to 85 years, inclusive at time of consent
  • 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).
  • Mini-mental state examination (MMSE) greater than (\>) 14 and less than (\<) 26 at Screening Visit
  • For DLB participants, have experienced visual hallucinations since onset of their DLB
  • 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.
  • 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.
  • 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.
  • 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.
  • Provide written informed consent.

You may not qualify if:

  • History of transient ischemic attacks or stroke within 12 months of Screening
  • Modified Hachinski Ischemic Scale \>4
  • Parkinsonian (extrapyramidal) features with Hoehn and Yahr Scale (HYS) stage 4 or higher
  • Any major psychiatric diagnosis, including schizophrenia, bipolar disorder and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition
  • Geriatric Depression Scale (GDS) score \>8
  • Severe visual or hearing impairment that may interfere with the participant study assessments including cognitive testing
  • Any contraindications to lumbar puncture
  • History of deep brain stimulation or other neurosurgical procedure for Parkinson's disease
  • Has thyroid stimulating hormone (TSH) above normal range
  • Abnormally low serum vitamin B12 levels (\< the lower limit of normal \[LLN\]) for the testing laboratory
  • Contraindications to MRI scanning
  • Evidence of other clinically significant lesions that suggest a dementia diagnosis other than DLB or PDD on brain MRI at Screening
  • Other significant pathological findings on brain MRI at Screening
  • Hypersensitivity to E2027 or any of the excipients
  • 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 \[msec\])
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Elias Research Associates (Allied Biomedical Research Institute)

Miami, Florida, 33155, United States

Location

Napa Research

Pompano Beach, Florida, 33064, United States

Location

University of South Florida, Department of Psychiatry and Behavioral Neurosciences

Tampa, Florida, 33613, United States

Location

Alzheimer's Research and Treatment Center

Wellington, Florida, 33414, United States

Location

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

Lexington, Kentucky, 40536, United States

Location

Advanced Memory Research Institute of NJPC

Toms River, New Jersey, 08755, United States

Location

Neurological Associates of Albany, PC

Albany, New York, 12208, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Neurology Diagnostics, Inc.

Dayton, Ohio, 45459, United States

Location

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

Lakewood, Ohio, 44107, United States

Location

Summit Research Network (Oregon) Inc.

Portland, Oregon, 97210, United States

Location

Toronto Memory Program

Toronto, M3B 2S7, Canada

Location

MeSH Terms

Conditions

Lewy Body DiseaseParkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesDementiaMovement DisordersSynucleinopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Limitations and Caveats

Due to insufficient numbers enrolled of participants with PDD and amyloid copathology, interpretation of results in this subgroup is limited.

Results Point of Contact

Title
Eisai Medical Information
Organization
Eisai, Inc.
esi_medinfo@eisai.com
+1-888-274-2378

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 19, 2021

First Posted

February 21, 2021

Study Start

February 25, 2021

Primary Completion

December 8, 2021

Study Completion

January 27, 2022

Last Updated

September 26, 2022

Results First Posted

September 26, 2022

Record last verified: 2022-08

Data Sharing

IPD Sharing
Will share

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Locations

US(13)CA(1)