Phase 2 N=34 Treatment

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

Lewy Body Disease · Parkinson Disease

Bottom Line

View on ClinicalTrials.gov: NCT04764669 ↗

Enrolled (actual)

Serious AEs

2.9%

Results posted

Sep 2022

Primary outcome: Primary: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9 — 230.412; 250.434; 186.869; 362.519 Percent Change in CSF (ng/mL)

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: E2027 (Drug)
Age: Adult, Older Adult · 50+ yrs
Sex: All
Sponsor: Eisai Inc.
Primary completion: Dec 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9	230.412; 250.434; 186.869; 362.519	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation	6; 4; 3; 2; 1; 0	—
SECONDARY Number of Participants With Treatment Emergent Orthostatic Hypotension	0; 1; 1; 0; 0; 3	—
SECONDARY Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia	0; 1; 0; 0	—
SECONDARY Number of Participants With Markedly Abnormal Laboratory Values	0; 0; 0; 2; 0; 0	—
SECONDARY Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)	0; 0; 0; 0; 0; 0	—
SECONDARY Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)	21.1; 24.6; 28.9; 38.0; 5.0; 6.5	—

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

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 ( 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 ( 450 millisecond [msec])
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
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
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.
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
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.
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
Taking any of the prohibited medications or not meeting the requirements regarding stable doses of permitted medications
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
Planned surgery which requires general, spinal or epidural anesthesia that will take place during the study.
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.
Females who are breastfeeding or pregnant at Screening or Baseline
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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04764669). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.