Evaluation of the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of E2609 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this single-center, randomized, double-blind, placebo-controlled, study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of E2609 when administered to healthy elderly subjects.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of E2609 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: E2609
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy males and females Female subjects must be of non-childbearing potential Aged 50 to 85 years, inclusive BMI of 18 to 32 kg/m2 at screening Thyroid function tests within normal rangeMini-Mental State Examination score of 28-30, inclusive Key Exclusion Criteria: History of neurological abnormalities, including seizures Any clinically significant abnormality of the ECG at Screening and Baseline including QTc prolongation History of ischemic heart disease, cardiac arrhythmias, cerebrovascular diseases Other medical conditions that are not stably controlled Presence of orthostatic hypotension

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E2609<br>E2609 at ascending doses | Drug: E2609<br>* E2609 to be administered for 14 days, concurrently with placebo controls. Doses will be 25, 50, and 200 mg once daily by the oral route, each dose administered to a separate cohort (group) of subjects. After each dose has been administered to all subjects in a given cohort, safety and tolerability findings will be evaluated and a decision made by the sponsor and investigators as to whether or not to proceed to the next higher dose.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* E2609 to be administered for 14 days, concurrently with placebo controls. Doses will be 25, 50, and 200 mg once daily by the oral route, each dose administered to a separate cohort (group) of subjects. After each dose has been administered to all subjects in a given cohort, safety and tolerability findings will be evaluated and a decision made by the sponsor and investigators as to whether or not to proceed to the next higher dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | 19 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Cmax and AUC (0-24h) of E2609 on Day 1 and Day 14 |  | 20 days | 
| Plasma Aβ(1-x) Amax (defined as maximum change (%) of E2609 levels compared to time-matched baseline at a single time point within 24 hours postdose) in plasma and cerebrospinal fluid, plasma and CSF |  | 20 days | 
| Time at which Amax occurs for plasma Aβ(1-x) |  | 20 days | 
| Area under the plasma Aβ(1-x) concentration, AUAC(0-24h), by time curve from time 0 to time 24 hours on Day -1, Day 1, and Day 14 |  | 20 days | 
| Change (%) in plasma Aβ(1-x) AUAC within 24 hours comparing Day 1 to Day -1 and Day 14 to Day -1 |  | 20 days | 
| Percent change of Aβ(1-x) in CSF from Day -2 to Day 14 |  | 20 days |