A Study to Assess Safety, Tolerability, and Pharmacokinetics of E2307 in Healthy Young and Elderly Japanese Subjects

Study Overview
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Brief Summary
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This study will be a single-center, single dose, randomized, double-blind, placebo-controlled study in healthy Japanese male subjects. The study will consist of 2 parts: Part A (young subjects) and Part B (elderly subjects). In Part A sequential cohorts of subjects will be treated with single ascending doses of E2307. The maximum tolerated dose (MTD) will be determined in Part A. Part B will be initiated after Part A is completed. In Part B one cohort of healthy elderly subjects will be treated with a single dose of E2307 at one dose level below the MTD. In part A, a total of 56 subjects will be enrolled into 7 cohorts sequentially and randomized 3:1 to receive either E2307 (1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 200 mg, or 300 mg) or placebo. In part B, a total of 8 subjects will be randomized, 6 subjects to a single dose of E2307 and 2 subjects to placebo.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single-Ascending Dose Study to Assess Safety, Tolerability, and Pharmacokinetics of E2307 in Healthy Young and Elderly Japanese Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: E2307
* Drug: E2307 Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parts A and B Provide written informed consent Willing and able to comply with all aspects of the protocol Part A: Young cohort Non-smoking, male subjects age >=20 years and less than 55 years old at the time of informed consent Part B: Elderly Cohort Non-smoking, male subjects age >=65 years and less than 85 years old at the time of informed consent Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from this study: Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing Any history of abdominal surgery that may affect PK profiles of E2307 (eg. hepatectomy, nephrectomy, digestive organ resection) Known history of clinically significant drug allergy (at Screening)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

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: Part A: 1 mg E2307 (young cohort)<br>E2307 (1 x 1 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule) | Drug: E2307<br> <br> Drug: E2307 Matching Placebo<br> <br> |
| Experimental: Part A: 3 mg E2307 (young cohort)<br>E2307 (3 x 1 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules) | Drug: E2307<br> <br> Drug: E2307 Matching Placebo<br> <br> |
| Experimental: Part A: 10 mg E2307 (young cohort)<br>E2307 (1 x 10 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule) | Drug: E2307<br> <br> Drug: E2307 Matching Placebo<br> <br> |
| Experimental: Part A: 30 mg E2307 (young cohort)<br>E2307 (3 x 10 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules) | Drug: E2307<br> <br> Drug: E2307 Matching Placebo<br> <br> |
| Experimental: Part A: 100 mg E2307 (young cohort)<br>E2307 (1 x 100 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule) | Drug: E2307<br> <br> Drug: E2307 Matching Placebo<br> <br> |
| Experimental: Part A: 200 mg E2307 (young cohort)<br>E2307 (2 x 100 mg E2307 capsules) or placebo (2 x 1 E2307 matching placebo capsules) | Drug: E2307<br> <br> Drug: E2307 Matching Placebo<br> <br> |
| Experimental: Part A: 300 mg E2307 (young cohort)<br>E2307 (3 x 100 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules) | Drug: E2307<br> <br> Drug: E2307 Matching Placebo<br> <br> |
| Experimental: Part B: Elderly cohort<br>One dose level below MTD from Part A | Drug: E2307<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events/serious adverse events |  | Up to 30 days | 
| Plasma pharmacokinetics (PK) of E2307: Cmax (maximum observed concentration) |  | Up to 12 days | 
| Plasma PK of E2307: tmax (time at which the highest drug concentration occurs) |  | Up to 12 days | 
| Plasma PK of E2307: AUC(0-t) [area under the concentration (AUC)-time curve from zero time to time of last quantifiable concentration] |  | Up to 12 days | 
| Plasma PK of E2307: AUC(0-inf) [area under the concentration-time curve from zero time extrapolated to infinite time] |  | Up to 12 days | 
| Plasma PK of E2307: t1/2 (terminal elimination phase half-life) |  | Up to 12 days | 
| Plasma PK of E2307: CL/F (apparent total clearance following oral administration) | CL/F are calculated for E2307 only | Up to 12 days | 
| Plasma PK of E2307: Vz/F (apparent volume of distribution at terminal phase) | Vz/F are calculated for E2307 only | Up to 12 days | 
| Plasma PK of E2307: AUC ratio (AUC ratio of metabolite to parent) |  | Up to 12 days | 
| Urine PK of E2307: Ae (cumulative amount of drug excreted in urine up to 264 hours postdose) |  | Up to 12 days | 
| Urine PK of E2307: CLR (renal clearance) |  | Up to 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean difference in change of mean blood pressure (BP) between E2307 and placebo |  | 24 hours predose and continue until 24 hours postdose (Day 2) | 
| QT interval assessment using Holter monitoring |  | 24 hours predose through Day 2 (at 24 hours postdose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Japanese Subjects, E2307, Pharmacokinetics