Healthy Subjects
Conditions
Keywords
Healthy Japanese Subjects, E2307, Pharmacokinetics
Brief summary
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.
Interventions
DRUGE2307
DRUGE2307 Matching Placebo
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Parts A and B 1. Provide written informed consent 2. Willing and able to comply with all aspects of the protocol Part A: Young cohort 3. Non-smoking, male subjects age \>=20 years and less than 55 years old at the time of informed consent Part B: Elderly Cohort 4. 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: 1. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing 2. Any history of abdominal surgery that may affect PK profiles of E2307 (eg. hepatectomy, nephrectomy, digestive organ resection) 3. Known history of clinically significant drug allergy (at Screening)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine PK of E2307: CLR (renal clearance) | 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 | — |
| 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) | Up to 12 days | CL/F are calculated for E2307 only |
| Plasma PK of E2307: Vz/F (apparent volume of distribution at terminal phase) | Up to 12 days | Vz/F are calculated for E2307 only |
Secondary
| Measure | 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) |
Countries
Japan
Outcome results
None listed