Clinical trial NCT02289599: A Study to Assess Safety, Tolerability, and Pharmacokinetics of E2307 in Healthy Young and Elderly Japanese Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Healthy Japanese Subjects
E2307
Pharmacokinetics
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2014-11-13
Enrollment: 24
Sex: MALE
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Number of adverse events/serious adverse events
timeFrame: Up to 30 days
measure: Plasma pharmacokinetics (PK) of E2307: Cmax (maximum observed concentration)
timeFrame: Up to 12 days
measure: Plasma PK of E2307: tmax (time at which the highest drug concentration occurs)
timeFrame: Up to 12 days
measure: Plasma PK of E2307: AUC(0-t) [area under the concentration (AUC)-time curve from zero time to time of last quantifiable concentration]
timeFrame: Up to 12 days
measure: Plasma PK of E2307: AUC(0-inf) [area under the concentration-time curve from zero time extrapolated to infinite time]
timeFrame: Up to 12 days
measure: Plasma PK of E2307: t1/2 (terminal elimination phase half-life)
timeFrame: Up to 12 days
measure: Plasma PK of E2307: CL/F (apparent total clearance following oral administration)
timeFrame: Up to 12 days
measure: Plasma PK of E2307: Vz/F (apparent volume of distribution at terminal phase)
timeFrame: Up to 12 days
measure: Plasma PK of E2307: AUC ratio (AUC ratio of metabolite to parent)
timeFrame: Up to 12 days
measure: Urine PK of E2307: Ae (cumulative amount of drug excreted in urine up to 264 hours postdose)
timeFrame: Up to 12 days
measure: Urine PK of E2307: CLR (renal clearance)
timeFrame: Up to 12 days
Secondary outcomes:
measure: Mean difference in change of mean blood pressure (BP) between E2307 and placebo
timeFrame: 24 hours predose and continue until 24 hours postdose (Day 2)
measure: QT interval assessment using Holter monitoring
timeFrame: 24 hours predose through Day 2 (at 24 hours postdose)
Other outcomes:
Locations:
city: Kagoshima
country: Japan
Study officials:
References: