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This study is primarily designed to bridge the pharmacokinetics (PK) and safety data for E2609 between Japanese subjects and non-Japanese (ie, white) subjects. To bridge these PK characteristics, the proposed study includes a cohort of white subjects treated for comparison with the cohort of Japanese subjects treated at the same dose. This comparison serves as a key PK bridge in assessing ethnic factors that may contribute to differences in plasma concentrations. Pharmacokinetic assessments in the proposed study will include confirmation of dose proportionality in Japanese subjects. This study will also evaluate safety and tolerability in Japanese subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| E2609 low-dose and placebo in healthy Japanese subjects | Experimental | Cohort 1 will consist of Japanese subjects randomized to a low-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance). |
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| E2609 mid-dose and placebo in healthy Japanese subjects | Experimental | Cohort 2 will consist of Japanese subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance). |
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| E2609 high-dose and placebo in healthy Japanese subjects | Experimental | Cohort 3 will consist of Japanese subjects randomized to a high-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance). |
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| E2609 mid-dose and placebo in healthy White subjects | Experimental | Cohort 4 will consist of White subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| E2609 | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of E2609: Cmax | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: tmax | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: AUC(0-24h)+D90 | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: AUC(0-72h) | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: AUC(0-t) | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: AUC(0-inf) | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: AUC Metabolite Ratio | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: t1/2 | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: CL/F | Up to Day 10 (216 hours postdose) | |
| Pharmacokinetics of E2609: V/F | Up to Day 10 (216 hours postdose) | |
| To evaluate the safety and tolerability of E2609 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Amax | Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10 | |
| Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): T(Amax) | Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10 |
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Inclusion Criteria:
The subject must meet all of the following criteria in order to be included in the study.
Japanese Subjects Only:
Birth in Japan to Japanese parents and grandparents of Japanese descent
Have been living outside Japan for less than 5 years
Lifestyle, including diet, has not changed significantly since leaving Japan
White Subjects Only:
A person having origins in any of the original peoples of Europe, the Middle East, or North Africa based on documented subject self-report
All Subjects:
Healthy male, 30 to 60 years inclusive, at the time of informed consent
BMI of 18 to 32 kg/m2 inclusive at Screening
Subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must not be of childbearing potential or must be practicing highly effective contraception (i.e. condom plus spermicide, condom plus diaphragm with spermicide, intrauterine device starting for at least one menstrual cycle before starting study drug[s]) and throughout the study period and for 30 days after study drug discontinuation. No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from this study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Glendale | California | United States |
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| Placebo | Drug | E2609 low-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy Japanese subjects, E2609 high-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy White subjects |
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Safety will be assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), regular monitoring of hematology, blood chemistry, urine values, regular measurement of vital signs, ECGs and performance of physical examinations
| Baseline and up to 30 days from last dosing of subject |
| Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(-24h-0h) | Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10 |
| Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(0-144h) | Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10 |
| Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Change in AUAC | Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10 |
| Change from baseline in QTcF obtained from ECGs extracted from Holter recordings | Holter ECG measurements will start on Day -1, at a time equivalent to 24 hours predose, and will continue for 24 hours postdose of Day 1, with interruptions allowed to adjust equipment. ECGs will be extracted from Holter monitors. | Baseline, Day 1, and Day 2 |