Single/ Multiple-Dose Study of E6007 in Healthy Japanese Male Subjects

Study Overview
=================
Brief Summary
-----------------
This is a single-center, placebo-controlled, randomized, ascending dose, double-blind study. This study will be evaluating ascending doses of 50, 100, 200, and 400 mg of E6007. This study consists of 5 steps, 1 to 5. In steps 1 to 4 (at ascending doses of 50, 100, 200, and 400 mg), subjects will be randomly assigned in a 6:2 ratio (E6007: placebo) to receive single dose of the study drug under fasted condition. Following 3 days of washout period, subject will receive the study drug once daily for 7 days starting on the fifth day from the single dose administration. For step 3 (200 mg), subjects will subsequently have at least 17 days of washout period before being escalated to step 5 (200 mg) to receive single dose of E6007 under fed condition, to evaluate food effect of the study drug.

Official Title
-----------------
A Phase 1 Single/ Multiple-Dose Study of E6007 in Healthy Japanese Male Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: E6007
* Drug: E6007 matching placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Subjects must meet all of the following criteria to be included in this study: Healthy Japanese male subjects aged 20 to 44 years at the time of informed consent. Has voluntarily consented, in writing, to participate in this study. Has been thoroughly briefed on the conditions for participation in the study, and is willing and able to comply with the conditions. Exclusion criteria Subjects who meet any of the following criteria will be excluded from this study: Has a clinically significant medical condition requiring treatment within 8 weeks before the initial study drug administration, or a history of clinically significant infection requiring treatment within 4 weeks before the initial drug administration. History of surgical treatment such as resection of the liver, kidney, or Gastrointestinal tract, that may affect the Pharmacokinetic profiles of study drugs. Ineligible for study participation in the opinion of the investigator or sub-investigator.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 44 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg E6007 fasted condition<br>E6007 50mg or E6007 matching placebo x 1, orally once daily in the morning under fasted condition. Drug administration on 1 day for single dose period (Day 1) and 7 days (Day 5 to 11) for repeated dose period. | Drug: E6007<br> <br> Drug: E6007 matching placebo<br> <br> |
| Experimental: 100 mg E6007 fasted condition<br>E6007 50mg or E6007 matching placebo x 2, orally once daily in the morning under fasted condition. Drug administration on 1 day for single dose period (Day 1) and 7 days (Day 5 to 11) for repeated dose period. | Drug: E6007<br> <br> Drug: E6007 matching placebo<br> <br> |
| Experimental: 200 mg E6007 fasted condition<br>E6007 50mg or E6007 matching placebo x 4, orally once daily in the morning under fasted condition. Drug administration on 1 day for single dose period (Day 1) and 7 days (Day 5 to 11) for repeated dose period. | Drug: E6007<br> <br> Drug: E6007 matching placebo<br> <br> |
| Experimental: 400 mg E6007 fasted condition<br>E6007 50mg or E6007 matching placebo x 8, orally once daily in the morning under fasted condition. Drug administration on 1 day for single dose period (Day 1) and 7 days (Day 5 to 11) for repeated dose period. | Drug: E6007<br> <br> Drug: E6007 matching placebo<br> <br> |
| Experimental: 200 mg E6007 fed condition<br>E6007 50mg or E6007 matching placebo x 4, orally once daily in the morning under fed condition. Drug administration on 1 day (Day 1). | Drug: E6007<br> <br> Drug: E6007 matching placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of E6007 as a measure of Adverse events |  | Screening and up to 17 days after last administration of drug | 
| Plasma E6007 concentration over time period - Cmax (maximum concentration) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - tmax (Time to achieve maximum concentration (Cmax)) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - AUC (0-t) (Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - AUC (0-inf) (AUC extrapolated to infinity) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - t1/2 (Terminal phase half-life) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - CL/F (Apparent clearance) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - Vz/F (Apparent volume of distribution) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - Css,max (maximum steady state concentration) |  | Up to 15 days | 
| Plasma E6007 concentration over time period - AUC (0-tau) (AUC from time zero to time tau over a dosing interval at steady state) |  | Up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose proportionality under fasted conditions with Cmax, AUC (0-t), AUC(0-inf), Cssmax and AUC(0-t) |  | Up to 15 days | 
| Geometric mean proportion (fed:fasted) of Cmax, AUC(0-t) and AUC(0-inf) for 200mg E6007 dose |  | Up to 5 days | 
| Evaluate relationship between E6007 plasma concentrations and electrocardiogram (ECG) parameter (QTcF) |  | Up to 15 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
E6007, Healthy Japanese male subjects