A Phase 1 Study of Single-dose Subcutaneous E6011 in Japanese Healthy Adult Male Subjects

Study Overview
=================
Brief Summary
-----------------
This study (Protocol No. E6011-J081-002) is a single-center, randomized, double-blind, placebo-controlled, single ascending dose (SAD) study to evaluate mainly the safety and tolerability of a single subcutaneous administration of E6011. A total of 32 subjects will be randomized into four cohorts (50, 100, 200 and 400 mg groups). Of eight subjects per cohort, six subjects will receive the single subcutaneous E6011 administration and two subjects will receive the single subcutaneous placebo administration.

Detailed Description
-----------------
This study consists of Screening Period, Observation Period, In-patient Period, and Follow-up Period. Screening assessments will be performed within 28 to 2 days before starting the study treatment, and Observation Period assessments will be performed on a day before starting the study treatment to confirm the eligibility of study subjects. The eligible subjects will be randomized into either E6011 arm or placebo arm using the drug allocation list prepared by the random code statistician. Each subjects dosing interval will be at least a 30-minutes.

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: E6011
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Non-smoking Japanese male subjects aged greater than or equal to 20 to less than 45 years BMI at screening is greater than or equal to 18.5 kg/m2 to less than 25.0 kg/m2 Males who have not had a successful vasectomy and their female partners must agree to practice highly effective contraception throughout the study period Exclusion criteria Has been treated with biologic product(s) (except for immunoglobulin) Has received immunoglobulin or blood preparation within 6 months before the study treatment Has received inoculation within 4 weeks before the study treatment Has a history of autoimmune disease or immunodeficiency Has a history of clinically significant angioedema, hematemesis, anal hemorrhage, or hemoptysis Has a history of acute myocardial infarction, cerebral infarction, cerebral hemorrhage, or arteriosclerosis obliterans With gross hematuria, occult bleeding in urine of greater than or equal to 1+ and urine protein of greater than or equal to 1+, or either of greater than or equal to 2+ is found at screening Has a clinically significant vasculitis (e.g., mononeuritis multiplex) Known to be positive for human immunodeficiency virus antigen/antibody (HIV antigen/antibody), hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis B core virus antibody (HBc antibody), hepatitis B virus (HBV) DNA, hepatitis C virus antibody (HCV antibody), human T cell lymphotropic virus type 1 antibody (HTVL-1 antibody), or syphilis serology test positive at screening. Known to be positive for tuberculosis test (T-spot.TB Test or QuantiFERON TB Gold Test) at screening. Treated with ethical drug (except for disinfectants, eye drops) within 4 weeks before the study treatment. Treated with non-prescription drug (except for disinfectants, eye drops) within 2 weeks before the study treatment. Has participated in another clinical trial and received an investigational drug or device within 16 weeks before the study treatment. Received blood transfusion within 1 year, 400 mL or more whole blood donation within 12 weeks, or 200 mL or more whole blood donation within 4 weeks, or blood constituent donation within 2 weeks before the study treatment.

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: 1<br>Subcutaneous administration of E6011 50 mg | Drug: E6011<br>* Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)<br>|
| Experimental: 2<br>Subcutaneous administration of E6011 100 mg | Drug: E6011<br>* Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)<br>|
| Experimental: 3<br>Subcutaneous administration of E6011 200 mg | Drug: E6011<br>* Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)<br>|
| Experimental: 4<br>Subcutaneous administration of E6011 400 mg | Drug: E6011<br>* Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)<br>|
| Placebo Comparator: 5<br>Subcutaneous administration of placebo | Drug: Placebo<br>* Subcutaneous administration of placebo<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of E6011: Maximum Concentration (Cmax) |  | Up to 10 Weeks | 
| Pharmacokinetics of E6011: Time to attain Cmax (tmax) |  | Up to 10 Weeks | 
| Pharmacokinetics of E6011: Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-t) |  | Up to 10 Weeks | 
| Pharmacokinetics of E6011: Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time AUC(0-inf) |  | Up to 10 Weeks | 
| Pharmacokinetics of E6011: Elimination half-life (t1/2) |  | Up to 10 Weeks | 
| Pharmacokinetics of E6011: CL/F | Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-?). | Up to 10 Weeks | 
| Pharmacokinetics of E6011: Apparent Volume of Distribution of Azacitidine (Vz/F) |  | Up to 10 Weeks | 
| Safety and Tolerability of E6011 | The safety will be assessed based on all adverse events (AEs), clinical laboratory test, vital signs, body weight, physical finding, administration site finding, electrocardiography and chest xray. | Up to 10 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Volunteers, Japanese, Males