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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: E6011; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kanagawa
    • Sagamihara, Kanagawa, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria

1. Non-smoking Japanese male subjects aged greater than or equal to 20 to less than 45 years
2. BMI at screening is greater than or equal to 18.5 kg/m2 to less than 25.0 kg/m2
3. 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

1. Has been treated with biologic product(s) (except for immunoglobulin)
2. Has received immunoglobulin or blood preparation within 6 months before the study treatment
3. Has received inoculation within 4 weeks before the study treatment
4. Has a history of autoimmune disease or immunodeficiency
5. Has a history of clinically significant angioedema, hematemesis, anal hemorrhage, or hemoptysis
6. Has a history of acute myocardial infarction, cerebral infarction, cerebral hemorrhage, or arteriosclerosis obliterans
7. 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
8. Has a clinically significant vasculitis (e.g., mononeuritis multiplex)
9. 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.
10. Known to be positive for tuberculosis test (T-spot.TB Test or QuantiFERON TB Gold Test) at screening.
11. Treated with ethical drug (except for disinfectants, eye drops) within 4 weeks before the study treatment.
12. Treated with non-prescription drug (except for disinfectants, eye drops) within 2 weeks before the study treatment.
13. Has participated in another clinical trial and received an investigational drug or device within 16 weeks before the study treatment.
14. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Subcutaneous administration of E6011 50 mg	Drug: E6011; Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)
Experimental: 2; Subcutaneous administration of E6011 100 mg	Drug: E6011; Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)
Experimental: 3; Subcutaneous administration of E6011 200 mg	Drug: E6011; Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)
Experimental: 4; Subcutaneous administration of E6011 400 mg	Drug: E6011; Subcutaneous administration of E6011 (at doses of 50, 100, 200 and 400 mg)
Placebo Comparator: 5; Subcutaneous administration of placebo	Drug: Placebo; Subcutaneous administration of placebo

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

Collaborators and Investigators

• Sponsor: Eisai Co., Ltd.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 22, 2014
• First Posted (Estimate): May 23, 2014

Study Record Updates

• Last Update Posted (Estimate): October 22, 2014
• Last Update Submitted That Met QC Criteria: October 20, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Japanese; Volunteers; Males
• Additional Relevant MeSH Terms: Antirheumatic Agents; Quetmolimab
• Other Study ID Numbers: E6011-J081-002