To Investigate the Pharmacokinetics of EPORON® and EPREX® After Subcutaneous Administration in Healthy Male Volunteers

Sponsor

Dong-A ST Co., Ltd. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02580006

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

10.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase I study is to compare pharmacokinetics, safety and pharmacodynamics of EPORON and EPREX after single subcutaneous administration.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: EPORON Drug: EPREX	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Active Control, Single Dosing, Crossover Clinical Trial to Investigate the Pharmacokinetics of EPORON® and EPREX® After Subcutaneous Administration in Healthy Male Volunteers

Study Start Date :

Nov 1, 2015

Anticipated Primary Completion Date :

Jan 1, 2016

Anticipated Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EPORON→EPREX EPORON PFS(PreFilled Syringe) 4000 IU/0.4 mL(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 1. And wash out for 4 weeks. EPREX INJ.(Injection) 4000 IU(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 29.	Drug: EPORON single dose administration subcutaneously Other Names: EPORON PFS 4000 IU/0.4 mL (Erythropoietin alfa 4000 IU) Drug: EPREX single dose administration subcutaneously Other Names: EPREX INJ. 4000 IU (Erythropoietin alfa 4000 IU)
Experimental: EPREX→EPORON EPREX INJ. 4000 IU(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 1. And wash out for 4 weeks. EPORON PFS 4000 IU/0.4 mL(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 29.	Drug: EPORON single dose administration subcutaneously Other Names: EPORON PFS 4000 IU/0.4 mL (Erythropoietin alfa 4000 IU) Drug: EPREX single dose administration subcutaneously Other Names: EPREX INJ. 4000 IU (Erythropoietin alfa 4000 IU)

Arm

Intervention/Treatment

Experimental: EPORON→EPREX

EPORON PFS(PreFilled Syringe) 4000 IU/0.4 mL(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 1. And wash out for 4 weeks. EPREX INJ.(Injection) 4000 IU(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 29.

Drug: EPORON

single dose administration subcutaneously

Other Names:

EPORON PFS 4000 IU/0.4 mL (Erythropoietin alfa 4000 IU)

Drug: EPREX

single dose administration subcutaneously

Other Names:

EPREX INJ. 4000 IU (Erythropoietin alfa 4000 IU)

Experimental: EPREX→EPORON

EPREX INJ. 4000 IU(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 1. And wash out for 4 weeks. EPORON PFS 4000 IU/0.4 mL(Erythropoietin alfa 4000 IU) will be administered subcutaneously after 10 hours fasting on Day 29.

Drug: EPORON

single dose administration subcutaneously

Other Names:

EPORON PFS 4000 IU/0.4 mL (Erythropoietin alfa 4000 IU)

Drug: EPREX

single dose administration subcutaneously

Other Names:

EPREX INJ. 4000 IU (Erythropoietin alfa 4000 IU)

Outcome Measures

Primary Outcome Measures

Area Under Curve last(AUClast) of Erythropoietin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35) hrs after administration for each period]
Maximum of concentration(Cmax) of Erythropoietin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35) hrs after administration for each period]
Reticulocyte count (%) compared to baseline [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 12, 24, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35), 216 (day 10/day 38), 312 (day 14/day 42) hrs after administration for each period]
The absolute difference from the most increased case and its relative percentage (%) when comparing the results before administration

Secondary Outcome Measures

Time of maximum concentration(Tmax) of Erythropoietin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35) hrs after administration for each period]
Terminal half-life(t1/2) of Erythropoietin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35) hrs after administration for each period]
Area Under Curve infinity(AUCinf) of Erythropoietin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35) hrs after administration for each period]
Apparent Clearance(CL/F) of Erythropoietin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35) hrs after administration for each period]
Mean Residence Time last(MRTlast) of Erythropoietin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35) hrs after administration for each period]
Hemoglobin [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 12, 24, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35), 216 (day 10/day 38), 312 (day 14/day 42) hrs after administration for each period]
Hematocrit [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 12, 24, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35), 216 (day 10/day 38), 312 (day 14/day 42) hrs after administration for each period]
RBC count [Twice every 10 minutes within 1hr before administration (day 1/day 29); immediately before administration; 12, 24, 48, 72, 96, 120 (day 6/day 34), 144 (day 7/day 35), 216 (day 10/day 38), 312 (day 14/day 42) hrs after administration for each period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy male volunteers between the ages of 19~50 at the time of screening
Weight between 55.0kg_{90.0kg with BMI of 18.0}27.0
Voluntarily participants who agree to observe the precautions in writing after receiving a complete explanation of this trial

Exclusion Criteria:

History of clinically significant illness related to liver (including viral hepatitis), kidney, nervous system, immune system, respiratory system, endocrine system, cardiovascular system, blood system and tumor as well as mental illness (mood disorder, obsessive-compulsive disorder, etc.)
Hypersensitivity or clinically significant hypersensitivity to the drug (e.g. aspirin, antibiotics, etc.)
Those whose results meet more than one of the followings in the screening including re-test; Hemoglobin level below 12g/dL or over 17g/dL, Vitamin B12 level below 200pg/mL, Ferritin level below 21.8ng/mL, Transferrin level below 190mg/dL, Reticulocyte, erythrocytes, platelets or serum potassium level over normal range
Positive on the HIV antibody, HBsAg, HCV(Hepatitis C Virus) antibody tests
Those whose vital signs measured in sitting position after resting over 3 minutes meet more than one of the following; Systolic BP below 90mmgHg or over 160mmgHg, Diastolic BP below 50mmgHg or over 100mmgHg, Pulse rate over 100
History of drug abuse, or tested positive in the urine drug screening
Administration of EPO(erythropoietin), darbepoetin or other EPO protein supply, immunoglobulin within 3 months from the scheduled first dose
Hypersensitivity to EPO, darbepoetin or excipient in the test drug or anaphylactic reaction towards iron supplement
Those who received the following diagnosis within 6 months from the screening; Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all kinds), Chronic or uncontrollable inflammatory diseases (e.g., rheumatoid arthritis, systemic erythematosus)
Those who took any ETC(Ethical) drugs or herbal medicine within 2 weeks, or any OTC(Over-the-counter) drugs or vitamins within a week from the scheduled first dose (However, they may be included as the trial subjects at the discretion of the investigator if other conditions are satisfactory.)
Those who participated other clinical trials and was administered other drugs within 3 months from the scheduled first dose
Those who bled over 400mL or donated blood within 8 weeks from the scheduled first dose
Those who have continued drinking (exceeding 21 units/week, 1 unit = 10g of pure alcohol) or who can't abstain from alcohol during the trial period
Those who have smoked over 10 cigarettes daily in average for the last 3 months or who can't renounce smoking during the trial period
Those who have ingested grapefruit or caffeine containing food within 3 days from the scheduled first dose or who can't abstain from the during the trial period.
Those who are preparing for pregnancy or who do not agree with contraception during the trial period
Those with peculiar eating habits or who can't have meals provided by the hospital
Those who are considered inappropriate for the trial by the trial investigator based on the result of clinical laboratory test or due to other reasons

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Hospital Clinical Trials Center	Seoul		Korea, Republic of	03080

Sponsors and Collaborators

Dong-A ST Co., Ltd.

Investigators

Principal Investigator: Kyung-sang Yu, MD, Ph.D, Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
Study Director: In-jin Jang, MD, Ph.D, Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
Study Director: Hyung-gi Lee, MD, Ph.D, Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
Study Director: Ju-yeon Cho, Ph.D, Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
Study Director: Seung-hwan Lee, MD, Ph.D, Seoul National University Hospital Clinical Trials Center / Clinical Pharmacology of Seoul National University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Dong-A ST Co., Ltd.

ClinicalTrials.gov Identifier:

NCT02580006

Other Study ID Numbers:

DA3285_SC_I

First Posted:

Oct 20, 2015

Last Update Posted:

Oct 20, 2015

Last Verified:

Oct 1, 2015

Additional relevant MeSH terms:

Epoetin Alfa

Study Results

No Results Posted as of Oct 20, 2015