Clinical trial NCT02580006: To Investigate the Pharmacokinetics of EPORON® and EPREX® After Subcutaneous Administration in Healthy Male Volunteers
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Dong-A ST Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-10-20
Enrollment: 42
Sex: MALE
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Area Under Curve last(AUClast) of Erythropoietin
timeFrame: 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
measure: Maximum of concentration(Cmax) of Erythropoietin
timeFrame: 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
measure: Reticulocyte count (%) compared to baseline
timeFrame: 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
Secondary outcomes:
measure: Time of maximum concentration(Tmax) of Erythropoietin
timeFrame: 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
measure: Terminal half-life(t1/2) of Erythropoietin
timeFrame: 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
measure: Area Under Curve infinity(AUCinf) of Erythropoietin
timeFrame: 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
measure: Apparent Clearance(CL/F) of Erythropoietin
timeFrame: 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
measure: Mean Residence Time last(MRTlast) of Erythropoietin
timeFrame: 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
measure: Hemoglobin
timeFrame: 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
measure: Hematocrit
timeFrame: 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
measure: RBC count
timeFrame: 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
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital Clinical Trials Center
Study officials:
affiliation: Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
name: Kyung-sang Yu, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
name: In-jin Jang, MD, Ph.D
role: STUDY_DIRECTOR
affiliation: Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
name: Hyung-gi Lee, MD, Ph.D
role: STUDY_DIRECTOR
affiliation: Clinical Pharmacology Class of Seoul National University College of Medicine / Clinical Pharmacology of Seoul National University Hospital
name: Ju-yeon Cho, Ph.D
role: STUDY_DIRECTOR
affiliation: Seoul National University Hospital Clinical Trials Center / Clinical Pharmacology of Seoul National University Hospital
name: Seung-hwan Lee, MD, Ph.D
role: STUDY_DIRECTOR
References: