The Study of PK, PD, Safety of Multiple Intravenous Injections of BCD-066 and Aranesp in Healthy Volunteers

Study Overview
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Brief Summary
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BCD-066 is a darbepoetin alfa. Clinical study BCD-066-3 is a double-blind controlled, randomized, parallel-group study of the pharmacokinetics, pharmacodynamics, tolerability, and safety of multiple intravenous injections of BCD-066 and Aranesp®. The purpose of the study is to confirm the equivalent pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple IV injections of BCD-066 and Aranesp® in healthy volunteers.

Official Title
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A Double-blind, Randomized, Controlled Clinical Study of the Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of Multiple Intravenous Injections of BCD-066 and Aranesp® in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: BCD-066
* Biological: Aranesp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Men from 18 to 45 years old (inclusive) BMI within the normal limits (18.5 to 30 kg/m2) Hemoglobin from 120 g/L to 150 g/L and hematocrit 41% to 49% at screening (before the first injection) Serum transferring 2.15 g/L to 3.6 g/L; serum ferritin from 20 μg/L to 250 μg/L Vitamin B12 from 187 pcg/mL to 883 pcg/mL; folic acid from 3.1 ng/mL to 20.5 ng/mL Endogenous serum erythropoietin < 30 mIU/mL at screening The subject is verified as Healthy according to results of standard clinical, laboratory and instrumental tests Subject's ability (in the investigator's opinion) to follow the protocol procedures The subject and his sexual partner with retained childbearing potential consent to implement reliable contraceptive methods starting 2 weeks before inclusion in the study and up to 2 weeks after the last dose of the test/reference drug. This requirement does not apply to surgically sterile subjects. Reliable contraception methods mean one barrier method in combination with one of the following: spermicides, intrauterine device and/or oral contraceptives used by the subject's partner. The subject agrees not to drink alcohol for 24 h prior to each injection of the test/reference drug and for 72 h after the injection. Exclusion Criteria: 1. Psychiatric disorders or other conditions that can affect the ability of the subject to follow the study protocol 2. Acute infections within 4 weeks before the study start 3. Results of laboratory and/or instrumental tests are outside the normal range 4. Chronic cardiovascular, bronchial and/or pulmonary, neuroendocrine GI, liver, kidney, and blood diseases, including ischemic heart disease, arterial hypertension, peripheral vascular and/or cerebral vascular disorders, and thrombocytosis 5. A history of chronic hemorrhages -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-066 1 µg/kg<br>Healthy volunteers will receive BCD-066 1 μg/kg as weekly IV injections on Day 1, Day 8, Day 15, and Day 22. | Biological: BCD-066<br>* BCD-066 will be administered once a week intravenously in a dose 1 µg/kg<br>* Other names: darbepoetin alfa;|
| Active Comparator: Aranesp 1 µg/kg<br>Healthy volunteers will receive Aranesp 1 μg/kg as weekly IV injections on Day 1, Day 8, Day 15, and Day 22. | Biological: Aranesp<br>* Aranesp will be administered once a week intravenously in a dose 1 µg/kg<br>* Other names: darbepoetin alfa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-72) | The area concentration curve for darbepoetin alfa from injection to 72 h (AUC(0-72) after the first and the fourth IV injection of BCD-066 or Aranesp | 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | The maximum concentration of darbepoetin alfa in the serum after the first and the fourth IV injection of BCD-066 or Aranesp® | 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h post-dose post-dose | 
| T½ | The elimination half-life | 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h post-dose | 
| AUC(0-∞) | The total area under the concentration curve from 0 to infinity | 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h post-dose | 
| Tmax | The time to maximum drug concentration in the serum | 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h post-dose | 
| Kel | The elimination constant: kel=1/MRT, where MRT is median residence time: MRT=AUMC(0-72)/AUC(0-72) | 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h post-dose | 
| CL | The total clearance | 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 48 h, 72 h post-dose |