Healthy
Conditions
Brief summary
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.
Interventions
BIOLOGICALBCD-066
BCD-066 will be administered once a week intravenously in a dose 1 µg/kg
BIOLOGICALAranesp
Aranesp will be administered once a week intravenously in a dose 1 µg/kg
Sponsors
Biocad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed informed consent form 2. Men from 18 to 45 years old (inclusive) 3. BMI within the normal limits (18.5 to 30 kg/m2) 4. Hemoglobin from 120 g/L to 150 g/L and hematocrit 41% to 49% at screening (before the first injection) 5. Serum transferring 2.15 g/L to 3.6 g/L; serum ferritin from 20 μg/L to 250 μg/L 6. Vitamin B12 from 187 pcg/mL to 883 pcg/mL; folic acid from 3.1 ng/mL to 20.5 ng/mL 7. Endogenous serum erythropoietin \< 30 mIU/mL at screening 8. The subject is verified as Healthy according to results of standard clinical, laboratory and instrumental tests 9. Subject's ability (in the investigator's opinion) to follow the protocol procedures 10. 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. 11. 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 \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T½ | 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 | The elimination half-life |
| AUC(0-∞) | 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 | The total area under the concentration curve from 0 to infinity |
| Cmax | 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 | The maximum concentration of darbepoetin alfa in the serum after the first and the fourth IV injection of BCD-066 or Aranesp® |
| Kel | 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 | The elimination constant: kel=1/MRT, where MRT is median residence time: MRT=AUMC(0-72)/AUC(0-72) |
| CL | 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 | The total clearance |
| Tmax | 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 | The time to maximum drug concentration in the serum |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BCD-066 1 µg/kg Healthy volunteers will receive BCD-066 1 μg/kg as weekly IV injections on Day 1, Day 8, Day 15, and Day 22.
BCD-066: BCD-066 will be administered once a week intravenously in a dose 1 µg/kg | 28 |
| Aranesp 1 µg/kg Healthy volunteers will receive Aranesp 1 μg/kg as weekly IV injections on Day 1, Day 8, Day 15, and Day 22.
Aranesp: Aranesp will be administered once a week intravenously in a dose 1 µg/kg | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Aranesp 1 µg/kg | Total | BCD-066 1 µg/kg |
|---|---|---|---|
| Age, Continuous | 27.50 years | 27.50 years | 24 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 56 Participants | 28 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 28 Participants | 56 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 5 / 28 | 16 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
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
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-066 1 µg/kg | AUC(0-72) | 328215.65 pg/ml·h |
| Aranesp 1 µg/kg | AUC(0-72) | 290827.12 pg/ml·h |
Secondary
AUC(0-∞)
The total area under the concentration curve from 0 to infinity
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-066 1 µg/kg | AUC(0-∞) | 331725.75 pg/ml·h |
| Aranesp 1 µg/kg | AUC(0-∞) | 296135.38 pg/ml·h |
Secondary
CL
The total clearance
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-066 1 µg/kg | CL | 230.358 ml/h |
| Aranesp 1 µg/kg | CL | 243.055 ml/h |
Secondary
Cmax
The maximum concentration of darbepoetin alfa in the serum after the first and the fourth IV injection of BCD-066 or Aranesp®
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-066 1 µg/kg | Cmax | 18365.15 pg/ml |
| Aranesp 1 µg/kg | Cmax | 17003.25 pg/ml |
Secondary
Kel
The elimination constant: kel=1/MRT, where MRT is median residence time: MRT=AUMC(0-72)/AUC(0-72)
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-066 1 µg/kg | Kel | 0.055 fraction of drug per hour |
| Aranesp 1 µg/kg | Kel | 0.055 fraction of drug per hour |
Secondary
T½
The elimination half-life
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-066 1 µg/kg | T½ | 12.53 hours |
| Aranesp 1 µg/kg | T½ | 12.69 hours |
Secondary
Tmax
The time to maximum drug concentration in the serum
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCD-066 1 µg/kg | Tmax | 0.125 hours |
| Aranesp 1 µg/kg | Tmax | 0.083 hours |