Pharmacokinetics and Pharmacodynamics Study of BCD-066 Compared to Aranesp® in Healthy Volunteers

Healthy Clinical Trial

Official title:

International Multicenter Comparative Randomized Double-blind Crossover Study of Pharmacokinetics, Pharmacodynamics and Safety of BCD-066 and Aranesp® After Single Subcutaneous and Intravenous Injection in Healthy Volunteers.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02506881
• Other study ID #: BCD-066-1
• Status: Completed
• Phase: Phase 1
• First received: July 22, 2015
• Last updated: July 22, 2015
• Start date: March 2013
• Est. completion date: July 2014

Study information

• Verified date: July 2015
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

This is a randomized double-blind crossover study of pharmacokinetics, pharmacodynamics and safety of BCD-066 (darbepoetin alfa manufactured by CJSC BIOCAD, Russia) and Aranesp® (Amgen Europe B.V., Netherlands) in healthy volunteers. The purpose of the study is to demonstrate the equivalence of pharmacokinetics, pharmacodynamics and safety parameters after single subcutaneous or intravenous injection. Each drug will be administered to each volunteer at a dose of 1 µg per kilogram as a single subcutaneous or intravenous injection with an interval of at least 25 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Signed written informed consent

• Male gender

• Age 18 - 45 years inclusively

• Body mass index (BMI) 19 - 29 kg/m2 inclusively

• Hemoglobin level 120-160 g/l (12 - 16 g/dL) inclusively during 14 days prior to first study drugs administration

• White blood cells count =3,0×109/L, Platelet count =140×109/L during 14 days prior to first study drugs administration

• Subjects must be in good health as determined by a medical history, medical examination, electrocardiogram, serum biochemistry, haematology, serology and urinalysis

• Absence of history of systematic alcohol and drug abuse

• Ability of the volunteer, in investigator's opinion, to follow the study protocol procedures and requirements

• Willingness of volunteers and their sexual partners of childbearing potential to use reliable contraception methods starting from 2 weeks before inclusion into the study and until 4 weeks after receiving the last dose of the investigational products. This criterion is not applicable to patients who underwent surgical sterilization. Reliable contraceptive measures include one barrier method in combination with one of the following methods: spermicides, intrauterine device or oral contraceptives used by participant's partner

• Consent to avoid alcohol intake within 24 hours before and 48 hours after each administration of the test or reference drugs

Exclusion Criteria:

• Clinically significant abnormalities on ECG or in laboratory tests, which could interfere with the objective of the study or the safety of the volunteer.

• Clinically significant illness within 4 weeks prior to the screening visit

• Subjects with past or present history of liver disease, angina, renal disease, hypertension, epilepsy, cardiovascular, cerebrovascular, peripheral vascular disease or thrombocytosis

• History of any oncological disease

• Prior exposure to any erythropoietins, darbepoetin

• Prior exposure to IV iron supplementation (within 2 years before randomisation)

• Subjects who have used any medication, including over-the-counter drugs, herbal medications, and nutritional supplements within 14 days prior to IDs administration with the exception of paracetamol (acetaminophen) up to 3g per day or ibuprofen up to 1g per day

• Subjects who smoke more than 10 cigarettes per day

• Subjects who have donated more than 450 ml of blood within the 1 month prior to ID injection

• Epileptic seizures within the 6 months prior to ID injection

• Major surgery within 1 month prior to the enrollment into the study

• Inability to install intravenous catheter (e.g., due to skin disease)

• Subjects who have received any experimental drug within 3 months preceding the 1st ID administration

• Subjects who have a clinically significant history of drug hypersensitivity or allergic disease

• Possibility that the subject will not cooperate with the requirements of the protocol as set out in the volunteer information

• Subjects who consume excessive amounts of caffeine (more than 5 cups of coffee per day)

• Participation in any other clinical study or any preceding participation in other studies within 3 months prior to the 1st ID administration

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Darbepoetin alfa

Locations

Country	Name	City	State
Russian Federation	City Mariin Hospital	St. Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC	Area Under Concentration-time Curve (AUC) of Darbepoetin Alfa From the Moment of Drug Administration Until 336 (sc administration) or 72 (iv administration) Hours and to Infinity(AUC(0-336)/AUC(0-72) and AUC(0-8) Respectively)	336 hours (sc) / 72 hours (iv)	No
Primary	Cmax	Maximal concentration of darbepoetin alfa From the Moment of Drug Administration Until 336 (sc administration) or 72 (iv administration) hours	336 hours (sc) / 72 hours (iv)	No
Primary	AUEC	Area Under Effect Curve (AUEC) of reticulocytes count from the Moment of Drug Administration Until 504 hours	504 hours	No
Primary	AC-Emax	Maximum elevation of absolute reticulocyte count from the baseline from the Moment of Drug Administration Until 504 hours	504 hours	No
Secondary	T1/2	Serum half-life of darbepoetin alfa after single sc of iv administration	336 hours (sc) / 72 hours (iv)	No
Secondary	Tmax	Time to achieve maximum serum concentration of darbepoetin alfa after single sc of iv administration	336 hours (sc) / 72 hours (iv)	No
Secondary	Cl	Serum clearance of of darbepoetin alfa after single sc of iv administration	336 hours (sc) / 72 hours (iv)	No
Secondary	Hemoglobin	Hemoglobin dynamics after single sc of iv administration of darbepoetin alfa	504 hours	No
Secondary	RBC	Red blood cells count dynamics after single sc of iv administration of darbepoetin alfa	504 hours	No
Secondary	Hematocrit	Hematocrit dynamics after single sc of iv administration of darbepoetin alfa	504 hours	No
Secondary	AE and SAE Incidence	Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) which have causal link with study therapy to Investigator's opinion.	53 days	Yes
Secondary	AE Grade 3-4 Incidence	Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) of CTCAE grade 3 to 4 which have causal link with study therapy to Investigator's opinion.	53 days	Yes
Secondary	Local reactions	Incidence of local reactions at drug administration site	53 days	Yes
Secondary	Study Withdrawal Rate Due to AE	Incidence of study withdrawal due to adverse events	53 days	Yes

External Links

•   Related info