Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Leucostim® Compared to Neupogen®

Single-center Open Randomized Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Leucostim® (JSC "BIOCAD", Russia) Compared to Neupogen® (F. Hoffman-La Roche Ltd., Switzerland)

BCD-002-1 is 1 phase clinical trial to evaluate pharmacokinetics, pharmacodynamics and safety of single-injection of Leucostim® to healthy volunteers compared to Neupogen®

Study Overview

• Status: Completed
• Conditions: Leucocytosis
• Intervention / Treatment: Biological: Leucostim®; Biological: Neupogen®

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Written informed consent.
• Male gender.
• Age between 18 and 45 years.
• Normal body mass index.
• Verified diagnosis "healthy", established according to the anamnesis, physical examination and laboratory findings.
• Absence of alcohol or drug abuse.

Exclusion Criteria:

• History of use of filgrastim.
• Allergy to any components of study drugs.
• Acute hemorrhage, donation of blood / plasma or blood transfusions during last 2 months prior to enrollment in the study, history of chronic bleeding.
• Surgical interventions during last 30 days prior to screening or planed surgical intervention during the study.
• Any diseases that could interfere with pharmacokinetics of filgrastim, including chronic liver, liver or blood diseases, diseases of cardiovascular, lung and neuroendocrine systems.
• Fever with body temperature higher than 40°С.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Leucostim® --> Neupogen®, subcutaneous injections; Healthy volunteers in this group will receive single subcutaneous injection Leucostim® on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.	Biological: Leucostim®; Leucostim® is filgrastim biosimilar.; Other Names: filgrastim; Biological: Neupogen®; Other Names: filgrastim
Experimental: Neupogen® --> Leucostim®, subcutaneous injections; Healthy volunteers in this group will receive single subcutaneous injection Neupogen®, on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.	Biological: Leucostim®; Leucostim® is filgrastim biosimilar.; Other Names: filgrastim; Biological: Neupogen®; Other Names: filgrastim
Experimental: Leucostim® --> Neupogen®, intravenous injections; Healthy volunteers in this group will receive single intravenous injection Leucostim® on Day 1 followed by single intravenous injection Leucostim® on Day 29.	Biological: Leucostim®; Leucostim® is filgrastim biosimilar.; Other Names: filgrastim; Biological: Neupogen®; Other Names: filgrastim
Experimental: Neupogen® --> Leucostim®, intravenous injections; Healthy volunteers in this group will receive single intravenous injection Neupogen® on Day 1 followed by single subcutaneous intravenous Leucostim® on Day 29.	Biological: Leucostim®; Leucostim® is filgrastim biosimilar.; Other Names: filgrastim; Biological: Neupogen®; Other Names: filgrastim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (0-48 Hours)	Area Under Curve (AUC) "concentration - time" from the moment of filgrastim injection to 48 hours	0 to 48 hours post-dose
Cmax After Subcutaneous Injection	Maximal concentration of filgrastim after subcutaneous injection of filgrastim	0 to 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax After Intravenous Injection	Maximal concentration of filgrastim after intravenous injection of filgrastim	0 to 48 hours post-dose
Tmax After Injection	Time after single injection to reach maximal concentration of filgrastim	0 to 48 hours post-dose
Т½	Half-life of filgrastim after single injection of filgrastim	0 to 48 hours post-dose
Kel	The elimination rate constant after single injection of filgrastim	0 to 48 hours post-dose
Clearance	Clearance of filgrastim after single injection	0 to 48 hours post-dose
ANC-AUEC (0-336 Hours)	Area Under Effect Curve (AUEC) "effect - time" from the moment of filgrastim injection to 336 hours based on absolute neutrophil count (ANC)	0 to 336 hours post-dose
ANC-Emax	Maximal absolute neutrophil count after single filgrastim injection	0 to 336 hours post-dose
CD34-AUEC (0-336 Hours)	Area Under Effect Curve (AUEC) "effect - time" from the moment of filgrastim injection to 336 hours based on CD-34 cells count (CD34)	0 to 336 hours post-dose
CD34-Emax	Maximal absolute count of CD34-cells after single filgrastim injection	0 to 336 hours post-dose
Overall Frequency of Serious Adverse Events (SAE)		0 to 336 hours post-dose
Overall Frequency of Adverse Events (AE)		0 to 336 hours post-dose
Frequency of Local Reactions		0 to 336 hours post-dose
Frequency of AE/SAE 3-4 Grade CTCAE 4.03	Grading scale of CTCAE 4.03 Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL (activities of daily living). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.	0 to 336 hours post-dose
Frequency of Preliminary Withdrawal Due to AE/SAE		0 to 336 hours post-dose
Proportion of Patients With Binding or Neutralizing Antibodies to Filgrastim	Proportion of patients who had developed binding or neutralizing antibodies to filgrastim after single injection.	0 to 336 hours post-dose

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2016
• Primary Completion (Actual): November 11, 2016
• Study Completion (Actual): November 11, 2016

Study Registration Dates

• First Submitted: April 1, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: December 17, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: filgrastim; neutrophil count; granulocyte colony-stimulating factor
• Additional Relevant MeSH Terms: Pathologic Processes; Hematologic Diseases; Leukocyte Disorders; Leukocytosis; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: BCD-002-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED