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

Study Overview
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Brief Summary
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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®

Official Title
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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)

Conditions
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Leucocytosis

Intervention / Treatment
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* Biological: Leucostim®
* Biological: Neupogen®


Participation Criteria
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Eligibility Criteria
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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.

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Leucostim® --> Neupogen®, subcutaneous injections<br>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®<br>* Leucostim® is filgrastim biosimilar.<br>* Other names: filgrastim;Biological: Neupogen®<br> <br> * Other names: filgrastim;|
| Experimental: Neupogen® --> Leucostim®, subcutaneous injections<br>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®<br>* Leucostim® is filgrastim biosimilar.<br>* Other names: filgrastim;Biological: Neupogen®<br> <br> * Other names: filgrastim;|
| Experimental: Leucostim® --> Neupogen®, intravenous injections<br>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®<br>* Leucostim® is filgrastim biosimilar.<br>* Other names: filgrastim;Biological: Neupogen®<br> <br> * Other names: filgrastim;|
| Experimental: Neupogen® --> Leucostim®, intravenous injections<br>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®<br>* Leucostim® is filgrastim biosimilar.<br>* Other names: filgrastim;Biological: Neupogen®<br> <br> * Other names: filgrastim;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neutrophil count, filgrastim, granulocyte colony-stimulating factor