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

Phase 1
Completed
Conditions
Leucocytosis
Interventions
Biological: Leucostim®
Biological: Neupogen®
Registration Number
NCT02762799
Lead Sponsor
Biocad
Brief Summary

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®

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
60
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Leucostim® --> Neupogen®, subcutaneous injectionsNeupogen®Healthy volunteers in this group will receive single subcutaneous injection Leucostim® on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.
Neupogen® --> Leucostim®, subcutaneous injectionsNeupogen®Healthy volunteers in this group will receive single subcutaneous injection Neupogen®, on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.
Neupogen® --> Leucostim®, intravenous injectionsNeupogen®Healthy volunteers in this group will receive single intravenous injection Neupogen® on Day 1 followed by single subcutaneous intravenous Leucostim® on Day 29.
Leucostim® --> Neupogen®, intravenous injectionsLeucostim®Healthy volunteers in this group will receive single intravenous injection Leucostim® on Day 1 followed by single intravenous injection Leucostim® on Day 29.
Leucostim® --> Neupogen®, intravenous injectionsNeupogen®Healthy volunteers in this group will receive single intravenous injection Leucostim® on Day 1 followed by single intravenous injection Leucostim® on Day 29.
Leucostim® --> Neupogen®, subcutaneous injectionsLeucostim®Healthy volunteers in this group will receive single subcutaneous injection Leucostim® on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.
Neupogen® --> Leucostim®, subcutaneous injectionsLeucostim®Healthy volunteers in this group will receive single subcutaneous injection Neupogen®, on Day 1 followed by single subcutaneous injection Leucostim® on Day 29.
Neupogen® --> Leucostim®, intravenous injectionsLeucostim®Healthy volunteers in this group will receive single intravenous injection Neupogen® on Day 1 followed by single subcutaneous intravenous Leucostim® on Day 29.
Primary Outcome Measures
NameTimeMethod
AUC (0-48 Hours)0 to 48 hours post-dose

Area Under Curve (AUC) "concentration - time" from the moment of filgrastim injection to 48 hours

Cmax After Subcutaneous Injection0 to 48 hours post-dose

Maximal concentration of filgrastim after subcutaneous injection of filgrastim

Secondary Outcome Measures
NameTimeMethod
Frequency of AE/SAE 3-4 Grade CTCAE 4.030 to 336 hours post-dose

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.

Cmax After Intravenous Injection0 to 48 hours post-dose

Maximal concentration of filgrastim after intravenous injection of filgrastim

Т½0 to 48 hours post-dose

Half-life of filgrastim after single injection of filgrastim

Overall Frequency of Adverse Events (AE)0 to 336 hours post-dose
Tmax After Injection0 to 48 hours post-dose

Time after single injection to reach maximal concentration of filgrastim

Kel0 to 48 hours post-dose

The elimination rate constant after single injection of filgrastim

Frequency of Local Reactions0 to 336 hours post-dose
Frequency of Preliminary Withdrawal Due to AE/SAE0 to 336 hours post-dose
Proportion of Patients With Binding or Neutralizing Antibodies to Filgrastim0 to 336 hours post-dose

Proportion of patients who had developed binding or neutralizing antibodies to filgrastim after single injection.

Clearance0 to 48 hours post-dose

Clearance of filgrastim after single injection

ANC-AUEC (0-336 Hours)0 to 336 hours post-dose

Area Under Effect Curve (AUEC) "effect - time" from the moment of filgrastim injection to 336 hours based on absolute neutrophil count (ANC)

ANC-Emax0 to 336 hours post-dose

Maximal absolute neutrophil count after single filgrastim injection

CD34-AUEC (0-336 Hours)0 to 336 hours post-dose

Area Under Effect Curve (AUEC) "effect - time" from the moment of filgrastim injection to 336 hours based on CD-34 cells count (CD34)

CD34-Emax0 to 336 hours post-dose

Maximal absolute count of CD34-cells after single filgrastim injection

Overall Frequency of Serious Adverse Events (SAE)0 to 336 hours post-dose
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