Double-blind, Randomized Comparative Cross-sectional Study of Pharmacodynamics and Pharmacokinetics of Drugs GP40141

Study Overview
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Brief Summary
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Bioequivalence Study of GP40141 (GEROPHARM) versus Enplate®. The study of comparative pharmacodynamics, pharmacokinetics and safety of drugs containing romiplostim in healthy volunteers after a single subcutaneous injection.

Detailed Description
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The goal of this study, conducted as a double-blind, randomized, cross-over study of comparative pharmacodynamics and pharmacokinetics, is to compare pharmacodynamics, pharmacokinetics, and safety of drugs containing romiplostim - GP40141 and Nplate® in healthy volunteers after a single subcutaneous injection. research objectives is: Evaluate pharmacodynamic and pharmacokinetic parameters of active ingredients of preparations GP40141 and Enplate®. Conduct a comparative analysis of pharmacodynamic and pharmacokinetic parameters of active substances drugs GP40141 and Enplate®. Conduct a comparative analysis of data on adverse events (AE) and evaluate immunogenicity after a single subcutaneous administration of GP40141 versus Enplate®. A conclusion about the biosimilarity of drugs will be made by assessing 90% confidence intervals for the ratios of the geometric mean values of the primary pharmacodynamic parameters. The safety of the compared drugs will be assessed by emergence and development of AE.

Official Title
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Double-blind, Randomized Comparative Cross-sectional Study of Pharmacodynamics and Pharmacokinetics of Drugs GP40141, Powder for Solution for Subcutaneous Administration, 250 µg (GEROPHARM LLC, Russia) and Enplate®, Powder for Solution for Subcutaneous Administration, 250 µg (Amgen Europe B.V. ., Netherlands) in Healthy Volunteers With a Single Subcutaneous Injection

Conditions
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Pharmacodynamics, Pharmacokinetics, Bioequivalence

Intervention / Treatment
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* Drug: GP40141
* Drug: Nplate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form. Male aged 18 to 45 years. Verified diagnosis is healthy according to data Standard clinical, laboratory and Instrumental methods of examination. The level of platelets count (according to the clinical blood test) at screening ranged from the lower threshold of reference values to 306×109/l (inclusive). Body mass index between 18,5 and 30 kg/m2, with body weight 60-100 kg Consent to comply with an adequate method of effective contraception throughout the study. The consent of volunteers to all restrictions imposed during the study. Russian Federation Citizens Exclusion Criteria: History of allergic problems/events. Hypersensitivity to heparin, romiplostim or any of the excipients of the drugs studied or E.coli protein. Any acute and chronic diseases, including but not limited to cardiovascular system diseases, bronchopulmonary diseases, neuroendocrine systems diseases, as well as diseases of the gastrointestinal tract, liver, kidneys, blood. Positive testing for hepatitis C (antibodies) or hepatitis B (surface antigen), HIV (antibodies to HIV-1/2), syphilis (antibodies to Treponema pallidum). The WHO norms deviations of the heart rate (60-89), Sistolic BP (90-139 mm Hg), Diatolic BP (60-89 mm Hg), respiratory rate (12-20), body temperature (35.7 - 37.0 °C). Abnormal ECG during screening. Abnormal results of laboratory methods research. Inaccessible veins of the upper extremities, vein thrombosis, thrombophlebitis in the anamnesis or in the family history of the next of kin, compromised veins due to frequent previous venipuncture. Surgical interventions on the spleen, splenectomy in anamnesis. Acute infectious diseases in less than 4 weeks before the start of the study. Diseases of the blood, hematopoietic organs and disorders, involving the immune mechanism (ICD-10: D50-D89) in history. History of arterial and venous thromboses. Presence of malignant (ICD-10: C00-C97) or unknown malignancy of neoplasms (ICD-10: D37-D48), as well as neoplasms in situ (ICD-10: D00-D09) within the last 5 years. Regular intake of medications, including vitamins, herbal preparations, and dietary supplements, less than 2 weeks before the start of the study. Incomplete recovery from surgery or surgery scheduled for the duration of the subject's participation in the study. Significant loss of blood within 3 months prior to screening, including but not limited to blood donation or extended surgery or trauma resulting in the blood loss. History of alcohol or drugs abuse or any indication of the regular use of more than 10 units of alcohol per week (1 Unit = 200 mL of wine or 500 mL of beer or 50 mL of alcohol 40%). Positive test results for alcohol or drug use. Nicotine addiction, regular use of tobacco, including all types of electronic cigarettes, less than 6 months prior to screening. Participation in a clinical trial of any drugs (including experimental) or experimental medical devices for 3 months or 5 half-lives, whichever is longer, before the study. Dehydration due to diarrhea, vomiting, or other causes within the last 24 hours before the start of the study. Any diet (for example, vegetarian, fasting, etc.) or lifestyle (including night work and extreme physical activity) that may interfere with the study. Psychiatric disorders, history of epilepsy and seizures. Taking medications that have a pronounced effect on hemodynamics, liver function, etc. (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before the start of the study. Volunteers who are obvious or likely, according to the investigator, are unable to understand and evaluate the information on this study as part of the process of signing informed consent, in particular regarding the expected risks and possible discomfort.

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: double-blind, randomized, cross-over study of comparative pharmacodynamics and pharmacokinetics
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TR Sequence<br>first Intervention period - subjects are administered test medecine (GP40141) and in seconde Intervention period subjects are administered reference medecine (Nplate) | Drug: GP40141<br>* Once, at a dose of 3 mcg/kg, Subcutaneously in the shoulder area<br>* Other names: romiplostim;Drug: Nplate<br>* Once, at a dose of 3 mcg/kg, Subcutaneously in the shoulder area<br>* Other names: romilostim;|
| Experimental: RT Sequence<br>first Intervention period subjects are administered reference medecine (Nplate) and in seconde Intervention period subjects are administered test medecine (GP40141) | Drug: GP40141<br>* Once, at a dose of 3 mcg/kg, Subcutaneously in the shoulder area<br>* Other names: romiplostim;Drug: Nplate<br>* Once, at a dose of 3 mcg/kg, Subcutaneously in the shoulder area<br>* Other names: romilostim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCplt | the total area under the curve amount platelets - time in the time interval from -45 minutes to the moment t (day 32 after injection) | -45, -30, -15 min and days 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32 post injection | 
| Pmax | maximum number of platelets count (any time) | -45, -30, -15 min and days 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32 post injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pmax/P0 | ratio: maximum number of platelets count to the basal level of platelets | -45, -30, -15 min and days 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32 post injection | 
| tPmax | time to reach the maximum number of platelets count | -45, -30, -15 min and days 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32 post injection | 
| AUC0-t | total area under the curve concentration of the active substance of the drug - time | -15 min and 1, 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 hour post injection, and additionally 4, 5, 6, 8, 10, 12, 16, 20 days post injection | 
| Cmax | blood maximum concentration of the active substance of the drug | -15 min and 1, 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 hour post injection, and additionally 4, 5, 6, 8, 10, 12, 16, 20 days post injection | 
| Tmax | time to reach the maximum blood concentration (Cmax) of the active substance of the drug | -15 min and 1, 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 hour post injection, and additionally 4, 5, 6, 8, 10, 12, 16, 20 days post injection | 
| T1/2 | half-life of the active substance of the drug | -15 min and 1, 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 hour post injection, and additionally 4, 5, 6, 8, 10, 12, 16, 20 days post injection | 
| AUC0-∞ | total area under the curve concentration of the active substance of the drug - time time interval from -15 min to infinity, after the administration of the drug | -15 min and 1, 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 hour post injection, and additionally 4, 5, 6, 8, 10, 12, 16, 20 days post injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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romiplostim