Trial Outcomes & Findings for Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics and Safety of Leucostim® Compared to Neupogen® (NCT NCT02762799)

NCT ID: NCT02762799

Last Updated: 2018-12-19

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 60 participants
• Primary outcome timeframe: 0 to 48 hours post-dose
• Results posted on: 2018-12-19

Participant Flow

Participant milestones

Measure	Leucostim® --> Neupogen®, Subcutaneous Injections Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 followed by single subcutaneous injection Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® --> Leucostim®, Subcutaneous Injections Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 followed by single subcutaneous injection Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® --> Neupogen®, Intravenous Injections Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 followed by single intravenous injection Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® --> Leucostim®, Intravenous Injections Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 followed by single subcutaneous intravenous Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Overall Study STARTED	18	18	12	12
Overall Study COMPLETED	18	18	11	12
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Leucostim® --> Neupogen®, Subcutaneous Injections n=18 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 followed by single subcutaneous injection Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® --> Leucostim®, Subcutaneous Injections n=18 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 followed by single subcutaneous injection Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® --> Neupogen®, Intravenous Injections n=12 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 followed by single intravenous injection Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® --> Leucostim®, Intravenous Injections n=12 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 followed by single subcutaneous intravenous Leucostim® on Day 29. Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Total n=60 Participants Total of all reporting groups
Age, Continuous	22.94 years n=18 Participants	25.41 years n=18 Participants	23.48 years n=12 Participants	27.30 years n=12 Participants	24.63 years n=60 Participants
Sex: Female, Male Female	0 Participants n=18 Participants	0 Participants n=18 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=60 Participants
Sex: Female, Male Male	18 Participants n=18 Participants	18 Participants n=18 Participants	12 Participants n=12 Participants	12 Participants n=12 Participants	60 Participants n=60 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: 0 to 48 hours post-dose

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

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
AUC (0-48 Hours)	168603.588 picogram per ml / hour Standard Deviation 47721.48	181152 picogram per ml / hour Standard Deviation 54706.439	411826.811 picogram per ml / hour Standard Deviation 204285.095	427355.99 picogram per ml / hour Standard Deviation 170878.6

PRIMARY outcome

Timeframe: 0 to 48 hours post-dose

Maximal concentration of filgrastim after subcutaneous injection of filgrastim

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Cmax After Subcutaneous Injection	21605.163 picogram per ml Standard Deviation 5247.467	23389.559 picogram per ml Standard Deviation 7549.536	—	—

SECONDARY outcome

Timeframe: 0 to 48 hours post-dose

Maximal concentration of filgrastim after intravenous injection of filgrastim

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=24 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=24 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Cmax After Intravenous Injection	79751.577 picogram per ml Standard Deviation 24810.907	90796.227 picogram per ml Standard Deviation 25925.283	—	—

SECONDARY outcome

Timeframe: 0 to 48 hours post-dose

Time after single injection to reach maximal concentration of filgrastim

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Tmax After Injection	4 hours Interval 4.0 to 4.0	4 hours Interval 4.0 to 6.0	0.5 hours Interval 0.5 to 2.0	0.5 hours Interval 0.5 to 0.5

SECONDARY outcome

Timeframe: 0 to 48 hours post-dose

Half-life of filgrastim after single injection of filgrastim

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Т½	4,386 hours	4,307 hours	2,746 hours	2,549 hours

SECONDARY outcome

Timeframe: 0 to 48 hours post-dose

The elimination rate constant after single injection of filgrastim

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Kel	0.158 hour-1 Interval 0.141 to 0.173	0.161 hour-1 Interval 0.145 to 0.17	0.252 hour-1 Interval 0.173 to 0.318	0.272 hour-1 Interval 0.219 to 0.316

SECONDARY outcome

Timeframe: 0 to 48 hours post-dose

Clearance of filgrastim after single injection

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Clearance	2048.087 ml per hour Interval 1893.882 to 2518.863	1981.707 ml per hour Interval 1581.655 to 2439.947	965.938 ml per hour Interval 595.547 to 1055.471	830.442 ml per hour Interval 724.578 to 941.928

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
ANC-AUEC (0-336 Hours)	1924.284 cells х10^9 per liter/hour Standard Deviation 326.455	1933.358 cells х10^9 per liter/hour Standard Deviation 309.533	1860.922 cells х10^9 per liter/hour Standard Deviation 372.861	1895.82 cells х10^9 per liter/hour Standard Deviation 426.826

SECONDARY outcome

Timeframe: 0 to 336 hours post-dose

Maximal absolute neutrophil count after single filgrastim injection

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
ANC-Emax	21.285 cells х10^9 per liter Standard Deviation 4.593	20.803 cells х10^9 per liter Standard Deviation 4.097	20.726 cells х10^9 per liter Standard Deviation 6.393	21.602 cells х10^9 per liter Standard Deviation 5.93

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
CD34-AUEC (0-336 Hours)	1289 cell per microliter / hour Standard Deviation 762.292	1200.667 cell per microliter / hour Standard Deviation 761.29	1350.783 cell per microliter / hour Standard Deviation 716.645	1251.652 cell per microliter / hour Standard Deviation 562.087

SECONDARY outcome

Timeframe: 0 to 336 hours post-dose

Maximal absolute count of CD34-cells after single filgrastim injection

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
CD34-Emax	7.694 cell per microliter Standard Deviation 4.839	7.056 cell per microliter Standard Deviation 5.248	9 cell per microliter Standard Deviation 6.267	7.522 cell per microliter Standard Deviation 4.22

SECONDARY outcome

Timeframe: 0 to 336 hours post-dose

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=23 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Overall Frequency of Serious Adverse Events (SAE)	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0 to 336 hours post-dose

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=23 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Overall Frequency of Adverse Events (AE)	36 Participants	35 Participants	22 Participants	22 Participants

SECONDARY outcome

Timeframe: 0 to 336 hours post-dose

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=23 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Frequency of Local Reactions	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0 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.

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=23 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Frequency of AE/SAE 3-4 Grade CTCAE 4.03	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0 to 336 hours post-dose

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=23 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Frequency of Preliminary Withdrawal Due to AE/SAE	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0 to 336 hours post-dose

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

Outcome measures

Measure	Leucostim® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single subcutaneous injection Leucostim® on Day 29 (in Neupogen® --\> Leucostim® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 Participants Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1 (in Neupogen® --\> Leucostim® group) or single subcutaneous injection Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group). Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim® Intravenous Injections n=24 Participants Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1 (in Leucostim® --\> Neupogen® group) or single intravenous injection Leucostim® on Day 29 (in Neupogen®--\> Leucostim® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Intravenous Injections n=23 Participants Healthy volunteers in this group received single intravenous injection Neupogen® on Day 1 (in Neupogen® --\> Leucostim® group) or subcutaneous intravenous Leucostim® on Day 29 (in Leucostim®--\>Neupogen® group) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Proportion of Patients With Binding or Neutralizing Antibodies to Filgrastim	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Leucostim®, Subcutaneous Injections

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Neupogen® Subcutaneous Injections

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Leucostim®, Intravenous Injections

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Neupogen®, Intravenous Injections

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Leucostim®, Subcutaneous Injections n=36 participants at risk Healthy volunteers in this group received single subcutaneous injection Leucostim® on Day 1(in group Leucostim®--\>Neupogen®) or single subcutaneous injection Leucostim® on Day 29 (in group Neupogen® --\> Leucostim®) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen® Subcutaneous Injections n=36 participants at risk Healthy volunteers in this group received single subcutaneous injection Neupogen®, on Day 1(in group Neupogen®--\>Leucostim®) or single subcutaneous injection Neupogen® on Day 29 (in group Leucostim®--\>Neupogen®) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Leucostim®, Intravenous Injections n=24 participants at risk Healthy volunteers in this group received single intravenous injection Leucostim® on Day 1(in group Leucostim®--\>Neupogen®) or single subcutaneous injection Leucostim® on Day 29 (in group Neupogen® --\> Leucostim®) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®	Neupogen®, Intravenous Injections n=23 participants at risk Healthy volunteers in this group received single intravenous injection Neupogen®, on Day 1(in group Neupogen®--\>Leucostim®) or single subcutaneous injection Neupogen® on Day 29 (in group Leucostim®--\>Neupogen®) Leucostim®: Leucostim® is filgrastim biosimilar. Neupogen®
Blood and lymphatic system disorders Lymphocytosis	30.6% 11/36	27.8% 10/36	20.8% 5/24	8.7% 2/23
Nervous system disorders head pain	25.0% 9/36	27.8% 10/36	0.00% 0/24	0.00% 0/23
Blood and lymphatic system disorders Monocytosis	88.9% 32/36	88.9% 32/36	83.3% 20/24	91.3% 21/23
Blood and lymphatic system disorders eosinophilia	27.8% 10/36	41.7% 15/36	37.5% 9/24	30.4% 7/23

Additional Information

Yulia Linkova Medical Director

Biocad

Phone: +7 (495) 992 66 28

Email: linkova@biocad.ru

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place