Pharmacokinetic / Pharmacodynamic Study Comparing MYL-1401H, EU-sourced Neulasta and US-licensed Neulasta

NCT02479646 | Completed Phase 1

• 2 other identifiers: MYL-1401H-10012014-002229-37
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, double-blind, randomized, comparative pharmacokinetic and pharmacodynamic study of MYL-1401H and Neulasta (from EU and US source) in Normal Healthy Volunteers.

Conditions

Healthy Volunteers

Keywords

Pegfilgrastim; G-CSF; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (4)

• Pharmacodynamics: Area under the curve above baseline of ANC [ANC_AUC(0-tlast)]

  Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), and on Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29

• Pharmacodynamics: Maximum change from baseline in absolute neutrophil count (ANC); ANC_Cmax

  Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29

• Area under the serum concentration-time curve (AUC0-inf) of Pegfilgrastim

  Pharmacokinetics as measured by total AUC after extrapolation from time t to time infinity

  Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29

• Maximum Serum Concentration (Cmax) of pegfilgrastim

  Pharmacokinetics as measured by peak serum concentration of Pegfilgrastim

  Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29

Secondary Outcomes (3)

• Frequency of Adverse Events

  Daily until Day 9, then on Day 12, 15, 22 of each study period, and at follow-up visit (day 84).

• Safety Variable - Tolerability as measured by Injection Site reactions

  Daily until Day 5 of each period

• Safety Variable - Immunogenicity as measured by presence of Anti Drug Antibodies

  Day 1 each period and at follow-up (Day 84)

Study Arms (3)

Treatment A

EXPERIMENTAL

MYL-1401H: single subcutaneous injection (2mg)

Biological: MYL-1401H

Treatment B

ACTIVE COMPARATOR

EU-Neulasta: single subcutaneous injection (2mg)

Biological: EU-Neulasta

Treatment C

ACTIVE COMPARATOR

US-Neulasta: single subcutaneous injection (2mg)

Biological: US-Neulasta

Interventions

MYL-1401H BIOLOGICAL

Also known as: Recombinant human granulocyte colony-stimulating factor (G-CSF), Pegfilgrastim

Treatment A

EU-Neulasta BIOLOGICAL

Also known as: Recombinant human granulocyte colony-stimulating factor (G-CSF), Pegfilgrastim

Treatment B

US-Neulasta BIOLOGICAL

Also known as: Recombinant human granulocyte colony-stimulating factor (G-CSF), Pegfilgrastim

Treatment C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Weight: ≥60 kg.
• Body mass index (BMI): 19.0-30.0 kg/m2
• Vital signs showing no clinically relevant deviations.
• Computerized 12-lead ECG recording without signs of clinically relevant pathology.
• Non-smoker or light smoker
• Ability and willingness to abstain from alcohol from 48 hours prior to each admission to the clinical research center and prior to ambulatory visits, and during the stays in the clinic.
• Fertile males and females participating in heterosexual sexual relations: willingness to use adequate contraception from screening until 90 days after the follow up visit
• Females must not be lactating and must have a negative pregnancy test at screening and each admission.
• ANC, total leukocyte count, platelet count, hematocrit and hemoglobin results within the reference ranges.
• All other values for hematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Principal Investigator

You may not qualify if:

• Unable to follow protocol instructions in the opinion of the Principal Investigator.
• Any past or concurrent medical conditions that potentially increase the subject's risks or affect the evaluation of any study results. Examples of these include medical history with evidence of clinically relevant pathology (e.g. sickle cell disorders, spleen pathologies, hematologic malignancies or myelodysplastic disorders, and pulmonary illnesses such as ARDS, interstitial pneumonia, pulmonary edema, pulmonary infiltrates and pulmonary fibrosis) and history of relevant drug and/or food allergies.
• Known history of previous exposure to filgrastim, pegfilgrastim, granulocyte colony stimulating factor (GCSF) or any analogue of these.
• Hypersensitivity to the constituents of Neulasta® (sorbitol E420, polysorbate 20 and acetate or acetic acid) or hypersensitivity to E. coli derived proteins.
• Any infection, cough or fever within 1 week prior to first study drug administration.
• Fructose intolerance.
• First degree relatives with hematological malignancy.
• Treatment with non-topical medications within 5 days prior to first admission to the clinical research center, with the exception of hormonal contraceptives, multivitamins, vitamin C, food supplements and a limited amount of paracetamol (acetaminophen), which may be used throughout the study.
• Participation in a drug study within 60 days prior to study drug administration.
• Donation or loss of more than 500 mL of blood over a period of 60 days prior to study drug administration. Donation of more than 1.5 L of blood (for men) / more than 1.0 L of blood (for women) in the 10 months preceding the start of this study.
• History of alcohol abuse or drug addiction
• Regular intake of more than 24 units of alcohol per week (one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits).
• Positive drug screen (opiates, methadone, cocaine, amphetamines (including ecstasy), cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol).
• Positive screen on hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or anti-human immunodeficiency virus (HIV) 1/2 antibodies.

Sponsors & Collaborators

• Mylan Inc.: lead
• Mylan GmbH: collaborator

Study Sites (1)

PRA Health Sciences - Early Development Services

Zuidlaren, 9471, Netherlands

Location

MeSH Terms

Interventions

MYL-1401H; Granulocyte Colony-Stimulating Factor; pegfilgrastim

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Renger Tiessen, MD, PhD

  PRA Health Sciences

  PRINCIPAL INVESTIGATOR

• Fausto Berti

  Mylan GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: June 24, 2015
• Study Start: September 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 14, 2022

Record last verified: 2022-02

Locations

NL (1)