Pharmacokinetics and Pharmacodynamics Comparison Study Between Two Pegfilgrastim Formulations

A Single-center, Open-label, Parallel Study With Single Subcutaneous Injection for Pharmacokinetics and Pharmacodynamics Comparison of Two Pegfilgrastim Formulations in Both Male and Female Healthy Volunteers, Test Formulation is an Injectable Solution Containing 6 mg of Pegfilgrastim, Manufactured by Eurofarma Laboratórios S/A, and Reference Formulation (Neulastim® Injectable Solution Containing 6 mg) Marketed by Produtos Roche Químicos e Farmacêuticos S/A

This study will evaluate the pharmacokinetics (relative bioavailability) and pharmacodynamics, after single subcutaneous application, in healthy volunteers of both sexes, between pegfilgrastim formulation, produced by Eurofarma Laboratorios S/A and Neulastim® (reference formulation), marketed by Produtos Roche Químicos e Farmacêuticos S/A.

In addition to that, a pharmacodynamics comparison will be performed, through change in absolute neutrophil count in leukogram performed in the same time of pharmacokinetics analysis collection and through CD34+ cell count in peripheral blood at timepoints 0:00, 96:00 and 384:00 hours.

Study Overview

• Status: Completed
• Conditions: Healthy; Neutropenia
• Intervention / Treatment: Biological: Pegfilgrastim

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Bragança Paulista, SP, Brazil
      • Unidade Integrada de Farmacologia e Gastroenterologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index equals to or higher than 18.5 and equals to or less than 29.9 kg/m2.
• The volunteer is in good health conditions and does not have clinically significant diseases, as per medical opinion, according to Medical History, measurements of Blood Pressure, Heart Rate and Temperature, Physical Exam, Electrocardiogram, and complementary Laboratorial Exams.
• Able to understand the study nature and objective, including risks and adverse events and who intends to cooperate with the researcher and act according to the whole study requirements, which is confirmed by the signature in the Informed Consent Form.

Exclusion Criteria:

• The volunteer is known to have hypersensitivity to the study drug product or to chemically-related compounds.
• History or presence of hepatic or gastrointestinal diseases or other condition interfering with drug product absorption, distribution, excretion or metabolism.
• Use of maintenance therapy with any drug product, except for oral contraceptive pills.
• History of hepatic, renal, pulmonary, gastrointestinal, neurological, hematological, psychiatric, cardiologic or allergic disease of any etiology requiring pharmacological treatment or that is considered clinically relevant by the researcher.
• Electrocardiographic findings are not recommended by the researcher for participating in the study.
• Results of complementary laboratorial exams outside the values considered normal according to this protocol rules, unless they are considered non-clinically significant by the researcher.
• Smoking.
• Daily intake of more than 5 cups of tea or coffee.
• History of drug or alcohol abuse.
• Use of regular medication within 2 weeks preceding the beginning of this study or use of any medication one week before starting this study.
• Hospital admission for any reason up to 8 weeks before the start of the first study treatment period.
• Treatment in the last 3 months before starting this study treatment with any drug product known to have a well-defined toxic potential in large organs.
• Participation in any pharmacokinetics study with collection of more than 300 mL of blood or intake of any experimental drug product in the last six months before starting the study treatment.
• Donation or loss of 450 mL or more of blood in the last three months preceding the study or donation of more than 1500 mL of blood in the last 12 months before starting the study treatment.
• Reagent result for urine βHCG exam, performed in female volunteers.
• Positive result in urine test for detection of abuse drugs.
• Result higher than 0.1 mg/L in ethylometer test.
• Any condition preventing participation in the study as per researcher's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pegfilgrastim; Pegfilgrastim (Hematopoietic Growth Factor) injectable solution 6 mg / 0,6mL in a single subcutaneous application.	Biological: Pegfilgrastim
ACTIVE_COMPARATOR: Neulastim (pegfilgrastim); Neulastim injectable solution 6 mg / 0,6mL in a single subcutaneous application.	Biological: Pegfilgrastim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of comparative pharmacokinetics of pegfilgrastim in healthy volunteers with parameter peak maximum concentration in plasma (Cmax).	A 90% confidence interval (CI) for the differences in transformed data means of test and comparator drugs, for Cmax. The CI antilog obtained constitutes the 90% CI for the ratio of geometric averages of the parameter: (Cmax test / Cmax comparator) Formulations are considered statistically bioequivalent if these intervals are between limits of 80% and 125%.	16 days
Evaluation of comparative pharmacokinetics of pegfilgrastim in healthy volunteers with parameter area under recombinant G-CSF concentration curve versus time (AUC 0-t).	A 90% confidence interval (CI) for the differences in transformed data means of test and comparator drugs, for AUC 0-t. The CI antilog obtained constitutes the 90% CI for the ratio of geometric averages of the parameter: (AUC0-t test / AUC0-t comparator) Formulations are considered statistically bioequivalent if these intervals are between limits of 80% and 125%.	16 days
Evaluation of comparative pharmacodynamics of pegfilgrastim in healthy volunteers with parameters: absolute neutrophil count (ANC) versus time.		16 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of comparative pharmacodynamics of pegfilgrastim in healthy volunteers with CD34+ count versus time.	CD34+ count until 144 hours	6 days

Collaborators and Investigators

• Sponsor: Eurofarma Laboratorios S.A.
• Investigators: Principal Investigator: José Pedrazzoli Junior, Unidade Integrada de Farmacologia e Gastroenterologia

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2015
• Primary Completion (ACTUAL): March 1, 2016
• Study Completion (ACTUAL): November 1, 2016

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: October 27, 2015
• First Posted (ESTIMATE): October 28, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): February 7, 2017
• Last Update Submitted That Met QC Criteria: February 6, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Neutropenia
• Other Study ID Numbers: EF143