Pharmacokinetic and Pharmacodynamic Equivalence of Pegfilgrastim-cbqv and Pegfilgrastim in Healthy Subjects

Abstract

Introduction: Pegfilgrastim-cbqv was developed as a biosimilar of pegfilgrastim, a pegylated form of recombinant human granulocyte colony-stimulating factor approved for decreasing febrile neutropenia-associated infection in patients receiving myelosuppressive drugs. This multicenter, randomized, single-blind, partial-reference-replicated, three-sequence crossover study assessed pharmacokinetic and pharmacodynamic bioequivalence of pegfilgrastim-cbqv and pegfilgrastim in healthy subjects. Methods: One hundred twenty-two subjects were randomized to one of three treatment sequences; each included one dose of pegfilgrastim-cbqv and two doses of pegfilgrastim separated by ≥ 28 days. The primary pharmacokinetic end points were area under the curve (AUC) from 0 to infinity (AUC0−∞) and maximum concentration (Cmax). The primary pharmacodynamic end points were maximum absolute neutrophil count (ANCmax) and ANC AUC from time 0 to the last measurable observation (ANC AUC0−last). Pharmacokinetic and pharmacodynamic bioequivalences were demonstrated if the 90% CI for the geometric mean ratio (GMR) of pegfilgrastim-cbqv to pegfilgrastim was within 80–125% for the primary end points. Results: Pharmacokinetic bioequivalence criteria were met for Cmax (GMR 105.0; 90% CI 95.5–115.4) and AUC0−∞ (GMR 97.5; 90% CI 88.6–107.2). Pharmacodynamic bioequivalence criteria were met for ANCmax (GMR 99.6; 90% CI 96.2–103.2) and ANC AUC0−last (GMR 96.7; 90% CI 92.2–101.4). Adverse events occurred in 76.0%, 76.6%, and 73.1% of subjects for pegfilgrastim-cbqv, first pegfilgrastim, and second pegfilgrastim dosing periods across treatment sequences, respectively. Investigators found no drug-related serious adverse events. Conclusion: This study established pharmacokinetic and pharmacodynamic bioequivalence of pegfilgrastim-cbqv to pegfilgrastim. The treatments displayed similar safety profiles, including immunogenicity, with no unexpected safety findings. Clinical Trials Registration: ClinicalTrials.gov, NCT02650973, February 2016.