title: Pharmacokinetic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial.
abstract: Recombinant human granulocyte colony-stimulating factor (filgrastim) has multiple hematologic and oncologic indications as Neupogen (Amgen filgrastim). Hospira has developed a biosimilar filgrastim (Nivestim). Here, results are reported from a phase I trial, primarily designed to compare the pharmacokinetic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, open-label, randomized trial was undertaken to demonstrate equivalence of the pharmacokinetic characteristics of Hospira filgrastim and Amgen filgrastim. Forty-eight healthy volunteers were randomized to receive intravenous (i.v.) or subcutaneous (s.c.) dosing and then further randomized to order of treatment. Volunteers in each of the two dosing groups received a single 10microg/kg dose of Hospira filgrastim or Amgen filgrastim, with subsequent crossover. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of 'test' to 'reference' treatment means were within the conventional equivalence limits of 0.80-1.25, then bioequivalence was concluded. Forty-six volunteers completed the study. Geometric mean area under the curve from time 0 to the last time point (primary endpoint) was similar in volunteers given Hospira filgrastim or Amgen filgrastim following i.v. (ratio of means: 0.96; 90% CI: 0.90-1.02) or s.c. (ratio of means: 1.02; 90% CI: 0.95-1.09) dosing; 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim in terms of its pharmacokinetic properties and may provide a clinically effective alternative.
authors.affiliation: Medizinische Universitätsklinik, Abt. Innere Medizin I, Hugstetter Strasse 55, Freiburg, Germany. cornelius.waller@uniklinik-freiburg.de
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Waller
authors.forename: Miguel
authors.initials: M
authors.lastname: Bronchud
authors.forename: Stuart
authors.initials: S
authors.lastname: Mair
authors.forename: Rodeina
authors.initials: R
authors.lastname: Challand
mesh_terms: D000293:Adolescent; D000328:Adult; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim