title: Recombinant filgrastim (BK0023) pharmacodynamics and pharmacokinetics after single and multiple escalating doses in an equivalence study in healthy men.
abstract: OBJECTIVE
  The new filgrastim formulation, BK0023, whose synthesis method is patented, was tested in a phase I clinical study that was aimed at investigating the pharmacodynamic and pharmacokinetic equivalence and the safety of BK0023 in healthy male subjects.
  
  
  METHODS
  Single and multiple escalating doses were administered to healthy male volunteers according to a double-blind, randomised, two-way crossover design. Thirty-two subjects received subcutaneous filgrastim 2.5 µg/kg/day for 7 consecutive days in each period, 36 subjects received 5 µg/kg/day for 7 days in each period, and 22 subjects received 10 µg/kg/day for 5 days. Absolute neutrophil count (ANC) and CD34+ cell count were measured in whole blood as primary and secondary pharmacodynamic parameters. Filgrastim concentrations were measured in serum to calculate the primary pharmacokinetic parameters.
  
  
  RESULTS
  The maximum ANC and the area under the curve of the ANC after the first dose and to the end of treatment satisfied the equivalence criterion (95 % confidence intervals within 85-115 or 85-117 % in case of log-transformation). At all three dose regimens, BK0023 was also bioequivalent to the reference product in terms of pharmacokinetic profile of serum filgrastim. The frequency of the treatment-emergent adverse events did not differ significantly between treatments, with the most frequent untoward effects being back and bone pain.
  
  
  CONCLUSIONS
  Equivalence could be established using both the baseline-adjusted values and the original unadjusted values. The tested formulation at all three dose regimens was also bioequivalent to the reference product in terms of pharmacokinetic profile.
authors.affiliation: CROSS Research S.A., Via F.A. Giorgioli, 6864, Arzo, Switzerland, andrea.distefano@croalliance.com.
authors.forename: Andrea F D
authors.initials: AF
authors.lastname: Di Stefano
authors.forename: Gaia
authors.initials: G
authors.lastname: Spinetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Rusca
authors.forename: Milko M
authors.initials: MM
authors.lastname: Radicioni
authors.forename: Luca
authors.initials: L
authors.lastname: Loprete
authors.forename: Domenica M G
authors.initials: DM
authors.lastname: Lamparelli
authors.forename: Jutta
authors.initials: J
authors.lastname: Michael Hepp
authors.forename: Davide
authors.initials: D
authors.lastname: Crobu
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Schrepfer
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tonon
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000069585:Filgrastim / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D011994:Recombinant Proteins; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D000069585:Filgrastim