title: Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple intravenous administrations: an open-label randomised controlled trial.
abstract: BACKGROUND
  HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway. Therefore, in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa, the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations.
  
  
  METHODS
  An open, randomised, parallel group study was conducted in 80 healthy adult males. Subjects were randomised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation.
  
  
  RESULTS
  The haematological profiles of both treatments were similar, as determined from their population mean curves and the AUECHb ratio and 90% confidence interval (99.9% [98.5-101.2%]), the primary pharmacodynamic endpoint of this study. The pharmacokinetic parameters after the treatments showed minor differences after single dosing, but not at steady state doses. After multiple doses, HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin (AUCtau ratio and 90% confidence interval: 89.2% [82.5-96.2%]). Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected.
  
  
  CONCLUSIONS
  HX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action. This supports the conclusion that HX575 and the comparator epoetin alfa, when administered intraveneously, will be equally efficacious and may be interchangeable as therapy.
authors.affiliation: IBMP-Institute for Biomedical and Pharmaceutical Research, Nürnberg, Germany. ibmp@osn.de
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.forename: Ursula
authors.initials: U
authors.lastname: Thyroff-Friesinger
authors.forename: Andrea
authors.initials: A
authors.lastname: Vetter
authors.forename: Bernhard
authors.initials: B
authors.lastname: Vens-Cappell
authors.forename: Martina
authors.initials: M
authors.lastname: Kinzig
mesh_terms: D000328:Adult; D000740:Anemia / Q000188:drug therapy* / Q000378:metabolism; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000068817:Epoetin Alfa; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006397:Hematinics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D006403:Hematologic Tests; D006801:Humans; D007262:Infusions, Intravenous; D044542:LEOPARD Syndrome; D008297:Male; D008657:Metabolic Clearance Rate; D011994:Recombinant Proteins / Q000008:administration & dosage; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa