title: ReFacto and Advate: a single-dose, randomized, two-period crossover pharmacokinetics study in subjects with haemophilia A.
abstract: ReFacto is a recombinant B-domain-deleted, monoclonal antibody-purified, solvent-detergent-treated factor VIII (BDDrFVIII) with no albumin added to the final formulation. Although ReFacto has been shown to be bioequivalent to a plasma-derived FVIII product (Hemophil-M) in a randomized, crossover pharmacokinetic (PK) study, the comparability of ReFacto with the full-length (complete sequence) recombinant FVIII (FLrFVIII, Advate) product has not been previously examined in this manner. The primary objective of this study was to compare the PKs of ReFacto with those of Advate in patients with severe haemophilia A. This was a third-party unblinded, randomized, multicentre, two-period crossover PKs study of ReFacto and Advate in subjects with severe haemophilia A (FVIII:C < or =1%). Blood samples were collected over a 48-h period after i.v. administration of each of the FVIII products. FVIII:C was determined using the chromogenic substrate assay (CSA) in a central laboratory. The plasma FVIII:C PK parameters of ReFacto and Advate were determined using non-compartmental analysis. Bioequivalence was assessed on maximum plasma concentration (C(max)) and the area under the plasma concentration vs. time curves (AUCs) using an anova. The two products were judged to be equivalent if the 90% confidence limits of the ratio of the geometric mean values of C(max) and AUCs fell within the interval of 80-125%. Results from this PKs comparison of two different rFVIII products, using chromogenic substrate assay to measure FVIII:C, showed that ReFacto and Advate are bioequivalent to each other.
authors.affiliation: University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. jorge-dipaola@uiowa.edu
authors.forename: J
authors.initials: J
authors.lastname: Di Paola
authors.forename: M P
authors.initials: MP
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Klamroth
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: C
authors.initials: C
authors.lastname: Kollmer
authors.forename: J
authors.initials: J
authors.lastname: Feingold
authors.forename: C
authors.initials: C
authors.lastname: Kessler
authors.forename: H
authors.initials: H
authors.lastname: Pollmann
authors.forename: M
authors.initials: M
authors.lastname: Morfini
authors.forename: C
authors.initials: C
authors.lastname: Udata
authors.forename: C
authors.initials: C
authors.lastname: Rothschild
authors.forename: C
authors.initials: C
authors.lastname: Hermans
authors.forename: R
authors.initials: R
authors.lastname: Janco
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003029:Coagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D032984:Ethics, Research; D005167:Factor VII / Q000008:administration & dosage / Q000493:pharmacokinetics; D005169:Factor VIII / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; C427184:recombinant factor VIII SQ; D005167:Factor VII; D005169:Factor VIII