title: B-domain deleted recombinant factor VIII preparations are bioequivalent to a monoclonal antibody purified plasma-derived factor VIII concentrate: a randomized, three-way crossover study.
abstract: BACKGROUND
  Deletion of the B-domain of recombinant blood coagulation factor VIII (BDDrFVIII) increases the manufacturing yield of the product but does not impair in vitro or in vivo functionality. BDDrFVIII (ReFacto) has been developed with the additional benefit of being formulated without human albumin.
  
  
  OBJECTIVE
  The primary objective of this three-way crossover-design study was to compare the pharmacokinetic (PK) parameters of two BDDrFVIII formulations (one reconstituted with 5 mL of sterile water, the other reconstituted with 4 mL sodium chloride 0.9% USP) with those of a plasma-derived, full-length FVIII preparation (Hemofil M) in patients with haemophilia A to determine bioequivalence.
  
  
  METHODS
  A series of blood samples were collected over a period of 48 h after i.v. administration of each of the FVIII preparations. Plasma FVIII activity was determined using a validated chromogenic substrate assay. Plasma FVIII activity vs. time curves was characterized for a standard set of PK parameter estimates. Two parameter estimates, the maximum plasma concentration (Cmax) and the area under plasma concentration vs. time curves (AUCs), were used to evaluate bioequivalence. The two preparations were considered bioequivalent if the 90% confidence intervals for the ratio of geometric means for Cmax and AUCs fell within the bioequivalence window of 80% to 125%.
  
  
  CONCLUSIONS
  Results show that each BDDrFVIII formulation is bioequivalent to Hemofil M and the two formulations of BDDrFVIII are bioequivalent to each other.
authors.affiliation: Georgetown University Medical Center, Washington, DC 20007-2197, USA. kesslerc@gunet.georgetown.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Kessler
authors.forename: J C
authors.initials: JC
authors.lastname: Gill
authors.forename: G C
authors.initials: GC
authors.lastname: White
authors.forename: A
authors.initials: A
authors.lastname: Shapiro
authors.forename: S
authors.initials: S
authors.lastname: Arkin
authors.forename: D A
authors.initials: DA
authors.lastname: Roth
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: J M
authors.initials: JM
authors.lastname: Lusher
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D019540:Area Under Curve; D018592:Cross-Over Studies; D005169:Factor VIII / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D010949:Plasma; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics; D016037:Single-Blind Method; D013810:Therapeutic Equivalency
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; C427184:recombinant factor VIII SQ; C078147:F8 protein, human; D005169:Factor VIII