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document
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 . 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 % . RESULTS/CONCLUSION Results show that each BDDrFVIII formulation is bioequivalent to Hemofil M and the two formulations of BDDrFVIII are bioequivalent to each other .
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Intervention_Pharmacological
B-domain deleted recombinant factor VIII preparations
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Intervention_Pharmacological
BDDrFVIII formulations ( one reconstituted with 5 mL of sterile water , the other reconstituted with 4 mL sodium chloride 0.9 % USP )
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Intervention_Control
full-length FVIII preparation ( Hemofil M )
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Intervention_Pharmacological
FVIII preparations
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Intervention_Pharmacological
BDDrFVIII formulation
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Outcome_Physical
blood samples
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Outcome_Physical
Plasma FVIII activity
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Outcome_Physical
Plasma FVIII activity
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Outcome_Other
time curves
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Outcome_Physical
maximum plasma concentration ( Cmax ) and the area under plasma concentration vs. time curves ( AUCs
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Outcome_Physical
ratio of geometric means for Cmax and AUCs
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Outcome_Other
bioequivalent
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Participant_Condition
haemophilia A