Bioequivalence between two serum-free recombinant factor VIII preparations (N8 and ADVATE®)--an open-label, sequential dosing pharmacokinetic study in patients with severe haemophilia A.

摘要: Recombinant coagulation factor VIII (rFVIII) concentrates provide a safe and efficacious replacement therapy for treatment prevention of bleeding in patients with severe haemophilia A. The aim this study was to compare the pharmacokinetic (PK) safety profiles two serum-free rFVIII products: N8, new manufactured by Novo Nordisk Advate(®), marketed product. Patients A >150 exposure days FVIII, without current or past inhibitors, were enrolled an open-label, first human dose (FHD), multicentre trial. Twenty-three received single 50 IU kg(-1) body weight Advate(®) followed N8 at next visit. 4-day washout period required prior each dosing. Blood samples PK analyses drawn dosing intervals up until 48 h postdosing. parameters based on FVIII clotting activity (FVIII:C) measurements. Occurrence adverse events closely monitored. mean FVIII:C all primary secondary comparable. 90% CI ratio (Advate(®)/N8) endpoints (incremental recovery, t(1/2), AUC Cl), (AUC(last) C(max)) within bioequivalence interval 0.8-1.25. There no concerns reports inhibitor formation 72-h following dose. In conclusion, is bioequivalent Advate(®). Furthermore, well tolerated FHD