A clinical trial of
BAY 14-2222, a recombinant
factor VIII preparation (rFVIII) manufactured by new purification and formulation processes using
sucrose as a stabilizer instead of
human serum albumin, was performed in 5 previously treated Japanese patients with severe
hemophilia A. In stage I, a single dose of
BAY 14-2222 and
Kogenate (a currently licensed rFVIII preparation) was administered alternately in the same patients to compare the pharmacokinetics of the 2 compounds using FVIII:C (FVIII clotting activity) as the measure of plasma
drug levels. The normalized area under the curve (AUCnorm) and normalized maximal concentration (Cmax,norm) were slightly lower following the administration of
BAY 14-2222 than those after the administration of
Kogenate (ratio of
BAY 14-2222/
Kogenate:AUCnorm = 0.88, P = .050; and Cmax,norm = 0.87, P = .041). However, the
biological half-life (t1/2) did not differ significantly between the 2 preparations (13.96 +/- 4.18 vs. 13.48 +/- 2.40 hours). The in vivo recovery of FVIII was 67.9 +/- 11.3% after the administration of
BAY 14-2222 and 74.4 +/- 5.3% after the administration of
Kogenate. In stage II,
BAY 14-2222 was administered regularly to the 5 patients with
hemophilia at single doses of 20 to 40 IU/kg 3 times weekly for 4 weeks, and its prophylactic effect on
bleeding was evaluated. Results indicated that
BAY 14-2222 has a good preventive effect on
bleeding. Sixty-six infusions were performed in stages I and II of this trial, and no adverse reactions related to
BAY 14-2222 were observed. In addition, there were no FVIII inhibitors or
antibodies to foreign
proteins detected. The trial confirmed that
BAY 14-2222 is similar to
Kogenate with respect to t1/2 and the in vivo recovery of FVIII:C and that periodic infusions for 4 weeks can be well tolerated. In addition, it was shown that
BAY 14-2222 is effective in preventing
bleeding. Thus it is expected that
BAY 14-2222 will exhibit a
hemostatic effect comparable to that of
Kogenate in patients with
hemophilia A.