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Clinical Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Recombinant Factor VIIa in Japanese Patients With Hemophilia With Inhibitors

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Abstract

A multicenter and open-labeled clinical trial of human recombinant factor VIIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study 1, the pharmacokinetics, pharmacodynamics, and safety of a single dose of 120 μg/kg ofrFVIIa were investigated in 8 patients. In the subsequent study 2, the hemostatic effect and safety ofrFVIIa were evaluated during a 24-week period in 10 patients. In study 1, the mean maximum FVII-coagulant activity (FVII:C) was found to occur after 10 minutes; activity then decreased rapidly and returned to the baseline within 24 hours after a single intravenous infusion of rFVIIa. The mean half-life of FVII:C was 3.5 hours. The activated partial thromboplastin time and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing. In study 2, 86 μg/kg to 120 μg/kg ofrFVIIa (mean, 97 μg/kg) was administered 1 to 85 times to 10 patients. A total of 58.0% (91/157) of bleeding episodes were treated excellently or effectively, with 5 (3.2%) ineffective episodes. There was no apparent trend in the relationship of the hemostatic effect with bleeding sites, mean dose, or number of injections. The efficacy rate, however, was significantly higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatment-related adverse events were observed, and there was no evidence of antibody formation to rFVIIa. In conclusion,rFVIIa is an effective and well-tolerated option for treatment of bleeding episodes in hemophilia patients with inhibitors.

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Authors and Affiliations

  1. Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan

    Akira Shirahata & Junji Kamizono

  2. Japanese Red Cross Aichi Blood Center, Aichi

    Tadashi Kamiya

  3. Department of Blood Transfusion, Nagoya University School of Medicine, Nagoya

    Junki Takamatsu

  4. First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya

    Tetsuhito Kojima & Hidehiko Saito

  5. Department of Clinical Pathology, Tokyo Medical University, Tokyo

    Katsuyuki Fukutake & Morio Arai

  6. Department of Hematology, Ogikubo Hospital, Tokyo

    Hideji Hanabusa & Hisamichi Tagami

  7. Department of Pediatrics, Nara Medical University, Kashihara, Nara

    Akira Yoshioka, Midori Shima & Hiroyuki Naka

  8. First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan

    Shigeru Fujita & Yoko Minamoto

Authors
  1. Akira Shirahata
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  2. Tadashi Kamiya
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  3. Junki Takamatsu
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  4. Tetsuhito Kojima
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  5. Katsuyuki Fukutake
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  6. Morio Arai
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  7. Hideji Hanabusa
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  8. Hisamichi Tagami
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  9. Akira Yoshioka
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  10. Midori Shima
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  11. Hiroyuki Naka
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  12. Shigeru Fujita
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  13. Yoko Minamoto
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  14. Junji Kamizono
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  15. Hidehiko Saito
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Shirahata, A., Kamiya, T., Takamatsu, J. et al. Clinical Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Recombinant Factor VIIa in Japanese Patients With Hemophilia With Inhibitors. Int J Hematol 73, 517–525 (2001). https://doi.org/10.1007/BF02994016

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  • DOI: https://doi.org/10.1007/BF02994016

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