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International Journal of Hematology

, Volume 88, Issue 1, pp 73–81 | Cite as

A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade®, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan

  • Keisuke MiyazawaEmail author
  • Kazuma Ohyashiki
  • Akio Urabe
  • Tomoko Hata
  • Shinji Nakao
  • Keiya Ozawa
  • Takayuki Ishikawa
  • Junji Kato
  • Yoichi Tatsumi
  • Hiraku Mori
  • Midori Kondo
  • Junsuke Taniguchi
  • Hiromi Tanii
  • Lisa Rojkjaer
  • Mitsuhiro Omine
Original Article

Abstract

The pharmacokinetics (PK) and pharmacodynamics (PD) of the once-daily, oral ironchelating agent, deferasirox (Exjade®, ICL670), have been evaluated further in a Phase I, openlabel, multicenter, dose-escalation study in Japanese patients with myelodysplastic syndromes, aplastic anemia, and other anemias. Deferasirox was initially administered as a single dose of 5 (= 6), 10 (= 7), 20 (= 6) or 30 (= 7) mg/(kg day) and then after 7 days seven daily doses were administered. Linear PK (Cmax and AUC) were observed at all doses after a single dose and at steady state, and dose-dependent iron excretion was observed. Pharmacokinetic/pharmacodynamic parameters were similar to those reported in a Caucasian β-thalassemia cohort. Following the single- and multiple-dose phases, 21 of 26 patients progressed to a 3-year extension phase of the study, where dose reductions and increases [5–30 mg/(kg day)] were allowed following safety and efficacy assessments. In the interim, 1-year data show that deferasirox was well tolerated, with generally infrequent and mild adverse events. Reductions in serum ferritin levels were observed and a negative iron balance achieved at doses of 20–30 mg/(kg day). These data suggest that deferasirox has a stable and predictable PK/PD profile, irrespective of underlying disease or race, and a predictable and manageable safety profile suitable for chronic administration.

Keywords

Iron chelation Deferasirox Iron overload Myelodysplastic syndrome 

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Copyright information

© The Japanese Society of Hematology 2008

Authors and Affiliations

  • Keisuke Miyazawa
    • 1
    Email author
  • Kazuma Ohyashiki
    • 1
  • Akio Urabe
    • 2
  • Tomoko Hata
    • 3
  • Shinji Nakao
    • 4
  • Keiya Ozawa
    • 5
  • Takayuki Ishikawa
    • 6
  • Junji Kato
    • 7
  • Yoichi Tatsumi
    • 8
  • Hiraku Mori
    • 9
  • Midori Kondo
    • 10
  • Junsuke Taniguchi
    • 10
  • Hiromi Tanii
    • 10
  • Lisa Rojkjaer
    • 11
  • Mitsuhiro Omine
    • 9
  1. 1.First Department of Internal Medicine (Hematology/Oncology)Tokyo Medical UniversityTokyoJapan
  2. 2.NTT Kanto Medical CenterTokyoJapan
  3. 3.Nagasaki UniversityNagasakiJapan
  4. 4.Kanazawa UniversityIshikawaJapan
  5. 5.Jichi Medical UniversityTochigiJapan
  6. 6.Kyoto UniversityKyotoJapan
  7. 7.Sapporo Medical UniversitySapporoJapan
  8. 8.Kinki UniversityOsakaJapan
  9. 9.Showa University Fujigaoka HospitalYokohamaJapan
  10. 10.Novartis Pharma K.K.TokyoJapan
  11. 11.Novartis Pharma A.G.BaselSwitzerland

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