2. Academic Validation
  3. Safety and pharmacokinetics of the oral iron chelator SP-420 in β-thalassemia

Safety and pharmacokinetics of the oral iron chelator SP-420 in β-thalassemia

  • Am J Hematol. 2017 Dec;92(12):1356-1361. doi: 10.1002/ajh.24914.
Ali T Taher 1,  Antoine N Saliba 2,  Kevin H Kuo 3,  Patricia J Giardina 4,  Alan R Cohen 5,  Ellis J Neufeld 6,  Yesim Aydinok 7,  Janet L Kwiatkowski 5,  Brenda I Jeglinski 8,  Keith Pietropaolo 8,  Gregory Berk 8,  Vip Viprakasit 9
Affiliations

Affiliations

  • 1 Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
  • 2 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
  • 3 Division of Medical Oncology and Hematology, University Health Network, Toronto, Ontario, Canada.
  • 4 Weill Medical College of Cornell University, New York, New York.
  • 5 Division of Hematology, The Children's Hospital of Philadelphia and Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania.
  • 6 St. Jude Children's Research Hospital, Memphis, Tennessee.
  • 7 Department of Pediatric Hematology, Ege University Hospital, Izmir, Turkey.
  • 8 Sideris Pharmaceuticals, Inc., Lexington, Massachusetts.
  • 9 Department of Pediatrics & Thalassemia Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
PMID: 28940308 DOI: 10.1002/ajh.24914
Abstract

Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for Cmax and AUC0-τ over the dose range evaluated. The median tmax ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16912
    99.71%, 铁螯合剂
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