Taher, Ali T.Saliba, Antoine N.Kuo, Kevin H.Giardina, Patricia J.Cohen, Alan R.Neufeld, Ellis J.Aydinok, YesimKwiatkowski, Janet L.Jeglinski, Brenda I.Pietropaolo, KeithBerk, GregoryViprakasit, Vip2017-11-152017-11-152017-12Taher, A. T., Saliba, A. N., Kuo, K. H., Giardina, P. J., Cohen, A. R., Neufeld, E. J., Aydinok, Y., Kwiatkowski, J. L., Jeglinski, B. I., Pietropaolo, K., Berk, G. and Viprakasit, V. (2017), Safety and Pharmacokinetics of the Oral Iron Chelator SP-420 in β-thalassemia. Am J Hematol. Accepted Author Manuscript. doi:10.1002/ajh.24914https://hdl.handle.net/1805/14549Our 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.enPublisher Policyβ-thalassemia majoriron overloadiron chelationArticle