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SP\u2010420 was administered as a single dose of 1.5 (<jats:italic>n<\/jats:italic>\u2009=\u20093), 3 (<jats:italic>n<\/jats:italic>\u2009=\u20093), 6 (<jats:italic>n<\/jats:italic>\u2009=\u20093), 12 (<jats:italic>n<\/jats:italic>\u2009=\u20093), and 24 (<jats:italic>n<\/jats:italic>\u2009=\u20096) mg\/kg or as a twice\u2010daily dose of 9 mg\/kg (<jats:italic>n<\/jats:italic>\u2009=\u20096) over 14\u201028 days. There was a near dose\u2010linear increase in the mean plasma SP\u2010420 concentrations and in the mean values for <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2010\u03c4<\/jats:sub> over the dose range evaluated. The median <jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub> 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\u2010420 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.<\/jats:p>","DOI":"10.1002\/ajh.24914","type":"journal-article","created":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T08:33:02Z","timestamp":1506069182000},"page":"1356-1361","source":"Crossref","is-referenced-by-count":14,"title":["Safety and pharmacokinetics of the oral iron chelator SP\u2010420 in \u03b2\u2010thalassemia"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8515-2238","authenticated-orcid":false,"given":"Ali T.","family":"Taher","sequence":"first","affiliation":[{"name":"Department of Internal Medicine American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine N.","family":"Saliba","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6744-9238","authenticated-orcid":false,"given":"Kevin H.","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology and Hematology University Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Giardina","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Children's Hospital of Philadelphia and Perelman School of Medicine of the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellis J.","family":"Neufeld","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesim","family":"Aydinok","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Ege University Hospital Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Children's Hospital of Philadelphia and Perelman School of Medicine of the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda I.","family":"Jeglinski","sequence":"additional","affiliation":[{"name":"Sideris Pharmaceuticals, Inc. 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