title: A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload.
abstract: BACKGROUND
  There is still a clinical need for a well-tolerated and safe iron chelator for the treatment of transfusional iron overload. We describe the pharmacokinetic properties and safety data after 7 days of dosing of FBS0701, a novel oral, once-daily iron chelator.
  
  
  METHODS
  This phase 1b dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload, was conducted in 16 adult patients with iron overloaded consequent to transfusions. FBS0701 was given daily for 7 days at doses up to 32 mg/kg and was well tolerated at all dose levels.
  
  
  RESULTS
  Pharmacokinetics showed dose-proportionality. The maxium plasma concentration (C(max)) was reached within 60-90 minutes of dosing and the drug was rapidly distributed at the predicted therapeutic doses. The plasma elimination half-life (t(1/2)) was approximately 19 hours. There were no serious adverse events associated with the drug. Conclusions On the basis of these safety and pharmacokinetic data, FBS0701 warrants further clinical evaluation in patients with transfusional iron overload. (Clinicaltrials.gov identifier: NCT01186419).
authors.affiliation: FerroKin BioSciences, Inc, San Carlos, CA, USA. hrienhoff@datahooks.com
authors.forename: Hugh Young
authors.initials: HY
authors.lastname: Rienhoff
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.forename: Lay
authors.initials: L
authors.lastname: Tay
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: Deborah
authors.initials: D
authors.lastname: Chirnomas
authors.forename: Janet L
authors.initials: JL
authors.lastname: Kwiatkowski
authors.forename: Amy
authors.initials: A
authors.lastname: Tapper
authors.forename: William
authors.initials: W
authors.lastname: Kramer
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
mesh_terms: D000284:Administration, Oral; D000328:Adult; D005019:Ethyl Ethers / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy*; D008297:Male; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D065227:Transfusion Reaction; D055815:Young Adult
chemical_list: C572777:4,5-dihydro-2-(2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl)-4-methyl-4-thiazolecarboxylic acid; D005019:Ethyl Ethers; D007502:Iron Chelating Agents; D013844:Thiazoles