title: A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload.
abstract: This was a 24-week, multicenter phase-2 study designed to assess safety, tolerability, and pharmacodynamics of FBS0701, a novel oral chelator, in adults with transfusional iron overload. Fifty-one patients, stratified by transfusional iron intake, were randomized to FBS0701 at either 14.5 or 29 mg/kg/d (16 and 32 mg/kg/d salt form). FBS0701 was generally well tolerated at both doses. Forty-nine patients (96%) completed the study. There were no drug-related serious adverse events. No adverse events (AEs) showed dose-dependency in frequency or severity. Treatment-related nausea, vomiting, abdominal pain, and diarrhea were each noted in < 5% of patients. Mean serum creatinine did not change significantly from Baseline or between dose groups. Transaminases wer increased in 8 (16%), three of whom acquired HCV on-study from a single blood bank while five had an abnormal baseline ALT. The 24 week mean change in liver iron concentration (ΔLIC) at 14.5 mg/kg/d was +3.1 mg/g (dw); 29% achieved a decrease in LIC. Mean ΔLIC at 29 mg/kg/d was -0.3 mg/g (dw); 44% achieved a decrease in LIC (P < .03 for ΔLIC between doses). The safety and tolerability profile at therapeutic doses compare favorably to other oral chelators.
authors.affiliation: Children's Hospital, Harvard University, Boston, MA, USA.
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aydinok
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Farrukh T
authors.initials: FT
authors.lastname: Shah
authors.forename: Rachael F
authors.initials: RF
authors.lastname: Grace
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.forename: Jennifer
authors.initials: J
authors.lastname: Peppe
authors.forename: Amber
authors.initials: A
authors.lastname: Jones
authors.forename: Hugh Young
authors.initials: HY
authors.lastname: Rienhoff
mesh_terms: D000293:Adolescent; D000328:Adult; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005019:Ethyl Ethers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006453:Hemoglobinopathies / Q000150:complications / Q000628:therapy; D006801:Humans; D007501:Iron / Q000032:analysis / Q000378:metabolism; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019190:Iron Overload / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D065227:Transfusion Reaction; D016896:Treatment Outcome; 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; D003404:Creatinine; D007501:Iron