title: Phase Ib clinical trial of starch-conjugated deferoxamine (40SD02): a novel long-acting iron chelator.
abstract: The most widely used drug for iron chelation is deferoxamine (DFO) mesylate. While effective in promoting iron excretion, it requires prolonged daily infusions, often resulting in poor compliance. A clinical trial was conducted using starch-conjugated DFO (S-DFO; 40SD02), a high-molecular-weight iron chelator possessing prolonged vascular retention. Single doses of S-DFO were infused intravenously into groups of four transfusion-dependent patients with beta-thalassaemia at doses of 150, 300, 600 and 900 mg/kg. Urinary iron excretion and various pharmacologic parameters were evaluated for 1 week and safety for 3 weeks. No drug-related effects were observed on clinical chemistries, haematological and coagulation parameters, urinalyses, vital signs or electrocardiograms. Drug-related adverse events were limited to four urticarial reactions, none requiring termination of the infusion. The drug stimulated clinically significant urinary iron excretion, with the highest dose (900 mg/kg) inducing excretion of 1.31 mg of iron/kg (range 0.79-1.90 mg/kg) over 1 week, with residual iron-binding capacity present in the plasma for over 6 d. In summary, treatment with S-DFO, administered weekly, has the potential to achieve iron balance in the poorly compliant patient.
authors.affiliation: Department of Gastroenterology, The Children's Hospital & Research Center Oakland, CA, USA. pharmatz@mail.cho.org
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grady
authors.forename: Paul
authors.initials: P
authors.lastname: Dragsten
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: Patricia
authors.initials: P
authors.lastname: Giardina
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Madden
authors.forename: Michael
authors.initials: M
authors.lastname: Jeng
authors.forename: Becky
authors.initials: B
authors.lastname: Miller
authors.forename: Gregory
authors.initials: G
authors.lastname: Hanson
authors.forename: Bo
authors.initials: B
authors.lastname: Hedlund
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015913:Chelation Therapy / Q000379:methods*; D003676:Deferoxamine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007501:Iron / Q000097:blood / Q000652:urine; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy* / Q000652:urine
chemical_list: D007502:Iron Chelating Agents; D007501:Iron; D003676:Deferoxamine