Phase Ib clinical trial of starch-conjugated deferoxamine (40SD02): a novel long-acting iron chelator.
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.
Harmatz
Paul
P
Department of Gastroenterology, The Children's Hospital & Research Center Oakland, CA, USA. pharmatz@mail.cho.org
Grady
Robert W
RW
Dragsten
Paul
P
Vichinsky
Elliott
E
Giardina
Patricia
P
Madden
Jacqueline
J
Jeng
Michael
M
Miller
Becky
B
Hanson
Gregory
G
Hedlund
Bo
B
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
D007502:Iron Chelating Agents; D007501:Iron; D003676:Deferoxamine