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: Ellis J Neufeld, Renzo Galanello, Vip Viprakasit, Yesim Aydinok, Antonio Piga, Paul Harmatz, Gian Luca Forni, Farrukh T Shah, Rachael F Grace, John B Porter, John C Wood, Jennifer Peppe, Amber Jones, Hugh Young Rienhoff Jr
• Journal: Blood (Blood) Vol. 119 Issue 14 Pg. 3263-8 (Apr 05 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22251482 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• 4,5-dihydro-2-(2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl)-4-methyl-4-thiazolecarboxylic acid
• Ethyl Ethers
• Iron Chelating Agents
• Thiazoles
• Creatinine
• Iron

Topics

• Adolescent
• Adult
• Creatinine (metabolism)
• Dose-Response Relationship, Drug
• Ethyl Ethers (adverse effects, pharmacology, therapeutic use)
• Female
• Hemoglobinopathies (complications, therapy)
• Humans
• Iron (analysis, metabolism)
• Iron Chelating Agents (adverse effects, pharmacology, therapeutic use)
• Iron Overload (diagnosis, drug therapy, etiology)
• Liver (metabolism)
• Male
• Middle Aged
• Thiazoles (adverse effects, pharmacology, therapeutic use)
• Transfusion Reaction
• Treatment Outcome
• Young Adult