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.

Design and 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).

Figures

Figure 1.

Mean plasma concentrations of FBS0701 after oral administration on day 7 of 3, 8, 16, or 32 mg/kg/day to patients with transfusional iron overload — linear axes, 0–24 hours.

Figure 2.

Mean plasma concentrations of FBS0701 after oral administration on day 7 of 3, 8, 16, or 32 mg/kg/day to patients with transfusional iron overload — log- linear axes, 0–192 hours.

Figure 3.

Relationship between the mean Cmax and AUC(0-24) of FBS0701 after oral administration on day 7 of 3, 8, 16, or 32 mg/kg/day to patients with transfusional iron overload.