Safety, pharmacokinetics and pharmacodynamics of the anti-hepcidin Spiegelmer lexaptepid pegol in healthy subjects

British Journal of Pharmacology
M BoyceKai Riecke

Abstract

Anaemia of chronic disease is characterized by impaired erythropoiesis due to functional iron deficiency, often caused by excessive hepcidin. Lexaptepid pegol, a pegylated structured l-oligoribonucleotide, binds and inactivates hepcidin. We conducted a placebo-controlled study on the safety, pharmacokinetics and pharmacodynamics of lexaptepid after single and repeated i.v. and s.c. administration to 64 healthy subjects at doses from 0.3 to 4.8 mg·kg(-1) . After treatment with lexaptepid, serum iron concentration and transferrin increased dose-dependently. Iron increased from approximately 20 μmol·L(-1) at baseline by 67% at 8 h after i.v. infusion of 1.2 mg·kg(-1) lexaptepid. The pharmacokinetics showed dose-proportional increases in peak plasma concentrations and moderately over-proportional increases in systemic exposure. Lexaptepid had no effect on hepcidin production or anti-drug antibodies. Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses ≥2.4 mg·kg(-1) and with local injection site reactions after s.c. but not after i.v. administration. Lexaptepid pegol inhibited hepcidin and dose-dependently raised serum iron and transferrin saturation. The compound ...Continue Reading

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Methods Mentioned

BETA
urine collection
surface plasmon resonance

Clinical Trials Mentioned

NCT01372137

Software Mentioned

winnonlin professional
Windows XP
SAS
lexaptepid

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