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Br J Pharmacol. 2016 May;173(10):1580-8. doi: 10.1111/bph.13433. Epub 2016 Apr 8.

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

Author information

1
Hammersmith Medicines Research, London, UK.
2
NOXXON Pharma AG, Berlin, Germany.
3
Hepcidinanalysis.com, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Abstract

BACKGROUND AND PURPOSE:

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.

EXPERIMENTAL APPROACH:

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) .

KEY RESULTS:

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.

CONCLUSIONS AND IMPLICATIONS:

Lexaptepid pegol inhibited hepcidin and dose-dependently raised serum iron and transferrin saturation. The compound is being further developed to treat anaemia of chronic disease.

PMID:
26773325
PMCID:
PMC4842915
DOI:
10.1111/bph.13433
[Indexed for MEDLINE]
Free PMC Article

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