title: Safety, pharmacokinetics and pharmacodynamics of the anti-hepcidin Spiegelmer lexaptepid pegol in healthy subjects.
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 is being further developed to treat anaemia of chronic disease.
authors.affiliation: Hammersmith Medicines Research, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Boyce
authors.affiliation: Hammersmith Medicines Research, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Warrington
authors.affiliation: Hammersmith Medicines Research, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Cortezi
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zöllner
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Vauléon
authors.affiliation: Hepcidinanalysis.com, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: Swinkels
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Summo
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schwoebel
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Riecke
mesh_terms: D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D064368:Healthy Volunteers; D064451:Hepcidins / Q000037:antagonists & inhibitors*; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D009843:Oligoribonucleotides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000032:analysis
chemical_list: D064451:Hepcidins; D009843:Oligoribonucleotides; D014168:Transferrin; C581096:NOX-H94; D007501:Iron