title: Safety and tolerability of carbamylated erythropoietin in Friedreich's ataxia.
abstract: BACKGROUND
  Erythropoietin (EPO) derivatives have been found to increase frataxin levels in Friedreich's ataxia (FRDA) in vitro. This multicenter, double-blind, placebo-controlled, phase II clinical trial aimed to evaluate the safety and tolerability of Lu AA24493 (carbamylated EPO; CEPO).
  
  
  METHODS
  Thirty-six ambulatory FRDA patients harboring >400 GAA repeats were 2:1 randomly assigned to either CEPO in a fixed dose (325 µg thrice-weekly) or placebo. Safety and tolerability were assessed up to 103 days after baseline. Secondary outcome measures of efficacy (exploration of biomarkers and ataxia ratings) were performed up to 43 days after baseline.
  
  
  RESULTS
  All patients received six doses of study medication. Adverse events were equally distributed between CEPO and placebo. There was no evidence for immunogenicity of CEPO after multiple dosing. Biomarkers, such as frataxin, or measures for oxidative stress and ataxia ratings did not differ between CEPO and placebo.
  
  
  CONCLUSIONS
  CEPO was safe and well tolerated in a 2-week treatment phase. Secondary outcome measures remained without apparent difference between CEPO and placebo.
authors: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors: Sylvia
authors: S
authors: Boesch
authors: Wolfgang
authors: W
authors: Nachbauer
authors: Caterina
authors: C
authors: Mariotti
authors: Francesco
authors: F
authors: Sacca
authors: Alessandro
authors: A
authors: Filla
authors: Thomas
authors: T
authors: Klockgether
authors: Thomas
authors: T
authors: Klopstock
authors: Ludger
authors: L
authors: Schöls
authors: Heike
authors: H
authors: Jacobi
authors: Boriana
authors: B
authors: Büchner
authors: Jennifer Müller
authors: JM
authors: vom Hagen
authors: Lorenzo
authors: L
authors: Nanetti
authors: Karen
authors: K
authors: Manicom
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D004311:Double-Blind Method; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005621:Friedreich Ataxia / Q000188:drug therapy*; D006801:Humans; D033862:Iron-Binding Proteins / Q000378:metabolism; D008297:Male; D016896:Treatment Outcome; D000096923:Frataxin
chemical_list: D015415:Biomarkers; D004921:Erythropoietin; D033862:Iron-Binding Proteins; D000096923:Frataxin; C488171:carbamylated erythropoietin
keywords: Friedreich's ataxia; carbamylated erythropoietin; erythropoietin; frataxin