Sweat chloride as a biomarker of CFTR activity: Proof of concept and ivacaftor clinical trial data

Academic Article


  • Background: We examined data from a Phase 2 trial {. NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with a G551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Methods: Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing, and analysis was employed for the first time. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Results: Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%-40% of normal. Conclusions: Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators. © 2013 European Cystic Fibrosis Society.
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    Author List

  • Accurso FJ; Van Goor F; Zha J; Stone AJ; Dong Q; Ordonez CL; Rowe SM; Clancy JP; Konstan MW; Hoch HE
  • Start Page

  • 139
  • End Page

  • 147
  • Volume

  • 13
  • Issue

  • 2