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

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. (C) 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.