title: Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data.
abstract: BACKGROUND
  We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with aG551D 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.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
authors.forename: Fredrick
authors.initials: F
authors.lastname: Van Goor
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Zha
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Stone
authors.forename: Qunming
authors.initials: Q
authors.lastname: Dong
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Ordonez
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
authors.forename: John Paul
authors.initials: JP
authors.lastname: Clancy
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
authors.forename: Heather E
authors.initials: HE
authors.lastname: Hoch
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
authors.forename: Preston W
authors.initials: PW
authors.lastname: Campbell
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Ashlock
mesh_terms: D000328:Adult; D000627:Aminophenols / Q000494:pharmacology*; D015415:Biomarkers; D002648:Child; D002712:Chlorides / Q000032:analysis / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009297:Nasal Mucosa / Q000378:metabolism / Q000503:physiopathology; D015363:Quinolones / Q000494:pharmacology*; D015203:Reproducibility of Results; D019141:Respiratory System Agents / Q000494:pharmacology; D013048:Specimen Handling / Q000379:methods / Q000592:standards; D013542:Sweat / Q000737:chemistry / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000627:Aminophenols; D015415:Biomarkers; D002712:Chlorides; D015363:Quinolones; D019141:Respiratory System Agents; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor