title: Effect of ivacaftor in patients with advanced cystic fibrosis and a G551D-CFTR mutation: Safety and efficacy in an expanded access program in the United States.
abstract: BACKGROUND
  Ivacaftor is the first therapeutic agent approved for the treatment of cystic fibrosis (CF) that targets the underlying molecular defect. Patients with severe lung disease were excluded from the randomized Phase 3 trials. This open-label study was designed to provide ivacaftor to patients in critical medical need prior to commercial product availability.
  
  
  METHODS
  CF patients aged ≥6 years with a G551D-CFTR mutation and FEV1 ≤ 40% predicted or listed for lung transplant received ivacaftor 150 mg every 12 h. The primary endpoint was safety as determined by adverse events. Secondary endpoints included assessment of lung function and weight.
  
  
  RESULTS
  The rate of serious adverse events was consistent with disease severity. At 24 weeks of treatment with ivacaftor, there was a mean absolute increase in percent predicted FEV1 of 5.5 percentage points and a 3.3 kg mean absolute increase in weight from baseline.
  
  
  CONCLUSIONS
  In patients with severe lung disease, ivacaftor was well tolerated and was associated with improved lung function and weight gain.
authors: National Jewish Health, Denver, CO, United States. Electronic address: Taylor-CousarJ@NJHealth.org.
authors: Jennifer
authors: J
authors: Taylor-Cousar
authors: Vertex Pharmaceuticals Incorporated, Boston, MA, United States.
authors: Minoo
authors: M
authors: Niknian
authors: Vertex Pharmaceuticals Incorporated, Boston, MA, United States.
authors: Geoffrey
authors: G
authors: Gilmartin
authors: University of Pittsburgh, Pittsburgh, PA, United States.
authors: Joseph M
authors: JM
authors: Pilewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000627:Aminophenols / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D002648:Child; D065101:Chloride Channel Agonists / Q000008:administration & dosage / Q000009:adverse effects; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects; D012129:Respiratory Function Tests / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000627:Aminophenols; C505032:CFTR protein, human; D065101:Chloride Channel Agonists; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: Cystic fibrosis (CF); Cystic fibrosis transmembrane conductance regulator (CFTR); Lung function