title: Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation.
abstract: BACKGROUND
  Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation.
  
  
  OBJECTIVE
  This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6-11 years with a G551D-CFTR mutation on at least one allele.
  
  
  METHODS
  Patients were randomly assigned to receive ivacaftor administered orally at 150 mg (n = 26) or placebo (n = 26) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies.
  
  
  RESULTS
  Despite near-normal mean baseline values in FEV1, patients receiving ivacaftor had a significant increase in percent predicted FEV1 from baseline through Week 24 versus placebo group (treatment effect, 12.5 percentage points; P < 0.001). Effects on pulmonary function were evident by 2 weeks, and a significant treatment effect was maintained through Week 48. Patients treated with ivacaftor gained, on average, 2.8 kg more than those receiving placebo at Week 48 (P < 0.001). The change from baseline through Week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor was -53.5 mmol/L (P < 0.001) versus placebo. The incidence of adverse events was similar in the two groups.
  
  
  CONCLUSIONS
  In patients who are younger and healthier than those in previously studied populations, ivacaftor demonstrated a significant improvement in pulmonary function, weight, and CFTR activity compared with placebo. Clinical trial registered with www.clinicaltrials.gov (NCT00909727).
authors.affiliation: Paediatric Respiratory Medicine and Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom. j.c.davies@imperial.ac.uk
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
authors.forename: Claire E
authors.initials: CE
authors.lastname: Wainwright
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Canny
authors.forename: Mark A
authors.initials: MA
authors.lastname: Chilvers
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Howenstine
authors.forename: Anne
authors.initials: A
authors.lastname: Munck
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Mainz
authors.forename: Sally
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Haihong
authors.initials: H
authors.lastname: Li
authors.forename: Karl
authors.initials: K
authors.lastname: Yen
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Ordoñez
authors.forename: Richard
authors.initials: R
authors.lastname: Ahrens
mesh_terms: D000284:Administration, Oral; D000483:Alleles; D000627:Aminophenols / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D009154:Mutation; D015363:Quinolones / Q000008:administration & dosage / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D016896:Treatment Outcome
chemical_list: D000627:Aminophenols; C505032:CFTR protein, human; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; D004247:DNA