Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation

Chest. 2012 Sep;142(3):718-724. doi: 10.1378/chest.11-2672.


Background: Ivacaftor (VX-770) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that was approved in the United States for the treatment of cystic fibrosis (CF) in patients ≥ 6 years of age who have a G551D mutation; however, the most prevalent disease-causing CFTR mutation, F508del, causes a different functional defect. The objectives of this study were to evaluate the safety of ivacaftor in a larger population and for a longer time period than tested previously and to assess the efficacy of ivacaftor in subjects with CF who are homozygous for F508del-CFTR.

Methods: This was a phase 2 study with a 16-week randomized (4:1), double-blind, placebo-controlled period (part A) and an open-label extension (part B) for subjects who met prespecified criteria.

Results: Part A: The safety profile of ivacaftor was comparable to that of the placebo. The overall adverse event frequency was similar in the ivacaftor (87.5%) and placebo (89.3%) groups through 16 weeks. The difference in the change of FEV₁ % predicted from baseline through week 16 (primary end point) between the ivacaftor and placebo groups was 1.7% (P = .15). Sweat chloride, a biomarker of CFTR activity, showed a small reduction in the ivacaftor vs placebo groups of -2.9 mmol/L (P = .04) from baseline through week 16. Part B: No new safety signals were identified. The changes in FEV₁ or sweat chloride in part A were not sustained with ivacaftor treatment from week 16 to week 40.

Conclusions: These results expand the safety information for ivacaftor and support its continued evaluation. Lack of a clinical effect suggests that a CFTR potentiator alone is not an effective therapeutic approach for patients who have CF and are homozygous for F508del-CFTR.

Trial registry: ClinicalTrials.gov; No.: NCT00953706; URL: www.clinicaltrials.gov.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Aminophenols / therapeutic use*
  • Biomarkers / analysis
  • Child
  • Chlorides / analysis
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Double-Blind Method
  • Female
  • Homozygote*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pharmacogenetics
  • Quinolones / therapeutic use*
  • Sweat / chemistry
  • Treatment Outcome
  • Young Adult


  • Aminophenols
  • Biomarkers
  • Chlorides
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor

Associated data

  • ClinicalTrials.gov/NCT00953706