Efficacy and Safety of Ivacaftor in Patients With Cystic Fibrosis and a non-G551D Gating Mutation

J Cyst Fibros. 2014 Dec;13(6):674-80. doi: 10.1016/j.jcf.2014.09.005. Epub 2014 Sep 26.


Background: Ivacaftor is used to treat patients with CF and a G551D gating mutation; the KONNECTION study assessed the efficacy and safety of ivacaftor in patients with CF and a non-G551D gating mutation.

Methods: Patients with CF ≥6-years- old with non-G551D gating mutations received ivacaftor 150mg q12h or placebo for 8weeks in this 2-part, double-blind crossover study (Part 1) with a 16-week open-label extension (Part 2). The primary efficacy outcome was absolute change in FEV1 through 8 and 24weeks of ivacaftor treatment; secondary outcomes were changes in BMI, sweat chloride, and CFQ-R and safety through 8 and 24weeks of treatment.

Results: Eight weeks of ivacaftor resulted in significant improvements in percent predicted FEV1, BMI, sweat chloride, and CFQ-R scores that were maintained through 24weeks. Ivacaftor was generally well tolerated.

Conclusions: Ivacaftor was efficacious in a group of patients with CF who had selected non-G551D gating mutations.

Keywords: G551D; Gating mutation; Ivacaftor; Potentiator.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols / therapeutic use*
  • Body Mass Index
  • Child
  • Cross-Over Studies
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Ion Channel Gating / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Outcome Assessment, Health Care
  • Quinolones / therapeutic use*
  • Young Adult


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