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

J Cyst Fibros. 2016 Jan;15(1):116-22. doi: 10.1016/j.jcf.2015.01.008. Epub 2015 Feb 11.

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.

Keywords: Cystic fibrosis (CF); Cystic fibrosis transmembrane conductance regulator (CFTR); Lung function.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols* / administration & dosage
  • Aminophenols* / adverse effects
  • Animals
  • Child
  • Chloride Channel Agonists / administration & dosage
  • Chloride Channel Agonists / adverse effects
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / genetics
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Female
  • Humans
  • Male
  • Mutation
  • Quinolones* / administration & dosage
  • Quinolones* / adverse effects
  • Respiratory Function Tests / methods
  • Treatment Outcome

Substances

  • Aminophenols
  • CFTR protein, human
  • Chloride Channel Agonists
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor