Effect of bronchodilators in healthy individuals receiving lumacaftor/ivacaftor combination therapy

J Cyst Fibros. 2017 Mar;16(2):246-249. doi: 10.1016/j.jcf.2016.11.001. Epub 2016 Nov 25.

Abstract

In an open-label, single-center phase 1 pharmacokinetic study in healthy subjects who received lumacaftor (LUM) in combination with ivacaftor (IVA), review of spirometry data showed a transient decline in percent predicted forced expiratory volume in 1s (ppFEV1) within 4h of drug administration. An additional cohort of healthy subjects with normal baseline ppFEV1 values was studied to evaluate the ppFEV1 response to LUM/IVA administration and assess the effect of long-acting bronchodilators (LABDs) and short-acting bronchodilators (SABDs) on ppFEV1 response. The ppFEV1 decline observed at 4h was attenuated following administration of an LABD and reversed following administration of an SABD. Concomitant administration of LUM/IVA with bronchodilators was well tolerated. These data show that a transient decline in ppFEV1 was observed in healthy subjects following administration of LUM/IVA combination therapy, which can be ameliorated with LABDs or SABDs.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aminophenols / pharmacokinetics*
  • Aminopyridines / pharmacokinetics*
  • Benzodioxoles / pharmacokinetics*
  • Bronchodilator Agents / pharmacokinetics
  • Chloride Channel Agonists / pharmacokinetics
  • Drug Therapy, Combination / methods
  • Female
  • Forced Expiratory Volume / drug effects*
  • Healthy Volunteers
  • Humans
  • Male
  • Quinolones / pharmacokinetics*
  • Respiratory System / drug effects*
  • Spirometry / methods

Substances

  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Bronchodilator Agents
  • Chloride Channel Agonists
  • Quinolones
  • ivacaftor
  • lumacaftor