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

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.