title: 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 ppFEV1values was studied to evaluate the ppFEV1response to LUM/IVA administration and assess the effect of long-acting bronchodilators (LABDs) and short-acting bronchodilators (SABDs) on ppFEV1response. The ppFEV1decline 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 ppFEV1was observed in healthy subjects following administration of LUM/IVA combination therapy, which can be ameliorated with LABDs or SABDs.
authors.affiliation: Vertex Pharmaceuticals Incorporated, 50 Northern Ave, Boston, MA 02110, United States. Electronic address: gautham_marigowda@vrtx.com.
authors.forename: Gautham
authors.initials: G
authors.lastname: Marigowda
authors.affiliation: Vertex Pharmaceuticals Incorporated, 50 Northern Ave, Boston, MA 02110, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Vertex Pharmaceuticals Incorporated, 50 Northern Ave, Boston, MA 02110, United States.
authors.forename: David
authors.initials: D
authors.lastname: Waltz
mesh_terms: D000328:Adult; D000627:Aminophenols / Q000493:pharmacokinetics*; D000631:Aminopyridines / Q000493:pharmacokinetics*; D052117:Benzodioxoles / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000493:pharmacokinetics; D065101:Chloride Channel Agonists / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D015363:Quinolones / Q000493:pharmacokinetics*; D012137:Respiratory System / Q000187:drug effects*; D013147:Spirometry / Q000379:methods
chemical_list: D000627:Aminophenols; D000631:Aminopyridines; D052117:Benzodioxoles; D001993:Bronchodilator Agents; D065101:Chloride Channel Agonists; D015363:Quinolones; C545203:ivacaftor; C569105:lumacaftor