title: Open-Label, Randomized, 6-Way Crossover, Single-Dose Study to Determine the Pharmacokinetics of Batefenterol (GSK961081) and Fluticasone Furoate When Administered Alone or in Combination.
abstract: To investigate the pharmacokinetics of inhaled batefenterol (BAT) and fluticasone furoate (FF) given alone or in combination via ELLIPTA® dry powder inhaler (DPI-E), and BAT monotherapy via DISKUS® DPI (DPI-D). In this open-label, 6-way crossover study, 48 healthy subjects were randomized to 1 of 6 treatment sequences, comprising 6 single-dose treatment regimens: (1) BAT 1200 μg via DPI-D; (2) BAT 1200 μg via DPI-E without a lactose-filled second strip; (3) BAT 1200 μg via DPI-E with a lactose-filled second strip; (4) BAT/FF 1200/300 μg via DPI-E; (5) FF 300 μg via DPI-E with a lactose-filled second strip; and (6) BAT/FF 900/300 μg via DPI-E. Pharmacokinetic data were analyzed using noncompartmental methods. Plasma BAT area under the curve (AUC) and maximum plasma concentration (Cmax ) were similar for all treatments containing BAT 1200 μg (geometric least-squares means [GLSM] ratio, 0.90-1.06). Plasma FF AUC and Cmax were reduced following BAT/FF 1200/300 μg and 900/300 μg versus FF 300 μg monotherapy (GLSM ratio, 0.62-0.77). BAT 1200 μg administered via DPI-E, alone or in combination with FF, resulted in similar systemic exposure versus BAT administered by DPI-D. FF exposure was reduced when administered in combination with BAT compared with FF alone.
authors.affiliation: Quantitative Sciences Division, GSK, Stockley Park West, Uxbridge, Middlesex, UK. claire.l.ambery@gsk.com.
authors.forename: Claire
authors.initials: C
authors.lastname: Ambery
authors.affiliation: GSK, Ermington, NSW, Australia.
authors.forename: Kylie
authors.initials: K
authors.lastname: Riddell
authors.affiliation: Clinical Pharmacology, GSK, Research and Development, Uxbridge, Middlesex, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Daley-Yates
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002219:Carbamates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D002219:Carbamates; D004338:Drug Combinations; D015363:Quinolones; C588122:batefenterol; C523187:fluticasone furoate
keywords: GSK961081; batefenterol; bifunctional molecule; bronchodilator; fluticasone furoate