Open-Label, Crossover Study to Determine the Pharmacokinetics of Fluticasone Furoate and Batefenterol When Administered Alone, in Combination, or Concurrently.

ABSTRACT

The study aim was to investigate the pharmacokinetics of single high doses and repeated therapeutic doses of fluticasone furoate (FF) and batefenterol (BAT; a bifunctional muscarinic antagonist and ß2 -agonist) administered in combination (BAT/FF) or as monotherapy. In this open-label, 6-period, crossover study of 48 subjects, the treatment sequences were (1) single high-dose BAT/FF 900/300 µg followed by repeated therapeutic doses of BAT/FF 300/100 µg (once daily for 7 days); (2) single high-dose BAT 900 µg administered concurrently with FF 300 µg; (3) single high-dose BAT 900 µg followed by repeated therapeutic-dose BAT 300 µg; (4) single high-dose FF 300 µg followed by repeated therapeutic-dose FF 100 µg; (5) single high-dose FF 300 µg (magnesium stearate); and (6) single high-dose FF/vilanterol 300/75 µg. Plasma FF area under the plasma drug concentration-time curve (AUC) was reduced after single high-dose BAT/FF versus FF alone (ratio of geometric least squares means 0.79; 90% confidence interval 0.75-0.83). After repeat dosing, FF AUC at the lower therapeutic dosage was similar for BAT/FF and FF (primary endpoint; AUC geometric least squares means 1.03). Adverse events were minor, the most common being cough. These data support the feasibility of developing BAT/inhaled corticosteroid triple therapy in a single inhaler.