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 β -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.

Triple Therapy for COPD: Historical Perspective and Current Controversies

“…Therefore, although, strictly speaking, the result is a combination of two drugs, a MABA plus an ICS, the therapeutic effect is actually that of triple therapy. This combination with triple therapy effect has been explored in Phase I and II trials with once-daily administration using the Ellipta multi-dose dry powder device 28,29 .…”

The future of inhalation therapy in chronic obstructive pulmonary disease

“…However, the use of MABAs will also simplify the possibility to deliver three different complementary pharmacological activities at the same time, the so-called triple therapy. There is documentation that a single high dose of batefenterol/fluticasone furoate reduced exposure to fluticasone furoate compared with the administration of fluticasone furoate alone ( Ambery et al., 2019 ).…”

Pharmacology and Therapeutics of Bronchodilators Revisited

“…Nonetheless, MABA compounds are believed to be a better opportunity than LABA/LAMA combinations to be coformulated in "triple therapy" combinations that could elicit three complementary therapeutic actions in patients with asthma or COPD (Page andCazzola, 2014, 2017). In fact, MABAs combined with an ICS are already in development and administration of a single high dose of batefenterol/fluticasone furoate resulted in a reduction of the fluticasone furoate exposure compared with administering fluticasone furoate alone (Ambery et al, 2019).…”