Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects

Abstract

Background: A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler® device (IND/GLY/MF) is being developed for treatment of asthma. We compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d. Methods: This was a single-centre, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (medium-dose ICS) or 150/50/160 μg o.d. (high-dose ICS) for 14 days in each period. Pharmacokinetics were characterised for 24h post-dose on Days 1 and 14. Results: In total, 16 Japanese (median age 31 years [range:20-40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range:21-43 years], mean weight 75.0 kg) were randomised. Geometric mean ratios (Japanese/Caucasian) for Cmax for IND, GLY and MF at the high dose on Day 14 were 1.31, 1.38 and 1.07, respectively. Those for AUC0-24h on Day 14 for IND, GLY and MF (Japanese/Caucasian) at the high dose were 1.17, 1.05 and 1.15, respectively. Similar trends were noted for all mono-components for the medium-dose treatment. IND/GLY/MF was safe and well tolerated; no study drug-related AEs were observed. Conclusion: Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as fixed-dose combination were comparable between Japanese and Caucasian subjects. IND/GLY/MF was safe and well tolerated in both ethnic groups. These results confirm that no dose adjustment for IND/GLY/MF is required in Asian population.