Pharmacokinetics and safety of indacaterol and glycopyrronium (IND/GLY) following repeated once daily inhalation from a fixed-dose combination in healthy Chinese subjects .

Abstract Indacaterol/glycopyrronium (IND/GLY) is a once-daily fixed-dose combination of two long-acting bronchodilators: indacaterol 110 µg (long-acting β2-adrenergic agonist, LABA) and glycopyrronium 50 µg (long-acting muscarinic antagonist, LAMA). This study assessed the pharmacokinetics of IND/GLY 110/50 µg following multiple once-daily inhaled administrations in healthy Chinese subjects. This was a single-centre, open-label, multiple-dose study of inhaled IND/GLY delivered via the Breezhaler® device. Pharmacokinetic samples were collected on day 1 after first dose, on days 5, 7, 10, and 12 (predose (trough)) and on day 14 (steady state) after last dose for pharmacokinetic analysis using non-compartmental analysis. Both IND and GLY were absorbed rapidly after inhalation of IND/GLY (tmax: IND, 15 minutes; GLY, 5 minutes). Accumulation through systemic exposure of both IND and GLY from day 1 to day 14 was observed (mean accumulation ratio (Racc) of AUC0-24h (day 14/day 1): IND, 3.02; GLY 2.94; estimated accumulation ratio of Cmax: IND 1.56; GLY 1.33). Mean effective half-life (t1/2,acc) was 41.3 h and 40.0 h for IND and GLY, respectively. Pharmacokinetic steady states were reached after 12 and 10 days of daily dosing for IND and GLY, respectively. There was one mild adverse event (AE) not related to the study drug. No discontinuations due to treatment related AEs/SAEs (adverse event/serious adverse event) were reported. In healthy Chinese subjects, multiple once-daily inhaled doses of IND/GLY 110/50 µg were rapidly absorbed and were safe and well tolerated. The comparison of systemic exposure data following inhalation of IND/GLY 110/50 µg in Chinese vs. the non-Chinese populations did not indicate any clinically relevant differences across ethnicities. .