Pharmacokinetics Of Indacaterol/Glycopyrronium/Mometasone Furoate In Healthy Chinese Volunteers: Results From A Randomized, Open-Label, Parallel-Group Study

Once-daily indacaterol/glycopyrronium/mometasone furoate (IND/GLY/MF) is the first inhaled long-acting muscarinic antagonist/long-acting β2-agonist/inhaled corticosteroid (LABA/LAMA/ICS) approved for maintenance treatment of asthma. The steady-state pharmacokinetics (PK) of IND, GLY and MF were characterized in healthy Chinese volunteers following multiple once-daily oral inhalations of IND/GLY/MF medium-dose (150/50/80 μg) or high-dose (150/50/160 μg). In this randomized, open-label, parallel-group, Phase I study, 24 healthy volunteers aged 18–45 years were randomized 1:1 to receive either IND/GLY/MF medium-dose or high-dose via Breezhaler®, once-daily for 14 days. The pharmacokinetic parameters of IND, GLY and MF were calculated by non-compartmental analysis. Of 22 volunteers who completed the study, PK analysis included 20 volunteers (11 in medium-dose group and 9 in high-dose group) and 2 were excluded due to protocol deviations. At steady state (Day 14), median Tmax was 0.25 h for IND, 0.08 h for GLY and 0.5 h for MF. Cmax and AUC0–24h of IND (mean Cmax: 449 and 395 pg/mL; mean AUC0–24h: 2340 and 2250 h*pg/mL, for medium-dose and high-dose respectively) and GLY (mean Cmax: 354 and 368 pg/mL; mean AUC0–24h: 723 and 713 h*pg/mL, for medium- and high-dose respectively) were similar between medium- and high-dose groups. Cmax (140 and 240 pg/mL) and AUC0–24h (885 and 1890 h*pg/mL) of MF were approximately 2-fold in high-dose versus medium-dose group. IND, GLY and MF were rapidly absorbed after administration. The exposure of IND and GLY were comparable between the IND/GLY/MF medium-dose and high-dose groups and that of MF increased with increasing dose of MF.