Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects

Abstract

Background: Indacaterol (IND [LABA]), is co-formulated with glycopyrronium (GLY [LAMA]), and mometasone furoate (MF [ICS]) as a once daily (o.d.) fixed dose combination (IND/GLY/MF) delivered with the Breezhaler® device for maintenance treatment of asthma. We evaluated the steady-state plasma pharmacokinetics (PK) of IND, GLY and MF following inhalation of IND/GLY/MF o.d. Methods: This was a randomised, open-label, four-way crossover study. Subjects received IND/GLY/MF 150/50/160 μg (high-dose ICS), IND 150 µg, GLY 50 µg or MF 190 µg (in vitro fine particle mass comparable to 160 μg MF in IND/GLY/MF) via the Breezhaler® device, o.d. for 14 days in each period, with a washout of at least 7 days. PK was characterised on Day 14 up to 24h post-dose. Results: In total 36 healthy subjects were randomised. For IND, the geometric mean ratios (GMR) [90% CI] for AUC0-24h, ss and Cmax, ss were 0.922 [0.878, 0.969] and 1.02 [0.967, 1.08], respectively, for IND/GLY/MF vs IND monotherapy. For GLY, the GMR [90% CI] for AUC0-24h, ss and Cmax, ss were 0.986 [0.944, 1.03] and 1.21 [1.09, 1.34], respectively for IND/GLY/MF vs. GLY. For MF, the GMR [90% CI] for AUC0-24h, ss and Cmax, ss were 1.16 [1.09, 1.24] and 1.17 [1.09, 1.25], respectively for IND/GLY/MF vs. MF. Similar systemic exposure was noted for IND/GLY/MF vs. monotherapy comparison for all monocomponents, indicating a lack of PK interaction. Multiple inhaled doses of IND, GLY and MF were safe and well tolerated, when administered alone or in combination. Conclusion: There was no clinically relevant pharmacokinetic interaction between IND, GLY and MF when administered as IND/GLY/MF.