Population pharmacokinetics of IND/GLY (indacaterol/glycopyrronium) in COPD patients

Objective: Indacaterol/glycopyrronium (IND/GLY) is a fixed-dose combination (FDC) of indacaterol, an inhaled long-acting beta(2)-agonist (LABA), and glycopyrronium, an inhaled long-acting muscarinic antagonist (LAMA), developed as a maintenance bronchodilator treatment for patients with chronic obstructive pulmonary disease (COPD). A population pharmacokinetic (PK) analysis was perfonned to describe the PK profiles of indacaterol and glycopyrronium following the twice daily (b.i.d.) and once daily (o.d.) inhalation regimens as FDC or as monotherapies and to determine the effect of covariates. Methods: PK data in 556 COPD patients were pooled from three phase 3 studies. Two phase 3 studies investigated IND/GLY 27.5/12.5 mu g b.i.d. and the third study investigated 1ND/GLY 110/50 mu g o.d. Body weight was included in the model with fixed allometric coefficients for indacaterol and glycopyrronium. Results: Statistically significant effects of smoking, age, and sex on apparent clearance of indacaterol; smoking, and estimated glomerular filtration rate at baseline on apparent clearance and Japanese ethnicity on apparent central volume of distribution of glycopyrronium were identified. Conclusion: Systemic exposure to indacaterol and glycopyrronium was shown to be dose-proportional and time-independent following inhalation either as monotherapies or FDC. None of the identified covariate effects was judged to be clinically relevant. There is no PK drug-drug interaction between indacaterol and glycopyrronium in its FDC.