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

• Published in: International journal of clinical pharmacology and therapeutics Vol. 55; no. 2; pp. 147 - 155
• Main Authors: Ren, Shuang, Sechaud, Romain, Su, Zhenzhong, Tillmann, Hanns-Christian, Hara, Hisanori, Tan, Xuemei, Hou, Jie, Woessner, Ralph, Zhao, Rong
• Format: Journal Article
• Language: English
• Published: Germany Dustri - Verlag Dr. Karl Feistle GmbH & Co. KG 01.02.2017
• Subjects: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - adverse effects; Adrenergic beta-2 Receptor Agonists - pharmacokinetics; Adult; Area Under Curve; Asian People; Biomedical research; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - adverse effects; Bronchodilator Agents - pharmacokinetics; Bronchodilators; China; Chronic obstructive pulmonary disease; Drug Administration Schedule; Drug Combinations; Drug dosages; FDA approval; Female; Glycopyrrolate - administration & dosage; Glycopyrrolate - adverse effects; Glycopyrrolate - pharmacokinetics; Half-Life; Healthy Volunteers; Humans; Indans - administration & dosage; Indans - adverse effects; Indans - pharmacokinetics; Male; Metabolic Clearance Rate; Models, Biological; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; Muscarinic Antagonists - pharmacokinetics; Nebulizers and Vaporizers; Pharmacokinetics; Quinolones - administration & dosage; Quinolones - adverse effects; Quinolones - pharmacokinetics; Respiratory Tract Absorption; Young Adult; China
• ISSN: 0946-1965
• DOI: 10.5414/CP202640

Indacaterol/glycopyrronium (IND/GLY) is a once-daily fixed-dose combination of two long-acting bronchodilators: indacaterol 110 µg (long-acting β -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 (t : 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 (R ) of AUC (day 14/day 1): IND, 3.02; GLY 2.94; estimated accumulation ratio of C : IND 1.56; GLY 1.33). Mean effective half-life (t ) 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.
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