Pharmacokinetics of Indacaterol, Glycopyrronium and Mometasone Furoate Administered As an Inhaled Fixed-dose Combination in Japanese and Caucasian Healthy Subjects

Overview

Journal BMC Pulm Med

Publisher Biomed Central

Specialty Pulmonary Medicine

Date 2021 Jan 8

PMID 33413291

Citations 3

Authors

Satoru Inoue

Soniya Vaidya

Hanns-Christian Tillmann

Yohei Sakita

Surendra Machineni

Olivier Heudi

Kenichi Furihata

Affiliations

Soon will be listed here.

Abstract

Background: A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler device (IND/GLY/MF) is being developed for treatment of asthma. This study compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d.

Methods: This was a single-center, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (inhaled corticosteroid [ICS] medium-dose) or 150/50/160 μg o.d. (ICS high-dose) for 14 days in each period. Pharmacokinetics were characterized up to 24 h post-dose on Days 1 and 14.

Results: In total, 16 Japanese (median age 31 years [range 20-40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range 21-43 years], mean weight 75.0 kg) were randomized. Geometric mean ratios (Japanese/Caucasian) [90% confidence interval (CI)] for C for IND, GLY and MF at the high ICS dose on Day 14 were 1.31 [1.13, 1.51] 1.38 [1.13, 1.69] and 1.07 [0.969, 1.18], respectively. Geometric mean ratios (Japanese/Caucasian) [90% CI] for AUC on Day 14 for IND, GLY and MF at the high ICS dose were 1.17 [1.01, 1.35], 1.05 [0.920, 1.20] and 1.15 [1.05, 1.27] respectively. Similar trends were noted for all components for the medium ICS dose treatment. IND/GLY/MF was safe and well tolerated; no AEs suspected to be study drug-related were observed.

Conclusion: Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as a fixed-dose combination were comparable between Japanese and Caucasian subjects. The IND/GLY/MF combination at the administrated doses was safe and well tolerated in both ethnic groups.

Trial Registration: Japan Registry of Clinical Trial: jRCT2031200227, retrospectively registered on 04, December, 2020.

Citing Articles

Pharmacokinetics of pulmonary indacaterol in rat lung using molecular imprinting solid-phase extraction coupled with RP-UPLC.

Tarek M, Ghoniem N, Hegazy M, Wagdy H Sci Rep. 2024; 14(1):23126.

PMID: 39366999 PMC: 11452728. DOI: 10.1038/s41598-024-72822-0.

Mometasone/Indacaterol/Glycopyrronium (MF/IND/GLY) and MF/IND at Different MF Strengths versus Fluticasone Propionate/Salmeterol Xinafoate (FLU/SAL) and FLU/SAL+ Tiotropium in Patients with Asthma.

van Zyl-Smit R, Chapman K, Kerstjens H, Gessner C, Sagara H, Tanase A J Asthma Allergy. 2023; 16:123-134.

PMID: 36714049 PMC: 9880009. DOI: 10.2147/JAA.S392975.

Effects of (a Combination of) the Beta-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction.

Maarsingh H, Oldenburger A, Han B, Zuidhof A, Elzinga C, Timens W Cells. 2021; 10(5).

PMID: 34069899 PMC: 8157597. DOI: 10.3390/cells10051237.

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