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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2021

Open Access 01-12-2021 | Pharmacokinetics | Research article

Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects

Authors: Satoru Inoue, Soniya Vaidya, Hanns-Christian Tillmann, Yohei Sakita, Surendra Machineni, Olivier Heudi, Kenichi Furihata

Published in: BMC Pulmonary Medicine | Issue 1/2021

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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 Cmax 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 AUC0–24h 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.
Appendix
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Metadata
Title
Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects
Authors
Satoru Inoue
Soniya Vaidya
Hanns-Christian Tillmann
Yohei Sakita
Surendra Machineni
Olivier Heudi
Kenichi Furihata
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2021
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-01382-6

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