Shimada, Sayaka, Vaidya, Soniya, Khindri, Sanjeev, Tashiro, Natsuka, Cheng, Yi, Woessner, Ralph, Furihata, Kenichi and Kobayashi, Kiyoshi (2015) Pharmacokinetics of QMF149 in Japanese versus Caucasian subjects: An open-label, randomized phase I study. International Journal of Clinical Pharmacology and Therapeutics, 53 (5). pp. 398-407. ISSN 0946-1965

Abstract

Objectives: This study aimed to evaluate influence of ethnic factors on the pharmacokinetics of orally inhaled QMF149, a novel combination of an approved long-acting β<inf>2</inf>-agonist, indacaterol (Onbrez® Breezhaler® for COPD), and an approved inhaled corticosteroid, mometasone furoate (MF), (Asmanex® Twisthaler® for asthma), following multiple dose administration of QMF149 (indacaterol acetate/MF) 150/80 μg and 150/320 μg via the Breezhaler® device in healthy Japanese and Caucasian subjects. Methods: This was a single-center, openlabel, multiple-dose, two-period, complete crossover study that randomized healthy Japanese and, age and weight matched Caucasian subjects to QMF149 150/80 μg or 150/320 μg once daily (o.d.) for 14 days in each period. Pharmacokinetics (PK) were assessed up to 24 hours on days 1 and 14. Results: 24 Japanese and 24 Caucasian healthy subjects were enrolled. Indacaterol and MF had similar PK profiles across both the doses and both ethnic groups. The maximum geometric mean ratios (90% confidence interval (CI)) for Japanese vs. Caucasian subjects for C<inf>max</inf> were 1.23 (1.11 - 1.38) and 1.24 (1.11 - 1.38) for indacaterol and MF, respectively. For AUC, the maximum ratios were 1.22 (1.09 - 1.36) and 1.30 (1.18 - 1.44) for indacaterol and MF, respectively. The mild trend towards higher exposure in Japanese subjects could be explained by the fact that the mean body weight was 14% higher for Caucasians compared to their Japanese counterparts. No serious adverse events or discontinuations related to study medication were reported. Conclusion: The study demonstrated increase of mean exposure parameters in Japanese subjects vs. Caucasian subjects, which ranged between 19 - 23% and 17 - 30%, for indacaterol and MF components, respectively. Multiple doses of both the QMF149 dose levels were safe and well-tolerated in all subjects. Body weight was considered a key contributory factor for the observed difference in exposure. These results suggest no dose adjustment for QMF149 is required in Asian populations.

Item Type:	Article
Keywords:	Caucasian Ethnic variation Indacaterol Japanese Mometasone furoate Pharmacokinetics QMF149
Date Deposited:	21 Nov 2017 00:45
Last Modified:	25 Jan 2019 00:45
URI:	https://oak.novartis.com/id/eprint/22782