Abstract

Objectives: This study aimed to evaluate influence of ethnic factors on the pharmacokinetics of orally inhaled QMF149, a novel combination of an approved longacting β2-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_max 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.

Author Details

Authors

• Sayaka Shimada¹
• Soniya Vaidya²
• Sanjeev Khindri³
• Natsuka Tashiro¹
• Yi Cheng⁴
• Hisanori Hara⁵
• Tapan Majumdar⁶
• Ralph Woessner⁵
• Kenichi Furihata⁷
• Kiyoshi Kobayashi¹

Departments

• ¹ Translational Sciences, Novartis Pharma K.K., Tokyo, Japan,
• ² Drug Metabolism and Pharmacokinetics, Clinical Pharmacokinetics/Pharmacodynamics, Novartis Institutes for BioMedical Research, Cambridge, MA, USA,
• ³ Translational Medicine, Novartis Institutes for BioMedical Research, Horsham, UK,
• ⁴ Beijing Novartis Pharma Co. Ltd., Shanghai, China,
• ⁵ Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Basel, Switzerland,
• ⁶ Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, East Hanover, NJ, USA, and
• ⁷ P-one Clinic, Keikokai Medical Corporation, Tokyo, Japan

Address

Sayaka Shimada
Novartis Pharma K.K.
23-1, Toranomon 1-chome, Minato-ku, Tokyo 105-6633, Japan
Email: [email protected]

Citation