Pharmacokinetics of QMF149 in Japanese versus Caucasian subjects: an open-label, randomized phase I study

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 beta(2)-agonist, indacaterol (Onbrez (R) Breezhaler (R) for COPD), and an approved inhaled corticosteroid, mometasone furoate (MF), (Asmanex (R) Twisthaler (R) for asthma), following multiple dose administration of QMF149 (indacaterol acetate/MF) 150/80 mu g and 150/320 mu g via the Breezhaler (R) device in healthy Japanese and Caucasian subjects. Methods: This was a single-center, open-label, multiple-dose, two-period, complete crossover study that randomized healthy Japanese and, age and weight matched Caucasian subjects to QMF149 150/80 mu g or 150/320 mu g 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.