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


CONCLUSIONS
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.
Sayaka
S
Shimada
Soniya
S
Vaidya
Sanjeev
S
Khindri
Natsuka
N
Tashiro
Yi
Y
Cheng
Hisanori
H
Hara
Tapan
T
Majumdar
Ralph
R
Woessner
Kenichi
K
Furihata
Kiyoshi
K
Kobayashi
D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D018592:Cross-Over Studies; D004338:Drug Combinations; D016903:Drug Monitoring; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007564:Japan; D008297:Male; D009330:Nebulizers and Vaporizers; D011244:Pregnadienediols / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D044465:White People; D055815:Young Adult
D018927:Anti-Asthmatic Agents; D004338:Drug Combinations; D007189:Indans; D011244:Pregnadienediols; C000600413:QMF149; D015363:Quinolones