Systemic Pharmacokinetics Of Indacaterol, An Inhaled Once-Daily Long-Acting Beta(2)-Agonist, In Different Ethnic Populations

Rationale: To assess ethnic sensitivity of indacaterol systemic pharmacokinetics in Japanese vs. non-Japanese patients. Methods: Analyses were in three parts: data front a single "all Asian" clinical study; and two on pooled data - one using a linear mixed effects (LME) model and the other a non-linear mixed effects (NLME) model. The NLME model analyzed pharmacokinetic data from nine indacaterol studies; the LME model analyzed peak (C-max) and trough (C-min) serum concentration using data from four of these studies. Results: In the all-Asian study, indacaterol serum concentration-time pharmacokinetic profiles in Japanese patients (n = 102) were similar to those in the overall population (n = 229). In the LME model, C-max (4,392 observations, 1,845 patients) and Cmin (4,664 observations, 1,796 patients) for Japanese patients (n = 94) were on average 25% and 18% higher, respectively, than non-Japanese patients. However, after adjusting for study differences, this apparent ethnicity effect was not significant (p = 0.25 and 0.39, respectively). In the NLME model (25,540 observations, 2,857 patients), there was no statistically significant effect of Japanese (n = 230) ethnicity on indacaterol scrum pharmacokinetics. Conclusion: No ethnicity effect was observed on indacaterol systemic pharmacokinetic profile for Japanese patients when compared with the overall Asian patient population or with the Caucasian patient population.