Abstract
Introduction: FF is an ICS still active at 24h, being developed as once daily (OD) inhaled treatment in combination with vilanterol (VI) a long-acting beta2-agonist, for asthma and COPD. Early data suggested that FF systemic exposure might be higher in Japanese subjects than in Caucasians.
Objective: To evaluate and compare the PK and systemic PD effects of FF in Caucasian (Ca), Chinese (Ch) Japanese (J) and Korean (K) subjects when delivered via a novel dry powder inhaler.
Methods: Open-label, randomised, two-way crossover study. Healthy male and female Ca, Ch, J and K subjects [20/group] received OD inhaled FF (200mcg (7 days) then 800mcg (7 days)) and single i.v. 250mcg FF. PK was obtained on Day (D) 1 and/or D7 and PD (cortisol) data on D7 at 200mcg only.
Results: FF Cmax and AUC values were consistently higher in Ch, J and K subjects compared with Ca subjects (Mean ratio: Cmax; 1.35-1.78 and AUC; 1.27-1.75). Repeat inhaled FF 200mcg showed no difference in serum cortisol 0-24h weighted mean between Ca and Ch or K subjects but this was 22% (90% CI:12-30) lower in J subjects compared to Ca subjects. All treatments were safe and well tolerated with no quantitative or qualitative differences in safety endpoints between ethnic groups.
Conclusion: FF systemic exposure was higher (< 2-fold) in Chinese, Japanese and Korean subjects compared to Caucasians. Lowered serum cortisol was only seen in Japanese subjects and was without any clinical consequence. Further clinical studies in Japanese subjects to evaluate the safety and efficacy of FF 100 and 200mcg are underway.
Funded by GSK (HZA113477; NCT01000597)
- © 2011 ERS