046: Model-Based Meta-Analyses to Compare Inhaled Fluticasone Furoate & Vilanterol Systemic Exposures in Japanese & Non-Japanese Pediatric Population With Asthma

Statement of Purpose: Fluticasone furoate (FF), a once-daily inhaled corticosteroid (ICS) administered alone, or in combination with vilanterol (VI), a once-daily long-acting beta2-adrenergic agonist (LABA) have been approved for the maintenance treatment of asthma in adults and adolescents 12 years and older. In addition, FF alone has been approved in the USA in children aged 5 years and older for the same indication. Studies evaluating efficacy and safety of FF and VI for treatment of asthma have been conducted in children aged 5 to 11 years. To facilitate FF/VI access to Japanese pediatric population with asthma, it is important to compare the exposures of FF and VI in Japanese to those in non-Japanese pediatric population. Therefore, the pharmacokinetics of FF and VI were characterized using a population pharmacokinetic approach in pediatric population of different race subgroups. The objective of the analyses was to compare model-predicted steady-state maximum plasma concentrations (C_max) and overall systemic exposure (AUC_0-24) of FF and VI in pediatric Japanese and non-Japanese population subgroups.

Description of Methods & Materials: Population pharmacokinetic models for FF and VI were developed using data from three Phase IIa (HZA102942, HZA112776 and HZA112777) and two Phase IIb (HZA106855 and HZA106853) pediatric studies to predict the steady-state C_max and AUC_0-24 of FF and VI following once-daily inhalation of FF/VI combination at 100/25 mcg, FF alone at 100 mcg, 50 mcg or 25 mcg and VI alone at 25 mcg via dry powder inhaler. The C_max and AUC_0-24 for each drug and each dose level were compared between Japanese and non-Japanese population subgroups. The pediatric non-Japanese subgroup consisted of African American/African heritage, American Indian/Native Alaskan, South East Asian heritage, Mixed race and White.

Data & Results: Data from children aged 5 to 11 years were included in the analyses. Overall, 306 children received FF (n=10 Japanese), whereas 142 children received VI (n=5 Japanese). We found the systemic exposures of inhaled FF and VI in Japanese subgroup were similar to, or slightly higher than the non-Japanese subgroups across all FF doses evaluated in this analysis (Figure 1) but this finding has no clinical relevance in terms of effect on serum cortisol (see below).

Interpretation, Conclusion or Significance: Our findings suggest that compared to non-Japanese subgroups, no dose-adjustment is required in Japanese children with asthma aged 5-11 years receiving inhaled FF or VI. Although the Japanese subgroup has slightly higher FF exposures compared to non-Japanese subgroup, the highest AUC_0-24 was 270.4 pg.h/mL, which is ~4-fold lower than the 1,000 pg.h/mL threshold associated with 20% decrease in 24h serum cortisol [1].

Disclosures: The study was funded by GSK. AAA is funded through a UF/GSK Post-Doctoral Fellowship; HC and RM are employees of GSK and hold shares; LH was an employee of GSK and holds shares.