Ethnic sensitivity assessment of fluticasone furoate/vilanterol in East Asian asthma patients from randomized double-blind multicentre Phase IIb/III trials

Abstract

Background: Fluticasone furoate (FF)/vilanterol (VI) is a once daily (OD) inhaled corticosteroid/long-acting β2-agonist combination asthma therapy approved in Japan and the EU. FF/VI efficacy and safety data from asthma studies including patients in East Asia were evaluated to assess ethnic sensitivity.

Methods: Randomized, double-blind, multicenter Phase IIb/III trials were assessed. Change from baseline relative to placebo or twice-daily fluticasone propionate 500 μg in trough FEV1 was compared between patients from Japan (N = 148) and Not-Japan (N = 3,066; three studies). Adverse events (AEs), laboratory results, and electrocardiograms were compared between patients from Japan + Korea (N = 188) and Not-Japan + Korea (N = 3,840; five studies).

Results: For trough FEV1, improvements from baseline (least-squares mean difference [95% confidence interval]) were reported for FF/VI 100/25 μg OD versus placebo at Week 12 (Japan: 0.323 L [0.104-0.542]; Not-Japan: 0.168 L [0.095-0.241]). Improvements from baseline (least-squares mean change [standard error]) were reported with FF/VI 200/25 μg OD at Week 24 (Japan: 0.355 L [0.1152]; Not-Japan: 0.396 L [0.0313]). A greater proportion of patients from Japan + Korea versus Not-Japan + Korea reported AEs in all treatment arms including placebo (FF/VI 100/25 μg: 79% versus 57%; FF/VI 200/25 μg: 64% versus 45%; placebo: 41% versus 23%). There were no notable differences in treatment-related or class-related AEs. No clinically significant changes in electrocardiogram assessments or statistically significant differences in 24 h urinary cortisol excretion were observed between the Japan + Korea and Not-Japan + Korea cohorts.

Conclusions: Good efficacy and an acceptable safety profile were observed for FF/VI 100/25 μg and 200/25 μg OD in East Asian asthma patients; these globally recommended doses are appropriate for asthma patients in Japan.

Trial registration: Clinicaltrials.gov registration numbers: NCT01165138 , NCT01134042 , NCT01086384 , NCT00603278 , NCT00603382 .

Figures

Fig. 1

Change from baseline in trough FEV1 at Week 12 (Efficacy population). Efficacy population consists of data from studies HZA106827, HZA106829, and HZA106837. Number of patients analyzed in a) Overall population: N = 193 placebo, N = 1,201 FF/VI 100/25 μg OD, N = 187 FF/VI 200/25 μg OD, N = 1,203 FF 100 μg OD, N = 186 FF 200 μg OD, N = 190 FP 500 μg BD; b) Japan cohort: N = 18 placebo, N = 46 FF/VI 100/25 μg OD, N = 13 FF/VI 200/25 μg OD, N = 46 FF 100 μg OD, N = 11 FF 200 μg OD, N = 10 FP 500 μg BD; c) Not-Japan cohort: N = 175 placebo, N = 1,155 FF/VI 100/25 μg OD, N = 174 FF/VI 200/25 μg OD, N = 1,157 FF 100 μg OD, N = 175 FF 200 μg OD, N = 180 FP 500 μg BD. The limits of the box represent the interquartile range (IQR) from the 25th to 75th percentiles, respectively, for the lower and upper limits of the box; error bars represent the minimum and maximum values within 1.5 × IQR below and above the 25th and 75th percentiles, respectively; the horizontal line within the box represents the median; + represents the mean; symbols represent data that are either <1.5 × IQR below the 25th percentile or >1.5 × IQR above the 75th percentile. BD twice daily, FEV1 forced expiratory volume in one second, FF fluticasone furoate, FP fluticasone propionate, OD once daily, VI vilanterol

Fig. 2

24h urinary cortisol excretion at the end of treatment relative to baseline (Urinary Cortisol population). Urinary cortisol population consists of data from studies HZA106827, HZA106829, FFA109685, and FFA109687. Number of patients analyzed in a) Overall population: N = 258 placebo, N = 153 FF/VI 100/25 μg OD, N = 140 FF/VI 200/25 μg OD, N = 301 FF 100 μg OD, N = 270 FF 200 μg OD, N = 70 FP 100 μg BD, N = 70 FP 250 μg BD, N = 123 500 μg BD; b) Japan/Korea cohort: N = 14 placebo, N = 12* FF/VI 100/25 μg OD, N = 10* FF/VI 200/25 μg OD, N = 21 FF 100 μg OD, N = 14 FF 200 μg OD, N = 2 FP 100 μg BD, N = 7 FP 250 μg BD, N = 8* FP 500 μg BD; c) Not-Japan/Korea cohort: N = 244 placebo, N = 141 FF/VI 100/25 μg OD, N = 130 FF/VI 200/25 μg OD, N = 280 FF 100 μg OD, N = 256 FF 200 μg OD, N = 68 FP 100 μg BD, N = 63 FP 250 μg BD, N = 115 FP 500 μg OD. See Fig. 1 for details of parameters represented by the box plot. *Patients from Japan only. BD twice daily, FP fluticasone propionate, OD once daily, FF fluticasone furoate, VI vilanterol