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Exhibit 99.1
POSTER NO. PS108
Efficacy and safety of once-daily fluticasone furoate/vilanterol 200/25mcg compared with twice-daily fluticasone propionate 500mcg in asthma patients of Asian ancestry
Jiangtao L(1), Crawford J(2), Jacques L(3), Stone S(3)
(1)Department of Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China
(2)Quantitative Sciences Division, GlaxoSmithKline, Uxbridge, UK
(3)Respiratory Medicines Development Centre, GlaxoSmithKline, Uxbridge, UK
INTRODUCTION
· Fluticasone furoate (FF)/vilanterol (VI) is a novel once-daily ICS/long-acting beta2-agonist (LABA) combination therapy for the treatment of asthma.
· Fluticasone proprionate (FP) is an inhaled corticosteroid (ICS) taken twice daily via the DISKUSTM inhaler for the treatment of asthma.
· FF/VI delivered via the ELLIPTATM dry powder inhaler, has demonstrated 24h effectiveness in asthma patients in global studies(1),(2)
· The 200/25mcg strength significantly improved lung function versus FP 500mcg twice daily over 24 weeks.(2)
· Responses to pharmacotherapy can vary across ethnic groups,(3),(4) including in Asian patients.(4)
OBJECTIVES
· To evaluate the efficacy and safety of once-daily FF/VI 200/25mcg administered in the evening, compared with twice-daily FP 500mcg administered in the morning and evening, in asthma patients of Asian ancestry.
METHODS
· A randomised, double-blind, double-dummy, active-comparator, parallel-group, 12-week multicentre study.
· Inclusion criteria: aged >12 years; FEV1 4090% predicted; reversibility of >12% and >200mL within 1040 minutes following 24 inhalations of salbutamol; treated with stable high-dose ICS or mid-dose ICS/LABA therapy for >4 weeks prior to Screening.
· Patients were randomised (1:1) to receive FF/VI 200/25mcg once daily via the ELLIPTA device (equivalent to a delivered dose of FF/VI 184/22mcg) or FP 500mcg twice daily via the DISKUS inhaler for 12 weeks.
· Primary endpoint: mean change from baseline in daily evening peak expiratory flow (PEF) averaged over the 12-week treatment period.
· Secondary endpoints (Weeks 112, unless stated)
· Change from baseline in % rescue-free 24h periods
· Mean change from baseline in morning PEF (averaged over Weeks 112)
· Change from baseline in % symptom-free 24h periods
· Change from baseline in AQLQ+12 Total score (measured at Week 12).
· A step-down statistical hierarchy was applied to account for multiplicity across endpoints. Testing of each endpoint was dependent on the achievement of significance at the 5% level for the previous endpoint, in the following order
· Evening PEF > % rescue-free 24h periods > morning PEF > % symptom-free 24h periods > AQLQ score.
· Safety endpoints included incidence of adverse events (AEs), vital signs, electrocardiogram and laboratory evaluations.
RESULTS
Table 1. Demographic and baseline characteristics
(ITT population)
|
|
FF/VI 200/25 |
|
FP 500 |
|
|
|
|
OD |
|
BD |
|
Total |
Age (years) |
|
46.9 (12.93) |
|
48.8 (13.41) |
|
47.9 (13.19) |
Male, n (%) |
|
59 (38) |
|
68 (44) |
|
127 (41) |
Duration of asthma |
|
12.39 |
|
13.44 |
|
12.91 |
(years) |
|
(12.857) |
|
(13.551) |
|
(13.196) |
Lung function parameters |
|
|
|
|
|
|
FEV1 (L) |
|
1.78 (0.493) |
|
1.77 (0.552) |
|
1.77 (0.523) |
% predicted FEV1 |
|
67.51 |
|
67.55 |
|
67.53 |
|
(13.249) |
|
(13.432) |
|
(13.319) | |
% reversibility FEV1 |
|
27.31 |
|
26.98 |
|
27.14 |
at screening |
|
(14.570) |
|
(14.262) |
|
(14.395) |
Data are mean (SD) unless otherwise stated; OD=once daily; BD=twice daily
RESULTS
Efficacy
· FF/VI and FP improved evening PEF compared with baseline
(Figure 1)
· Change from baseline with FF/VI was 39.1L/min (standard error=3.01) and with FP was 10.5L/min (3.03)
· The effect was statistically significantly better (p<0.001) with FF/VI compared with FP (28.5L/min; 95% confidence interval [CI]: 20.1, 36.9).
· Improvements in % rescue-free 24h periods were similar for FF/VI and FP
· The equivalent number of rescue-free days per week was 2.3 with FF/VI and 2.2 with FP
· The adjusted treatment difference (1.0%; 95% CI: 7.3, 9.2) was not statistically significant (p=0.821) (Figure 2).
· Due to the statistical hierarchy, significance for remaining endpoints could not be inferred.
· There were numerical improvements in the remaining secondary endpoints for FF/VI compared with FP (Figure 2).
RESULTS
Safety
· Incidence of AEs, treatment-related AEs and serious AEs was low and similar for FF/VI and FP (Table 2).
· There were no fatal AEs.
· The only treatment-related SAE was asthma (FP 500mcg).
· Pneumonia was reported by two patients (both with FF/VI 200/25mcg); neither required hospitalisation.
· There were no clinically significant changes in vital signs, electrocardiogram parameters or clinical laboratory evaluations.
Table 2. Summary of adverse events (ITT population)
|
|
FF/VI 200/25 |
|
FP 500 |
|
|
|
OD |
|
BD |
|
|
|
N=155 |
|
N=154 |
|
All AEs |
|
|
|
|
|
On-treatment |
|
40 (26) |
|
41 (27) |
|
On-treatment, treatment-related |
|
5 (3) |
|
5 (3) |
|
On-treatment leading to withdrawal |
|
2 (1) |
|
2 (1) |
|
Post-treatment |
|
0 |
|
1 (<1) |
|
SeriousAEs |
|
|
|
|
|
On-treatment |
|
1 (<1) |
|
2 (1) |
|
On-treatment, treatment-related |
|
0 |
|
1 (<1) |
|
Most frequent(a) on-treatment AEs |
|
|
|
|
|
Upper respiratory tract infection |
|
13 (8) |
|
18 (12) |
|
Nasopharyngitis |
|
6 (4) |
|
6 (4) |
|
Rhinitis allergic |
|
5 (3) |
|
2 (1) |
|
Oropharyngeal pain |
|
4 (3) |
|
1 (<1) |
|
(a)Occurring in >3% of patients in either treatment group
CONCLUSIONS
· FF/VI 200/25mcg once daily demonstrated clinically and statistically significant improvements in evening PEF compared with FP 500mcg twice daily in Asian asthma patients uncontrolled on high-dose ICS or mid-dose ICS/LABA.
· There were numerical improvements across the secondary endpoints with FF/VI 200/25mcg versus FP 500mcg.
· The safety profile of FF/VI 200/25mcg was broadly similar to that of FP 500mcg.
· The results are generally consistent with a previously published global study that compared FF/VI 200/25mcg with FP 500mcg.(2)
REFERENCES
(1) Woodcock A, et al. Chest 2013;144:12229.
(2) OByrne PM, et al. Eur Respir J 2013;Oct 17:ePub ahead of print.
(3) Bjornsson TD,et al. J Clin Pharmacol 2003;43:94367.
(4) Huang SM, et al. Clin Pharmacol Ther 2008;84:28794.
ACKNOWLEDGMENTS
· The presenting author, Dr Jiangtao Lin has received speakers honoraria from AstraZeneca, GlaxoSmithKline and MSD, and has been a member of global advisory boards for Boehringer Ingelheim.
· The study was funded by GlaxoSmithKline (GSK study code HZA113714 (clinicaltrials.gov registration number: NCT01498653).
· Editorial support (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and referencing) was provided by Laura Maguire, MChem at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by GlaxoSmithKline.
DISKUS and ELLIPTA are trade marks of the GlaxoSmithKline group of companies
Presented at the 18th Congress of the Asian Pacific Society of Respirology, Yokohama, Japan, 1114 November 2013