EX-99.7 8 a12-19541_1ex99d7.htm EX-99.7

Exhibit 99.7

 

POSTER P1795

 

Efficacy and safety of fluticasone furoate (FF)/vilanterol (VI) compared with fluticasone propionate/salmeterol combination (FP/SAL) in adults and adolescents with persistent asthma

 

Woodcock A(1), Bleecker ER(2), Lötvall J(3), O’Byrne PM(4), Bateman ED(5), Medley H(6), Ellsworth A(7), Jacques L(6), Busse WW(8)

 

(1)University of Manchester, Manchester, UK; (2)Wake Forest University Health Sciences Winston-Salem, NC, USA; (3)University of Gothenburg, Sweden; (4)Michael G DeGroote School of Medicine, Hamilton, Ontario, Canada; (5)University of Cape Town, Cape Town, South Africa; (6)Respiratory Medicines Development Centre, GlaxoSmithKline, London, UK; (7)Quantitative Sciences Division, GlaxoSmithKline, Research Triangle Park, NC, USA; (8)University of Wisconsin, Madison, WI, USA

 

INTRODUCTION

 

·                  For asthma patients symptomatic despite ICS therapy, a long-acting beta2 agonist (LABA) may be added.(1),(2)

 

·                  Current ICS/LABA combinations for asthma such as FP/SAL are administered twice daily; once-daily dosing of ICS/LABA may improve symptom control by improving patient adherence.

 

·                  The combination of FF (an ICS) and VI (a LABA) is in development as a once-daily therapy for asthma.

 

OBJECTIVES

 

·                  To compare the efficacy of FF/VI 100/25mcg administered once daily in the evening with FP/SAL 250/50mcg administered twice daily (morning and evening) over a 24-week treatment period in patients >12 years of age with persistent asthma.

 

METHODS

 

·                  Phase III, multi-centre, randomised, double-blind, double-dummy, parallel group study.

 

·                  Eligible patients: aged >12 years; >12% and >200mL reversibility of FEV1 with salbutamol; evening pre-bronchodilator FEV1 40–85% pred; documented use of ICS for >12 weeks with stable ICS dose (FP 250mcg twice daily or equivalent) for >4 weeks.

 

·                  After 4-week run-in on FP 250mcg twice daily, patients were randomised to 24 weeks’ treatment with

 

·                  FF/VI 100/25mcg once daily (evening dosing) via novel dry power inhaler

 

·                  FP/SAL 250/50mcg twice daily via DISKUSTM/ACCUHALERTM.

 

RESULTS

 

Study population and demographics (Table 1)

 

·                  Of 1564 patients screened, 806 were randomised (intent-to-treat [ITT] population) and 715 completed the study.

 

Efficacy

 

·                  Clinically important improvements from baseline in 0–24h serial weighted mean (wm) FEV1 after 24 weeks (primary endpoint) were seen with both FF/VI (341mL) and FP/SAL (377mL)  

 

·      the adjusted mean treatment difference was not statistically significant (–37mL [95% CI: –88, 15], p=0.162; Fig. 1).

 


 

Table 1. Patient demographics and baseline lung function (ITT population)

 

 

 

FF/VI

 

FP/SAL

 

 

 

100/25mcg

 

250/50mcg

 

 

 

once daily

 

twice daily

 

 

 

(N=403)

 

(N=403)

 

Mean age, years (range)

 

43.8 (12–79)

 

41.9 (12–80)

 

Female, n (%)

 

244 (61)

 

245 (61)

 

Race, n (%)

 

 

 

 

 

White

 

242 (60)

 

232 (58)

 

Asian

 

124 (31)

 

125 (31)

 

African American/African heritage

 

36 (9)

 

43 (11)

 

Other(a)

 

1 (<1)

 

3 (<1)

 

%reversibility of FEV1(b), L, mean (SD)

 

26.4 (14.44)

 

29.0 (18.04)

 

Pre-dose FEV1 (L), mean (SD)

 

2.011 (0.6389)

 

2.048 (0.6246)

 

%predicted FEV1 , mean (SD)

 

68.0 (11.68)

 

68.8 (11.01)

 

 

(a)Native Hawaiian or other Pacific islander (n=1 [<1%] FF/VI; n=1 [<1%] FP/SAL); African American/African heritage and White (n=0 FF/VI; n= 2 [<1%] FP/SAL)

(b)Screening values

 

Figure 1. Adjusted means for 0–24h wmFEV1 at Week 24 (ITT population)

 

 

LS=least squares; CI=confidence interval

 


 

·                  No statistically significant differences were reported between FF/VI and FP/SAL for serial wmFEV1 (0–4h) and clinic visit trough FEV1 (secondary endpoints).

 

·                  A greater number of patients receiving FF/VI vs. FP/SAL had an improvement of >0.5 points (minimally important difference)(3) from baseline in their Total Asthma Quality of Life Questionnaire (+12) score (‘other’ endpoint; post-hoc analysis) at Week 24 (46% vs. 38%).

 

Safety

 

·                  Incidences of on-treatment adverse events (AEs), treatment-related AEs and serious AEs (SAEs) were similar between treatments (Table 2)

 

·                  no SAEs were considered treatment-related

 

·                  no deaths were reported during the study.

 

·                  No clinically relevant differences between FF/VI and FP/SAL were reported for 24-h urinary cortisol (UC) excretion (adjusted treatment ratio 0.85 [95% CI: 0.72, 1.02], p=0.075) (Fig. 2) or vital signs.

 

Figure 2. Adjusted ratios to baseline for 24-h UC excretion at Week 24 (UC population)

 

 

LS=least squares; CI=confidence interval

 


 

Table 2. Summary of AEs and SAEs (ITT population)

 

 

 

 

 

FP/SAL

 

 

 

FF/VI 100/25mcg

 

250/50mcg

 

 

 

once daily

 

twice daily

 

n (%)

 

(N=403)

 

(N=403)

 

On-treatment AEs

 

213 (53)

 

198 (49)

 

Nasopharyngitis

 

46 (11)

 

46 (11)

 

Headache

 

34 (8)

 

41 (10)

 

Upper respiratory tract infection

 

26 (6)

 

16 (4)

 

Treatment-related AEs

 

19 (5)

 

15 (4)

 

SAEs

 

4 (<1)

 

5 (1)

 

 

AEs occurring in >5% of patients in any treatment group are presented

 

CONCLUSIONS

 

·                  There was no difference between once-daily FF/VI and twice-daily FP/SAL in improving lung function in patients with persistent asthma.

 

·                  FF/VI improved quality of life (post-hoc analysis) compared with FP/SAL.

 

·                  No safety issues were identified with either treatment.

 

REFERENCES

 

(1)   National Institutes of Health. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/index.htm. Last accessed 6 August 2012.

(2)   GINA 2011. Available at: http://www.ginasthma.org/uploads/users/files/ GINA_Report_2011.pdf. Last accessed 6 August 2012.

(3)   Juniper EF, et al. J Clin Epidemiol 1994;47:81–7.

 

ACKNOWLEDGEMENTS

 

·                  The presenting author, L Jacques, is an employee of and holds stocks/shares in GlaxoSmithKline.

 

·                  This study was funded by GlaxoSmithKline; GSK Study Code HZA113091, Clinicaltrials.gov NCT01147848.

 

·                  Editorial support (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and referencing) was provided by Lisa Moore at Gardiner-Caldwell Communications and was funded by GlaxoSmithKline.

 

 

Presented at the European Respiratory Society Annual Congress 2012 Vienna, Austria, 1–5 September, 2012