EX-99.1 2 a12-14721_1ex99d1.htm EX-99.1

Exhibit 99.1

 

POSTER NO. 1188

 

Fluticasone furoate and vilanterol suppress allergen-induced bronchial hyper-responsiveness to methacholine

 

Oliver A(1), Quinn D(2), Saggu P(1), Thomas P(3), Lötvall J(4), Bjermer L(5)*

 

(1)GlaxoSmithKline Respiratory and Immuno-Inflammation Medicines Development Centre, Uxbridge, UK; (2)P3 Research, Wellington, NZ; (3)Faculty of Medicine, The University of New South Wales, Sydney NSW 2052, Australia; (4)Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden; (5)Department of Respiratory Medicine and Allergology, Institute for Clinical Science, Lund, Sweden, *Presenting Author

 

INTRODUCTION

 

·                  A high proportion of people with asthma are affected by airborne allergens.(1)

 

·                  Allergen exposure may lead to a biphasic decline in lung function consisting of the early asthmatic response (EAR) and the late asthmatic response (LAR); the latter is associated with the development of airway hyper-responsiveness (AHR).(2)

 

·                  Fluticasone furoate (FF)(3) and vilanterol trifenatate (VI)(4) are promising agents for a combined, long-acting, once-daily treatment of asthma.

 

OBJECTIVES

 

·                  Primary: to compare the effect of FF/VI combination on EAR (vs FF or VI monotherapy) and LAR (vs placebo).

 

·                  Secondary: to compare the effects of treatments on AHR.

 

METHODS

 

·                  Randomised, double-blind, 4-way crossover study

 

·                  21 days treatment administered in the morning via a novel dry powder inhaler (Figure 1).

 

Figure 1. Study design

 

 

* Allergen challenge on Day 21, 1h post-final dose

 

† Assessment of AHR on Day 22, 24h post-allergen challenge (25h post-dose) using doubling concentrations of methacholine to induce a 20% fall in forced expiratory volume in 1s (FEV1) (PC20)

 

RESULTS

 

Study population and demographics

 

·                  Baseline characteristics of study participants are outlined in Table 1.

 

·                  Of the 27 patients randomised, one withdrew consent and four protocol deviations during treatment period 1 led to those data being excluded from the analysis for that treatment period.

 

Pre-challenge lung function

 

·                  FEV1 improved from Day 1 to Day 21 with FF/VI, FF and VI by 230mL (95% CI: 145, 315), 116mL (30, 202) and 183mL (95, 272) respectively. With placebo, FEV1 declined by 61mL (-147, 24).

 


 

Figure 2. Methacholine challenge treatment differences (PC20) performed 25h post-dose and 24h following an inhaled allergen challenge

 

 

Table 1. Baseline characteristics

 

Demographics

 

Mean age,

 

30.8

years (range)

 

(18-49)

Female, %

 

30

Mean BMI,

 

25.5

kg/m2 (range)

 

(19.2-35.0)

White race, %

 

93

 

Lung function

 

Mean pre-bronchodilator FEV1, L

 

3.7

(range)

 

(2.7-5.0)

Mean pre-bronchodilator FEV1

 

92.3

% pred. (range)

 

(71.3-119.8)

Methacholine PC20, mg/mL

 

<8

 

Allergen, n (%)

 

House dust mite

 

15 (56)

Cat hair/dander

 

10 (37)

Birch tree

 

1 (4)

Grass pollen

 

1 (4)

 

BMI = body mass index

 

Allergen challenge (EAR/LAR)

 

·                  At all time points assessed, FF/VI exhibited the greatest attenuation of the allergen-induced response; the LAR to allergen challenge was significantly reduced with all active treatments, while the EAR was significantly reduced by FF/VI and FF, relative to placebo.

 

AHR

 

·                  25h post-dose FF alone and combined with VI significantly reduced AHR vs placebo (Figure 2).

 

·                  Combination therapy with FF/VI was superior to monotherapy with FF or VI alone (Figure 2).

 

Safety

 

·                  No serious adverse events or withdrawals were reported.

 


 

Safety cont’d.

 

·                  On-treatment, treatment-related adverse events occurring in >2 patients are listed in Table 2.

 

Table 2. Treatment-related adverse events

 

 

 

 

 

 

 

 

 

FF/VI

 

 

 

PBO

 

FF 100

 

VI 25

 

100/25

 

n (%)

 

(n=27)

 

(n=27)

 

(n=27)

 

(n=27)

 

Any AE

 

7 (26)

 

5 (19)

 

4 (15)

 

6 (22)

 

Headache

 

4 (15)

 

1 (4)

 

2 (8)

 

4 (15)

 

Oral candidiasis

 

2 (7)

 

0

 

0

 

0

 

Oropharyngeal pain

 

1 (4)

 

1 (4)

 

0

 

2 (7)

 

Throat irritation

 

0

 

1 (4)

 

1 (4)

 

0

 

 

CONCLUSION

 

·                  FF/VI provides significant protection from allergen-induced airway hyper-responsiveness shown by an increase in PC20 methacholine at 25h post-dose, compared with placebo and FF and VI alone.

 

REFERENCES

 

(1) Lötvall J, et al. J Allergy Clin Immunol 2011;127:355–360.
(2) O’Byrne PM. Allergy Asthma Immunol Rev 2009;1:3–9.
(3) Woodcock A, et al. Respir Res 2011;12:160.
(4) Lötvall J, et al. Eur Respir J 2012 [Epub ahead of print].

 

ACKNOWLEDGEMENTS

 

·                  The presenting author, Dr L Bjermer, declares the following real or perceived conflicts of interest during the last 3 years in relation to this presentation: received honoraria for speaking and consulting and/or financial support for attending meetings from Almirall, AstraZeneca, Airsonette, Andre Pharma, Boehringer Ingelheim, GlaxoSmithKline, Merck, Mundipharma, Nigaard, Novartis, Nycomed/Takeda and Orion Pharma.

 

·                  This study was funded by GlaxoSmithKline; GSK Study Code HZA113126, Clinicaltrials.gov NCT01128595.

 

·                  Editorial support was provided by Geoff Weller, PhD, at Gardiner-Caldwell Communications; this support was funded by GlaxoSmithKline.

 

 

Presented at the European Academy of Allergy and Clinical Immunology Congress 2012 Geneva, Switzerland, 16–20 June, 2012