PT  - JOURNAL ARTICLE
AU  - Gail Gauvreau
AU  - Louis-Philippe Boulet
AU  - J. Mark FitzGerald
AU  - Donald Cockcroft
AU  - Beth Davis
AU  - Richard Leigh
AU  - Masaya Tanaka
AU  - John Fourre
AU  - Makoto Tanaka
AU  - Toshiya Nabata
AU  - Paul O'Byrne
TI  - Late-breaking abstract: Effects of a dual CysLT1/2 antagonist, ONO-6950, on allergen-induced airway responses in subjects with mild allergic asthma
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P2813
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P2813.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P2813.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Background: The cysteinyl leukotrienes (CysLTs) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, CysLTs contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation and mucus secretion.Aim: To test the activity of the dual CysLT1/2 antagonist, ONO-6950, against allergen-induced airway responses.Methods: Subjects with documented allergen-induced early (EAR) and late (LAR) asthmatic responses were randomized in a 3-way crossover study to receive ONO -6950 (200 mg) or montelukast (10 mg) or placebo q.d. on Days 1-8 of the 3 treatment periods. Allergen was inhaled on Day 7 and forced expiratory volume in 1 second (FEV1) was measured for 7 hours following challenge. Sputum eosinophils, and airway hyperresponsiveness were measured before and after allergen challenge. The primary outcome was the effect of ONO-6950 versus placebo on the EAR and LAR.Results: Twenty-five non-smoking subjects with mild allergic asthma were enrolled and 20 subjects completed all 3 treatment periods per protocol. ONO-6950 was well tolerated. Compared to placebo, ONO-6950 significantly attenuated the maximum % fall in FEV1 and area under the %FEV1/time curve during the early and late asthmatic responses (p<0.05), and allergen-induced sputum eosinophils. There were no significant differences between ONO-6950 and montelukast.Conclusions: Attenuation of EAR, LAR, and airway inflammation is consistent with CysLT1 blockade. Whether dual CysLT1/2 antagonism offers additional benefit for treatment of asthma requires further study.Funded by ONO Pharmaceutical Co., Ltd., and AllerGen NCE Inc.