The effects of a CCR3 inhibitor, AXP1275, on allergen-induced airway responses in adults with mild-to-moderate atopic asthma
| Autor: | Gail M. Gauvreau, Linda Hui, JM FitzGerald, S Boehme, Abbey Schlatman, J Kum, Richard M. Watson, Paul M. O'Byrne, L.-P. Boulet, Caitlin Obminski, K B Bacon, H Villineuve, Tara Scime, T W Ly |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Receptors CCR3 Immunology medicine.disease_cause Placebo Gastroenterology Bronchial Provocation Tests 03 medical and health sciences 0302 clinical medicine Double-Blind Method immune system diseases Internal medicine medicine Humans Immunology and Allergy Anti-Asthmatic Agents Organic Chemicals Adverse effect Asthma Cross-Over Studies business.industry Aeroallergen Allergens Eosinophil medicine.disease respiratory tract diseases 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Exhaled nitric oxide Sputum Female Methacholine medicine.symptom business medicine.drug |
| Zdroj: | Clinical & Experimental Allergy. 48:445-451 |
| ISSN: | 0954-7894 |
| Popis: | Background CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. Objective This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. Methods Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind cross-over study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo. Results There was a significant increase in methacholine PC20 after 12 days of AXP1275 treatment compared to placebo (increase of 0.92 doubling doses versus 0.17 doubling doses, P = .01), but this protection was lost post-allergen challenge. There was no effect of AXP1275 on allergen-induced late asthmatic responses, or eosinophils in blood and sputum. The early asthmatic response and exhaled nitric oxide levels were slightly lower with AXP1275, but this did not reach statistical significance. The number of subjects who experienced treatment-emergent adverse events while receiving AXP1275 was comparable placebo. Conclusions & clinical relevance AXP1275 50 mg administered daily was safe and well tolerated, and there was no difference in the type, severity or frequency of treatment-emergent adverse events in subjects while receiving AXP1275 compared to placebo. AXP1275 increased the methacholine PC20 ; however, the low and variable exposure to APX1275 over a short treatment period may have contributed to poor efficacy on other outcomes. |
| Databáze: | OpenAIRE |
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