医学
敌手
腺苷
腺苷受体
药理学
内科学
受体
兴奋剂
作者
David Ramos-Barbón,Nadia S. Brienza,Teresa Bigorra Rodríguez,Éder Fredy Mateus Medina,Ignasi Gich Saladich,Montserrat Puntes Rodríguez,Rosa M. Antonijoan Arbos,Santiago Quirce Gancedo,Nahomi Castro Palomino Laria,Julio Castro Palomino Laria
标识
DOI:10.1183/13993003.congress-2020.4784
摘要
Background: PBF-680 is an oral A1 adenosine receptor antagonist in development for asthma. Aims and Objectives: To evaluate PBF-680 efficacy to inhibit the LAR, a standard goal for asthma therapies development. Methods: Double-blind, randomized, cross-over trial with once-daily 10-mg PBF-680 or placebo for 5 days, on 8 atopic asthmatics on withdrawn low-to-medium-dose inhaled corticosteroid, showing both early allergic response (EAR, ≥20% FEV1 drop) and LAR (FEV1 drop ≥15% at 3-10h post-aeroallergen challenge). The primary outcome was the LAR area under the FEV1 curve (AUC3-10h). Data analysis: repeated-measures general linear model or Kruskal-Wallis/Wilcoxon. Results: LAR AUC3-10h was (mean ± standard error [SEM]) -64.84±14.14 (placebo), and 13.71±13.61 (PBF-680; P<0.001 vs. placebo, Fig. 1). EAR was -26.3% FEV1 drop (placebo) and -20.0% (PBF-680, P=0.049 vs. placebo). Exhaled breath nitric oxide fraction (FeNO, ppb) was 34.0±2.5 (placebo) and 19.7±3.0 (PBF-680, P=0.042 vs. placebo). Blood eosinophils/mcL were 283±64 (placebo) and 60±13 (PBF-680, P=0.01 vs. placebo). No relevant adverse events were recorded. Conclusions: In mild-to-moderate asthmatics, PBF-680 abrogated the LAR, and reduced the EAR, FeNO, and, remarkably, blood eosinophils, with correct safety profile. The data position the adenosine modulator PBF-680 as a promising oral asthma therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI