Phase 2a, randomized, double‐blind, placebo‐controlled, multicentre, parallel‐group study of an H 4 R‐antagonist ( JNJ ‐39758979) in adults with uncontrolled asthma

Autor:	Matthew J. Loza, Xie Xu, Bei Zhou, R. L. Thurmond, P. E. Silkoff, Andrew Greenspan, Elliot S. Barnathan, Bin Chen, A. Kollmeier, J.Z. Jiang
Rok vydání:	2018
Předmět:	0301 basic medicine medicine.medical_specialty Immunology Population Placebo 03 medical and health sciences 0302 clinical medicine Internal medicine Eosinophilic medicine Immunology and Allergy education Adverse effect Asthma education.field_of_study business.industry medicine.disease respiratory tract diseases 030104 developmental biology 030228 respiratory system Exhaled nitric oxide Salbutamol Sputum medicine.symptom business medicine.drug
Zdroj:	Clinical & Experimental Allergy. 48:957-969
ISSN:	1365-2222 0954-7894
DOI:	10.1111/cea.13154
Popis:	Background The effects of H4 R antagonists in preclinical asthma models support the study of antagonists of the H4 R in the treatment of asthma in humans. JNJ-39758979 is a potent and highly selective oral H4 R antagonist. Objective We sought to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult patients with uncontrolled asthma. Methods One hundred and fifteen eligible patients were randomly assigned to JNJ-39758979 300 mg or placebo once daily for 12 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-12 change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1 ). Secondary efficacy assessments included patient-reported outcome (PRO) asthma assessments (Asthma Daily Diary data [AM and PM peak expiratory flow rate, number of puffs of albuterol/salbutamol, the presence of nocturnal awakenings and asthma symptom score]). Results The study did not meet the primary end-point. However, nominally significant improvements in pre-bronchodilator FEV1 were observed with JNJ-39758979 versus placebo at week 12 in pre-specified subgroups with elevated exhaled nitric oxide, sputum eosinophils or blood eosinophils at baseline. Nominally significant improvements across PRO assessments were consistently observed in the overall population, as well as in eosinophilic subgroups. Safety, such as adverse event rates, was comparable between JNJ-39758979 and placebo. No serious adverse events were reported. No clinically relevant changes in laboratory values were observed. Conclusions and clinical relevance The findings suggest potential benefit of H4 R antagonists on lung function and asthma control in eosinophilic asthma patients and warrant further evaluation of this mechanism in asthma with eosinophilic inflammation. NCT00946569.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::d0c94134b792e7b2018127980ae12692 https://doi.org/10.1111/cea.13154 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.