Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma.
Can Respir J
; 22(4): 230-4, 2015.
Article
em En
| MEDLINE
| ID: mdl-26252534
ABSTRACT
OBJECTIVES:
To evaluate the safety, tolerability and clinical activity of ASM-024, a new cholinergic compound with dual nicotinic and muscarinic activity, in mild allergic asthma.METHODS:
The present study involved 24 stable, mild allergic asthmatic subjects. In a cross-over design, ASM-024 (50 mg or 200 mg) or placebo were administered once daily by nebulization over three periods of nine consecutive days separated by a three-week washout. The effect of each treatment on the forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% decline in FEV1 (PC20), early and late asthmatic responses, and allergen-induced inflammation were measured.RESULTS:
Seventeen subjects completed the study. During treatment with ASM-024 at 50 mg or 200 mg, the PC20 value increased respectively from a mean (± SD) 2.56±3.86 mg/mL to 4.11 mg/mL (P=0.007), and from 3.12±4.37 mg/mL to 5.23 mg/mL (P=0.005) (no change with placebo). On day 7 (day preceding allergen challenge), postdosing FEV1 increased by 2.0% with 50 mg (P=0.005) and 1.9% with 200 mg (P=0.008) (placebo -1.1%). ASM-24 had no inhibitory effect on early and late asthmatic responses, nor on sputum eosinophil or neutrophil levels. ASM-024 induced no serious adverse events, but caused cough in 22% and 48% of the subjects with 50 mg and 200 mg, respectively, compared with 10% who were on placebo.CONCLUSIONS:
ASM-024 did not inhibit allergen-induced asthmatic response and related airway inflammation, but reduced methacholine airway responsiveness and slightly improved lung function. The mechanism by which ASM-024 improves these outcomes requires further study.
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Asma
/
Broncodilatadores
/
Hipersensibilidade
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article