Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma.

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.

• Authors: Louis-Philippe Boulet, Gail M Gauvreau, Donald W Cockcroft, Beth Davis, Luc Vachon, Yvon Cormier, Paul M O'Byrne
• Journal: Canadian respiratory journal (Can Respir J) 2015 Jul-Aug Vol. 22 Issue 4 Pg. 230-4 ISSN: 1916-7245 [Electronic] Egypt
• PMID: 26252534 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• ASM-024
• Allergens
• Bronchoconstrictor Agents
• Bronchodilator Agents
• Piperazines
• Methacholine Chloride

Topics

• Adolescent
• Adult
• Allergens
• Asthma (drug therapy, immunology)
• Bronchial Provocation Tests
• Bronchoconstrictor Agents
• Bronchodilator Agents (therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Eosinophils
• Female
• Forced Expiratory Volume
• Humans
• Hypersensitivity (drug therapy, immunology)
• Male
• Methacholine Chloride
• Middle Aged
• Neutrophils
• Piperazines (therapeutic use)
• Severity of Illness Index
• Sputum (cytology)
• Young Adult