title: Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma.
abstract: OBJECTIVE
  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.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.forename: Donald W
authors.initials: DW
authors.lastname: Cockcroft
authors.forename: Beth
authors.initials: B
authors.lastname: Davis
authors.forename: Luc
authors.initials: L
authors.lastname: Vachon
authors.forename: Yvon
authors.initials: Y
authors.lastname: Cormier
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009504:Neutrophils; D010879:Piperazines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology; D055815:Young Adult
chemical_list: C000603639:ASM-024; D000485:Allergens; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D010879:Piperazines; D016210:Methacholine Chloride