Effects of Asm‐024, A Modulator of Acetylcholine Receptor Function, On Airway Responsiveness and Allergen‐Induced Responses in Patients with Mild Asthma
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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.
