P112 Differences in AX-8 and placebo effects on cough bouts in refractory or unexplained chronic cough: a new count- and duration-based analysis

<h3>Background</h3> Previous analyses from the AX8–003 clinical study indicated that in patients with refractory or unexplained chronic cough (RCC/UCC) and throat discomfort (baseline visual analogue scale [VAS] score ≥55 mm), the TRPM8 agonist AX-8 reduced bout frequency (cough bouts are defined as clusters of ≥2 coughs separated by ≤2 seconds),¹ more effectively than cough frequency. This study further explores how AX-8 preferentially targets bouts, examining detailed count- and duration-based metrics. <h3>Methods</h3> This was a randomized, double-blind, placebo-controlled crossover study of RCC/UCC patients (≥1 year cough duration, cough severity VAS score ≥40 mm, and 24h cough frequency ≥10 coughs/h at screening). In the throat discomfort subgroup (n=24), we compared the effect of AX-8 (40 mg orally disintegrating tablet BID) versus placebo on cough and bout frequencies, as previously, as well as on single and bout cough frequencies, mean number of coughs per bout, and total and mean bout durations. Analyses below focus on the 4-hour period following the first dose on day 1. <h3>Results</h3> AX-8 showed a non-significant decrease in single cough frequency (15.5%, p&gt;0.2) but significantly reduced bout cough frequency (50.4%, p=0.001) without affecting the number of coughs per bout (p&gt;0.2). Placebo, conversely, moderately reduced the number of coughs per bout. In terms of cough duration, AX-8 significantly lowered the total bout duration (51.4%, p&lt;0.01), primarily by reducing bout frequency (p&lt;0.001) but not the mean bout duration (p&gt;0.1). In contrast, placebo’s small benefit arose from shortening the mean bout duration. <h3>Conclusion</h3> These data demonstrate that AX-8 selectively targets the initiation of bouts rather than single coughs, which are less important for RCC/UCC patients. The different effects of AX-8 and placebo on bout characteristics may reflect distinct underlying neurophysiological mechanisms. <h3>Clinical Trial Registry</h3> NCT04866563 <h3>Reference</h3> Holt KJ, <i>et al. ERJ Open Res.</i> 2024;<b>10</b>(6):00316–2024. https://doi.org/10.1183/23120541.00316-2024