Background and objectives <p>Iclepertin, a selective glycine transporter-1 inhibitor, was investigated as a potential treatment for cognitive impairment associated with schizophrenia. The objective of this trial was to determine the effect of food on the pharmacokinetics of iclepertin 10 mg.</p> Methods <p>This Phase I, open-label, 2-period cross-over trial randomised (1:1) healthy volunteers to 2 treatment sequences (fasted–fed or fed–fasted) to receive a single oral dose of iclepertin 10 mg once&#xa0;daily in either the fasted or fed state followed by cross-over to the other state. Primary endpoints included maximum measured concentration in plasma (<i>C</i>_max) and area under the concentration–time curve over the time interval from 0 to the last quantifiable data point (AUC_0–tz). The secondary endpoint was area under the concentration–time curve over the time interval from 0 extrapolated to infinity (AUC_0–inf). Relative bioavailability was estimated by calculating an adjusted geometric mean (gMean) fed/fasted ratio using analysis of variance. Safety was assessed.</p> Results <p>Of 16 participants enrolled [mean (SD) age: 37.1 (10.1) years], 15 were included in the analysis. The <i>C</i>_max, AUC_0–tz and AUC_0–inf of iclepertin were higher in the fed versus fasted state; adjusted gMean ratios (90% confidence intervals) were 118.33% (110.01, 127.28), 114.61% (110.13, 119.27) and 114.38% (110.11, 118.80), respectively. Iclepertin 10 mg was well tolerated.</p> Conclusion <p>Iclepertin exposure was higher in fed versus fasted conditions, but the increase was minor, suggesting food has no meaningful effect on the pharmacokinetics of iclepertin 10&#xa0;mg.</p> Study Registration <p>ClinicalTrials.gov (NCT05347004; registered: 20 April 2022).</p>