Assessing the Effect of Food on the Pharmacokinetics of Iclepertin in Healthy Volunteers: A Phase I, Open-Label, Randomised, Cross-over Trial.

BACKGROUND AND OBJECTIVES

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.

METHODS

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 daily in either the fasted or fed state followed by cross-over to the other state. Primary endpoints included maximum measured concentration in plasma (C) and area under the concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC). The secondary endpoint was area under the concentration-time curve over the time interval from 0 extrapolated to infinity (AUC). Relative bioavailability was estimated by calculating an adjusted geometric mean (gMean) fed/fasted ratio using analysis of variance. Safety was assessed.

RESULTS

Of 16 participants enrolled [mean (SD) age: 37.1 (10.1) years], 15 were included in the analysis. The C, AUC and AUC 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.

CONCLUSION

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 mg.

STUDY REGISTRATION

ClinicalTrials.gov (NCT05347004; registered: 20 April 2022).