THE EFFECT OF FOOD ON THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF ICLEPERTIN (BI 425809), A GLYCINE TRANSPORTER 1 INHIBITOR, IN HEALTHY VOLUNTEERS: A PHASE I OPEN-LABEL, RANDOMIZED, CROSSOVER TRIAL

Abstract Background Iclepertin (BI 425809) is a glycine transporter 1 inhibitor being developed for the treatment of cognitive impairment associated with schizophrenia (CIAS). Aims and Objectives To investigate the effect of food on the pharmacokinetics (PK) of iclepertin in healthy volunteers (HV). Methods This Phase I, open-label, two-period, two-sequence crossover trial included Caucasian HV (18–55 years of age). HV were randomized (1:1) to a single oral dose of iclepertin 10 mg (film-coated tablet) when fasted (reference, R) and following a standard high-fat, high-calorie meal (test, T), or received T then R. Iclepertin administrations were separated by a wash-out period of at least 14 days. The primary endpoints were area under the concentration– time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) and maximum measured concentration (Cmax) of iclepertin in plasma. The secondary endpoint was area under the concentration– time curve over the time interval from 0 extrapolated to infinity (AUC0-∞) of iclepertin in plasma. Relative bioavailability was estimated by calculating a geometric mean (gMean) T/R ratio using an analysis of variance. Safety and tolerability assessments included adverse event (AE) reporting; HVs with AEs were analysed descriptively. Results The 16 enrolled HV (9 women, 7 men) had a mean (standard deviation) age of 37.1 (10.1) years. The treatment adjusted gMean AUC0-tz, Cmax and AUC0-∞ and the adjusted gMean T/R ratios for the PK endpoints were higher following iclepertin 10 mg administration in the fed versus the fasted state (Table). Overall, 8/16 HV (50.0%) reported at least 1 AE; 6/16 HV (37.5%) reported drug-related AEs (fasted: 4/16 HV [25%]; fed: 3/15 HV [20.0%]) and headache was reported most frequently. Discussion and Conclusion Although the exposure (AUC0-tz, Cmax and AUC0-∞) and relative bioavailability of a single oral dose of iclepertin 10 mg was higher in the fed versus the fasted state, increases were deemed minor and not clinically meaningful. Further, iclepertin was generally well tolerated by Caucasian HV participating in this trial and no new safety signals were identified. These findings may be relevant to the Asian population (Rosenbrock et al., 2023). Funding Boehringer Ingelheim (1346-0053; NCT05347004). References Rosenbrock, H., Desch, M. and Wunderlich, G. (2023). Development of the novel GlyT1 inhibitor, iclepertin (BI 425809), for the treatment of cognitive impairment associated with schizophrenia. Eur Arch Psychiatry Clin Neurosci, 273(7), pp.1557–1566.