METHODS: In this phase 1, open-label, randomized, two-period crossover study, healthy adults aged 18-55 years were given a single dose of revexepride 1 mg or revexepride 1 mg + omeprazole 40 mg. Pharmacokinetic parameters were assessed for up to 48 hours after administration of the investigational product. Adverse events, clinical chemistry and hematology parameters, electrocardiograms, and vital signs were monitored.
RESULTS: In total, 42 participants were enrolled and 40 completed the study. The median age was 24 years (18-54 years), 55% were women and 93% were white. The pharmacokinetic parameters of revexepride were similar without or with omeprazole co-administration. The mean area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) was 23.3 ng · h/mL (standard deviation [SD]: 6.33 ng · h/mL) versus 24.6 ng · h/mL (SD: 6.31 ng · h/mL), and maximum plasma concentrations (Cmax) were 3.89 ng/mL (SD: 1.30 ng/mL) and 4.12 ng/mL (SD: 1.29 ng/mL) in participants without and with omeprazole, respectively. For AUC0-∞ and Cmax, the 90% confidence intervals for the ratios of geometric least-squares means (with:without omeprazole) were fully contained within the pre-defined equivalence limits of 0.80-1.25. Mean apparent terminal phase half-life was 9.95 hours (SD: 2.06 hours) without omeprazole, and 11.0 hours (SD: 3.25 hours) with omeprazole.
CONCLUSIONS: Co-administration of the 5-hydroxytryptamine receptor 4 agonist revexepride with omeprazole did not affect the pharmacokinetics of revexepride in healthy adults.