RESUMO
Trazpiroben, a dopamine D2 /D3 receptor antagonist under development to treat gastroparesis, displays decreasing solubility with increasing pH. This single-sequence, open-label, two-period, crossover study evaluated the effect of esomeprazole, a proton pump inhibitor that raises gastric pH, on the single-dose pharmacokinetics, safety, and tolerability of trazpiroben in healthy adults (NCT03849690). In total, 12 participants were enrolled and entered period 1 (days 1-3), receiving a single oral dose of trazpiroben 25 mg on day 1. After a 4-day washout, participants then entered period 2 (days 8-13) and received esomeprazole 40 mg once daily on days 8-12, with a single oral dose of trazpiroben 25 mg co-administered 1 h post esomeprazole dosing on day 11. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞ ) and maximum plasma concentration (Cmax ) values were generally similar when trazpiroben was administered alone versus alongside esomeprazole (AUC∞ , 44.03 vs. 38.85 ng h/ml; Cmax , 19.76 vs. 17.24 ng/ml). Additionally, the associated geometric mean ratio (GMR; co-administration: administration alone) 90% confidence intervals (CIs) suggested no clinically meaningful difference between treatment groups (AUC∞ , GMR 0.88, 90% CI 0.78-1.00; Cmax , 0.87, 90% CI 0.70-1.09). Mean apparent first-order terminal elimination half-life values were similar between treatments, illustrating co-administration with esomeprazole had minimal effect on trazpiroben elimination. Trazpiroben was well-tolerated in healthy adults following administration alone and alongside esomeprazole, with no clinically relevant adverse events reported. The lack of evidence of any clinically meaningful drug-drug interaction supports the co-administration of esomeprazole with trazpiroben.