The complete bioavailability of asundexian is unaffected by tablet formulation, gastric pH or food

Abstract Background Anticoagulation and antiplatelet therapy, mainstays for the prevention of thromboembolic disorders, are associated with an increased bleeding risk. Asundexian, a novel, potent reversible oral inhibitor factor XIa, is independent extrinsic coagulation pathway thus not expected to increase Purpose To determine absolute bioavailability (FAB), assess impact gastric pH modulators, tablet formulation, food on PK safety asundexian. Methods Four studies enrolled healthy White males aged 18–45 years. For FAB (20463), participants received microdose 50 μg stable [13C7,15N]-labelled asundexian intravenously (iv) 2 hours after 25 mg orally in fasted state. The remaining randomized each 3 treatment sequences. Tablet formulation effects were explored 19663 21660; (immediate release [IR] vs amorphous solid dispersion [ASD] phase [Ph] [19663] or ASD Ph [21660]) states. Food effect was using tablets. Gastric modulators (omeprazole antacid) given state (20459). Blood samples taken over 72–96 post dose. Key parameters area under concentration/time curve (AUC; AUC/dose [D]) maximum observed concentration (Cmax; Cmax/D). derived as (AUC/D)oral/(AUC/D)iv. Relative (FR) from ratios (ASD 2:IR 3:ASD 2) AUC/D Cmax/D (fasted); modulation asundexian+pH modulator:asundexian fed:fasted AUC Cmax, respectively. Results data available 59 participants. Asundexian completely bioavailable (FAB, 103.9%). tablets exhibited FR 94.3% 95.1% compared IR tablet, results similar (95.5% 88.7%, respectively). A high-calorie, high-fat meal reduced Cmax 91.1% 78.3%, respectively tablet), 96.9% 95.1%, tablet). Coadministration omeprazole had no influence asundexian, whereas antacid slightly by 10% 16%, Geometric least-squares mean (90% confidence intervals) AUC(/D) Cmax(/D) shown Figure 1. There serious adverse events (AEs) deaths; most AEs mild moderate. Conclusions Orally administered almost bioavailable. First pass metabolism gut liver does play important role asundexian; there clinically relevant changes due conditions modulation. used guide dosing recommendations subsequent (completed) (planned) studies. Funding Acknowledgement Type funding sources: Private company. Main source(s): BAYER AG