Evaluating the Safety, Tolerability, and Disposition of Trazpiroben, a D(2)/D(3) Receptor Antagonist: Phase I Single‐ and Multiple‐Ascending Dose Studies in Healthy Japanese Participants

Trazpiroben (TAK‐906) is a peripherally selective dopamine D(2)/D(3) receptor antagonist being developed to treat chronic gastroparesis. This phase I, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, parallel‐group study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of trazpiroben in healthy Japanese men. Findings were compared with those from a prior US trial in healthy individuals. Overall, 24 participants were enrolled into 3 cohorts (each n = 8). Per cohort, 6 participants received trazpiroben (cohort 1, 50 mg; 2, 100 mg; 3, 10 mg) once on day 1 and twice daily on days 3 through 7, and two received placebo. Trazpiroben was well tolerated, with no clinically meaningful adverse events observed. Following single‐ and multiple‐dose administration, trazpiroben was rapidly absorbed and eliminated (mean elimination half‐life, 1.89‐6.45 hours; median time to maximum serum concentration [steady state], 1.00‐1.25 hours). Serum prolactin increased with trazpiroben treatment (mean maximum serum concentration 93.32 ng/mL [10 mg] vs. 10.83 ng/mL [placebo]), illustrating receptor target engagement. Results reflected those from healthy US participants, indicating a lack of differences between these ethnic populations in trazpiroben disposition and safety profile. Trazpiroben may represent a promising therapy for chronic gastroparesis across different populations, with further evaluation ongoing in a phase IIb study (NCT03544229).