2023 Volume 54 Issue 5 Pages 197-203
Objective: To assess the safety, tolerability, and pharmacokinetics of belumosudil, a selective Rho-associated coiled-coil-containing protein kinase 2 inhibitor, in healthy Japanese male adults, a phase Ⅰ, randomized, double-blind, placebo-controlled trial was conducted.
Methods: In the single-dose study, 200, 400, or 800 mg of belumosudil or matching placebo was orally administered to 3 separate cohorts. In the multiple-dose study, 200 mg once daily, 200 mg twice daily, or 400 mg once daily of belumosudil or placebo was orally administered for 7 days to 3 separate cohorts. In each cohort, 8 participants were randomly assigned in a 3：1 ratio to receive belumosudil or placebo.
Results: In each cohort of the single-dose and multiple-dose studies, 6 participants received belumosudil and 2 received placebo. All participants completed the study. In the single-dose study, the increases in Cmax and AUC were almost linear between the doses of 200 and 400 mg, but were lower than dose-proportional at 800 mg. In the multiple-dose study, tmax and t1/2 on Day 7 were similar to those after single-dose administration, irrespective of the dosage regimen. Cmax and AUC increased as the dose increased. Accumulation of belumosudil after multiple administrations was minimal. In the single-dose and multiple-dose studies, 2 and 5 participants receiving belumosudil experienced adverse events, respectively. All adverse events were mild in severity, and no event led to study discontinuation.
Conclusion: The pharmacokinetic profiles of belumosudil in these studies were similar to those obtained from healthy volunteers in western countries. Belumosudil was well tolerated in both studies.
