J Clin Pharmacol. 2026 May;66(5):e70196. doi: 10.1002/jcph.70196.
ABSTRACT
Vorasidenib was first approved in 2024 for the treatment of Grade 2 gliomas with isocitrate dehydrogenase 1 and 2 mutations and is now approved in over 40 countries, including Japan. During early development, vorasidenib pharmacokinetics (PK) was estimated in populations without Japanese participants. In 2019, this Phase 1 single ascending (two levels) dose study (NCT04145128) was conducted to evaluate PK and safety of single oral 10- and 50-mg vorasidenib doses in healthy Japanese participants versus non-Asian participants to determine whether vorasidenib PK was ethnically sensitive. Thirty-two participants (16 Japanese, 16 non-Asian) were enrolled. After a single oral dose of 10 or 50 mg, vorasidenib was rapidly absorbed, distributed, and eliminated in a biexponential manner. Geometric mean maximum plasma concentration (Cmax), area under the concentration-time curve (AUC) from time 0 to last measurable concentration, and AUC from time 0 extrapolated to infinity were generally comparable between race and dose groups (geometric mean ratios: 1.00-1.38). There were no new safety concerns, deaths, serious adverse events (AEs), study-drug-related AEs, or discontinuations due to AEs. In conclusion, vorasidenib was generally safe and well tolerated, and plasma exposures were generally similar between Japanese and non-Asian participants following single oral 10- and 50-mg vorasidenib doses. These results enabled vorasidenib clinical development in Japan and supported inclusion of Japanese sites in subsequent vorasidenib clinical trials without dose adjustments.
PMID:42053456 | DOI:10.1002/jcph.70196
