Siponimod pharmacokinetics, safety, and tolerability in combination with the potent CYP3A4 inhibitor itraconazole in healthy subjects with different CYP2C9 genotypes

PurposeTo evaluate the PK and safety of siponimod, a substrate of CYP2C9/3A4, in the presence or absence of a CYP3A4 inhibitor, itraconazole.MethodsThis was an open-label study in healthy subjects (aged 18–50 years; genotype: CYP2C9 *1*2 [cohort 1; n = 17] or *1*3 [cohort 2; n = 13]). Subjects received siponimod 0.25-mg single dose in treatment period 1 (days 1–14), itraconazole 100 mg twice daily in treatment period 2 (days 15–18), and …