Pharmacokinetics, Safety and Tolerability of Siponimod (BAF312) in Subjects with Different Levels of Hepatic Impairment Compared to Demographically Matched Healthy Subjects (P1.135)

• DOI: 10.1212/wnl.84.14_supplement.p1.135
• Publication Date: 2023-12-06T23:42:28Z
• Authors: Kasra Shakeri-Nejad; Vassilios Aslanis; Uday Kiran Veldandi; Anne Gardin; Andreas Zaehringer; Angela Dodman; Zhenzhong Su; Eric Legangneux
• Keywords: Tolerability

OBJECTIVE:To assess the pharmacokinetics (PK), safety and tolerability of siponimod major metabolites in subjects with mild, moderate severe hepatic impairment (HI) versus healthy (HS). BACKGROUND:Following oral administration, is mainly eliminated by metabolism biliary excretion. Alterations excretory/metabolic activities due to HI can lead drug/metabolite accumulation an extent that may require dosage adjustment. METHODS:This was open-label, parallel-group study, 8 each moderate, demographically matched HS (n=16). Enrollment staggered starting mild followed groups upon interim analysis. The study consisted a screening period (Days -21 -2), baseline (Day -1), treatment 1, 0.25mg siponimod), 21-day follow-up during which PK (total/unbound siponimod, M3 M5) data were collected. RESULTS:All 40 enrolled completed study. Baseline characteristics similar. No significant changes plasma exposure observed HI groups vs. HS: Cmax changed 16[percnt], -13[percnt], -16[percnt]; AUC 5[percnt], 15[percnt], respectively. unbound similar increased 15[percnt] 17[percnt] respectively 11[percnt] 50[percnt] HI. AUCinf 3-5 folds higher HS, whereas, M5 AUClast 2-fold group. Three AEs intensity (2 1 related siponimod) reported. CONCLUSIONS:Single doses well tolerated did not significantly alter siponimod. Increase requires further evaluation. Study Supported Novartis Pharma AG Disclosure: Dr. Shakeri-Nejad has received personal compensation for as employee. Aslanis Veldandi Gardin Zaehringer Dodman Su Legangneux