No abstract

Background: Ponesimod is a potent, orally active, selective, reversible sphingosine-1-phosphate receptor 1 (S1P 1 ) modulator. Singledose administration of ponesimod leads to a reduction of circulating lymphocytes reflecting their sequestration within lymphoid organs. Modulation of the S1P 1 receptor has been described to be an effective treatment of autoimmune diseases (eg, multiple sclerosis). The aim of these studies was to compare the relative bioavailability of two polymorphic forms of ponesimod in capsules (Form A vs. C, Study 1) and of a capsule vs. a tablet formulation (both of polymorphic Form C, Study 2).Methods: Two open-label, randomized, two-way crossover studies in healthy subjects were performed. In Study 1, 12 male and female (ratio 1:1) subjects received a single dose of ponesimod (20 mg) of polymorphic Form A and C in capsules. In Study 2, 14 male subjects received a single administration of ponesimod (Form C, 40 mg) either in a capsule or a tablet formulation. Pharmacokinetic and safety (clinical laboratory, vital signs, and electrocardiogram) variables were assessed. Results: When comparing the exposure to ponesimod following the formulations in Study 1, the geometric mean ratios for AUC 0-∞ , AUC 0-t , t 1/2 , and C max and the responding 90% CIs were all within the 0.80 to 1.25 interval. In Study 2, a more rapid absorption of ponesimod was observed with the tablet compared to the capsule formulation. There was no marked difference in the nature, severity, and incidence of adverse events reported for the different formulations in Study 1 and Study 2. However, a dose relationship regarding the number of adverse events reported was observed. Conclusions: The 2 polymorphic forms of ponesimod and the tablet versus capsule formulation were similar in terms of PK, except the more rapid absorption of the tablet formulation. At the same dose strength safety and tolerability were similar.