Clinical pharmacology of ponesimod, a selective S1P1 receptor modulator, after uptitration to supratherapeutic doses in healthy subjects

Biocomparison of THREE formulations of the S1P1 receptor modulator ponesimod in healthy subjects

“…Between Study 1 and Study 2, the increases in C max were dose proportional and the increases in AUC were slightly greater than dose proportional, which is in line with the findings of previous clinical studies performed with ponesimod [8][9][10][11]. Whereas similar exposure in male and female subjects has been seen previously [10], the findings of a recent study [11] are in good agreement with the greater exposure in female subjects that was observed in the present work.…”

“…The maximum decrease was observed 2.5 h after ponesimod administration, and the heart rate returned to baseline within 10 h, as previously observed [9][10][11]. When comparing Study 1 and Study 2, no clear dose-dependent effect was observed.…”

“…In terms of safety and tolerability, a similar incidence and nature of adverse events was observed in Study 1 and Study 2. No new findings were observed, in comparison with previous studies [7][8][9][10][11][12][13]. The incidence of adverse events and the percentage of subjects displaying adverse events were dose dependent.…”

“…Increases in C max are dose proportional, while increases in the area under the curve (AUC) are slightly greater than dose proportional [9][10][11]. A previous study [9] revealed low variability in pharmacokinetic parameters (inter-subject variability \36 %).…”

“…Single-and multiple-dose administration of ponesimod results in a dose-dependent decrease in circulating lymphocytes in healthy subjects and is associated with heart rate reduction, a delay in atrioventricular conduction, and pulmonary effects [9][10][11][12][13].…”