A Randomized Trial on the Combined Effect of Ponesimod and Propranolol on Heart Rate, Cardiac Safety, and Pharmacokinetics in Healthy Adults.

ABSTRACT: The objective of this phase 1 study was to evaluate the pharmacokinetics (PK), pharmacodynamics, and cardiac effect following administration of ponesimod (a selective sphingosine-1-phosphate receptor modulator) and propranolol in healthy adults. In treatment period (TP) 1, participants received ponesimod (2 mg). In TP2, if resting heart rate (HR) was ≥ 55 bpm, the ponesimod up-titration regimen was initiated. Participants were randomized to TP2A (placebo plus ponesimod up-titration) or TP2B (80 mg propranolol plus ponesimod up-titration). Concomitant administration resulted in an increased bradyarrhythmic effect on HR versus ponesimod alone. The mean maximum difference in mean hourly HR from time-matched baseline for TP2B compared with TP2A during the first 12 h post-dose was -12.4 bpm. Th

SUBMITTER: Ouwerkerk-Mahadevan S 

PROVIDER: S-EPMC12413561 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature