Cardiovascular Evaluation of Etrasimod, a Selective Sphingosine 1 ‐phosphate Receptor Modulator, in Healthy Adults: Results of a Randomized, Thorough QT/QTc Study

AbstractEtrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator used as an oral treatment option for immune-mediated inflammatory disorders. This randomized, double-blind, placebo- and positive-controlled, parallel-group, healthy adult study investigated etrasimod's effect on the QT interval and other electrocardiogram parameters. All participants received etrasimod-matched placebo on day 1. Group A received once-daily, multiple ascending doses of etrasimod (2-4  mg) on days 1-14 and moxifloxacin-matched placebo on days 1 and 15. Group B received etrasimod-matched placebo on days 1-14 and either moxifloxacin 400 mg or moxifloxacin-matched placebo on days 1 and 15. The primary analysis was a concentration-QTc analysis using a corrected QT interval by Frid ericia (QTcF). The etrasimod concentration-QTc analysis predicted placebo-corrected change from baseline QTcF (ΔΔQTcF) values and associated 90% confidence intervals remained<10  milliseconds over the observed etrasimod plasma concentration range (≤279 ng/mL). Etrasimod was associated with mild, transient, asymptomatic heart rate slowing that was most pronounced on day 1 (2 mg, first dose). The largest-by-time point mean placebo-corrected changes in heart rate from tim e-matched day −1 baseline (∆∆HR) on days 1, 7 (2 mg, last dose), and 14 (4 mg, last dose) were −15.1, −8.5, and −6.0 bpm, respectively. Etrasimod's effects on PR interval were sma...
Source: Clinical Pharmacology in Drug Development - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research