ponesimod and Long-QT-Syndrome

ponesimod has been researched along with Long-QT-Syndrome* in 1 studies

Trials

1 trial(s) available for ponesimod and Long-QT-Syndrome

Article	Year
Effect of ponesimod, a selective S1P1 receptor modulator, on the QT interval in healthy individuals. Basic & clinical pharmacology & toxicology, 2015, Volume: 116, Issue:5 Ponesimod is an orally active selective sphingosine-1-phosphate receptor 1 modulator under investigation for the treatment of multiple sclerosis. This was a single-centre, double-blind, randomized, placebo- and positive-controlled parallel-group study investigating the effects of ponesimod on the QTc interval in healthy individuals. A nested cross-over comparison between moxifloxacin and placebo was included in the combined moxifloxacin/placebo treatment group. Subjects in group A received multiple doses of 10-100 mg ponesimod according to an uptitration regimen on days 2-23 and moxifloxacin-matching placebo on days 1 and 24. Subjects in group B received ponesimod-matching placebo on days 2-23 and were randomized to receive either a single dose of 400 mg moxifloxacin or matching placebo on days 1 and 24. The primary end-point was the baseline-adjusted, placebo-corrected effect on the individually corrected QT interval (QTcI) on days 12 (after 5 days of 40 mg ponesimod) and 23 (after 5 days of 100 mg ponesimod). Ponesimod caused a mild QTcI prolongation with a largest effect of 6.9 ms (90% two-sided confidence interval (CI): 2.5-11.3) and 9.1 ms (90% CI: 4.1-14.0) for doses of 40 mg and 100 mg, respectively. A concentration-effect analysis confirmed the QTcI-prolonging effect of ponesimod with a shallow slope of 0.0053 ms per ng/mL. Using the concentration-effect analysis, the QTc prolongation caused by 20 mg ponesimod and the current highest therapeutic dose was predicted to be below the level of clinical concern (i.e. an upper bound of the two-sided 90% CI of ≥10 ms). Topics: Action Potentials; Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Electrocardiography; Female; Fluoroquinolones; Healthy Volunteers; Heart Conduction System; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; Moxifloxacin; Receptors, Lysosphingolipid; Risk Assessment; Sphingosine-1-Phosphate Receptors; Thiazoles; Time Factors; Young Adult	2015

Article

Year

Effect of ponesimod, a selective S1P1 receptor modulator, on the QT interval in healthy individuals.

Basic & clinical pharmacology & toxicology, 2015, Volume: 116, Issue:5

Ponesimod is an orally active selective sphingosine-1-phosphate receptor 1 modulator under investigation for the treatment of multiple sclerosis. This was a single-centre, double-blind, randomized, placebo- and positive-controlled parallel-group study investigating the effects of ponesimod on the QTc interval in healthy individuals. A nested cross-over comparison between moxifloxacin and placebo was included in the combined moxifloxacin/placebo treatment group. Subjects in group A received multiple doses of 10-100 mg ponesimod according to an uptitration regimen on days 2-23 and moxifloxacin-matching placebo on days 1 and 24. Subjects in group B received ponesimod-matching placebo on days 2-23 and were randomized to receive either a single dose of 400 mg moxifloxacin or matching placebo on days 1 and 24. The primary end-point was the baseline-adjusted, placebo-corrected effect on the individually corrected QT interval (QTcI) on days 12 (after 5 days of 40 mg ponesimod) and 23 (after 5 days of 100 mg ponesimod). Ponesimod caused a mild QTcI prolongation with a largest effect of 6.9 ms (90% two-sided confidence interval (CI): 2.5-11.3) and 9.1 ms (90% CI: 4.1-14.0) for doses of 40 mg and 100 mg, respectively. A concentration-effect analysis confirmed the QTcI-prolonging effect of ponesimod with a shallow slope of 0.0053 ms per ng/mL. Using the concentration-effect analysis, the QTc prolongation caused by 20 mg ponesimod and the current highest therapeutic dose was predicted to be below the level of clinical concern (i.e. an upper bound of the two-sided 90% CI of ≥10 ms).

Topics: Action Potentials; Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Electrocardiography; Female; Fluoroquinolones; Healthy Volunteers; Heart Conduction System; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; Moxifloxacin; Receptors, Lysosphingolipid; Risk Assessment; Sphingosine-1-Phosphate Receptors; Thiazoles; Time Factors; Young Adult

2015