Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.
Article Details
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Tran JQ, Hartung JP, Olson AD, Mendzelevski B, Timony GA, Boehm MF, Peach RJ, Gujrathi S, Frohna PA
Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.
Clin Pharmacol Drug Dev. 2018 Mar;7(3):263-276. doi: 10.1002/cpdd.383. Epub 2017 Aug 7.
- PubMed ID
- 28783871 [ View in PubMed]
- Abstract
Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17. The primary end point was the time-matched, placebo-corrected, baseline-adjusted mean QTcF (DeltaDeltaQTcF). A total of 113/124 (91.1%) subjects completed the study. The upper limits of the 2-sided 90% confidence intervals for DeltaDeltaQTcF for both ozanimod 1 and 2 mg were below the 10-millisecond regulatory threshold. No QTcF >480 milliseconds or postdose change in QTcF of >60 milliseconds was observed. There was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and DeltaDeltaQTcF. Although ozanimod blunted the observed diurnal increase in heart rate, excursions below predose heart rates were no greater than with placebo. Results demonstrate that ozanimod does not prolong the QTc interval or cause clinically significant bradycardia, supporting ozanimod's evolving favorable cardiac safety profile.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Ozanimod Alcohol dehydrogenase class-3 Protein Humans NoSubstrateDetails Ozanimod Fatty aldehyde dehydrogenase Protein Humans NoSubstrateDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Ozanimod P-glycoprotein 1 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareOzanimodBeclomethasone dipropionate Beclomethasone dipropionate may decrease the excretion rate of Ozanimod which could result in a higher serum level. OzanimodImatinib Imatinib may decrease the excretion rate of Ozanimod which could result in a higher serum level. OzanimodSulfasalazine Sulfasalazine may decrease the excretion rate of Ozanimod which could result in a higher serum level. OzanimodDexamethasone Dexamethasone may decrease the excretion rate of Ozanimod which could result in a higher serum level. OzanimodDasatinib Dasatinib may decrease the excretion rate of Ozanimod which could result in a higher serum level.