Format

Send to

Choose Destination
Clin Pharmacol Drug Dev. 2018 Mar;7(3):263-276. doi: 10.1002/cpdd.383. Epub 2017 Aug 7.

Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.

Author information

1
Receptos, a wholly owned subsidiary of Celgene Corporation, San Diego, California, USA.
2
Bioclinica Inc, London, UK.

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 (ΔΔQTcF). A total of 113/124 (91.1%) subjects completed the study. The upper limits of the 2-sided 90% confidence intervals for ΔΔQTcF 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 ΔΔQTcF. 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.

KEYWORDS:

cardiac repolarization; inflammatory bowel disease; multiple sclerosis; ozanimod; thorough QT/QTc study

PMID:
28783871
PMCID:
PMC5901414
DOI:
10.1002/cpdd.383
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center