Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator

Clin Pharmacol Drug Dev. 2018 Aug;7(6):634-640. doi: 10.1002/cpdd.409. Epub 2017 Nov 10.

Abstract

Ozanimod (RPC1063) is an oral selective modulator of the sphingosine-1-phosphate 1 and 5 receptors under development for the treatment of relapsing multiple sclerosis and inflammatory bowel disease. The effects of high-fat and low-fat meals on the pharmacokinetics (PK) of a single oral dose of ozanimod were evaluated in 24 healthy volunteers in a randomized, open-label crossover trial. Each subject received a 1-mg dose of ozanimod hydrochloride under 3 meal conditions (fasted, high-fat, and low-fat), each separated by 7 days. Mean plasma concentration-time profiles for ozanimod and its active metabolites (RP101988 [major], RP101075 [minor]) were similar under all 3 conditions. Moreover, all PK parameters for ozanimod, RP101988, and RP101075 were similar under the 3 meal conditions. The 90% confidence intervals (CIs) for the ratios of geometric least-squares mean (fed/fasted) were within the equivalence limits of 0.80 to 1.25 for area under the concentration-time curve from time 0 to infinity (AUC0-∞ ) and maximum plasma concentration (Cmax ) for ozanimod, RP101988, and RP101075, except for the high-fat effect on RP101075 Cmax (90%CI, 0.76-0.88). Given this lack of a food effect on the exposure of ozanimod and its active metabolites, ozanimod can be taken without regard to meals.

Keywords: bioavailability; clinical trial; food effects; ozanimod; pharmacokinetics.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Cross-Over Studies
  • Diet, Fat-Restricted*
  • Diet, High-Fat*
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Female
  • Food-Drug Interactions*
  • Healthy Volunteers
  • Humans
  • Indans / administration & dosage
  • Indans / blood
  • Indans / pharmacokinetics*
  • Male
  • Middle Aged
  • Oxadiazoles / administration & dosage
  • Oxadiazoles / blood
  • Oxadiazoles / pharmacokinetics*
  • Receptors, Lysosphingolipid / metabolism*
  • Young Adult

Substances

  • Indans
  • Oxadiazoles
  • Receptors, Lysosphingolipid
  • ozanimod