Cenerimod, a sphingosine-1-phosphate 1 receptor modulator, is in development for the treatment of systemic lupus erythematosus, a disease mainly affecting women of childbearing potential. The effect of cenerimod on the pharmacokinetics (PK) of a combined oral contraceptive (COC, 100 µg levonorgestrel and 20 µg ethinylestradiol (EE)) was investigated. A randomized, double-blind, parallel-group study was performed in 24 healthy male and female subjects. A single oral dose of COC was administered alone and after 35 days of once daily (o.d.) administration of cenerimod 0.5 (n = 10) or 4 (n = 14) mg. Exposure to EE alone or in combination with cenerimod was comparable as reflected by the geometric mean ratios and the respective 90% confidence intervals, while a slight increase in exposure (approximately 10-25%) to levonorgestrel was observed at clinically relevant concentrations of cenerimod. Overall, COC alone or in combination with cenerimod was safe and well tolerated. Two subjects reported one adverse event each (one headache after COC alone, and gastroenteritis in combination with cenerimod 4 mg). In conclusion, cenerimod does not affect the PK of levonorgestrel or EE to a clinically relevant extent. Therefore, COC can be selected as method of contraception during and after cenerimod therapy without the risk of interaction.
Keywords: cenerimod; ethinylestradiol; levonorgestrel; pharmacokinetics; sphingosine-1-phosphate.