Effect of oral siponimod (BAF312) on the pharmacokinetics and pharmacodynamics of a monophasic oral contraceptive in healthy female subjects.

OBJECTIVE: To evaluate the effects of siponimod (BAF312) on the pharmacokinetics (PK) and pharmacodynamics (PD) of a monophasic oral contraceptive (OC). MATERIALS AND METHODS: This was a phase 1 single-center open-label multipledose single-sequence study in healthy females. Eligible subjects (n = 23) were exposed sequentially to two treatment periods: period 1 (OC alone) and period 2 (OC + siponimod) in two consecutive menstrual periods. PK parameters were assessed on day 21 of both treatment periods. Follicle-stimulating hormone (FSH) luteinizing hormone (LH) estradiol and progesterone concentrations were measured at baseline and days 3 6 8 11 14 16 19 21 and 23 of each period. Largest ovarian follicle size and sex hormone-binding globulin (SHBG) concentration were measured and Hoogland score was calculated at baseline and day 21 of each period. Safety and tolerability of siponimod was also assessed. RESULTS: Co-administration (OC + siponimod) increased the AUC(tauss) and C(maxss) of levonorgestrel by 28% and 18% respectively but had no effect on the PK of ethinylestradiol. No significant changes in estradiol FSH and LH were noted with co-administration vs. OC alone. Progesterone levels < 5 nmol/L largest follicle size < 10 mm and Hoogland score of 1 on day 21 indicated lack of ovulation in all subjects during co-administration. Co-administration was well tolerated. CONCLUSION: In conclusion PK and PD of the OC were not altered to a clinically significant extent and contraceptive efficacy was maintained with co-administration. Hence OC as a contraceptive measure can be safely co-administered with siponimod.