title: Effect of oral siponimod (BAF312) on the pharmacokinetics and pharmacodynamics of a monophasic oral contraceptive in healthy female subjects.
abstract: OBJECTIVE
  To evaluate the effects of siponimod (BAF312) on the pharmacokinetics (PK) and pharmacodynamics (PD) of a monophasic oral contraceptive (OC).
  
  
  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(τ,ss) and C(max,ss) 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Shibadas
authors.initials: S
authors.lastname: Biswal
authors.forename: Uday Kiran
authors.initials: UK
authors.lastname: Veldandi
authors.forename: Caroline
authors.initials: C
authors.lastname: Derne
authors.forename: GangaRaju
authors.initials: G
authors.lastname: Golla
authors.forename: Naguib
authors.initials: N
authors.lastname: Muhsen
authors.forename: Eric
authors.initials: E
authors.lastname: Legangneux
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001384:Azetidines / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology*; D003276:Contraceptives, Oral / Q000493:pharmacokinetics* / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D016912:Levonorgestrel / Q000493:pharmacokinetics; D006080:Ovarian Follicle / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
chemical_list: D001384:Azetidines; D001593:Benzyl Compounds; D003276:Contraceptives, Oral; D012738:Sex Hormone-Binding Globulin; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D005640:Follicle Stimulating Hormone; C578989:siponimod