Effect of Cladribine Tablets on the Pharmacokinetics of a Combined Oral Contraceptive in Pre-Menopausal Women With Relapsing Multiple Sclerosis.

This study assessed the effect of cladribine tablets (CladT) on the pharmacokinetics (PK) of a combined oral contraceptive (COC) in pre-menopausal women with relapsing multiple sclerosis. It was a randomized, double-blind, two-period, two-sequence crossover study to assess steady-state plasma PK (area under the concentration-time curve and peak concentration) of COC (ethinylestradiol [EE] 30 μg and levonorgestrel [LNG] 150 μg) when co-administered with CladT or placebo. Participants received 2 weeks of active CladT treatment per course (Weeks 1 and 5 per year) to have a cumulative dose of 3.5 mg/kg over 2 years as per label. Of the 24 randomized participants, 23 completed the study. The results showed that the concentration-time profiles as well as PK parameters of EE and LNG in the plasma were similar when co-administered with CladT or placebo. Analysis of variance confirmed the bioequivalence of EE and LNG in COC when co-administered with either CladT or placebo. All participants were adequately exposed to cladribine. Repeat-dose administration of CladT had no apparent effect on serum luteinizing hormone, follicle-stimulating hormone, progesterone, or sex hormone-binding globulin concentrations during concomitant treatment with COC. Co-administration with COC did not change the known safety and tolerability profile of CladT and did not alter the PK of EE or LNG in a COC during the study. Therefore, the concomitant use of CladT is not expected to decrease the efficacy of COCs containing EE and LNG. Trial Registration: EudraCT Number: 2018-001015-70.