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

Abstract

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.