Delayed-Release Dimethyl Fumarate Does Not Adversely Affect the Pharmacokinetics of a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women: Drug-Drug Interaction Study Results (P2.097)

OBJECTIVE: To evaluate the effect of delayed-release dimethyl fumarate (DMF), a multiple sclerosis (MS) therapeutic, on the pharmacokinetics (PK) of a commonly used oral contraceptive (OC; norgestimate/ethinyl estradiol) in healthy women. BACKGROUND: As women of childbearing age comprise a large proportion of the MS population, it is important to study the potential drug-drug interaction between DMF and OCs. DESIGN/METHODS: 46 healthy volunteers were enrolled and 32 completed this randomized, open-label, crossover study. All subjects received OC once daily (QD) in the Lead-in Period; eligible subjects were then randomized 1:1 to one of two treatment sequences. In Sequence 1, subjects received OC QD and DMF 240 mg twice daily (OC+DMF) in Period 1, then OC QD alone in Period 2. In Sequence 2, these regimens were reversed. Each period was 28 days in duration; DMF was administered only for the first 21 days when applicable. To evaluate the PK profiles of norgestimate (via its primary metabolite, norelgestromin) and ethinyl estradiol, blood samples were collected pre-dose and at multiple time points (up to 24 hours) post-first dose on Day 21 of both treatment periods. RESULTS: Mean plasma norelgestromin and ethinyl estradiol concentration profiles were superimposable following OC alone and OC+DMF treatments. There was no statistically significant effect of DMF on the PK parameters of norelgestromin and ethimyl estradiol, with 90[percnt] confidence intervals of geometric mean ratios for AUC0-τ and Cmax contained within the 0.8 to 1.25 range. The median values of plasma progesterone, a pharmacodynamic endpoint, were also comparable for each treatment (OC alone and OC+DMF). In addition, the safety profile of concurrent use of OC and DMF was consistent with that observed for DMF in previous studies. CONCLUSIONS: No impact of DMF on the PK or PD of norgestimate/ethinyl estradiol was observed. Study Supported by: Biogen Disclosure: Dr. Zhu holds stock and/or stock options in Biogen Idec. Dr. Galil has received personal compensation for activities with Biogen as a consultant. Dr. Nestorov holds stock and/or stock options in Biogen Idec. Dr. Zhao holds stock and/or stock options in Biogen Idec. Dr. Meka has received personal compensation for activities with Biogen as an employee. Dr. Meka holds stock and/or stock options in Biogen, which sponsored research in which Dr. Meka was involved as an investigator. Dr. Kam has received personal compensation for activities with Covance as an employee. Dr. Sheikh holds stock and/or stock options in Biogen Idec.