A Multi-Center, Open-Label, Pharmacokinetic Drug Interaction Study of Erenumab and a Combined Oral Contraceptive in Heal
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ORIGINAL RESEARCH ARTICLE
A Multi‑Center, Open‑Label, Pharmacokinetic Drug Interaction Study of Erenumab and a Combined Oral Contraceptive in Healthy Females Yang Xu1 · Kristin Gabriel1 · Yi Wang1 · Yanchen Zhou2 · Osaro Eisele1 · Apinya Vutikullird3 · Daniel D. Mikol1 · Edward Lee1 © The Author(s) 2019
Abstract Background Erenumab is a human anti-calcitonin gene-related peptide monoclonal antibody developed for migraine prevention. Migraine predominately affects women of childbearing age; thus, it is important to determine potential drug–drug interactions between a common oral contraceptive and drugs used to treat migraine. Objectives We sought to evaluate potential drug–drug interactions between erenumab and a common oral contraceptive. Methods Healthy women received three cycles of a norgestimate/ethinyl estradiol-containing oral contraceptive with a single 140-mg subcutaneous dose of erenumab during cycle three. Norgestimate metabolites (norgestrel and norelgestromin) and ethinyl estradiol pharmacokinetics were evaluated in the absence and presence of erenumab. Primary endpoint was peak plasma concentration (Cmax) and area under concentration-time curve from time 0 to 24 h (AUCtau). Luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations were evaluated as pharmacodynamic markers. Results Erenumab did not influence the pharmacokinetics of norelgestromin, norgestrel, or ethinyl estradiol. Least-squares mean estimates (90% confidence interval) for Cmax ratios were 1.05 (0.90–1.23), 1.06 (0.97–1.16), and 1.04 (0.88–1.22) for norelgestromin, norgestrel, and ethinyl estradiol, respectively. Respective AUCtau ratios were 1.02 (0.94–1.12), 1.03 (0.96–1.10), and 1.02 (0.91–1.14). Luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations were similar after exposure to oral contraceptive alone and with erenumab. Conclusion Erenumab did not alter the pharmacokinetics of the active components of an estrogen/progestin combination oral contraceptive. Thus, no change in contraceptive efficacy is expected with erenumab. Trial Registration ClinicalTrials.gov NCT02792517. Key Points
1 Introduction
Drug–drug interactions can impact the efficacy of oral contraceptives.
Erenumab (in the US, erenumab-aooe) is a human monoclonal antibody against the canonical calcitonin generelated peptide (CGRP) receptor developed for prevention of migraine [1, 2]. As a monoclonal antibody and not a cytokine modulator, pharmacokinetic-based drug–drug interaction of erenumab with low molecular weight concomitant medications are not expected. Nonetheless, given that migraine is most prevalent in women of childbearing age [3] and oral contraceptives are a common concomitant medication, the effects of erenumab on the pharmacokinetics of a commonly used combination oral contraceptive were evaluated. In this population, estrogen/progestin combination oral contraceptive (COC) is the most widely used method of contraception, of which the most commonly used comprises ethinyl estradiol as the es
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