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Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants

The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene‒related peptide receptor—in development for migraine prevention—is thus likely to be used by...

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Autores principales: Ankrom, Wendy, Xu, Jialin, Vallee, Marie‐Helene, Dockendorf, Marissa F., Armas, Danielle, Boinpally, Ramesh, Min, K. Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496689/
https://www.ncbi.nlm.nih.gov/pubmed/32297990
http://dx.doi.org/10.1002/jcph.1610
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author Ankrom, Wendy
Xu, Jialin
Vallee, Marie‐Helene
Dockendorf, Marissa F.
Armas, Danielle
Boinpally, Ramesh
Min, K. Chris
author_facet Ankrom, Wendy
Xu, Jialin
Vallee, Marie‐Helene
Dockendorf, Marissa F.
Armas, Danielle
Boinpally, Ramesh
Min, K. Chris
author_sort Ankrom, Wendy
collection PubMed
description The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene‒related peptide receptor—in development for migraine prevention—is thus likely to be used by women taking oral contraceptives. This phase 1, open‐label, single‐center, 2‐period, fixed‐sequence study examined the effect of multiple‐dose atogepant 60 mg once daily on the single‐dose pharmacokinetics of a combination oral contraceptive, ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg (EE/LNG), in healthy postmenopausal or oophorectomized women. For participants in period 1, a single dose of EE/LNG was followed by a 7‐day washout. In period 2, atogepant was given once daily on days 1‐17; an oral dose of EE/LNG was coadministered with atogepant on day 14. Plasma pharmacokinetic parameters for EE and LNG were assessed following administration with and without atogepant. Twenty‐six participants aged 45‐64 years enrolled; 22 completed the study in accordance with the protocol. The area under the concentration‐time curve extrapolated to infinity (AUC(0‐∞)) of LNG was increased by 19% when administered with atogepant. Coadministration of atogepant and a single dose of EE/LNG did not substantially alter the pharmacokinetics of EE; the ∼19% increase in plasma AUC(0‐∞) of LNG is not anticipated to be clinically significant. Overall, atogepant alone and in combination with EE/LNG was generally well tolerated, with no new safety signals identified.
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spelling pubmed-74966892020-09-25 Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants Ankrom, Wendy Xu, Jialin Vallee, Marie‐Helene Dockendorf, Marissa F. Armas, Danielle Boinpally, Ramesh Min, K. Chris J Clin Pharmacol NON COVID ARTICLES The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene‒related peptide receptor—in development for migraine prevention—is thus likely to be used by women taking oral contraceptives. This phase 1, open‐label, single‐center, 2‐period, fixed‐sequence study examined the effect of multiple‐dose atogepant 60 mg once daily on the single‐dose pharmacokinetics of a combination oral contraceptive, ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg (EE/LNG), in healthy postmenopausal or oophorectomized women. For participants in period 1, a single dose of EE/LNG was followed by a 7‐day washout. In period 2, atogepant was given once daily on days 1‐17; an oral dose of EE/LNG was coadministered with atogepant on day 14. Plasma pharmacokinetic parameters for EE and LNG were assessed following administration with and without atogepant. Twenty‐six participants aged 45‐64 years enrolled; 22 completed the study in accordance with the protocol. The area under the concentration‐time curve extrapolated to infinity (AUC(0‐∞)) of LNG was increased by 19% when administered with atogepant. Coadministration of atogepant and a single dose of EE/LNG did not substantially alter the pharmacokinetics of EE; the ∼19% increase in plasma AUC(0‐∞) of LNG is not anticipated to be clinically significant. Overall, atogepant alone and in combination with EE/LNG was generally well tolerated, with no new safety signals identified. John Wiley and Sons Inc. 2020-04-16 2020-09 /pmc/articles/PMC7496689/ /pubmed/32297990 http://dx.doi.org/10.1002/jcph.1610 Text en © 2020 Merck Sharp & Dohme Corp. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle NON COVID ARTICLES
Ankrom, Wendy
Xu, Jialin
Vallee, Marie‐Helene
Dockendorf, Marissa F.
Armas, Danielle
Boinpally, Ramesh
Min, K. Chris
Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants
title Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants
title_full Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants
title_fullStr Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants
title_full_unstemmed Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants
title_short Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants
title_sort atogepant has no clinically relevant effects on the pharmacokinetics of an ethinyl estradiol/levonorgestrel oral contraceptive in healthy female participants
topic NON COVID ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496689/
https://www.ncbi.nlm.nih.gov/pubmed/32297990
http://dx.doi.org/10.1002/jcph.1610
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