Clinical Pharmacokinetics of Atogepant in Healthy Japanese and White Adults.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY Neurology and Therapy Pub Date : 2025-02-01 Epub Date: 2025-01-04 DOI:10.1007/s40120-024-00699-2

Ramesh R Boinpally, Brian McNamee

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Abstract

Introduction: Atogepant is a calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults in the USA, EU, and several other countries. The objectives of this study were to evaluate the pharmacokinetics (PK) and dose proportionality of atogepant in healthy Japanese participants, evaluate the safety and tolerability of atogepant in Japanese participants, and explore the differences in the PK and safety of atogepant in Japanese vs white participants.

Methods: A total of 50 participants (40 Japanese and 10 white) were enrolled into five cohorts; Japanese cohorts were randomized in a 4:1 ratio to atogepant (10 mg, 30 mg, or 60 mg daily dosing and 60 mg twice daily) or placebo. The white participants were randomized to atogepant (60 mg twice daily) or placebo. Doses were administered on day 1 and days 3-8, with those on days 1 and 8 administered after an overnight fast.

Results: In Japanese participants, atogepant exposure increased with dose, and there was no accumulation with once-daily dosing and minimal (~ 20%) accumulation with twice-daily dosing. Atogepant steady-state exposure appeared to be marginally lower in Japanese participants compared with white participants and was well tolerated. There were no treatment-related adverse events, serious adverse events, clinically significant changes in vital signs, or signs of suicidal ideation or behaviors.

Conclusion: Atogepant exposure increased with dose in healthy Japanese participants and was well tolerated within the dose range tested.

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atgeagent在健康日本人和白人成人中的临床药代动力学。

atoggepant是一种降钙素基因相关肽受体拮抗剂，在美国、欧盟和其他几个国家被批准用于成人偏头痛的预防性治疗。本研究的目的是评价同聚剂在健康日本受试者中的药代动力学（PK）和剂量比例，评价同聚剂在日本受试者中的安全性和耐受性，并探讨同聚剂在日本与白人受试者中的PK和安全性差异。方法：50名参与者（40名日本人，10名白人）被分为5个队列；日本队列以4:1的比例随机分配给联合剂（每日10mg、30mg或60mg，每日两次60mg）或安慰剂。白人参与者被随机分配到atgeagent组（60毫克，每日两次）或安慰剂组。第1天和第3-8天给药，第1天和第8天给药，禁食一夜后给药。结果：在日本参与者中，增毒剂暴露量随剂量增加而增加，每日一次给药时没有积累，每日两次给药时最小（约20%）积累。与白人受试者相比，日本受试者的抗凝止剂稳态暴露似乎略低，并且耐受性良好。无治疗相关不良事件、严重不良事件、临床显著生命体征改变、自杀意念或行为的迹象。结论：在健康的日本参与者中，抗氧剂暴露量随剂量增加而增加，并且在试验剂量范围内耐受性良好。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Neurology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted, it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model, this allows for the rapid and efficient communication of the latest research and reviews to support scientific discovery and clinical practice. Open Access All articles published by Neurology and Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital Features and Plain Language Summaries Neurology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/ Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5250/$6000/£4300. The journal will consider fee discounts and waivers for developing countries and this is decided on a case-by-case basis. Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviews conflict, an Editorial Board Member will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed. Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised, it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments, if appropriate. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Copyright Neurology and Therapy is published under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0. Contact For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.