書誌事項
- タイトル別名
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- Consideration from the Smallest Starting Dose Used in Clinical Trials and the Approved Minimum Clinical Dose for Microdose of Antibody Pharmaceuticals in Japan
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説明
<p>Microdose (MD) clinical study for antibody pharmaceuticals has not been defined by any guidance. The exploratory investigational new drug application (IND) guidance published in 2006 by the Food and Drug Administration (FDA) defined MD for protein products as less than 1/100th of the therapeutic range or 30 nanomoles. In Japanese domestic guidances for MD studies (2008) including ICH-M3R2, definition of MD is provided for low molecular weight compounds but not for biologics. In this study, we examined retrospectively the starting dose in first-in-human (FIH) clinical trials of antibody pharmaceuticals.</p><p>We studied 52 antibody agents listed in the website of National Institute of Health Sciences as of October 2018, which were approved in Japan. We searched the online databases including the Pharmaceuticals and Medical Devices Agency (PMDA) website and reviewed the information from package inserts, interview forms, and review reports.</p><p>We defined the lowest approved therapeutic dose as minimum clinical dose (MIN), and the smallest starting dose used in clinical trials as first human dose (FHD). In 45 of 52 agents, FHD was greater than 1/100th of MIN. FHD was less than 100 micrograms in 3 agents. Also, FHD was approximately 30 nanomoles in 10 agents and exceeding 30 nanomoles in 38 agents.</p><p>FHD is usually selected assuming to be just below the lower limit of the therapeutic range. The MD is expected to be lower than the dose expected not to exert any pharmacological actions. One hundred microgram or 30 nanomole appears to be low enough as MD for antibody pharmaceuticals, and may be set as one of the starting doses for clinical trials.</p>
収録刊行物
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- 臨床薬理
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臨床薬理 51 (1), 1-10, 2020-01-31
一般社団法人 日本臨床薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390283659853060224
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- NII論文ID
- 130007800437
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- ISSN
- 18828272
- 03881601
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
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