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新規脂肪酸アミド加水分解酵素阻害薬ASP3652のバイオマーカーを用いた医薬品開発に関する研究

滝澤, 昌臣 筑波大学 DOI:10.15068/0002005713

2022.11.28

概要

第1章では,ASP3652 の安全性,忍容性および薬物動態を評価するために First in human (FIH)試験として欧州健康成人を対象とし実施した第 I 相単回投与試験[3652- CL-0001]について記載した。この試験の中でバイオマーカーである FAAH 活性の評価も行った。

第 2 章では,3652-CL-0001 にて,ASP3652 単回投与時の安全性,忍容性,薬物動態およびFAAH 活性を確認した上で実施した欧州健康成人を対象とした第I 相反復投与試験[3652-CL-0002]について記載した。この試験においては,ASP3652 反復投与時の安全性,忍容性,薬物動態および薬力学(FAAH 活性,血漿中 AEA,Oleoylethanolamide(OEA)および Palmitoylethanolamide(PEA)濃度)を評価した(図 1.1)。

第 3 章では,日本人における ASP3652 の薬物動態およびバイオマーカーの調査をするために実施した日本人第 I 相単回および反復投与試験[3652-CL-0013]について記載した。この試験においては,日本人における安全性,忍容性,薬物動態および薬力学(FAAH 活性,血漿中 AEA,OEA,および PEA 濃度)を評価し,次相試験で用いる臨床試験での推定有効用量を検討した。

これらの結果を踏まえ,安全かつ忍容であり適切な薬理作用を示すと考えられる第II 相試験の用量推定を検討した。

第 4 章では,第 1 章から第 3 章までの結果から,臨床試験で用いる至適投与量を想定し,その用量において血中と脳脊髄液(CSF:Cerebrospinal fluid)中における薬物動態およびバイオマーカーの調査を行うために実施した欧州反復投与試験[3652-CL- 0048]を,さらに ASP3652 高用量投与におけるCNS への影響を評価するために実施した欧州単回投与試験[3652-CL-0049]について記載した。これらの試験では,ASP3652の CSF への移行性および CNS への影響を評価し,薬理作用に起因する可能性のある副作用の評価を行った。

第 5 章では,総括として 5.1 新規脂肪酸アミド加水分解酵素阻害薬 ASP3652のバイオマーカーを用いた医薬品開発と臨床試験計画に関する研究の総括ならびにバイオマーカーを用いた医薬品開発の重要性と臨床試験計画にかかわる考察について記載した。

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