JP2018534348A - 重水素化されたcftr増強剤の投与 - Google Patents
重水素化されたcftr増強剤の投与 Download PDFInfo
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- JP2018534348A JP2018534348A JP2018534496A JP2018534496A JP2018534348A JP 2018534348 A JP2018534348 A JP 2018534348A JP 2018534496 A JP2018534496 A JP 2018534496A JP 2018534496 A JP2018534496 A JP 2018534496A JP 2018534348 A JP2018534348 A JP 2018534348A
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Abstract
Description
本出願は、2015年9月21日に出願された米国仮特許出願第62/221,531号;2015年10月7日に出願された米国仮特許出願第62/238,511号;および2016年6月10日に出願された米国仮特許出願第62/348,855号の利益およびこれらに対する優先権を主張する。前述の出願の内容は、それらの全体が本明細書において参照として援用される。
多くの現代の薬は、そのより広範な使用を妨げるか、またはある特定の適応症にその使用を制限する、不十分な吸収、分布、代謝および/または排泄(ADME)特性に悩まされている。不十分なADME特性は、治験における薬物候補の失敗の主要な理由でもある。ある特定のADME特性を改善するために、製剤技術およびプロドラッグ戦略を用いることができる場合もあるが、これらの手法は、多くの薬物および薬物候補に存在する、根底にあるADMEの課題に対処することができないことが多い。1つのこのような課題は、急速な代謝であり、これは、そうでなければ疾患を処置するのに非常に有効であるいくつかの薬物が、身体からあまりに急速に排除される原因となる。急速な薬物クリアランスに対する可能な解決策は、十分に高い薬物の血漿レベルを達成するための、高頻度または高用量での投薬である。しかし、このことにより、患者の投薬レジメン遵守が不十分であること、高用量に伴いより急性になる副作用、および処置コストの増加などのいくつかの潜在的な処置課題が誘導される。急速に代謝された薬物は、望ましくない毒性または反応性の代謝物に患者をさらす場合もある。
多くの薬に影響を及ぼす別のADME制限は、毒性または生体反応性代謝物の形成である。結果として、薬物を受ける一部の患者は毒性を経験する場合があり、またはこのような薬物の安全な投与が制限され、その結果患者が最適以下の量の活性剤を受けることになる場合がある。ある特定の場合には、投与間隔または製剤手法を改変することが臨床上の有害作用を低減させる助けとなりうるが、このような望ましくない代謝物の形成は、化合物の代謝に固有のものである場合が多い。
アイバカフトールの有益な活性にもかかわらず、前述の疾患および状態を処置するために、新規化合物に対する必要性が継続して存在する。
ここで、アイバカフトールの重水素化された類似体(CTP−656、D9−アイバカフトールまたは化合物106とも称される化合物(I)、および化合物105またはD18−アイバカフトールとも称される化合物(II)を含む)が、被験体に投与された場合に、アイバカフトールと比較して向上された代謝プロファイルを有することが見出された。特に、化合物(I)の親の代謝物に対する比は、アイバカフトールに対して見られるプロファイルより大きい。化合物(I)は、以下の構造式:
一実施形態の本発明は、化合物(I)もしくは(II)、またはその薬学的に許容される塩を含むある特定の投薬レジメンおよびある特定の医薬組成物に関する、化合物(I)もしくは(II)、またはその薬学的に許容される塩の使用方法に関する。医薬組成物および投薬レジメンは、CFTR(嚢胞性線維症膜コンダクタンス制御因子)によって媒介される状態を処置するために有用である。特に、化合物(I)もしくは(II)、またはその薬学的に許容される塩ならびに医薬組成物および方法は、CFTRの活性を増強させる化合物によって処置することができる状態を処置するために有用である。
用語「処置する」は、疾患(例えば、本明細書で描写されている疾患または障害)の発症または進行を低下させる、抑制させる、減弱させる、消失させる、休止させる、または安定化させ、疾患の重症度を弱め、または疾患に伴う症状を改善することを意味する。
第1相、単一漸増用量(SAD)臨床試験
親対代謝物の薬物動態プロファイル
CTP−656およびアイバカフトール活性の測定
D9−アイバカフトールおよびD18−アイバカフトールに対するヒトのクロスオーバー研究
錠剤形態の調製
D9−アイバカフトールとアイバカフトールに対するヒトのクロスオーバー研究
D9−アイバカフトールに対するヒトの複数回漸増用量研究
Claims (13)
- 被験体における、CFTRによって媒介される状態を処置する方法であって、50mgから200mgの範囲の量の、以下の構造式:
- 前記状態が、嚢胞性線維症である、請求項1に記載の方法。
- 1日あたり、100mgの化合物(I)またはその薬学的に許容される塩を、前記被験体に投与することを含む、請求項1または2に記載の方法。
- 前記化合物が経口投与される、請求項1から3のいずれか一項に記載の方法。
- 前記化合物が、錠剤である医薬製剤で投与される、請求項4に記載の方法。
- 前記化合物が、顆粒剤である医薬製剤で投与される、請求項4に記載の方法。
- 上記の実施形態のいずれにおいても重水素として指定されていない任意の原子が、その天然の同位体存在度で存在する、請求項1から6のいずれか一項に記載の方法。
- 薬学的に許容される担体または希釈剤、および50mgから200mgの、以下の構造式:
- 100mgの化合物(I)を含む、請求項8に記載の医薬組成物。
- 前記医薬組成物が、経口投与に適している、請求項8または9に記載の医薬組成物。
- 前記組成物が、錠剤である、請求項8または9に記載の医薬組成物。
- 前記組成物が、顆粒剤である、請求項8または9に記載の医薬組成物。
- 前記組成物が、1日に1回投与される、請求項8から12のいずれか一項に記載の医薬組成物。
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KR20200097293A (ko) | 2017-12-08 | 2020-08-18 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막횡단 전도 조절자의 조정제의 제조 방법 |
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KR20180058745A (ko) | 2018-06-01 |
JP2021091723A (ja) | 2021-06-17 |
JP7196217B2 (ja) | 2022-12-26 |
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MA42950A (fr) | 2018-08-01 |
AU2022201135B2 (en) | 2024-03-28 |
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CA2998911C (en) | 2023-05-23 |
US20180353500A1 (en) | 2018-12-13 |
EP4292588A2 (en) | 2023-12-20 |
SG10201913588YA (en) | 2020-02-27 |
BR112018005454A2 (pt) | 2018-10-09 |
RU2018114447A3 (ja) | 2020-02-21 |
AU2016326441B2 (en) | 2021-11-25 |
WO2017053455A1 (en) | 2017-03-30 |
RU2018114447A (ru) | 2019-10-23 |
JP6849686B2 (ja) | 2021-03-24 |
IL257993A (en) | 2018-05-31 |
RU2761344C2 (ru) | 2021-12-07 |
EP3352757A4 (en) | 2018-08-01 |
CN108367002A (zh) | 2018-08-03 |
HK1258472A1 (zh) | 2019-11-15 |
EP3352757C0 (en) | 2023-08-16 |
AU2022201135A1 (en) | 2022-03-17 |
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