JP2023513076A - チルゼパチドの治療的使用 - Google Patents
チルゼパチドの治療的使用 Download PDFInfo
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Abstract
Description
認知低下の発症または進行は、Montreal Cognitive Assessment(MoCA)およびDigit Symbol Substitution Test(DSST)などの認知力状態の測定の実施を通じて生成されるスコアに反映され得る。
拡張不全(HFpEF)は、駆出率-各心拍で左心室から排出される血液の量を左心室が最大に満たされたときの血液の量によって除算したもののパーセンテージ-が、正常であり、50%超と定義されている、心不全の形態である。HFpEFの発生率が増加しているにもかかわらず、HFpEFを効果的に治療するための取り組みはほとんど成功していない。
患者における認知障害の発症を治療、防止、または遅延させる方法であって、治療有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、患者に投与することを含む、方法。一実施形態では、認知障害は、MCIおよび認知症からなる群から選択される。
患者における心不全の発症を治療、防止、または遅延させる方法であって、治療有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、患者に投与することを含む、方法。一実施形態では、心不全は、HFpEFおよびHFrEFからなる群から選択される。
肥満およびHFpEFを有する患者において、52週間の3相最大耐量、最大15mg/週、6分歩行試験(「6MWT」)研究を行う。500人の患者の試料サイズは、プラセボとチルゼパチドで1:1にランダム化する(最大耐量は最大15mg/週)。研究は、6MWT、体重減少、Kansas City Cardiomyopathy Questionnaire(「KCCQ」)、Churg-Strauss Syndrome(「CSS」)、左心室容積指数(「LAVI」)、異所性心室頻脈(「EAT」)、および例えば、左心室(「LV」)ひずみ、LV筋重量係数を含む、目的の磁気共鳴画像診断(「MRI」)測定を測定するであろう。
2相研究(GPGB)では、15mg/週のチルゼパチドを投与されているチルゼパチド患者は、C反応性タンパク質(「CRP」)、血管細胞接着分子1(「VCAM-1」)、および細胞間接着分子-1(「ICAM-1」)の改善を示している。血漿コラーゲンタイプIII(「Pro-C3」)バイオマーカーの改善は、10mg/週および15mg/週の患者群で観察されている。
配列番号1
チルゼパチド
YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS
式中、X1が、Aibであり、X2が、Aibであり、20位のKが、(2-[2-(2-アミノ-エトキシ)-エトキシ]-アセチル)2-(γGlu)1-CO-(CH2)18-CO2HでのK側鎖のイプシロン-アミノ基への結合を通じて化学的に修飾され、C末端アミノ酸が、C末端一級アミドとしてアミド化されている。
Claims (29)
- 患者における認知障害の発症を治療、防止、または遅延させる方法であって、有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含む、方法。
- 前記認知障害が、MCIおよび認知症からなる群から選択される、請求項1に記載の方法。
- 患者における認知低下を防止または遅延させる方法であって、有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含む、方法。
- 前記患者が、2型糖尿病を有する、請求項1~3のいずれか一項に記載の方法。
- 2型糖尿病を有する患者における患者における血糖制御を改善し、認知低下を防止または遅延させる方法であって、有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含む、方法。
- 前記方法が、前記患者が認知低下を経験する危険性の低減を生じる、請求項1~5のいずれか一項に記載の方法。
- 2型糖尿病を有する患者における血糖制御を改善する方法であって、有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含み、前記方法が、前記患者が認知低下を経験する危険性の低減を生じる、方法。
- 前記患者の認知低下の危険性が、約14%低減される、請求項1~7のいずれか一項に記載の方法。
- 前記患者の、以下の転帰:認知低下、脳卒中、一過性脳虚血発作、または死亡の複合的な発生の危険性が低減される、請求項1~8のいずれか一項に記載の方法。
- 前記チルゼパチドの治療有効量が、約5.0mg、約10.0mg、および約15.0mgからなる群から選択される、請求項1~9のいずれか一項に記載の方法。
- 前記チルゼパチドの治療有効量が、約15.0mgである、請求項10に記載の方法。
- チルゼパチドの週1回の投与が、少なくとも2年間継続される、請求項1~11のいずれか一項に記載の方法。
- 前記患者が、心血管疾患に罹患しておらず複数の心血管危険因子を有するか、または心血管疾患に罹患しているかのいずれかである、請求項1~12のいずれか一項に記載の方法。
- 患者における心不全の発症を治療、防止、または遅延させる方法であって、有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含む、方法。
- 前記心不全が、HFrEFおよびHFpEFからなる群から選択される、請求項14に記載の方法。
- 前記心不全が、HFpEFである、請求項15に記載の方法。
- 患者におけるHFpEFを防止または遅延させる方法であって、有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含む、方法。
- 前記患者が、2型糖尿病を有する、請求項14~17のいずれか一項に記載の方法。
- 前記患者の体重が、肥満である、請求項14~18のいずれか一項に記載の方法。
- 前記患者の体重が、肥満ではない、請求項14~18のいずれか一項に記載の方法。
- 2型糖尿病を有する患者における患者における体重管理を改善し、HFpEFを防止または遅延させる方法であって、有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含む、方法。
- 前記方法が、HFpEFによる入院の危険性の低減を提供する、請求項14~21のいずれか一項に記載の方法。
- 有効量のチルゼパチドまたはその薬学的に許容される塩を週1回、前記患者に投与することを含み、前記方法が、HFpEFによる死亡の危険性の低減を生じる、請求項14~22のいずれか一項に記載の方法。
- 前記患者の6分歩行試験が、約10%改善される、請求項14~23のいずれか一項に記載の方法。
- 前記患者の、以下の転帰:認知低下、HFpEFによる入院、または死亡の複合的な発生の危険性が低減される、請求項14~24のいずれか一項に記載の方法。
- 前記チルゼパチドの治療有効量が、約5.0mg、約10.0mg、および約15.0mgからなる群から選択される、請求項14~25のいずれか一項に記載の方法。
- 前記チルゼパチドの治療有効量が、約15.0mgである、請求項26に記載の方法。
- チルゼパチドの週1回の投与が、少なくとも2年間継続される、請求項14~27のいずれか一項に記載の方法。
- 前記患者が、心血管疾患に罹患しておらず複数の心血管危険因子を有するか、または心血管疾患に罹患しているかのいずれかである、請求項14~28のいずれか一項に記載の方法。
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