JPWO2020102628A5 - - Google Patents

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JPWO2020102628A5
JPWO2020102628A5 JP2021526553A JP2021526553A JPWO2020102628A5 JP WO2020102628 A5 JPWO2020102628 A5 JP WO2020102628A5 JP 2021526553 A JP2021526553 A JP 2021526553A JP 2021526553 A JP2021526553 A JP 2021526553A JP WO2020102628 A5 JPWO2020102628 A5 JP WO2020102628A5
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pharmaceutical composition
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Priority claimed from PCT/US2019/061626 external-priority patent/WO2020102628A1/en
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約２４０ｍｇの以下の式の化合物：About 240 mg of a compound of the formula:
Figure 2020102628000001
Figure 2020102628000001
 、及び,as well as
約１２ｍｇの以下の式の化合物：About 12 mg of a compound of the formula:
Figure 2020102628000002
Figure 2020102628000002
 を含む、対象におけるパーキンソン病の治療に使用するための医薬組成物であって、パーキンソン病患者の集団に前記組成物を連続皮下投与することにより、投与後２～１６時間の期間にわたって約０．３以下の変動度を有するレボドパの平均血漿濃度が達成され、変動度は、所与の期間に関して（［ＣA pharmaceutical composition for use in treating Parkinson's disease in a subject comprising, by continuous subcutaneous administration of said composition to a population of Parkinson's disease patients, about 0.0. Mean plasma concentrations of levodopa with a variability of ≤3 were achieved, the variability being ([C ｍａｘmax －Ｃ-C ｍｉｎmin ／Ｃ/C ａｖｅave ］）として定義される、医薬組成物。]). 約６．５～約９．２のｐＨを有する、請求項１に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 1, having a pH of about 6.5 to about 9.2. 約６．８～約７．８のｐＨを有する、請求項２に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 2, having a pH of about 6.8 to about 7.8. 約９％未満の酸素を有する１０ｃｃのバイアル中にパッケージングされ、かつ、１気圧で２℃～８℃の温度で保存した場合に、少なくとも３ヶ月間安定である、請求項３に記載の使用のための医薬組成物。4. Use according to claim 3, which is stable for at least 3 months when packaged in a 10 cc vial with less than about 9% oxygen and stored at a temperature of 2°C to 8°C at 1 atmosphere. A pharmaceutical composition for 酸化防止剤を実質的に含まない、請求項４に記載の使用のための医薬組成物。5. A pharmaceutical composition for use according to claim 4, substantially free of antioxidants. ２５℃で５日間、続いて、５℃で３０日間保存した後に、約１５マイクログラム／ｍＬ未満のヒドラジンを含む、請求項４に記載の使用のための医薬組成物。5. The pharmaceutical composition for use according to claim 4, comprising less than about 15 micrograms/mL of hydrazine after storage at 25[deg.]C for 5 days followed by 5[deg.]C for 30 days. ヒト成人の集団に前記組成物を連続皮下投与することにより、投与後２～７２時間にわたって約０．４０の変動度を有するレボドパの平均血漿濃度が達成される、請求項１に記載の使用のための医薬組成物。The use of claim 1, wherein continuous subcutaneous administration of said composition to a human adult population achieves a mean plasma concentration of levodopa with a variability of about 0.40 over 2-72 hours after administration. A pharmaceutical composition for 前記使用では、前記使用の１０日後に皮膚結節発生の発生率なしである、請求項１に記載の使用のための医薬組成物。2. A pharmaceutical composition for use according to claim 1, wherein said use has no incidence of skin nodule development after 10 days of said use. ヒト成人に投与された場合に、ＡＵＣ（When administered to human adults, the AUC ( ０－ｔ0-t ）対ＡＵＣ（) versus AUC ( ０－ｔ0-t ）によって測定された６．５７～８．０３のレボドパ対約１のカルビドパのレボドパ対カルビドパの平均血漿曝露比を提供する、請求項１に記載の使用のための医薬組成物。2. The pharmaceutical composition for use according to claim 1, which provides a mean plasma exposure ratio of levodopa to carbidopa of 6.57 to 8.03 levodopa to carbidopa of about 1, as measured by ). 約２４０ｍｇの以下の式の化合物：About 240 mg of a compound of the formula:
Figure 2020102628000003
Figure 2020102628000003
 、及び,as well as
約１２ｍｇの以下の式の化合物：About 12 mg of a compound of the formula:
Figure 2020102628000004
Figure 2020102628000004
 を含む、パーキンソン病患者における運動変動（ｍｏｔｏｒ ｆｌｕｃｔｕａｔｉｏｎ）の治療に使用するための医薬組成物であって、パーキンソン病患者の集団に前記医薬組成物を連続皮下投与することにより、ベースラインからのオフ時間の約４６％の平均パーセントの改善が達成される、医薬組成物。1. A pharmaceutical composition for use in the treatment of motor fluctuation in Parkinson's disease patients, said pharmaceutical composition comprising: A pharmaceutical composition wherein an average percent improvement of about 46% of the time is achieved. 約６．５～約９．２のｐＨを有する、請求項１０に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 10, having a pH of about 6.5 to about 9.2. 約６．８～約７．８のｐＨを有する、請求項１１に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 11, having a pH of about 6.8 to about 7.8. 約９％未満の酸素を有する１０ｃｃのバイアル中にパッケージングされ、かつ、１気圧で２℃～８℃の温度で保存した場合に、少なくとも３ヶ月間安定である、請求項１１に記載の使用のための医薬組成物。12. Use according to claim 11, which is stable for at least 3 months when packaged in a 10 cc vial with less than about 9% oxygen and stored at a temperature of 2°C to 8°C at 1 atmosphere. A pharmaceutical composition for 酸化防止剤を実質的に含まない、請求項１３に記載の使用のための医薬組成物。14. A pharmaceutical composition for use according to claim 13, which is substantially free of antioxidants. ２５℃で５日間、続いて、５℃で３０日間保存した後に、約１５マイクログラム／ｍＬ未満のヒドラジンを含む、請求項１０に記載の使用のための医薬組成物。11. The pharmaceutical composition for use according to claim 10, comprising less than about 15 micrograms/mL of hydrazine after storage at 25[deg.]C for 5 days followed by 5[deg.]C for 30 days. ヒト成人の集団に前記組成物を連続皮下投与することにより、投与後２～７２時間にわたって約０．４０の変動度を有するレボドパの平均血漿濃度が達成され、変動度は、所与の期間に関して（［ＣContinuous subcutaneous administration of the composition to a human adult population achieves mean plasma concentrations of levodopa with a variability of about 0.40 over 2-72 hours post-dose, the variability being ([C ｍａｘmax －Ｃ-C ｍｉｎmin ／Ｃ/C ａｖｅave ］）として定義される、請求項１０に記載の使用のための医薬組成物。]) for use according to claim 10. 前記使用では、前記使用の１０日後に皮膚結節発生の発生率なしである、請求項１０に記載の使用のための医薬組成物。11. A pharmaceutical composition for use according to claim 10, wherein said use has no incidence of skin nodule development after 10 days of said use. ヒト成人に投与された場合に、ＡＵＣ（When administered to human adults, the AUC ( ０－ｔ0-t ）対ＡＵＣ（) versus AUC ( ０－ｔ0-t ）によって測定された６．５７～８．０３のレボドパ対約１のカルビドパのレボドパ対カルビドパの平均血漿曝露比を提供する、請求項１０に記載の使用のための医薬組成物。11. The pharmaceutical composition for use according to claim 10, which provides a mean plasma exposure ratio of levodopa to carbidopa of 6.57 to 8.03 levodopa to carbidopa of about 1, as measured by ). 約２４０ｍｇの以下の式の化合物：About 240 mg of a compound of the formula:
Figure 2020102628000005
Figure 2020102628000005
 、及び,as well as
約１２ｍｇの以下の式の化合物：About 12 mg of a compound of the formula:
Figure 2020102628000006
Figure 2020102628000006
 を含む、ベースライン運動障害学会統一パーキンソン病評価尺度（Ｍｏｖｅｍｅｎｔ Ｄｉｓｏｒｄｅｒ Ｓｏｃｉｅｔｙ－Ｕｎｉｆｉｅｄ Ｐａｒｋｉｎｓｏｎ’ｓ Ｄｉｓｅａｓｅ Ｒａｔｉｎｇ Ｓｃａｌｅ）（ＭＤＳ－ＵＰＤＲＳ）スコアを有するパーキンソン病の治療を必要とする対象におけるＭＤＳ－ＵＰＤＲＳ合計スコアの改善に使用するための医薬組成物であって、MDS-UPDRS total score in subjects in need of treatment for Parkinson's disease who have a baseline Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score, including A pharmaceutical composition for use in improving
対象への前記医薬組成物の投与により、ベースラインＭＤＳ－ＵＰＤＲＳ合計スコアが少なくとも９単位低減する、医薬組成物。A pharmaceutical composition, wherein administration of said pharmaceutical composition to a subject reduces a baseline MDS-UPDRS total score by at least 9 units. 約６．５～約９．２のｐＨを有する、請求項１９に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 19, having a pH of about 6.5 to about 9.2. 約６．８～約７．８の間のｐＨを有する、請求項２０に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 20, having a pH between about 6.8 and about 7.8. 約９％未満の酸素を有する１０ｃｃのバイアル中にパッケージングされ、かつ、１気圧で２℃～８℃の温度で保存した場合に、少なくとも３ヶ月間安定である、請求項２０に記載の使用のための医薬組成物。Use according to claim 20, which is stable for at least 3 months when packaged in a 10 cc vial with less than about 9% oxygen and stored at a temperature of 2°C to 8°C at 1 atmosphere. A pharmaceutical composition for 酸化防止剤を実質的に含まない、請求項２２に記載の使用のための医薬組成物。23. A pharmaceutical composition for use according to claim 22, which is substantially free of antioxidants. ２５℃で５日間、続いて、５℃で３０日間保存した後に、約１５マイクログラム／ｍＬ未満のヒドラジンを含む、請求項２２に記載の使用のための医薬組成物。23. The pharmaceutical composition for use according to claim 22, comprising less than about 15 micrograms/mL of hydrazine after storage at 25[deg.]C for 5 days followed by 5[deg.]C for 30 days. 前記使用では、前記使用の１０日後に皮膚結節発生の発生率なしである、請求項１９に記載の使用のための医薬組成物。20. A pharmaceutical composition for use according to claim 19, wherein said use has no incidence of skin nodule development after 10 days of said use. ヒト成人に投与された場合に、ＡＵＣ（When administered to human adults, the AUC ( ０－ｔ0-t ）対ＡＵＣ（) versus AUC ( ０－ｔ0-t ）によって測定された６．５７～８．０３のレボドパ対約１のカルビドパのレボドパ対カルビドパの平均血漿曝露比を提供する、請求項１９に記載の使用のための医薬組成物。20. The pharmaceutical composition for use according to claim 19, which provides a mean plasma exposure ratio of levodopa to carbidopa of 6.57 to 8.03 levodopa to carbidopa of about 1, as measured by ). 約２４０ｍｇの以下の式の化合物：About 240 mg of a compound of the formula:
Figure 2020102628000007
Figure 2020102628000007
 、及び,as well as
約１２ｍｇの以下の式の化合物：About 12 mg of a compound of the formula:
Figure 2020102628000008
Figure 2020102628000008
 を含む、ベースラインパーキンソン病質問票３９項目（ＰＤＱ－３９）サマリーインデックススコアを有するパーキンソン病の治療を必要とする対象における生活の質の改善に使用するための医薬組成物であって、A pharmaceutical composition for use in improving quality of life in a subject in need of treatment for Parkinson's disease who has a Baseline Parkinson's Disease Questionnaire 39 (PDQ-39) Summary Index score, comprising:
対象への前記医薬組成物の皮下投与により、ベースラインＰＤＱ－３９スコアが少なくとも６．９単位低減する、医薬組成物。A pharmaceutical composition, wherein subcutaneous administration of said pharmaceutical composition to a subject reduces a baseline PDQ-39 score by at least 6.9 units. 約６．５～約９．２のｐＨを有する、請求項２７に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 27, having a pH of about 6.5 to about 9.2. 約６．８～約７．８のｐＨを有する、請求項２８に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 28, having a pH of about 6.8 to about 7.8. 約９％未満の酸素を有する１０ｃｃのバイアル中にパッケージングされ、かつ、１気圧で２℃～８℃の温度で保存した場合に、少なくとも３ヶ月間安定である、請求項２９に記載の使用のための医薬組成物。Use according to claim 29, which is stable for at least 3 months when packaged in a 10 cc vial with less than about 9% oxygen and stored at a temperature of 2°C to 8°C at 1 atmosphere. A pharmaceutical composition for 酸化防止剤を実質的に含まない、請求項３０に記載の使用のための医薬組成物。31. A pharmaceutical composition for use according to claim 30, which is substantially free of antioxidants. ２５℃で５日間、続いて、５℃で３０日間保存した後に、約１５マイクログラム／ｍＬ未満のヒドラジンを含む、請求項３０に記載の使用のための医薬組成物。31. The pharmaceutical composition for use according to claim 30, comprising less than about 15 micrograms/mL of hydrazine after storage at 25[deg.]C for 5 days followed by 5[deg.]C for 30 days. 前記使用では、前記使用の１０日後に皮膚結節発生の発生率なしである、請求項２７に記載の使用のための医薬組成物。28. A pharmaceutical composition for use according to claim 27, wherein said use has no incidence of skin nodule development after 10 days of said use. ヒト成人に投与された場合に、ＡＵＣ（When administered to human adults, the AUC ( ０－ｔ0-t ）対ＡＵＣ（) versus AUC ( ０－ｔ0-t ）によって測定された６．５７～８．０３のレボドパ対約１のカルビドパのレボドパ対カルビドパの平均血漿曝露比を提供する、請求項２７に記載の使用のための医薬組成物。28. The pharmaceutical composition for use according to claim 27, which provides a mean plasma exposure ratio of levodopa to carbidopa of 6.57 to 8.03 levodopa to carbidopa of about 1, as measured by ). 約２４０ｍｇの以下の式の化合物：About 240 mg of a compound of the formula:
Figure 2020102628000009
Figure 2020102628000009
 、及び,as well as
約１２ｍｇの以下の式の化合物：About 12 mg of a compound of the formula:
Figure 2020102628000010
Figure 2020102628000010
 を含む、ベースラインパーキンソン病睡眠尺度－２（ＰＤＳＳ－２）合計スコアを有するパーキンソン病の治療を必要とする対象における睡眠の改善に使用するための医薬組成物であって、A pharmaceutical composition for use in improving sleep in a subject in need of treatment for Parkinson's disease who has a baseline Parkinson's Disease Sleep Scale-2 (PDSS-2) total score, comprising:
対象への前記医薬組成物の皮下投与により、ベースラインＰＤＳＳ－２合計スコアが少なくとも２単位低減する、医薬組成物。A pharmaceutical composition, wherein subcutaneous administration of said pharmaceutical composition to a subject reduces a baseline PDSS-2 total score by at least 2 units. 約６．５～約９．２のｐＨを有する、請求項３５に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 35, having a pH of about 6.5 to about 9.2. 約６．８～約７．８のｐＨを有する、請求項３６に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 36, having a pH of about 6.8 to about 7.8. 約９％未満の酸素を有する１０ｃｃのバイアル中にパッケージングされ、かつ、１気圧で２℃～８℃の温度で保存した場合に、少なくとも３ヶ月間安定である、請求項３７に記載の使用のための医薬組成物。Use according to claim 37, which is stable for at least 3 months when packaged in a 10 cc vial with less than about 9% oxygen and stored at a temperature of 2°C to 8°C at 1 atmosphere. A pharmaceutical composition for 酸化防止剤を実質的に含まない、請求項３８に記載の使用のための医薬組成物。39. A pharmaceutical composition for use according to claim 38 which is substantially free of antioxidants. ２５℃で５日間、続いて、５℃で３０日間保存した後に、約１５マイクログラム／ｍＬ未満のヒドラジンを含む、請求項３８に記載の使用のための医薬組成物。39. The pharmaceutical composition for use according to claim 38, comprising less than about 15 micrograms/mL of hydrazine after storage at 25[deg.]C for 5 days followed by 5[deg.]C for 30 days. 前記使用では、前記使用の１０日後に皮膚結節発生の発生率なしである、請求項３５に記載の使用のための医薬組成物。36. A pharmaceutical composition for use according to claim 35, wherein said use has no incidence of skin nodule development after 10 days of said use. ヒト成人に投与された場合に、ＡＵＣ（When administered to human adults, the AUC ( ０－ｔ0-t ）対ＡＵＣ（) versus AUC ( ０－ｔ0-t ）によって測定された６．５７～８．０３のレボドパ対約１のカルビドパのレボドパ対カルビドパの平均血漿曝露比を提供する、請求項３５に記載の使用のための医薬組成物。36. The pharmaceutical composition for use according to claim 35, which provides a mean plasma exposure ratio of levodopa to carbidopa of 6.57 to 8.03 levodopa to carbidopa of about 1, as measured by ). 以下の式の化合物：A compound of the formula:
Figure 2020102628000011
Figure 2020102628000011
 、及び,as well as
以下の式の化合物：A compound of the formula:
Figure 2020102628000012
Figure 2020102628000012
 の組み合わせを含む、運動変動（ｍｏｔｏｒ ｆｌｕｃｔｕａｔｉｏｎ）の治療を必要とする対象における運動変動の治療に使用するための医薬組成物であって、A pharmaceutical composition for use in treating motor fluctuations in a subject in need thereof, comprising a combination of
連続皮下投与用に製剤化され、formulated for continuous subcutaneous administration,
化合物（Ａ－１）対化合物（Ｂ－１）の重量比が、約２０：１である、医薬組成物。A pharmaceutical composition wherein the weight ratio of compound (A-1) to compound (B-1) is about 20:1. 前記治療が安全である、請求項４３に記載の使用のための医薬組成物。44. A pharmaceutical composition for use according to claim 43, wherein said treatment is safe. 前記連続皮下治療が、前記患者においてベースラインからの統計的に有意な臨床結果の変化をもたらす、請求項４４に記載の使用のための医薬組成物。45. The pharmaceutical composition for use according to claim 44, wherein said continuous subcutaneous treatment results in a statistically significant change in clinical outcome from baseline in said patient. 約２４０ｍｇの化合物（Ａ－１）及び約１２ｍｇの化合物（Ｂ－１）を含む、請求項４３に記載の使用のための医薬組成物。A pharmaceutical composition for use according to claim 43, comprising about 240 mg of compound (A-1) and about 12 mg of compound (B-1).
JP2021526553A 2018-11-15 2019-11-15 Pharmaceutical product for subcutaneous administration Pending JP2022507528A (en)

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
US201862767546P 2018-11-15 2018-11-15
US62/767,546 2018-11-15
US201962843945P 2019-05-06 2019-05-06
US62/843,945 2019-05-06
US201962863113P 2019-06-18 2019-06-18
US201962863093P 2019-06-18 2019-06-18
US201962863101P 2019-06-18 2019-06-18
US62/863,101 2019-06-18
US62/863,093 2019-06-18
US62/863,113 2019-06-18
US201962898214P 2019-09-10 2019-09-10
US62/898,214 2019-09-10
PCT/US2019/061626 WO2020102628A1 (en) 2018-11-15 2019-11-15 Pharmaceutical formulations for subcutaneous administration

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JPWO2020102628A5 true JPWO2020102628A5 (en) 2022-11-29

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