JP7430669B2 - 透析患者に適用される注射用医薬組成物 - Google Patents
透析患者に適用される注射用医薬組成物 Download PDFInfo
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- JP7430669B2 JP7430669B2 JP2021123323A JP2021123323A JP7430669B2 JP 7430669 B2 JP7430669 B2 JP 7430669B2 JP 2021123323 A JP2021123323 A JP 2021123323A JP 2021123323 A JP2021123323 A JP 2021123323A JP 7430669 B2 JP7430669 B2 JP 7430669B2
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- difelikephalin
- acid
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Description
前記注射用医薬組成物は、医療現場における用量調製に伴う人的過誤を低減し、かつ、労力を軽減するための注射用医薬組成物であり、
前記注射用医薬組成物は、ジフェリケファリンのフリー体換算で17.5μg、25.0μg、35.0μg又は42.5μgの量のジフェリケファリン又はその薬理学的に許容される塩を含有し、それぞれ対応して、45kg未満、45kg以上65kg未満、65kg以上85kg未満又は85kg以上のドライウェイト体重の透析患者に投与されるための注射用医薬組成物であり、
前記注射用医薬組成物は、1回投与で使い切るための単位用量においてプレフィルドシリンジに封入されている、
注射用医薬組成物。
実施例1
そう痒症を有する血液透析患者を対象とした臨床試験(二重盲検並行群間比較試験)
1.試験方法
(1)投与方法
患者247例を対象として、A群(61例)、B群(61例)、C群(62例)及びプラセボ群(63例)に、各治験薬を週3回、8週間、透析終了時の返血時に透析回路静脈側に注入し、投与した。試験期間は、前観察期(治療期移行前2週間)、治療期(8週間)、後観察期(治療期終了後2週間)の順序とし、前観察期と後観察期には治験薬は投与しなかった。
(2)治験薬
A群:0.04M等張緩衝酢酸溶液(pH4.5)にジフェリケファリンを0.025 mg/mLで溶解した注射液
B群:0.04M等張緩衝酢酸溶液(pH4.5)にジフェリケファリンを0.05 mg/mLで溶解した注射液
C群:0.04M等張緩衝酢酸溶液(pH4.5)にジフェリケファリンを0.1 mg/mLで溶解した注射液
プラセボ群:0.04M等張緩衝酢酸溶液(pH4.5)
(3)投与量
各投与群の治験薬の投与液量及びジフェリケファリンの投与量は下表に従い、投与日の各患者のドライウェイト区分に基づき決定した。
有効性については、以下のかゆみに関する自覚症状等により評価した。以下の各スコアにおいて、治療期0週時をベースラインとし、ベースラインとの差を変化量とした。
(1)NRSスコア
1日の中で最も強く感じたかゆみに対して、「かゆみなし」を0、「考えられる最大のかゆみ」を10として、0から10までの整数で評価した。
(2)白取の重症度基準に基づくかゆみスコア
1日1回、評価前日の起床時から当日の起床時まで(就寝中を含む)のかゆみの程度を、「症状なし」から「激烈な痒み」までをそれぞれ0から4までのスコアとして、日中及び夜間のそれぞれの症状を評価した。
(3)Skindex-16スコア
週はじめの来院時(治験薬投与前)に過去1週間のかゆみによって悩まされた頻度を判定した。「まったく悩まされなかった」から「いつも悩まされた」までをそれぞれ0から6までのスコアとして評価した。
(4)5-D Itch Scaleスコア
週はじめの来院時(治験薬投与前)に過去2週間のかゆみの状況を振り返り、かゆみの5つの構成要素(持続、程度、傾向、悪影響、分布)を判定した。
(5)PGICスコア
週はじめの来院時に前観察期と比較したかゆみの全般的症状を「非常に良くなった」、「良くなった」、「少し良くなった」、「変わらなかった」、「少し悪くなった」、「悪くなった」及び「非常に悪くなった」の7段階で評価した。
3.結果
(1)治療期8週時のNRSスコアの変化量を図1に示した。
(2)B群およびC群における、ドライウェイト区分毎のNRSスコアの変化量について、有効性が最大化された治療期4週時の変化量を図2および図3に示した。図2および図3に示す通り、B群及びC群において、いずれのドライウェイト区分においても、NRSスコアの改善が確認された。
(3)治療期8週時の白取の重症度基準に基づくかゆみスコアの変化量(日中、夜間いずれかのうちスコアが大きい方の変化量)は、プラセボ群-1.00に対し、A群-1.14、B群-1.31及びC群-1.31であり、B群及びC群でプラセボ群に比して有意な改善を示した(MMRM、P<0.05)。
(4)治療期8週時のSkindex-16総合スコアの変化量は、プラセボ群-24.04に対し、A群-24.25、B群-27.79及びC群-22.69であり、B群で改善傾向が認められた。
(5)治療期8週時の5-D Itch Scale合計スコアの変化量は、プラセボ群-5.8に対し、A群-6.6、B群-6.5及びC群-6.8であり、A群以上の用量で改善傾向が認められた。
(6)治療期最終評価時のPGICが「良くなった」及び「非常によくなった」であった被験者の割合は、プラセボ群24.2及び17.7%に対し、A群34.4及び19.7%、B群28.8及び37.3%、C群38.3及び31.7%であり、B群及びC群でプラセボに比して有意な改善を示した(2標本Wilcoxon 検定、P<0.01)。
(7)治療期の有害事象の発現率は、プラセボ群66.7%、A群72.1%、B群77.0%及びC群85.5%と用量依存的に増加し、C群の発現率はプラセボ群に比して有意に高かった(Fisherの正確検定、P<0.05)。
4.薬物動態に関する評価項目
(1)測定方法:B群及びC群において、「血漿中薬物濃度:血漿中ジフェリケファリン(未変化体)濃度」は、LC-MS/MS法により測定した。
(2)結果:B群(45kg未満(4例)、45kg以上65kg未満(32例)、65kg以上85kg未満(15例)、85kg以上(1例))のドライウェイト区分での7週時の透析前トラフ値(透析前血漿中ジフェリケファリン濃度)の幾何平均値は、それぞれ順に0.5903 ng/mL、0.5826 ng/mL、0.5275 ng/mL及び0.7480 ng/mLであった。C群(45kg未満(3例)、45kg以上65kg未満(32例)、65kg以上85kg未満(15例)、85kg以上(2例))のドライウェイト区分での7週時の透析前トラフ値(透析前血漿中ジフェリケファリン濃度)の幾何平均値は、それぞれ順に0.9306 ng/mL、0.9700 ng/mL、1.0671 ng/mL及び1.0396 ng/mLであった。
したがって、本発明の注射用医薬組成物により、医療現場における用量調製に伴う人的過誤を低減し、かつ、労力を軽減することが可能となることが示された。
Claims (1)
- 透析患者のそう痒症治療用の、ジフェリケファリン又はその薬理学的に許容される塩を含有する注射用医薬組成物であって、
前記注射用医薬組成物は、医療現場における用量調製に伴う人的過誤を低減し、かつ、労力を軽減するための注射用医薬組成物であり、
前記注射用医薬組成物は、ジフェリケファリンのフリー体換算で17.5μg、25.0μg、35.0μg又は42.5μgの量のジフェリケファリン又はその薬理学的に許容される塩を含有し、それぞれ対応して、45kg未満、45kg以上65kg未満、65kg以上85kg未満又は85kg以上のドライウェイト体重の透析患者に投与されるための注射用医薬組成物であり、
前記注射用医薬組成物は、1回投与で使い切るための単位用量においてプレフィルドシリンジに封入されている、
注射用医薬組成物。
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Title |
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."コセンティクス(R)皮下注150mgペン/シリンジ", 医薬品インタビューフォーム (2016改訂) |
."ペグイントロン(R)皮下注用50μg/0.5mL用", 医薬品インタビューフォーム (2021.4改訂) |
"XOLAIR(R) (omalizumab) for injection, for subcutaneous use", HIGHLIGHTS OF PRESCRIBING INFORMATION (Revised:2016) |
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