JP2021534160A - 疾患処置のためのリルゾール口腔内崩壊錠の使用 - Google Patents
疾患処置のためのリルゾール口腔内崩壊錠の使用 Download PDFInfo
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Abstract
Description
本願は、2018年8月16日に出願した米国仮出願第62/764,864号の優先権および利益を主張する(出典明示によりその全体として本明細書の一部とする)。
本発明は、リルゾール口腔内崩壊錠および種々の疾患の処置におけるその使用に関する。
グルタメートは、正常な脳機能におけるシグナル伝達の調節に関与している主要な興奮性神経伝達物質である。グルタメートシグナル伝達の研究は主に中枢神経系(CNS)に焦点が当てられてきたが、他の研究では、末梢組織におけるそれらの機能的役割が強調されている。例えば、非特許文献1および非特許文献2を参照のこと。
R23は、H、CH3、CH2CH3、CH2CH2CH3、CH2CCH、CH(CH3)2、CH2CH(CH3)2、CH(CH3)CH2CH3、CH2OH、CH2OCH2Ph、CH2CH2OCH2Ph、CH(OH)CH3、CH2Ph、CH2(シクロヘキシル)、CH2(4−OH−Ph)、(CH2)4NH2、(CH2)3NHC(NH2)NH、CH2(3−インドール)、CH2(5−イミダゾール)、CH2CO2H、CH2CH2CO2H、CH2CONH2、およびCH2CH2CONH2からなる群から選択される]
を有するものおよびその薬学的に許容される塩である。
(a)固体成形口腔内速分散錠中にリルゾールまたはその薬学的に許容できる塩の治療有効量を含む固体成形口腔内速分散錠の医薬組成物;および
(b)該医薬組成物を投与するための使用説明書
を含むキットであり、該治療有効量が、プラセボの投与と比較して少なくとも10VASポイント減少させる、キットが提供される。
以下の詳細な説明は、本発明を実施する際に当業者を助けるために提供される。当業者は、本開示の精神または範囲から逸脱することなく、本明細書に記載された実施態様の変更および変形を行うことができる。別段の定義がない限り、本明細書で使用されるすべての技術的および科学的用語は、本開示が属する技術分野の当業者によって一般的に理解されるのと同じ意味を有する。本明細書で使用される用語は、特定の実施態様のみを記載するためのものであり、限定することを意図するものではない。
R23は、H、CH3、CH2CH3、CH2CH2CH3、CH2CCH、CH(CH3)2、CH2CH(CH3)2、CH(CH3)CH2CH3、CH2OH、CH2OCH2Ph、CH2CH2OCH2Ph、CH(OH)CH3、CH2Ph、CH2(シクロヘキシル)、CH2(4−OH−Ph)、(CH2)4NH2、(CH2)3NHC(NH2)NH、CH2(3−インドール)、CH2(5−イミダゾール)、CH2CO2H、CH2CH2CO2H、CH2CONH2、およびCH2CH2CONH2からなる群から選択される]
を有する。
この試験は、1605017768と呼ばれている。この試験は、さらにClinicalTrials.govにて、ClinicalTrials.gov Identifier: NCT03017508で説明されている。https://clinicaltrials.gov/ct2/show/NCT03017508?term=NCT03017508&rank=1を参照。
今回の試験の目的は、舌下リルゾール(BHV−0223)が、パブリックスピーキングタスク中の社交不安障害を持つ人の不安を軽減できるかどうかを調べることである。
パブリックスピーキング不安に対するBHV−0223の効果を調べる二重盲検プラセボ対照クロスオーバー試験を実施した。DSM−5で定義された社交不安障害を持っており、即興スピーチタスク(Impromptu Speech Task)で臨床的に有意なパブリックスピーキング不安を持つ20人の参加者をチャレンジ試験に登録した。参加者に、2つの即興スピーチタスクのそれぞれを行う1時間前に、二重盲検クロスオーバー条件下でBHV−0223(またはプラセボ)を投与した。BHV−0223(またはプラセボ)の投与および即興スピーチタスクを含む2つの試験日は、投薬ウォッシュアウトを可能にするために2日〜10日の間隔を置いた。2〜10日後に最終的なフォローアップ訪問を行い、完全な身体検査を行い、フォローアップ肝機能検査および全血球計算を行った。主要アウトカムは、即興スピーチタスク中の自己評価不安に対するBHV−0223の効果(プラセボとの比較)を調べることであった。研究者はまた、副次的アウトカムとして、不安の生理学的測定値、不安の臨床医評価測定値、およびスピーチパフォーマンスの測定値を収集した。
主要アウトカム指標:
1.即興スピーチタスク後のVAS不安[タイムフレーム: 10分]不安誘発スピーチタスクを行った後の不安レベルを評価する視覚アナログスケール。
1.18歳から65歳までの男性または女性(閉経後であるか手術による生殖不能であるかまたはスクリーニング時の妊娠検査が陰性であり、試験期間中に完全な禁欲を含む確立された避妊法を利用することに同意していること)。
2.構造化臨床インタビュー(SCID)により社交不安障害についてのDSM−5基準を満たし、LSASパブリックスピーキングサブスケールスコアが6を超える。
3.安定な向精神薬。参加者は、処置前の1か月間、すべての向精神薬を安定に服用していなければならず、試験登録前の少なくとも1か月間、SSRIおよび抗うつ薬を安定に服用していなければならない。必要に応じて、被験者が試験前の48時間ベンゾジアゼピンの使用を控える限り、ベンゾジアゼピンの使用は認められる。
4.身体検査、SMAC−20(LFT、TFTを含む)、VDRL、CBC w/diff、尿検査、尿毒物学、EKG、および病歴に基づき、医学的および神経学的に健康であること。CNSに影響を及ぼさないかまたは投与された薬剤(例えば、経口血糖降下薬)を妨害しない安定した医学的問題を抱えている個人は、エントリー前のその月に薬剤の調整が行われていない場合でも含まれることがある。
5.乱用薬物について陰性の尿毒物学スクリーニング。
6.Yale Human Investigation Committee(HIC)のガイドラインに従って、書面によるインフォームドコンセントを提供できること。
1.妊娠検査陽性。
2.授乳中の女性。
3.過去6か月以内の物質乱用障害(ETOH、コカイン、アヘン、PCP)の病歴、またはスクリーニング時(過去6か月以内)の尿毒物学陽性。
4.DSM−IV−TR基準による広汎性発達障害または精神病性障害の病歴。
5.投与時に有床義歯、ブレース(brace)、ピアス穴の存在、または、治験責任医師の見解では投与手順を正常に完了することを妨げる可能性がある口もしくは舌の物理的所見。
6.生理的吸収および運動を妨げる可能性のある医学的状態(例えば、胃バイパス、十二指腸切除)または胃バンドを持つ参加者。
7.臨床的に有意な異常または異常な臨床検査結果を有する参加者。
8.参加者が、現在ウイルス性肝炎(HBsAGまたはHVC)の診断を受けているか、または肝疾患の病歴がある。
9.参加者に、小児期の単発の熱性発作(single childhood febrile seizure)(例えば、癲癇)以外の発作性障害の重大な病歴がある。
10.CYP 1A2代謝を誘導または阻害することが知られている薬剤(誘導剤の例: リファンピン、カルバマゼピンなど;阻害剤の例: フルボキサミン、シプロフロキサシン、フルオロキノロンなど)を最初の治験薬投与前30日以内に使用している参加者。
11.リルゾールまたは他の関連薬物に対してアレルギー反応の病歴を有する参加者。
12.参加者が、いずれかの薬剤に対して、アナフィラキシーの病歴、確認された過敏性反応、または臨床的に重要な反応を有する。
13.参加者が、初回投与前30日(生物製剤の場合は90日)以内に他の治験薬またはデバイスを受けたことがあるか、または現在、薬剤の投与を伴わない治験に参加している。
14.スクリーニングまたはベースライン(1日目)において、臨床的に有意な心電図(ECG)異常(QTcF>450ミリ秒)またはバイタルサイン異常(収縮期血圧が90mmHg未満または140mmHgを超えるか、拡張期血圧が50mmHg未満または90mmHgを超えるか、心拍数が50bpm未満または100bpmを超える)を有する参加者。
15.治験責任医師の見解で、参加者が研究に参加することを妨げる理由。
実施例1に記載されたプロトコルに実質的に記載された試験を行った。
実施例1に示したプロトコルに実質的に記載された試験を行った。
実施例1に示したプロトコルに実質的に記載された試験を行った。非常に驚くべきことに、以下の図3に示すように、この試験では、実施された認知的安全性テストの改善が実証され、遅延想起記憶の改善が示された、p<0.05。
Claims (15)
- 不安障害の処置を必要とする患者における不安障害の処置方法であって、プラセボの投与と比較して少なくとも10VASポイント減少させるために、該患者に、リルゾールまたはその薬学的に許容される塩もしくはプロドラッグの治療有効量を含む固体成形口腔内速分散剤形の形態の医薬組成物を投与することを含む、方法。
- 固体成形口腔内速分散錠中のリルゾールの用量が20〜50mgである、請求項1記載の方法。
- 固体成形口腔内速分散錠中のリルゾールの用量が約35mgである、請求項2記載の方法。
- 投与により、少なくとも12VASポイント減少する、請求項1記載の方法。
- 投与により、少なくとも14VASポイント減少する、請求項4記載の方法。
- 投与により、約10〜25VASポイント減少する、請求項1記載の方法。
- 投与により、平均VASスコアが約49〜60となる、請求項1記載の方法。
- 投与により、平均VASスコアが約52〜58となる、請求項7記載の方法。
- 疾患がSADである、請求項1記載の方法。
- 患者の記憶の向上をもたらす、請求項1記載の方法。
- 固体成形口腔内速分散剤形がリルゾールまたはその薬学的に許容される塩もしくはプロドラッグ約50〜70重量%、魚ゼラチン約10〜30重量%、充填剤約10〜20重量%および矯味矯臭剤0.1〜5.0重量%を含む、請求項1記載の方法。
- 充填剤がマンニトールである、請求項11記載の方法。
- リルゾールプロドラッグが、以下の式:
R23は、H、CH3、CH2CH3、CH2CH2CH3、CH2CCH、CH(CH3)2、CH2CH(CH3)2、CH(CH3)CH2CH3、CH2OH、CH2OCH2Ph、CH2CH2OCH2Ph、CH(OH)CH3、CH2Ph、CH2(シクロヘキシル)、CH2(4−OH−Ph)、(CH2)4NH2、(CH2)3NHC(NH2)NH、CH2(3−インドール)、CH2(5−イミダゾール)、CH2CO2H、CH2CH2CO2H、CH2CONH2、およびCH2CH2CONH2からなる群から選択される]
を有するものおよびその薬学的に許容される塩である、請求項1記載の方法。 - 患者において疾患を処置するためのキットであって、
(a)固体成形口腔内速分散錠中にリルゾールまたはその薬学的に許容できる塩の治療有効量を含む医薬組成物;および
(b)該医薬組成物を投与するための使用説明書
を含むキットであり、該治療有効量が、プラセボの投与と比較して少なくとも10VASポイント減少させる、キット。
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EP4171554A1 (en) * | 2020-06-24 | 2023-05-03 | Biohaven Therapeutics Ltd. | Compositions and methods for treating obsessive-compulsive disorder |
CA3193824A1 (en) * | 2020-10-05 | 2022-04-14 | Ana PEREIRA | Riluzole for the treatment of alzheimer's disease |
US11672761B2 (en) | 2020-11-16 | 2023-06-13 | Orcosa Inc. | Rapidly infusing platform and compositions for therapeutic treatment in humans |
CN114177153B (zh) * | 2021-12-20 | 2023-04-07 | 平顶山市第二人民医院 | 一种利鲁唑口崩片及其制备方法 |
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JP2017535613A (ja) * | 2014-11-21 | 2017-11-30 | バイオヘイブン・ファーマシューティカル・ホールディング・カンパニー・リミテッドBiohaven Pharmaceutical Holding Company Ltd. | リルゾールの舌下製剤 |
JP2018508525A (ja) * | 2015-03-03 | 2018-03-29 | バイオヘイブン・ファーマシューティカル・ホールディング・カンパニー・リミテッドBiohaven Pharmaceutical Holding Company Ltd. | リルゾールプロドラッグおよびそれらの使用 |
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JP2003524622A (ja) * | 1999-04-08 | 2003-08-19 | アール.ピー. シェーラー コーポレイション | 魚類ゼラチン含有の急速分散型投与形態 |
JP2017535613A (ja) * | 2014-11-21 | 2017-11-30 | バイオヘイブン・ファーマシューティカル・ホールディング・カンパニー・リミテッドBiohaven Pharmaceutical Holding Company Ltd. | リルゾールの舌下製剤 |
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KR20210045423A (ko) | 2021-04-26 |
CA3109769A1 (en) | 2020-02-20 |
EP3836922A4 (en) | 2022-05-04 |
IL280657A (en) | 2021-03-25 |
EP3836922A1 (en) | 2021-06-23 |
BR112021002692A2 (pt) | 2021-05-11 |
MX2021001563A (es) | 2021-06-15 |
US20210315865A1 (en) | 2021-10-14 |
AU2019322889A1 (en) | 2021-03-04 |
PH12021550218A1 (en) | 2021-12-06 |
JP2024010017A (ja) | 2024-01-23 |
CN112584831A (zh) | 2021-03-30 |
EA202190544A1 (ru) | 2021-06-18 |
WO2020037152A1 (en) | 2020-02-20 |
SG11202100880VA (en) | 2021-02-25 |
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