JP2017518330A - 大うつ病性障害(mdd)の治療のためのプロトコル - Google Patents
大うつ病性障害(mdd)の治療のためのプロトコル Download PDFInfo
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- 208000024714 major depressive disease Diseases 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims description 23
- 238000004458 analytical method Methods 0.000 claims description 14
- 238000011156 evaluation Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 5
- 230000019771 cognition Effects 0.000 claims 1
- 239000006186 oral dosage form Substances 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 16
- 238000000338 in vitro Methods 0.000 abstract 1
- 210000005036 nerve Anatomy 0.000 abstract 1
- 230000004936 stimulating effect Effects 0.000 abstract 1
- 239000000902 placebo Substances 0.000 description 23
- 229940068196 placebo Drugs 0.000 description 23
- 238000005259 measurement Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 10
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- 238000000537 electroencephalography Methods 0.000 description 6
- 230000001149 cognitive effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 230000000971 hippocampal effect Effects 0.000 description 3
- 230000003285 pharmacodynamic effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 208000020401 Depressive disease Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000007514 neuronal growth Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
- 238000011256 aggressive treatment Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002567 electromyography Methods 0.000 description 1
- 230000010482 emotional regulation Effects 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
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- 238000012544 monitoring process Methods 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 231100001079 no serious adverse effect Toxicity 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- -1 small molecule compounds Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
Description
本出願は、2014年6月16日に出願された米国仮出願第62/012,880号からの優先権を主張するものである。該出願の内容は、その全体が参照により本明細書に組み入れられる。
本発明は、うつ病、特に大うつ病性障害(Major Depressive Disorder: MDD)の治療に関する。この治療は、特に有効な量の特定のベンジルピペラジン−アミノピリジン化合物および同等の開鎖形態を約1ヶ月間にわたって投与することを含む。
したがって、一態様において、本発明は、ヒト対象者における大うつ病性障害(MDD)を治療する方法に関し、本方法は、該対象者に、式(1)または式(2)の化合物:
qEEGにより測定された応答
式(1)の化合物を用いた二重盲検プラセボ対照複数回投与漸増用量試験を症候性MDDの患者において行った。マサチューセッツ総合病院(Massachusetts General Hospital: MGH)のClinical Trials Network and Institute(CTNI)の評価者から、独立した遠隔SAFERインタビュー(Targum, S. D., et al., CNS Neurosci. Ther. (2008) 14:2−9)により、診断と病気の重症度が確認された24人の被験者が集められた。各患者は適格性についてのスクリーニングを受け(−37日目から−6または−3日目まで)、適格患者は、−5日目に病棟に入院してウォッシュアウトを完了し、適格性およびベースライン評価について再確認された。1日目に開始して28日間、毎日、式(1)の化合物またはプラセボを患者に投与し、退院するまで安全性、薬物動態(PK)および薬力学(PD)について患者を追跡した。院内投薬の終了時(28日目)に、患者は、精神科医の判断で、病棟内にさらに最大3日間とどまった。35(±3)日目、42(±3)日目、49(±3)日目、および70(±3)日目に、外来患者の追跡調査来院が行われた。患者は、56(±3)日目と84(±3)日目(試験終了時)に更なる追跡調査のために病棟に戻った。
標準テストによる評価
この実施例では、実施例1の試験結果が、モンゴメリ・アスベルグうつ病評価尺度(MADRS)、臨床全般印象−改善度(CGI−I)、うつ病質問票による症状(SDQ)、および認知・身体機能質問票(CPFQ)を含む有効性評価により評価された。28日目にプラセボ処置患者の間で最小限の改善が観察されたにもかかわらず、有効性の測定値は、2つのより低い用量(40mg/日および80mg/日)では、全ての測定においてうつ症状と認知症状の臨床的に意義のある減少を示すが、最高用量(120mg/日)では示さないようであった。しかし、さらなる解析から、最高用量(120mg/日)もまた、これらの患者の状態を改善するのに有効であることが示された。こうした改善は、MADRS、SDQおよびCPFQについての追跡調査期間中、持続した。
Claims (10)
- ヒト対象者における大うつ病性障害(MDD)を治療する方法において使用するための、式(1)または式(2)の化合物を含む組成物であって、
- 提供される化合物の量が30〜100mg/日である、請求項1に記載の組成物。
- 提供される化合物の量が40〜90mg/日である、請求項1に記載の組成物。
- 投与が、少なくとも25日間にわたり毎日投与されることにより行われる、請求項1に記載の組成物。
- 前記対象者が投与終了時とその少なくとも1ヶ月後に評価される、請求項1に記載の組成物。
- 前記評価が、モンゴメリ・アスベルグうつ病評価尺度(MADRS)、および/または、臨床全般印象−改善度(CGI−I)、および/または、うつ病質問票による症状(SDQ)、および/または、認知・身体機能質問票(CPFQ)を行い、その結果を評価することを含む、請求項5記載の組成物。
- 前記評価が、定量的脳波検査(qEEG)を行い、その結果を評価することを含む、請求項5記載の組成物。
- 前記評価が共分散分析を含む、請求項5記載の組成物。
- 前記組成物が1日1回、1日2回、または1日3回投与される、請求項1〜4のいずれか1項に記載の組成物。
- 前記組成物が経口剤形である、請求項1〜4のいずれか1項に記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462012880P | 2014-06-16 | 2014-06-16 | |
US62/012,880 | 2014-06-16 | ||
PCT/US2015/035859 WO2015195567A1 (en) | 2014-06-16 | 2015-06-15 | Protocols for treatment of major depressive disorder (mdd) |
Publications (2)
Publication Number | Publication Date |
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JP2017518330A true JP2017518330A (ja) | 2017-07-06 |
JP6675330B2 JP6675330B2 (ja) | 2020-04-01 |
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Application Number | Title | Priority Date | Filing Date |
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JP2016573079A Active JP6675330B2 (ja) | 2014-06-16 | 2015-06-15 | 大うつ病性障害(mdd)の治療のためのプロトコル |
Country Status (9)
Country | Link |
---|---|
US (1) | US9572807B2 (ja) |
EP (1) | EP3154545A4 (ja) |
JP (1) | JP6675330B2 (ja) |
KR (1) | KR102475363B1 (ja) |
CN (1) | CN106572996B (ja) |
AU (1) | AU2015277406B2 (ja) |
CA (1) | CA2952452C (ja) |
SG (2) | SG11201610536XA (ja) |
WO (1) | WO2015195567A1 (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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JP7204640B2 (ja) * | 2016-09-12 | 2023-01-16 | ニューラルステム・インコーポレーテッド | 糖尿病に関連する神経障害の改善 |
US10413534B2 (en) | 2017-02-13 | 2019-09-17 | Neuralstem, Inc. | Amelioration of certain deficiencies due to stroke |
WO2022256636A2 (en) | 2021-06-03 | 2022-12-08 | Alto Neuroscience, Inc. | Method of treatment of depressed patients with poor cognition and selection of other patients benefiting from a benzylpiperazine-aminopyridine agent |
WO2024123695A1 (en) | 2022-12-05 | 2024-06-13 | Alto Neuroscience, Inc. | Effective treatment of depression in patients having impaired learning and/or memory or certain eeg characteristics with a benzylpiperazine-aminopyridine agent |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8362262B2 (en) * | 2003-08-08 | 2013-01-29 | Neuralstem, Inc. | Compositions to effect neuronal growth |
WO2013080046A1 (en) * | 2011-12-02 | 2013-06-06 | Dainippon Sumitomo Pharma Co., Ltd. | Lurasidone novel dosage regimens and use thereof for the treatment, prevention, and/or management of at least one cns disorder |
-
2015
- 2015-06-15 SG SG11201610536XA patent/SG11201610536XA/en unknown
- 2015-06-15 KR KR1020177001207A patent/KR102475363B1/ko active IP Right Grant
- 2015-06-15 SG SG10201811203TA patent/SG10201811203TA/en unknown
- 2015-06-15 US US14/740,070 patent/US9572807B2/en active Active
- 2015-06-15 AU AU2015277406A patent/AU2015277406B2/en active Active
- 2015-06-15 CA CA2952452A patent/CA2952452C/en active Active
- 2015-06-15 CN CN201580043884.1A patent/CN106572996B/zh active Active
- 2015-06-15 WO PCT/US2015/035859 patent/WO2015195567A1/en active Application Filing
- 2015-06-15 JP JP2016573079A patent/JP6675330B2/ja active Active
- 2015-06-15 EP EP15809513.3A patent/EP3154545A4/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8362262B2 (en) * | 2003-08-08 | 2013-01-29 | Neuralstem, Inc. | Compositions to effect neuronal growth |
WO2013080046A1 (en) * | 2011-12-02 | 2013-06-06 | Dainippon Sumitomo Pharma Co., Ltd. | Lurasidone novel dosage regimens and use thereof for the treatment, prevention, and/or management of at least one cns disorder |
Non-Patent Citations (1)
Title |
---|
NEURALSTEM INC. MULTIPLE-DOSE PHARMACOKINETICS(PK), AND PHARMACODYNAMIC(PD) EFFECT OF NSI-189 PHOSPH, JPN6019007043, ISSN: 0004064267 * |
Also Published As
Publication number | Publication date |
---|---|
US9572807B2 (en) | 2017-02-21 |
US20150359792A1 (en) | 2015-12-17 |
CA2952452C (en) | 2022-07-26 |
KR20170029509A (ko) | 2017-03-15 |
WO2015195567A1 (en) | 2015-12-23 |
EP3154545A1 (en) | 2017-04-19 |
EP3154545A4 (en) | 2017-12-20 |
AU2015277406A1 (en) | 2017-01-12 |
CN106572996A (zh) | 2017-04-19 |
JP6675330B2 (ja) | 2020-04-01 |
SG10201811203TA (en) | 2019-01-30 |
KR102475363B1 (ko) | 2022-12-07 |
SG11201610536XA (en) | 2017-01-27 |
AU2015277406B2 (en) | 2019-09-19 |
CN106572996B (zh) | 2020-04-07 |
CA2952452A1 (en) | 2015-12-23 |
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