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「ヴィアレブ™」について、米国FDAより進行期パーキンソン病成人患者さんの治療薬として承認を取得


アッヴィ合同会社は、進行期パーキンソン病の成人患者向けの治療薬として「ヴィアレブ™」が米国FDAより承認されたことを発表しました。ヴィアレブ™は24時間持続可能なレボドパ含有の皮下注射剤で、従来の経口製剤よりも日常生活に支障を及ぼすジスキネジアを避けつつ、「オン」時間を延ばすことができます。承認はピボタル試験に基づいており、試験結果では、ヴィアレブ™によって患者の運動機能が顕著に改善されたことが確認されました。本製品は用量調整が可能で、副作用も軽度から中程度です。この承認は、進行期のパーキンソン病患者に対する新しい非外科的治療選択肢を提供します。

2024年11月14日
アッヴィ合同会社

「ヴィアレブ™(ホスレボドパ/ホスカルビドパ水和物配合剤)」について、米国FDAより進行期パーキンソン病成人患者さんの治療薬として承認を取得

ー ヴィアレブ™は、進行期パーキンソン病における運動症状の日内変動を改善する治療薬として初めてかつ唯一の24時間持続投与可能なレボドパ含有皮下注射剤
ー ヴィアレブによる治療を行った成人患者さんは、経口カルビドパ/レボドパ速放性製剤比較して、日常生活に支障となるジスキネジア(不随意運動)が生じることなく「オン」の時間における優れた改善を報告1
ー ヴィアレブは、朝・昼・夜の時間帯や個人のニーズに合わせて用量調整が可能

イリノイ州ノースシカゴ、2024年10月17日(米国時間)—アッヴィ(NYSE:ABBV)は本日、米国食品医薬品局(FDA)が「ヴィアレブ™(ホスレボドパ/ホスカルビドパ水和物配合剤)」を進行期パーキンソン病の運動機能の変動を改善する治療薬として、初めてかつ唯一の24時間持続投与可能なレボドパ含有皮下注射剤として承認したことを発表しました。

サウスフロリダ大学パーキンソン病・運動障害センター所長および同大学神経学分野教授(professor of Neurology and Director of the Parkinson's and Movement Disorder Center at the University of South Florida)であるRobert A. Hauser, M.D., MBAは、次のように述べています。「パーキンソン病患者さんたちにとって、あまりにも長い間、進行期における治療選択肢が限られてきました。パーキンソン病は進行性の疾患であるため、経口薬ではやがて運動症状を十分にコントロールできなくなり、外科的手術が必要となる場合もあります。この新しい外科的手術を必要としない治療方法では、レボドパを朝、昼、夜を問わず持続的に投与します」

本承認は、ヴィアレブの長期安全性と有効性を評価する52週の非盲検試験2に加え、進行期パーキンソン病の成人患者さんを対象にヴィアレブの持続皮下注射の有効性を経口カルビドパ/レボドパ速放性製剤(CD/LD IR)1との比較において評価する12週におよぶ第III相ピボタル試験に基づいています。

本ピボタル試験の結果により、ヴィアレブを投与された患者さんは、経口投与のCD/LD IRと比較して日内運動に著しい改善が見られ、日常生活に支障となるジスキネジアが生じることなく「オン」の時間が増加し「オフ」の時間が減少しました1。「オン」の時間は、患者さんの運動症状がよく制御されている状態にある期間を意味し、「オフ」時間は症状が再び出現する状態を指します3,4。

ヴィアレブの副作用の大部分は非重篤で、軽度から中程度のものでした。最も多く現れた副作用(10%以上かつCD/LD IRの発生率を上回る)は、注入部反応、幻覚症状およびジスキネジアでした1,2。

アッヴィのexecutive vice president, research and development 兼 chief scientific officer である
Roopal Thakkar, M.D.は、次のように述べています。「進行期パーキンソン病の患者さんは運動症状の日内変動のコントロールが困難であり、日常生活に支障を抱えています。これは特に病気が進行するにつれて顕著になります。今回、ヴィアレブの24時間持続投与により運動症状を制御できる可能性のある患者さんにこのイノベーションをお届けできることを誇りに思います」

パーキンソン病は、脳におけるドパミン産生細胞の消失によって引き起こされる、振戦(ふるえ)、筋強剛、動作緩慢、および平衡障害を特徴とする進行性かつ慢性の神経障害です5。

パーキンソン病について
パーキンソン病の患者数は全世界で1,000万人以上といわれています6。パーキンソン病は、振戦(ふるえ)、筋固縮、動作緩慢、および平衡障害を特徴とする進行性かつ慢性の神経障害です5。パーキンソン病の運動症状は、脳におけるドパミン産生細胞の約60~80%が消失した時点で発現し始め、症状は経時的かつ緩徐に悪化し続けます7。パーキンソン病に対する根治的治療法は知られていませんが、症状の軽減に有用な治療法があります7。

パーキンソン病が進行すると、運動機能および非運動機能の日内変動やジスキネジアなどの合併症が発現します。「オン」状態(症状が概ねよく制御されている)から「オフ」状態(振戦やこわばりが再び出現し、動作がさらに困難になる)への変動が起こることが患者さんから報告されています4。進行期のパーキンソン病患者さんでは、日常活動を著しく妨げるジスキネジア(不随意運動)が現れることもあります4。これらの運動合併症の発現は、神経変性と血漿中のレボドパ濃度の変動に起因しており、診断後2~5年後に50%、10年後では約80~100%の患者さんで報告されています8。

第III相M15-736試験1について
第III相、無作為化、二重盲検、ダブルダミー、実薬対照試験において、進行期パーキンソン病の患者さんを対象として、ヴィアレブの有効性、安全性および忍容性を経口CD/LD IRと比較しました。患者さんへ日中の運動機能の状態を評価するためのパーキンソン病日誌(PD日誌)を提供しました。主要評価項目である良好な「オン」時間は、ジスキネジアを伴わない「オン」時間および日常生活に支障とならないジスキネジアを伴う「オン」時間と定義しました。良好な「オン」時間を収集し、連続した3日間で平均を算出、一般的な覚醒時間である16時間で標準化しました。ベースライン値は、無作為割付前のPD日誌による3日間に収集し、標準化された良好な「オン」時間の平均としました。米国とオーストラリアの80施設において、進行期パーキンソン病の成人患者さん約130名が本試験に参加しました。本試験は患者さんを1:1に無作為に割り付け、一方の群の患者さんには、ヴィアレブ溶液を持続皮下投与し、さらにCD/LD IRのプラセボの経口カプセル剤を投与しました。他方の群の患者さんには、ヴィアレブのプラセボ溶液を持続皮下投与し、さらにCD/LD IRを含む経口カプセル剤を投与しました。治療期間は12週間でした。12週目での日常生活に支障とならないジスキネジアを伴う「オン」時間の増加は、ヴィアレブの2.72時間に対し、経口CD/LD IRでは0.97時間でした(p=0.0083)。「オン」時間の改善は1週目から認められ、12週間継続しました。本試験に関する詳細はwww.clinicaltrials.gov(NCT04380142)およびThe Lancet Neurology(https://doi.org/10.1016/S1474-4422(22)00400-8)をご覧ください。

ヴィアレブ™について
ヴィアレブ(ホスレボドパ/ホスカルビドパ配合剤)は、進行期パーキンソン病成人患者さんの運動症状の日内変動の治療として24時間持続皮下投与するレボドパ/カルビドパのプロドラッグの溶液です。ヴィアレブはPRODUODOPA(R)としても知られており、35か国で承認され、世界各地で4,200人の患者さんが治療を開始しています。アッヴィは、進行期パーキンソン病患者さんにヴィアレブをお届けするために各国の規制当局と継続的に協働しています。

精神 ・神経疾患領域におけるアッヴィ
アッヴィは、世界中の精神・神経障害を抱える患者さんがその人らしく生きられるよう、継続した取組みを行っています。当社は、精神・神経疾患領域における30年を超える経験を活かし、有意義な治療選択肢を提供するとともに、未来に向けて技術革新を押し進めています。当社の精神・神経疾患領域のポートフォリオは、片頭痛、運動障害、精神障害などの精神・神経障害に対する承認された治療法に加え、革新的な治療法の強固なパイプラインで構成されています。当社は研究に対して積極的に投資を行い、精神・神経障害への理解を一層深めるよう努めています。挑戦を重ねるごとに、患者さん、介助者や臨床医の皆さんのためにソリューションを発見し提供していくという固い決意と情熱を抱き前進しています。詳細な情報はwww.abbvie.com.をご覧ください。

アッヴィについて
アッヴィのミッションは現在の深刻な健康課題を解決する革新的な医薬品の創製とソリューションの提供、そして未来に向けて医療上の困難な課題に挑むことです。一人ひとりの人生を豊かなものにするため次の主要領域に取り組んでいます。免疫疾患、がん、精神・神経疾患、アイケア、さらに美容医療関連のアラガン・エステティックスポートフォリオの製品・サービスです。アッヴィの詳細については、www.abbvie.comをご覧ください。X(旧Twitter)@abbvieFacebookLinkedInInstagramでも情報を公開しています。 

References:
1.Soileau, M., et al. Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. Lancet Neurol. 2022 Dec;21(12):P1099-1109.
2.Aldred, J., et al. Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study. Neurol Ther. 2023 Dec;12(6):1937-1958.
3."Motor fluctuations." Parkinson's Foundation. Available at: https://www.parkinson.org/library/fact-sheets/motor-fluctuations#:~:text=As%20levodopa%20begins%20to%20lose,are%20at%20their%20highest%20point. Accessed October 16, 2024. 
4."Off" Time in Parkinson's Disease." The Michael J. Fox Foundation for Parkinson's Research. Available at: https://www.michaeljfox.org/time-parkinsons-disease. Accessed October 16, 2024.
5."About Parkinson's: Parkinson's 101." The Michael J. Fox Foundation for Parkinson's Research. Available at: https://www.michaeljfox.org/understanding-parkinsons/i-have-got-what.php#q2. Accessed October 16, 2024.
6."Statistics." Parkinson's Foundation. Available at: https://www.parkinson.org/understanding-parkinsons/statistics#:~:text=Nearly%2090%2C000%20people%20in%20the,worldwide%20are%20living%20with%20PD. Accessed October 16, 2024.  
7."Parkinson's Disease: Hope Through Research." National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Parkinsons-Disease-Hope-Through-Research#:~:text=Loss%20of%20dopamine%20results%20in,by%20the%20time%20symptoms%20appear. Accessed October 16, 2024.
8.Freitas, ME., et al. Motor Complications of Dopaminergic Medications in Parkinson's Disease. Semin Neurol. 2017;37(2):147-157.

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      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
      Line: 114
      Function: getRenderedTemplateCode

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
      Line: 217
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
      Line: 386
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
      Line: 116
      Function: _subTemplateRender

      File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
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      Function: endChild

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      Function: content_675a781dcbf339_49719938

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
      Line: 114
      Function: getRenderedTemplateCode

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
      Line: 217
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
      Line: 238
      Function: render

      File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
      Line: 116
      Function: _execute

      File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
      Line: 45
      Function: fetch

      File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
      Line: 32
      Function: view

      File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
      Line: 292
      Function: require_once

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    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Undefined offset: 1

    Filename: smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php

    Line Number: 41

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 24

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 24
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 186
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 156
    Function: process

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/fbdaa42e51518f8881faeabdc1199f6dd175d1ce_0.file.base_index_layout.tpl.php
    Line: 88
    Function: instanceBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3cb92fa0_94546305

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 116
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 71
    Function: endChild

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_675a781dcbf339_49719938

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 238
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_templatebase.php
    Line: 116
    Function: _execute

    File: /www/wwwroot/homev2.kingsoft.jp/application/libraries/SmartyLibrary.php
    Line: 45
    Function: fetch

    File: /www/wwwroot/homev2.kingsoft.jp/application/controllers/ArticleController.php
    Line: 32
    Function: view

    File: /www/wwwroot/homev2.kingsoft.jp/public/index.php
    Line: 292
    Function: require_once

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    Severity: Notice

    Message: Trying to access array offset on value of type null

    Filename: smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php

    Line Number: 29

    Backtrace:

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/49292b3df7e5bd60f7381ff16c5ca4532cf9476f_0.file.card.tpl.php
    Line: 29
    Function: _error_handler

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d136f97_11902452

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 384
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/08d1cc69876d91563afb9c1f4d21cc8b7b96caa4_0.file.tips.tpl.php
    Line: 41
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b3d14aa11_83151422

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/d064ec4523cd2f49c67136b7b84705846d19c90b_0.file.side.tpl.php
    Line: 43
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_resource_base.php
    Line: 123
    Function: content_66f26b47775ef5_14228348

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_template_compiled.php
    Line: 114
    Function: getRenderedTemplateCode

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 217
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_template.php
    Line: 386
    Function: render

    File: /www/wwwroot/homev2.kingsoft.jp/application/cache/smarty/597cefa22c7600eaa32b117569a9685c70819274_0.file.show.tpl.php
    Line: 416
    Function: _subTemplateRender

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 248
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
    Line: 184
    Function: callBlock

    File: /www/wwwroot/homev2.kingsoft.jp/application/third_party/smarty/libs/sysplugins/smarty_internal_runtime_inheritance.php
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