The purpose of this study is to evaluate the efficacy of clorazepate in addition to the usual medication for treating migraine attack in the emergency room

开始日期2021-07-08

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

EUCTR2018-000503-16-FR / Not yet recruiting临床3期IIT

Randomized, double-blind, single-centre, randomized study evaluating the efficacy of CLORazepate dipotassium in the treatment of migraine crisis in the emergency department. - CLORMIG

开始日期2021-02-12

申办/合作机构-

NCT00775996 / CompletedN/A

The Objective of This Study Was to Compare the Single-Dose Relative Bioavailability of Ranbaxy and Abbott (Tranxene® T-Tab®) 15 mg Clorazepate Dipotassium Tablets Under Fasting Conditions.

The objective of this study was to compare the single-dose relative bioavailability of Ranbaxy and Abbott (TranxeneeT-Tab®) 15 mg clorazepate dipotassium tablets under fasting conditions.

开始日期2003-08-01

申办/合作机构

Ranbaxy Laboratories Ltd.

100 项与氯卓酸二钾相关的临床结果

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100 项与氯卓酸二钾相关的转化医学

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100 项与氯卓酸二钾相关的专利（医药）

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项与氯卓酸二钾相关的文献（医药）

2023-04-18·Antioxidants (Basel, Switzerland)

A Study on the Planarian Model Confirms the Antioxidant Properties of Tameron against X-ray- and Menadione-Induced Oxidative Stress.

Article

作者: Kolotova, Anastasia ; Blagodatski, Artem ; Ermakov, Artem ; Afanasyeva, Vera ; Ermakova, Olga ; Filippova, Kristina ; Tsarkova, Elena

Ionizing radiation and radiation-related oxidative stress are two important factors responsible for the death of actively proliferating cells, thus drastically reducing the regeneration capacity of living organisms. Planarian flatworms are freshwater invertebrates that are rich in stem cells called neoblasts and, therefore, present a well-established model for studies on regeneration and the testing of novel antioxidant and radioprotective substances. In this work, we tested an antiviral and antioxidant drug Tameron (Monosodium α-Luminol or 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt) for its ability to reduce the harm of X-ray- and chemically induced oxidative stress on a planarian model. Our study has revealed the ability of Tameron to effectively protect planarians from oxidative stress while enhancing their regenerative capacity by modulating the expression of neoblast marker genes and NRF-2-controlled oxidative stress response genes.

2023-03-10·Alcohol and alcoholism (Oxford, Oxfordshire)

Effect of Clomethiazole Vs. Clorazepate on Hepatic Fat and Serum Transaminase Activities in Alcohol-Associated Liver Disease: Results from a Randomized, Controlled Phase II Clinical Trial

Article

作者: Haefeli, Walter E ; Mueller, Sebastian ; Burhenne, Jürgen ; Seitz, Helmut K ; Schröder, Fabian ; Hohmann, Nicolas ; Moreira, Bernardo ; Bruckner, Thomas ; Teng, Haidong

Abstract:

Aims:

Alcohol-associated liver disease (ALD) is a global health problem caused, among other factors, by oxidative stress from the formation of reactive oxygen species (ROS). One important source of ROS is microsomal ethanol metabolism catalyzed by cytochrome P450 2E1 (CYP2E1), which is induced by chronic ethanol consumption. Inhibition of CYP2E1 by clomethiazole (CMZ) decreases oxidative stress in cell cultures and improves ALD in animal studies. Our study aimed to assess the benefits of a CYP2E1 inhibitor (clomethiazole) in detoxification of patients with ALD.

Methods:

Open label, randomized controlled clinical trial to study whether CYP2E1 inhibition improves ALD in the patients with alcohol use disorders admitted for alcohol detoxification therapy (ADT). Patients had to have a serum aspartate aminotransferase (AST) activity exceeding twice the upper normal limit at time of admission and be non-cirrhotic defined by fibroscan value <12 kPa. Sixty patients were randomly assigned to ADT with either CMZ or clorazepate (CZP) for 7–10 days in a 1:1 ratio. The chlorzoxazone test of CYP2E1 activity was performed at enrolment and at 2 points during the study.

Results:

ADT improved hepatic steatosis (controlled attenuation parameter) in both groups significantly. A trend towards a greater improvement in hepatic fat content during ADT (−21.5%) was observed in the CMZ group (252 ± 48 dB/m vs. 321 ± 38 dB/m; P < 0.0001) compared with the CZP group (−13.9%; 273 ± 38 dB/m vs. 317 ± 39 dB/m; P < 0.0001). As already reported, serum AST (P < 0.004) and alanine aminotransferase (ALT) activities (P < 0.0006) significantly decreased in CMZ patients as compared with patients on CZP by the end of hospitalization. A significant correlation was found between AST (P = 0.023), ALT (P = 0.009), GGT (P = 0.039) and CAP.

Conclusion:

This study demonstrates that CMZ improves clinical biomarkers for ALD in humans most likely due to its inhibitory effect on CYP2E1. Because of its addictive potential, CMZ can only be given for a short period of time and therefore other CYP2E1 inhibitors to treat ALD are needed.

2022-04-01·Gut

Clomethiazole inhibits cytochrome P450 2E1 and improves alcoholic liver disease

Letter

作者: Haefeli, Walter E ; Mueller, Sebastian ; Burhenne, Jürgen ; Seitz, Helmut K ; Schröder, Fabian ; Hohmann, Nicolas ; Moreira, Bernardo ; Teng, Haidong ; Bruckner, Thomas

In their article on recent advances in alc. liver disease (ALD), Avila and coworkers also mention the little- studied approach of inhibiting overexpressed cytochrome P 450 2E1 (CYP2E1), which is induced by chronic ethanol consumption, causes generation of reactive oxidative species (ROS) and oxidative stress and stimulates hepatic steatosis and fibrosis.To study whether CYP2E1 inhibition improves ALD in humans, we performed an open, randomized controlled clin. trial in alc.-dependent patients who were admitted to the hospital for alc. detoxification therapy (ADT).ADT was performed either with clomethiazole or clorazepate, which are both recom- mended as first- line therapies by the German S3-guidelines for the treatment of ADT.Already after the first dose of clomethiazole, CYP2E1 activity decreased significantly by 95%, while no effect was seen with clorazepate.The molar metabolite- to- parent drug ratio reflects CYP2E1 activity.Recovery of liver damage demonstrated by the improvement of serum transaminase activities was more pronounced during clomethiazole treatment.In summary, this randomised controlled clin. trial demonstrates for the first time in humans that clomethiazole accelerates the early recovery from ALD as demon- strated by a more rapid improvement of serum transaminase activity compared with treatment with a benzodiazepine.Because clomethiazole is a potent CYP2E1 inhibitor, it also supports the presumed involvement of CYP2E1 in the pathogenesis of ALD, which is well documented in vitro and in animal studies.Thus, it seems it is time to search for other inhibitors of CYP2E1 activity without toxicity and addiction potential, which can be used safely for longer periods of time.

项与氯卓酸二钾相关的新闻（医药）

2024-07-02

·drugs

Use of 'Benzo' Sedatives Like Valium, Xanax Won't Raise Dementia Risk: Study

TUESDAY, July 2, 2024 -- Benzodiazepines do not appear to increase dementia risk, but could have subtle long-term effects on brain structure, a new study reports. Researchers found no link between use of the sedative drug and a higher risk of dementia in a group of more than 5,400 adults in the Netherlands, according to findings published July 2 in the journal BMC Medicine . That runs counter to two previous meta-analyses reporting increased dementia risk with benzodiazepine use, researchers noted. However, brain MRI scans taken of more than 4,800 participants revealed that benzodiazepine use is associated with accelerated shrinking of some brain regions, results show. The findings “support current guidelines cautioning against long-term benzodiazepine prescription,” concluded the research team led by Dr. Frank Wolters , a senior scientist of epidemiology and radiology and nuclear medicine at Erasmus Medical Center in the Netherlands. “Further research is needed to investigate the potential effects of benzodiazepine use on brain health,” the team adds. Benzodiazepines promote the release of a neurotransmitter that makes the nervous system less active, the Cleveland Clinic says. Different types are used as sedatives or to treat anxiety , insomnia and seizures. Analysis of medical records between 2005 and 2020 and pharmacy records between 1991 and 2008 revealed no association between benzodiazepines and increased risk of dementia, regardless of the total quantity of sedatives people took over time. The team also found no link between dementia risk and specific types of benzodiazepines or the time it took for dosages to wear off. However, benzodiazepine use was associated with an accelerated reduction in the volume of the hippocampus and amygdala, which are brain regions involved in memory and mood regulation. Certain types of benzodiazepines also were associated with changes in the size of white matter, which transmits nerve signals between brain regions, researchers said. Anxiolytic benzodiazepines prescribed for anxiety caused less shrinkage of white matter, results show. These include alprazolam (Xanax), clonazepam (Klonopin), clorazepate (Tranxene) and lorazepam (Ativan, Loreev), according to the Cleveland Clinic. On the other hand, sedative-hypnotic benzodiazepines prescribed for sleep problems caused a quicker reduction in white matter volume. These include temazepam (Restoril), triazolam (Halcion) and quazepam (Doral), the Cleveland Clinic says. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

2022-07-24

·药渡Daily

2022.07.09-07.15全球药物研发进展周报

扫描文末二维码，申请药渡数据3天免费试用1全球新药研发进展2022.07.09-07.15这一周，全球新药研发各个领域均有新的突破，包括：肿瘤、精神、神经、消化系统、心血管、感染、免疫、皮肤和结缔组织疾病、内分泌系统等多个领域。其中，肿瘤等热门领域依旧同时涵盖了化学药、生物药、细胞疗法的最新研究进展。Moderna宣布Nipah病毒(NiV) 候选疫苗mRNA-1215的I期临床研究完成首例受试者给药2022年7月12日，Moderna宣布，公司与名为VRC（疫苗研发中心）的NIAID&NIH的一个分支机构，合作开发的针对NiV的候选疫苗mRNA-1215完成I期临床的首例受试者给药。此项研究是一项首次在健康成人群体中进行的剂量递增、开放标签的临床研究，旨在评估NiV mRNA疫苗的安全性、耐受性和免疫原性。NiV是一种人畜共患病毒，这意味着它可以在动物和人之间传播。该病毒可以通过食用受污染的食物或直接从其他感染者传播给受感染的动物传播给人类。NiV是一种致命的病原体，可引起快速进展的疾病，包括急性呼吸道感染和脑炎，可导致昏迷或死亡。虽然有可能康复，但估计有40%至75%的NiV感染者因感染而死亡。自1999年在马来西亚首次发现NiV以来，它经常从动物蔓延到人类，几乎每年在亚洲一些地区都有爆发。虽然NiV的动态是不可预测的，但该病毒具有高突变率，被认为是一种重大的大流行威胁和具有生物恐怖主义潜力的病原体。由于其高大流行潜力，NiV被世界卫生组织（WHO）、疾病控制和预防中心（CDC）以及流行病防范创新联盟（CEPI）列为高度优先病原体。来源：Moderna官网NexImmune宣布获得美国FDA对NEXI-003用于治疗HPV相关癌症的IND许可2022年7月14日，NexImmune宣布，公司首个针对实体瘤的细胞治疗候选产品已获得IND许可。NEXI-003是一种自体抗原特异性T细胞产物（CD3+/CD4-），正在为复发或难治性人瘤病毒（HPV）相关癌症患者开发。NEXI-003是公司的第三种T细胞疗法，也是第一个解决实体瘤的候选药物。NEXI-003由同时针对多个HPV肿瘤相关抗原靶标的T细胞群组成。候选产品中的T细胞将包括对潜在抗肿瘤活性至关重要的T细胞亚型和旨在产生持久反应所需的长期免疫记忆的表型。I期试验将在美国各地的多个临床地点招募患者。拟议的研究是一项由两部分、多中心、开放标签、剂量发现、首次进行的人体（FIH）研究，旨在表征NexImmune的HPV肿瘤相关抗原特异性CD8+T细胞候选物（NEXI-003）在复发或难治性局部晚期或转移性HPV相关口咽癌患者（已确认组织病理学检测HPV-16和/或HPV-18表达）的安全性和临床活性，这些患者根据当地标准护理指南。剂量递增阶段将包括多个安全队列，研究NEXI-003的剂量增加，然后是扩展阶段，根据剂量递增的数量，总共招募24至36名患者。所有患者都将接受至少一年的随访。根据初始数据和推荐的II期剂量得到确认后，NexImmune计划扩大NEXI-003开发计划，以包括其他与HPV相关的恶性肿瘤，并评估患者群体中潜在的SOC组合选择。来源：NexImmune官网2022.07.09-07.15全球新药研发进展（部分）更多具体信息，请联系小编获取2国内新药研发进展2022年7月9日-7月15日，国内新药研发同样突飞猛进，治疗肿瘤的生物药进展迅速。和黄医药首次公布赛沃替尼与泰瑞沙®联合疗法之SAVANNAH全球II期研究数据2022年7月13日，和黄医药宣布，将于国际肺癌研究协会（IASLC）主办的2022年世界肺癌大会（WCLC）上首次公布正在进行中的SAVANNAH全球II期研究数据，大会将于2022年8月6日至9日在奥地利维也纳举行。SAVANNAH研究是一项全球II期临床试验，旨在评估和黄医药与阿斯利康合作开发的赛沃替尼与阿斯利康的泰瑞沙®联合疗法治疗既往曾接受泰瑞沙®治疗后疾病进展的表皮生长因子受体（“EGFR”）突变、间充质上皮转化因子（“MET”）驱动的非小细胞肺癌患者。患者除持续接受泰瑞沙®治疗以外，亦按300毫克每日一次、300毫克每日两次或600毫克每日一次的剂量接受了赛沃替尼的给药治疗。研究已共招募了294名患者。赛沃替尼是一种强效、高选择性的口服MET酪氨酸激酶抑制剂，在晚期实体瘤中表现出临床活性。赛沃替尼可阻断因突变（例如外显子14跳跃突变或其他点突变）或基因扩增而导致的MET受体酪氨酸激酶信号通路的异常激活。赛沃替尼在中国以商品名沃瑞沙®上市，用于治疗接受全身性治疗后疾病进展或无法接受化疗的MET外显子14跳跃突变的非小细胞肺癌患者。目前，赛沃替尼正作为单药疗法或与其他药物的联合疗法，开发用于治疗包括肺癌、肾癌和胃癌在内的多种肿瘤类型。继赛沃替尼由和黄医药自主研发及初步开发后，和黄医药与阿斯利康于2011年达成一项全球许可和合作协议，旨在共同开发赛沃替尼并促进其商业化。赛沃替尼在中国的联合开发由和黄医药主导，并由阿斯利康主导其海外开发。和黄医药负责赛沃替尼在中国的上市许可、生产和供应，而阿斯利康则负责赛沃替尼在中国乃至全球范围内的商业化。赛沃替尼的销售收入由阿斯利康确认。来源：和黄医药官网北海康成治疗胆道闭锁的CAN108（Maralixibat）II期全球EMBARK研究完成首例中国患者给药2022年7月15日，北海康成宣布，在北京首都儿科学研究所开展的CAN108（maralixibat）治疗胆道闭锁（BA）的II期EMBARK研究中，已完成在中国的首例患者给药。该治疗BA的全球EMBARK研究，是一项多中心、随机对照的II期研究，旨在评价CAN108治疗Kasai手术后BA患者的有效性和安全性，预期将在全球招募72例患者，其中包括在中国招募20例患者。北海康成和Mirum已签订了maralixibat在大中华区开发和商业化独家许可协议。根据协议条款，北海康成已获得在大中华区针对阿拉杰里综合征（ALGS）、进行性家族性肝内胆汁淤积症（PFIC）和胆道闭锁（BA）开发和商业化的独家授权。胆道闭锁（BA）是一种在出生后前几周出现的胆管系统进行性炎症性疾病，表现为长时间的黄疸、无胆汁粪便和尿色较深。BA的病因和发病机制仍不明确，可能是多因素的。西方国家BA的患病率估计为0.5 - 0.8/10,000例活产婴儿，低于亚洲人报告的患病率（日本1.04/10,000；中国台湾地区1.78/10,000）。BA在西方国家是公认的孤儿病，其与胆汁淤积性肝病损伤、进行性纤维化直至肝硬化相关，导致门静脉高压和肝衰竭，需要进行肝移植，如果不给予治疗，将会危及生命。标准治疗是Kasai手术作为一线干预。然而，大约40%-50%接受Kasai手术的患者在2岁之前仍需要进行肝移植，这使BA成为全球儿童肝移植的主要原因，且突显了BA大量未满足的医疗需求。EMBARK是Mirum申办的全球II期研究，旨在评价maralixibat治疗Kasai术后BA受试者的有效性和安全性（NCT04524390）。此研究包括26周的随机对照治疗，然后是78周开放性扩展期，正在北美、欧洲和亚洲（包括中国）的多个研究中心开展。目前尚无药物获批用于BA患者的治疗。 LIVMARLI® （maralixibat）口服溶液是一种口服的、每日一次的回肠胆汁酸转运蛋白（IBAT）抑制剂，已经获得美国食品和药物管理局批准用于治疗一岁以上的阿拉杰里综合征（ALGS）患者的胆汁淤积性瘙痒症，而且也是唯一获得FDA批准的治疗与阿拉杰里综合征相关的胆汁淤积性瘙痒症的药物。LIVMARLI®目前正在其他罕见胆汁淤积性肝病的后期临床研究中进行评估，包括进行性家族性肝内胆汁淤积症（PFIC）和胆道闭锁（BA）。在美国，LIVMARLI® 已获得阿拉杰里综合征和进行性家族性肝内胆汁淤积症II型的突破性疗法资格，以及阿拉杰里综合征、进行性家族性肝内胆汁淤积症和胆道闭锁的孤儿药资格。来源：北海康成官网2022.07.09-07.15国内新药研发进展（部分）更多具体信息，请联系小编获取3国内临床默示许可进展2022.07.09-07.15临床默示许可进展（部分）更多具体信息，请联系小编获取4全球医药交易事件Neuraxpharm与赛诺菲就多个成熟产品达成收购协议2022年7月12日，Neuraxpharm与赛诺菲达成一项最终协议，根据协议内容，Neuraxpharm将从赛诺菲收购两个用于中枢神经系统疾病、疼痛和血管疾病的产品组合。随着即将到来的收购，Neuraxpharm将加强其作为专注于CNS的欧洲领先专业制药公司的地位。Neuraxpharm收购的成熟产品在将全球50多个国家销售。第一个产品组合结合了15种针对中枢神经系统疾病的产品，涵盖精神病学和神经病学。第二个产品组合包括两种疼痛和血管疾病产品。收购这些新投资组合后，Neuraxpharm的年总销售额将达到6亿欧元左右。这些产品使各种疾病的患者受益，包括抑郁症、焦虑症、精神病、酒精依赖、重症肌无力和帕金森病。CNS产品组合主要包括Nozinan，Tranxene，Tiapridal，Dogmatil，Largactil。疼痛和血管组合包括托帕吉克和特伦塔尔。两个产品组合包括代表38个品牌的17个分子。这些全球品牌将进一步巩固Nuraxpharm作为欧洲领先的CNS制药公司的地位，并增加公司的全球足迹和业务。来源：Neuraxpharm官网MaxCyte与LG化学签署战略平台许可，以推进LG化学的同种异体CAR-T计划2022年7月12日，MaxCyte与LG化学签署战略平台许可证（SPL）。根据协议条款，LG化学获得使用MaxCyte流动电穿孔®技术和ExPERT™平台的非独家临床和商业权利。作为回报，MaxCyte有权获得平台许可费和与计划相关的收入。LG化学进一步加快了全球新药临床开发的努力，通过先进的细胞药物平台技术建设，加强其抗癌领域。LR19023是新一代CAR-T细胞治疗，目前处于临床前阶段，正在开发中，作为固体癌症治疗药物。来源：MaxCyte官网2022.07.09-07.15全球医药交易（部分）更多具体信息，请联系小编获取▲编辑：胡桃声明：药渡数据出品，未经允许禁止转载扫描二维码，申请药渡数据免费试用

细胞疗法免疫疗法孤儿药并购合作

2022-07-13

·Endpoints

Sanofi CEO Paul Hudson offloads two portfolios to German pharma company in continued effort to prune products

Sanofi warned earlier this year that some serious cuts were in order. CEO Paul Hudson made good on that promise this week, pruning more than a dozen marketed products. Germany-based Neuraxpharm revealed yesterday that it struck a deal for Sanofi’s CNS and pain and vascular disease portfolios. While the companies are keeping the financial terms under wraps for now, Neuraxpharm did say it’s swallowing 17 products representing 38 brands, including neuroleptics Nozinan and Tiapridal, anxiety med Tranxene and antipsychotics Dogmatil and Largactil. Within the pain and vascular portfolio, Neuraxpharm is getting pain narcotic Topalgic and Trental, which is used to improve blood flow. Neuraxpharm expects that the new products will boost sales to about $600 million this year. “There is significant growth potential in the pharmaceutical sector, especially in the CNS market driven by an aging population and an increasing awareness of mental health,” CEO Jörg-Thomas Dierks said in a news release. “With the upcoming acquisition, we will not only strengthen our presence in Europe, but also lay the ground for further expanding our international presence.” The new drugs will contribute to a portfolio of CNS drugs, as well as generics and consumer healthcare products such as nutraceuticals and probiotics, according to Neuraxpharm’s website. The company has main offices in Germany and Spain, with additional locations throughout Europe. Hudson has been on a mission to reshape Sanofi since he took the helm in 2019. He said earlier this year that nothing is off the table when it comes to restructuring, and has already culled a handful of programs. During the Q1 call, EVP of general medicines Olivier Charmeil said the company is looking to shave the general medicines unit down to about 125 product families, either by divesting or discontinuing programs. That’s a big difference from late 2019 and early 2020, when the unit boasted more than 350 product families. The company also revealed in its Q4 results that it plans on axing about 6,000 jobs in an effort to become more “agile.” Execs said at the time that they were aiming for a headcount of around 90,000 by the end of the year.

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KEGG	Wiki	ATC	Drug Bank
D00694	氯卓酸二钾	N05BA05	DB00628

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适应症	国家/地区	公司	日期
戒酒	美国	AJENAT PHARMACEUTICALS LLC	1972-06-23
焦虑症	美国	AJENAT PHARMACEUTICALS LLC	1972-06-23
癫痫部分性发作	美国	AJENAT PHARMACEUTICALS LLC	1972-06-23