A 52-Week, Open-Label Evaluation of the Long-term Efficacy and Safety of Single and Repeated Treatments with Methylone for the Treatment of PTSD IMPACT-EXT (Investigation of Methylone for Post-Traumatic Stress Disorder [PTSD]) - TSND201-PTSD-203

开始日期2024-09-03

申办/合作机构

Transcend Therapeutics, Inc.

NCT06215261 / Recruiting临床2期

An Evaluation of the Safety and Efficacy of Methylone for the Treatment of PTSD IMPACT-2 (Investigation of Methylone for Post-Traumatic Stress Disorder [PTSD])

This study is evaluating the safety and efficacy of methylone in adults with PTSD. The study is conducted in two parts.
* Part A is open-label and will enroll up to 15 participants with PTSD
* Part B is randomized (1:1), double-blind, placebo-controlled and will enroll up to 64 participants with PTSD
Eligible participants will enter a 3-week Treatment Period where they will receive methylone (or placebo in Part B) once weekly for 3 weeks (3 treatment sessions). Following the Treatment Period, participants will enter a 6-week Follow-up Period.

开始日期2024-04-04

申办/合作机构

Transcend Therapeutics, Inc.

NCT06303648 / Recruiting临床1期

A Single, Ascending Dose Evaluation of the Safety, Pharmacokinetics of Methylone in Healthy Subjects

This is an open-label, single, ascending dose study evaluating the PK and safety of methylone in healthy subjects.

开始日期2024-03-20

申办/合作机构

Transcend Therapeutics, Inc.

100 项与 Transcend Therapeutics, Inc. 相关的临床结果

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0 项与 Transcend Therapeutics, Inc. 相关的专利（医药）

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项与 Transcend Therapeutics, Inc. 相关的文献（医药）

1997-05-01·Journal of Urology1区 · 医学

Protective Effect of L-2-Oxothiazolidine-4-Carboxylate Treatment of Cyclophosphamide-Induced Cystitis in Rats

1区 · 医学

Article

作者: Rice, D. ; Safron, J. ; Gordon, D. ; White, R. ; Leaf, C.

PURPOSEHemorrhagic cystitis is a therapy-limiting side effect of cyclophosphamide (CP) treatment for cancer. The purpose of this study was to investigate the potential protective effect of L-2-oxothiazolidine-4-carboxylate (OTZ; Procysteine) on CP-induced cystitis in the rat.MATERIALS AND METHODSThirty-six rats were divided into 6 groups: Group 1--Untreated controls, Group 2--OTZ alone (100 mg./kg., p.o.), Group 3--CP alone (68 mg./kg., i.v.), Group 4--CP + OTZ (68 mg./kg., i.v. + 100 mg.,/kg., p.o.), Group 5--CP + OTZ (68 mg./kg., i.v. + 1.0 g./kg., i.v.), and Group 6--CP + OTZ (68 mg./kg.,i.v. + 1.0 gm./kg., i.p.). OTZ was given once a day to groups 2 and 4 on the day prior to and on the day of CP administration. OTZ was given twice a day to groups 5 and 6 on the day prior to, the day of, and the day after CP administration. On the day of CP administration, CP was given 30 minutes prior to OTZ. Blood and bladder samples were taken for evaluation two days after CP administration.RESULTSExpected depression in blood cell parameters were identified in all groups receiving CP with no differences noted between the CP-treated groups. Histologic changes (cystitis) were identified in the bladders of all CP treated groups. The lesions in the CP + OTZ groups were found to be less severe than the groups that received CP alone, with higher dosages of OTZ resulting in a significant (p < 0.05) decrease in lesion incidence and severity.CONCLUSIONSUnder the conditions of this study, L-2-oxothiazolidine-4 carboxylate caused a reduction in the incidence and severity of cyclophosphamide-induced lesions in the urinary bladder of rats. Further studies are needed to investigate optimal dosage scheme, mechanism of action, and interference with anti-tumor activity and prevention of long-term side effects of cyclophosphamide.

1997-05-01·Carcinogenesis2区 · 医学

Urinary excretion of 3-methyladenine after consumption of fish containing high levels of dimethylamine

2区 · 医学

Article

作者: Eric Gremaud ; Laurent B. Fay ; David E.G. Shuker ; Cynthia D. Leaf ; Christel Steen ; Robert J. Turesky ; Jean Marc Aeschlimann

The urinary excretion of the DNA alkylation product, 3-methyladenine (3-MeAde), was measured in human volunteers who were on controlled diets and consumed fresh fish, or frozen-stored fish that contained 50-fold higher levels of dimethylamine (DMA), with or without ingested nitrate. DMA potentially could react with nitrosating agents in the diet or within the body, and produce the potent carcinogen N-nitrosodimethylamine (NDMA), which can then react with DNA to form several adducts including 3-MeAde. Our findings show that there was no increase in urinary levels of 3-MeAde after consumption of fish preserved by frozen storage relative to levels after consumption of fresh fish. Furthermore, consumption of 225 mg sodium nitrate (equal to the nitrate content in a large glass of beet juice) at 1 h prior to consumption of the frozen-stored fish did not increase urinary 3-MeAde levels as would be expected if nitrate enhanced endogenous nitrosation of DMA. In contrast, urinary excretion of 3-MeAde from a volunteer who was a moderate cigarette smoker (11 cigarettes per day) was approximately 3- to 8-fold higher than dietary 3-MeAde intake. These findings indicate that consumption of high levels of DMA in fish does not result in detectable levels of NDMA formation and genetic damage as measured by the urinary biomarker 3-MeAde.

The role of dietary nitrate and nitrite in human cancer

作者: Tannenbaum, Steven R. ; Leaf, Cynthia D.

A review with 57 references on evidence linking exposure to nitrate and nitrite and an increased risk of some types of cancer.

项与 Transcend Therapeutics, Inc. 相关的新闻（医药）

2024-02-19

·CPHI制药在线

新药 | 小分子疗法辅助治疗PTSD获FDA优先审评资格，该领域还有哪些新药已在路上？

关注并星标CPHI制药在线Lykos Therapeutics近日宣布，美国FDA已接受该公司为3，4-亚甲基二氧基甲基苯丙胺（MDMA）递交的新药申请（NDA），与心理学干预手段结合，辅助治疗被诊断出患有创伤后应激障碍（PTSD）的个体。FDA同时授予这一申请优先审评资格，预计在今年8月11日之前给出审评结果。如果获批，MDMA有望成为第一个获得 FDA 批准的迷幻剂，也将打破20 多年没有批准新的 PTSD 治疗方法的困局。这一NDA的提交包含多项研究的结果，包括两项随机双盲、含安慰剂对照的3期临床研究（MAPP1和MAPP2），MAPP1和MAPP2研究均达到了其主要和次要终点，并发表在Nature Medicine杂志上。在 MAPP2这项随机3期试验中，53 名患者随机接受 MDMA 辅助谈话疗法，51 名患者随机接受谈话疗法和安慰剂。28 名患者为西班牙裔或拉丁裔，35 名患者为非白人。患者接受了 3 个疗程的 MDMA 或安慰剂治疗。试验结果：86.5% 接受 MDMA 治疗的患者表现出 PTSD 症状减轻（如失眠、闪回和噩梦）。相比之下，接受安慰剂治疗的患者中有 69% 的症状有所减轻。临床试验结束时，71.2% 接受 MDMA 治疗的患者症状消除，并且不符合 PTSD 诊断标准。相比之下，接受安慰剂的患者中有 47.6% 不再被诊断为PTSD患者。在MAPP1 3期临床试验中，46名PTSD患者随机接受三个疗程的MDMA和心理治疗，44名患者随机接受安慰剂和心理治疗。试验结果：67% 接受 MDMA 的患者不再被诊断为PTSD患者。相比之下，接受安慰剂的患者中只有 32% 不再被诊断为PTSD患者。3,4-甲基二氧基甲基苯丙胺(MDMA)长时间以来作为兴奋致幻剂被列为非法毒品，直到2017年，MDMA获得美国食品和药物管理局(FDA) 突破性疗法认定，并获准在临床试验中使用。MDMA分子结构式（图片来源：PubChem）MDMA通过与转运蛋白结合，增加单胺（如血清素、去甲肾上腺素、多巴胺）的释放。MDMA 还抑制单胺再摄取。它还会降低与过度活跃的恐惧反应相关的岛叶和杏仁核的活动。关于创伤后应激障碍（PTSD）PTSD是一种精神疾病，可由对创伤性事件（人际暴力、战斗、危及生命的事故或自然灾害）的反应而引发。PTSD的核心特征包括多种症状：例如重新体验现象（即回忆和噩梦）、回避行为、麻木（即健忘症、快感缺乏、戒断、消极情绪）和增加的唤醒行为（即失眠、烦躁、注意力不集中、过度警觉）。军人、性虐待受害者和急救人员患这种精神障碍的风险很高。精神病合并症也很常见，PTSD患者可能滥用药物，出现情绪和其它焦虑性情感障碍，有冲动和危险的行为以及自我伤害。在不同的人群和国家，PTSD的患病率为0.2-4%。尽管目前心理治疗通常被视为PTSD的一线治疗方法，但是大部分就诊的PTSD患者还是会被开具精神药物处方。原因可能包括个人选择、存在共病或特定症状、心理治疗排不上、病情不稳导致无法接受心理治疗及心理治疗下仍迁延不愈。改善PTSD的症状可以用SSRIs类（氟西汀、帕罗西汀和舍曲林）和SNRIs类（文拉法辛）药物来治疗。目前，这四种抗抑郁药物拥有确切的证据使其成为治疗PTSD的重要选择。但大约 40% 至 60% 的 PTSD 患者对这些药物没有反应。图片来源：蓝色心灵港湾多款在研PTSD新药来袭创伤后应激障碍会严重影响个体的生活质量，且持续时间漫长，究其关键因素就是条件恐惧的难以消退。但FDA 已有 20 多年没有批准新的 PTSD 治疗方法，目前急需有效的新型疗法出现以达到病症的持续缓解。下面笔者将简单介绍几款处于2期临床阶段的PTSD新药，希望能给行业内人士带来一些启发。BNC210BNC210是Bionomics开发的一款靶向α7烟碱乙酰胆碱受体的负向变构调节剂，正在被开发用于治疗社交恐惧症（SAD）和PTSD。2021年12月，BNC210获FDA授予快速通道资格，用于治疗PTSD和其他创伤和压力源相关疾病以及急性治疗SAD和其他焦虑相关疾病。去年9月BNC210 治疗PTSD的2b期ATTUNE试验达到主要终点，显著减轻了PTSD患者的症状且具良好的安全性。TSND-201TSND-201是一种快速起效的神经功能重塑因子，是Transcend公司开发的methylone的专有制品。TSND-201具有明确的主要药理学特征，其主要作用位点是单胺转运蛋白，对5HT-2a没有活性（即不会致幻）。Transcend正在开发TSND-201作为治疗PTSD、抑郁症和其他中枢神经系统疾病的一种快速且持久的疗法。去年12月，Transcend Therapeutics在美国神经精神药理学学会（ACNP）年会上公布了其神经功能重塑因子（neuroplastogen）TSND-201（methylone）用于治疗创伤后应激障碍（PTSD）的2期临床试验IMPACT-1的积极结果。结果显示，超过六成患者的PTSD症状和抑郁症状得到改善。ALTO-100ALTO-100是由Alto Neuroscience利用其人工智能生物标志物平台所开发的一款口服药物，其靶点为脑源性神经营养因子（BDNF），针对治疗MDD与创伤后应激障碍（PTSD）所开发。可恢复患者的神经可塑性，使大脑能够灵活适应新信息。去年9月，Alto Neuroscience公司公布了ALTO-100的2a期临床试验中PTSD队列的研究结果，证明了ALTO-100对PTSD患者的疗效和良好的安全性。参考来源：1.各企业官网2.Feduccia, A. A., & Mithoefer, M. C. (2018). MDMA-assisted psychotherapy for PTSD: are memory reconsolidation and fear extinction underlying mechanisms?. Progress in neuro-psychopharmacology and biological psychiatry, 84, 221-228.3.Mitchell, J. M., Ot’alora G, M., van der Kolk, B., Shannon, S., Bogenschutz, M., Gelfand, Y., ... & MAPP2 Study Collaborator Group. (2023). MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine, 1-8.【智药研习社课程预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

优先审批临床3期突破性疗法临床结果

2023-12-18

·Outsourcing Pharma

Anxiety treated with single dose of psychedelic drug in phase 2b trial

Four weeks after receiving a 100 µg dose of the drug candidate, patients saw a significant reduction in anxiety symptoms compared to a placebo, shown by a 7.6 point drop in the Hamilton Anxiety rating scale (HAM-A). According to the scale, a score lower than 17 signals mild anxiety and 25-30 indicates moderate to severe anxiety. GAD is a common condition that causes feelings of persistent anxiety, fear and excessive worry, and can negatively impact daily life. “The pharmaceutical industry has largely ignored GAD over recent decades as it has proved extremely difficult to target,” said Daniel Karlin, Chief Medical Officer of MindMed in a public statement. “Few new treatment options have shown robust activity in GAD since the last new drug approval in 2004, making the strong, rapid, and durable clinical activity of a single dose of MM-120 observed in the trial particularly notable.” MindMed’s trial enrolled 198 participants who received either MM-120 at 25, 50, 100 or 200 µg or a placebo. The participants had severe GAD at baseline, with an average HAM-A score of approximately 30. A total of 78% of patients receiving either 100 µg or 200 µg of the drug candidate saw a clinical response, a drop of 50% or more in their HAM-A score, compared to 31% in the placebo group. Meanwhile, half of the patients given 100 µg of MM-120 saw a clinical remission, represented by a HAM-A score of less than 7. The company saw the drug was overall well-tolerated and that the mostly mild-to-moderate adverse events, such as illusion, hallucinations, euphoric mood, happened on the day of dosing. googletag.cmd.push(function () { googletag.display('text-ad1'); }); MindMed now plans to discuss its results with the US Food and Drug Administration (FDA) in early 2024 and to launch a larger phase 3 trial in the second half of the same year. “We are excited by the strong positive results for MM-120 in GAD, particularly given that this is the first study to assess the standalone drug effects of MM-120 in the absence of any psychotherapeutic intervention,” said Robert Barrow, Chief Executive Officer and Director of MindMed. “These promising findings represent a major step forward in our goal to bring a paradigm-shifting treatment to the millions of patients who are profoundly impacted by GAD.” MM-120 is a small molecule drug with the name of lysergide d-tartrate, and is designed to partially activate the human serotonin-2A receptor. While there is a wide range of therapies to treat psychiatric disorders, many can take weeks to show a benefit and can come with side effects such as insomnia, nausea and headaches, according to MindMed’s website. Psychedelic drugs, meanwhile, are attracting increasing attention for their potential to rewire the brain in order to treat psychiatric disorders including depression and post-traumatic stress disorder. They can show benefits beginning as fast as the day of the treatment and can maintain the improvement for a long time with fewer major side effects. MindMed is also developing MM-120 for the treatment of attention hyperactivity deficit disorder. The company is also working on a form of MDMA for the treatment of autism spectrum disorder and another treatment candidate for opioid use disorder. There are many other players championing psychedelics for the improvement of mental health. In October, Transcend Therapeutics partnered with Clerkenwell Health to trial the use of methylone in patients with severe PTSD. Meanwhile, Psycheceutical is developing its own psychedelic to treat the same condition, this time based on a form of ketamine.

临床结果临床2期

2023-12-08

·药明康德

速递 | 超六成患者症状得到改善，非致幻性PTSD潜在新药2期临床结果积极

▎药明康德内容团队编辑近日，Transcend Therapeutics在美国神经精神药理学学会（ACNP）年会上公布了其神经功能重塑因子（neuroplastogen）TSND-201（methylone）用于治疗创伤后应激障碍（PTSD）的2期临床试验IMPACT-1的积极结果。结果显示，超过六成患者的PTSD症状和抑郁症状得到改善。IMPACT-1旨在评估TSND-201治疗PTSD的安全性和有效性。A部分是开放标签研究，B部分是随机、双盲、安慰剂对照研究。患者每周接受给药一次，同时接受一位经过培训的导师的非指导性心理支持，共接受4周的治疗。在4周的治疗期结束后，受试者在最后一次治疗后的第1、2、3和6周接受随访。14名A部分受试者的结果显示，TSND-201能够对PTSD的症状产生迅速而强大的影响。在每次给药后，受试者的DSM-5创伤后应激障碍量表（CAPS-5）得分与基线相比均产生了统计学显著的变化。首次给药2天后，受试者的CAPS-5得分与基线相比的平均变化为-8.4分（p=0.002），这表明TSND-201起效迅速。TSND-201在整个治疗期中在CAPS-5得分上为患者提供了强有力的改善。在最后一次给药后一周，受试者的CAPS-5得分与基线相比的平均变化为-31.9分（p<0.0001）。在最后一次给药后6周，受试者的CAPS-5得分与基线相比的平均变化为-36.2分（p<0.0001），表明TSND-201的疗效持久。在研究结束时，大多数受试者（61.5%）达到了缓解，即CAPS-5总分≤11。▲与基线相比CAPS-5得分的平均变化（图片来源：参考资料[2]）除了改善PTSD症状外，每次给药后，受试者的MADRS抑郁评定量表（一种用于评估抑郁症状严重程度的工具）评分与基线相比有显著减少。在最后一次给药后一周，与基线相比的平均变化为-19.4分（p=0.002）。在最后一次给药后6周，与基线相比的平均变化为-21.4分（p<0.0001），同样表明TSND-201的疗效持久。此外，61.5%的受试者达到了抑郁症状缓解，即MADRS总分≤10。▲与基线相比MADRS抑郁评定量表评分的平均变化（图片来源：参考资料[2]）安全性方面，TSND-201治疗总体上是安全和可耐受的。最常见的治疗相关不良事件是头痛，未报告与治疗相关的严重不良事件。TSND-201是一种快速起效的神经功能重塑因子，是Transcend公司开发的methylone的专有制品。TSND-201具有明确的主要药理学特征，其主要作用位点是单胺转运蛋白，对5HT-2a没有活性（即不会致幻）。Transcend正在开发TSND-201作为治疗PTSD、抑郁症和其他中枢神经系统疾病的一种快速且持久的疗法。药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Transcend Therapeutics Announces Positive Open-Label Data From IMPACT-1. Retrieved December 5, 2023, from https://www.transcendtherapeutics.com/transcend-therapeutics-announces-positive-open-label-data-from-impact-1/[2] TSND-201 (methylone) for the Treatment for PTSD: Initial Results from an Open-Label Study (IMPACT-1). Retrieved December 5, 2023, from http://www.transcendtherapeutics.com/app/uploads/2023/12/2023-ACNP_IMPACT-1-Part-A-Open-label.pdf免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床2期

100 项与 Transcend Therapeutics, Inc. 相关的药物交易

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100 项与 Transcend Therapeutics, Inc. 相关的转化医学

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