A Multicenter, Randomized Withdrawal, Double-blind, Parallel, Placebo-controlled Design Clinical Trial of Toludesvenlafaxine Hydrochloride Extended-Release Tablets

This is a multicenter, randomized withdrawal, double-blind, parallel, placebo-controlled design clinical trial of Toludesvenlafaxine Hydrochloride Extended-Release Tablets to evaluate the long-term efficacy and safety in the treatment of Chinese patients with depression.

开始日期2024-05-30

申办/合作机构

綠葉製藥集團有限公司

NCT06278038 / RecruitingN/AIIT

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Venlafaxine Hydrochloride Sustained-release Tablets in Patients With Major Depression Disorder: a Multicentre, Open-label, Parallel-group, Randomised Controlled Trial

The purpose of this study is to evaluate efficacy and safety of toludesvenlafaxine hydrochloride sustained-release tablets in the treatment of major depression disorder compared to venlafaxine hydrochloride sustained-release tablets, to provide evidence-based basis for clinical rational drug use.

开始日期2024-02-22

申办/合作机构

The First Affiliated Hospital, Zhejiang University School of Medicine

100 项与盐酸托鲁地文拉法辛相关的临床结果

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100 项与盐酸托鲁地文拉法辛相关的转化医学

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100 项与盐酸托鲁地文拉法辛相关的专利（医药）

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项与盐酸托鲁地文拉法辛相关的文献（医药）

2024-07-01·European Journal of Nuclear Medicine and Molecular Imaging

PET/CT study of dopamine transporter (DAT) binding with the triple reuptake inhibitor toludesvenlafaxine in rats and humans

Article

作者: Huang, Zhiwei ; Shen, Yifeng ; Xie, Fang ; Guan, Yihui ; Wu, Junhao ; Wei, Yumei

PURPOSEToludesvenlafaxine is a recently developed antidepressant that belongs to the triple reuptake inhibitor class. Despite the in vitro evidence that toludesvenlafaxine inhibits the reuptake of serotonin (5-HT), norepinephrine (NE) and dopamine (DA), there is no in vivo evidence that toludesvenlafaxine binds to DAT and increases DA level, a mechanism thought to contribute to its favorable clinical performance.METHODSPositron emission tomography/computed tomography (PET/CT) was used to examine the DAT binding capacity in healthy rats and human subjects and microdialysis was used to examine the striatal DA level in rats. [¹⁸F]FECNT and [¹¹C]CFT were used as PET/CT radioactive tracer for rat and human studies, respectively.RESULTSIn rats, 9 mg/kg of toludesvenlafaxine hydrochloride (i.v.) followed by an infusion of 3 mg/kg via minipump led to the binding rate to striatum DAT at 3.7 - 32.41% and to hypothalamus DAT at 5.91 - 17.52% during the 45 min scanning period. 32 mg/kg oral administration with toludesvenlafaxine hydrochloride significantly increased the striatal DA level with the AUC_{0 - 180 min} increased by 63.9%. In healthy volunteers, 160 mg daily toludesvenlafaxine hydrochloride sustained-release tablets for 4 days led to an average occupancy rates of DAT at 8.04% ± 7.75% and 8.09% ± 7.00%, respectively, in basal ganglion 6 h and 10 h postdose.CONCLUSIONThese results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine.CLINICALTRIALSGOV IDENTIFIERSNCT05905120. Registered 14 June 2023. (retrospectively registered).

2023-05-10·Translational psychiatry

A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder.

Article

作者: Xie, Shiping ; Chen, Zhenhua ; Zhou, Yunfei ; Wang, Yiming ; Yang, Dong ; Wu, Bin ; Wang, Huaning ; Wang, Guoqiang ; Mi, Weifeng ; Jiang, Zhiwei ; Zhang, Hongyan ; Yi, Qizhong ; Zhang, Kerang ; Li, Lehua ; Lv, Shuyun ; Li, Yi ; Luo, Jiong ; Tian, Feng ; Zhong, Hua ; Chen, Jindong ; Di, Xiaolan ; Tian, Jingwei ; Xu, Xiufeng ; Yang, Chanjuan ; Li, Huafang

Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice.Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need.A multicenter, double-blind, randomized, placebo-controlled phase 3 clin. trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine.Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-wk treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185).The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study.Safety indexes included adverse events, vital signs, phys. examination, laboratory tests, 12-lead ECG (ECG), and evaluation of suicide tendency and sexual function.Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, -20.0; 160 mg, -19.9) vs. placebo (-14.6; p < 0.0001).All doses of ansofaxine were generally well-tolerated.Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group.The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group.The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD.

2023-05-01·Journal of Affective Disorders

A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder

Article

作者: He, Ruifeng ; Xu, Xiufeng ; Lyu, Nan ; Li, Junqing ; Pan, Xiaoyue ; Zhang, Xuehua ; Li, Hengfen ; Wang, Gang ; Xu, Xiangdong ; Yang, Chuang ; Lu, Zheng ; Chen, Ce ; Li, Keqing ; Huang, Guangbiao ; Pan, Zhenyu ; Zhao, Qian ; Li, Yi ; Tan, Yunlong ; Wang, Wenqiang ; Wei, Bo ; Zhao, Jingyuan ; Guo, Hua ; Li, Shuang ; Hu, ZhenYu ; Li, Lehua ; Zou, Shaohong ; Fu, Bingbing ; He, Shunqiang ; Wang, Xueyi ; He, Hongbo ; Wang, Qian ; Zhao, Jinghua ; Wang, Zhiqiang

BACKGROUNDDesvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD).METHODSIn this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD₁₇) total score. Secondary endpoints and safety were evaluated.RESULTSLeast-squares mean change in HAM-D₁₇ total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%).LIMITATIONSA short-term non-inferiority study without a placebo arm.CONCLUSIONSThis study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.

128

项与盐酸托鲁地文拉法辛相关的新闻（医药）

2024-11-11

·绿叶制药

绿叶制药靶向NET/DAT/GABAAR的抗抑郁1类创新药获准开展临床试验

绿叶制药集团宣布，1类创新药LY03021已获得中国国家药品监督管理局药品审评中心批准开展临床试验，拟用于治疗抑郁症。 LY03021为去甲肾上腺素转运体（NET）/多巴胺转运体（DAT）抑制剂、γ-氨基丁酸A受体正向变构调节剂（GABAAR PAM）。该产品基于绿叶制药新分子实体/新治疗实体技术平台（NCE/NTE）自主开发，是全新的三靶点作用机制抗抑郁药物，具有同类首创（First-in-Class）的潜质。目前尚未检索到相同机制的产品在研。抑郁症是各种原因引起的以显著和持久的抑郁症状群为主要临床特征并损害社会功能的一类心境障碍。流行病学数据显示：我国抑郁症患病人数呈上升趋势，抑郁症的终生患病率为3.4%、12个月患病率为2.1%1。抑郁症伴随高复发率、高自杀率、高致残率，严重影响家庭和社会。现有抗抑郁药总体有效率和治愈率低，且普遍存在起效较慢、残留症状多、复发风险高、不良反应多等局限。因此，如何快速有效的控制抑郁症的临床症状，进一步改善治疗效果和预后成为当下抗抑郁药物研发中需要攻克的难题。 LY03021同时针对NET、DAT和GABAAR三个靶点发挥作用。该产品通过作用于突触内GABAA受体亚型α1β2γ2和突触外GABAA受体亚型α4β3δ，增强GABA对GABAA受体激活，调节脑内谷氨酸-GABA能平衡，抑制下丘脑-垂体-肾上腺（HPA）轴过度激活，快速发挥抗抑郁作用。同时，LY03021通过抑制NET和DAT，增加脑内去甲肾上腺素（NE）和多巴胺（DA）水平，可显著改善抑郁症患者的核心症状、快感缺失和性功能障碍，并通过NE和DA的“唤醒机制”，消除因GABA受体激活引起的镇静、嗜睡和意识丧失等不良反应。非临床研究显示，LY03021给药后24小时即显著改善模型动物抑郁症状，且连续用药，药效可维持至为期21天的研究结束时，展现出兼具快速起效和长期连续用药保持疗效的优势。同时，该产品具有良好的安全性，NOAEL（未观察到毒副作用剂量）超出有效剂量50倍以上。绿叶制药集团创新研究院常务副院长田京伟博士表示：“抑郁症的发病机制复杂，涉及大脑中多种神经递质的相互作用。基于脑神经环路的多靶点调节是开发新型抗抑郁药物的一大突破口。NET、DAT和GABAAR三个靶点的协同，可快速发挥抗抑郁作用，并有望提升疗效，减少不良反应，以更好的满足临床需求。绿叶制药深耕CNS治疗领域十余年，已成功开发并上市多款创新产品组合。同时，我们持续洞察患者所需，结合CNS治疗领域的基础研究积累和研发技术优势，积极探索和布局全新作用机制的下一代创新药，为提升大众健康水平而努力。” 包括抑郁症在内的CNS治疗领域患者需求庞大，但新药研发进展相对较缓。绿叶制药拥有一系列具有国际竞争力的创新药和创新制剂，成为该治疗领域的领军力量。围绕CNS领域，绿叶制药的产品组合包括：在美获批上市的Erzofri®（棕榈酸帕利哌酮缓释混悬注射液）、Rykindo®（利培酮缓释微球注射剂），在中国上市的若欣林®（盐酸托鲁地文拉法辛缓释片）、金悠平®（注射用罗替高汀微球）等。此外，公司另有包括TAAR1/ 5-HT2CR双靶点激动剂（LY03020）、VMAT2/Sigma1双靶点新药（LY03015）等多个1类创新药处于临床阶段。绿叶制药集团是致力于创新药物的研发、生产和销售的国际化制药公司。绿叶制药在中国、美国和欧洲设有研发中心，拥有超过30个中国在研药物和10多个海外在研药物。绿叶制药在微球、脂质体、透皮释药等先进药物递送技术领域达到国际先进水平，在新分子实体、生物抗体领域收获多项创新成果，并在细胞治疗、基因治疗等领域进行了积极布局和开发。绿叶制药深度布局全球供应链体系，已在全球建有8大生产基地并建立了与国际接轨的GMP质量管理和控制体系。公司现有30余个上市产品，产品覆盖肿瘤、中枢神经系统、心血管、消化与代谢等治疗领域；业务遍及全球80多个国家和地区，其中包括中国、美国、欧洲、日本等全球主要医药市场，以及高速增长的各地新兴市场。参考文献： 1.Yueqin Huang, Yu Wang, Hong Wang, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry.2019 Mar;6(3):211-224. 内容来源于网络，如有侵权，请联系删除。

申请上市

2024-11-11

·Pharma CMC

绿叶制药：抗抑郁1类新药获批临床

今日（11月11日），绿叶制药发布公告，集团的1类创新药LY03021已获得国家药监局药品审评中心批准开展临床试验，拟用于治疗抑郁症。 Y03021为去甲肾上腺素转运体（NET）/多巴胺转运体（DAT）抑制剂、g－氨基丁酸A受体正向变构调节剂（GABAARPAM），是全新的三靶点作用机制抗抑郁药物，具有同类首创(First-in-Class)的潜质。据公告披露，目前尚未检索到相同机制的产品在研。 LY03021同时针对NET、DAT和GABAAR三个靶点发挥作用。该产品通过作用于突触内GABAA受体亚型a1b2g2和突触外GABAA受体亚型a4b3d，增强GABA对GABAA受体的激活，调节脑内谷氨酸－GABA能平衡，抑制下丘脑－垂体－肾上腺（HPA）轴的过度激活，快速发挥抗抑郁作用。同时，LY03021通过抑制NET和DAT，增加脑内去甲肾上腺素（NE）和多巴胺（DA）水平，可显着改善抑郁症患者的核心症状、快感缺失和性功能障碍，并通过NE和DA的「唤醒机制」，消除因GABA受体激活引起的镇静、嗜睡和意识丧失等不良反应。非临床研究显示，LY03021给药后24小时即显着改善模型动物抑郁症状，且连续用药，药效可维持至为期21天的研究结束时，展现出兼具快速起效和长期连续用药保持疗效的优势。同时，该产品具有良好的安全性，NOAEL（未观察到毒副作用剂量）超出有效剂量50倍以上。包括抑郁症在内的CNS治疗领域患者需求庞大，但新药研发进展相对较缓。绿叶制药围绕CNS领域，产品组合包括：在美国获批上市的Erzofri®（棕榈酸帕利呱酮缓释混悬注射液）、Rykindo（利培酮缓释微球注射剂）®，在中国上市的若欣林®（盐酸托鲁地文拉法辛缓释片）、金悠平®（注射用罗替高汀微球）等。此外，绿叶制药另有包括TAAR1/5-HT2CR双靶点激动剂(LY03020)、VMAT2/Sigma1双靶点新药(LY03015)等多个1类创新药处于临床阶段。

申请上市上市批准

2024-11-09

·医药观澜

绿叶制药抗抑郁症1类新药首次在中国获批临床

▎药明康德内容团队报道中国国家药监局药品审评中心（CDE）官网近日最新公示，绿叶制药申报的1类新药LPM682000012片获得临床试验默示许可，拟开发治疗抑郁症。通过CDE官网查询可知，这是该产品首次在中国获批临床。根据受理号可知，这是一款小分子化药。目前尚未从公开渠道查询到该产品的作用机制。截图来源：CDE官网抑郁症是一种常见的严重心理疾病，主要临床表现为精力缺乏、心境低落等核心症状，以及认知功能减退、性功能减退等伴随症状。在接受抗抑郁治疗后，许多患者的核心症状得以缓解，但伴随症状的残留可能造成其社会功能受损，甚至进而导致抑郁症的复发。根据绿叶制药公开资料，该公司研发的化药1类创新药盐酸托鲁地文拉法辛缓释片此前已经在中国获批上市，这是一款5-HT/NE/DA再摄取抑制剂；每月一次的棕榈酸帕利哌酮缓释混悬注射液已经获美国FDA批准上市，可抗抑郁药的辅助疗法用于分裂情感性障碍成人患者的治疗。 CNS治疗领域患者需求庞大，但新药研发进展相对较缓，究其原因主要与相关疾病机制复杂、药物难以到达靶点部位、研发风险高等多种因素有关。目前，绿叶制药的产品广泛覆盖CNS领域的多种疾病，适应症涵盖精神分裂症、抑郁症、帕金森病、阿尔茨海默病等。参考资料： [1]中国国家药监局药品审评中心（CDE）官网.Retrieved Oct 07，2024,from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d [2]绿叶制药2024中期报告. From http://www.cninfo.com.cn/new/disclosure/detail?plate=hke&orgId=9900028975&stockCode=02186&announcementId=1221323037&announcementTime=2024-09-29%2018:20 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。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。

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100 项与盐酸托鲁地文拉法辛相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15052

研发状态

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适应症	国家/地区	公司	日期
抑郁症	中国	山东绿叶制药有限公司	2022-11-01

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适应症	最高研发状态	国家/地区	公司	日期
广泛性焦虑障碍	临床3期	中国	綠葉製藥集團有限公司	2023-07-12
抑郁症	临床1期	-	-	2013-10-31
重度抑郁症	临床前	美国	綠葉製藥集團有限公司	2020-03-04
慢性疼痛	临床前	中国	山东绿叶制药有限公司	2019-05-18
糖尿病周围神经性疼痛	临床前	中国	山东绿叶制药有限公司	2019-05-18
纤维肌痛	临床前	中国	山东绿叶制药有限公司	2019-05-18
骨关节炎	临床前	中国	山东绿叶制药有限公司	2019-05-18

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04853407 (NEWS) 人工标引	临床3期	抑郁症	-	若欣林	(簾築鹹襯範鹹壓壓鏇繭) = 若欣林®在治疗8周末的蒙哥马利-艾斯伯格抑郁量表（MADRS）总分较基线的变化显著优于安慰剂築廠選繭壓顧衊製簾簾 (製築夢遞製顧憲範顧願 ) 更多	积极	2022-12-06
				Placebo