Bioequivalence Study of Sertraline 50 mg tablet manufactured by Shafa Pharmaceutical and Zoloft manufactured by Pfizer in 24 Healthy Volunteers under fasting condition

开始日期2023-06-09

申办/合作机构-

IRCT20090117001556N147

/ Suspended临床2/3期IIT

Evaluating the effectiveness of citalopram and sertraline in the treatment of depression with respect to the level of BDNF, IL-6, and cortisol in men and women with major depressive disorder: A randomized double-blinded clinical trial

开始日期2022-11-22

申办/合作机构

Tehran University of Medical Sciences

IRCT20120718010324N70

/ Recruiting临床3期IIT

The effect of sertraline with or without propranolol on the panic attack in postmenopausal women: a double blind randomized controlled trial

开始日期2022-08-10

申办/合作机构

Tabriz University of Medical Sciences

100 项与枸橼酸舍曲林相关的临床结果

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100 项与枸橼酸舍曲林相关的转化医学

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100 项与枸橼酸舍曲林相关的专利（医药）

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项与枸橼酸舍曲林相关的文献（医药）

2023-09-14·Medicina (Kaunas, Lithuania)

Effects of Aphrodite (an Herbal Compound) on SSRI-Induced Sexual Dysfunctions and Depression in Females with Major Depressive Disorder: Findings from a Randomized Clinical Trial.

Article

作者: Shahmoradi, Nasrin ; Brühl, Annette Beatrix ; Brand, Serge ; Davarinejad, Omran

Background and Objectives: Almost by default, people with major depression disorder (MDD) also report sexual health issues. This holds even more true when sexual dysfunctions are SSRI-induced. Herbal compounds may have the power to counterbalance such sexual dysfunctions, though research is still scarce. Therefore, we assessed females with diagnosed MDD treated with a standard SSRI (sertraline) and reporting SSRI-induced sexual dysfunctions, and we asked whether compared to placebo, Aphrodite (a blend of ginger, saffron, cinnamon, thistle, and Tribulus terrestris) may favorably impact on sexual dysfunctions, and on symptoms of depression, anxiety, and sleep disturbances. Materials and Methods: A total of 41 females (mean age: 35.05 years) with diagnosed MDD, treated with sertraline (a standard SSRI) at therapeutic dosages, and reporting SSRI-induced sexual dysfunction, were randomly assigned either to Aphrodite or to the placebo condition. At baseline and four and eight weeks later (study end), participants completed a series of self-rating questionnaires covering symptoms of sexual dysfunction, depression, anxiety, and sleep complaints. Results: Symptoms of sexual dysfunction, depression, and anxiety decreased over time, but more so in the Aphrodite condition, compared to the placebo condition (significant p-values and large effect sizes). Over time, sleep disturbances decreased irrespective of the study condition. Conclusions: The pattern of results suggests that compared to placebo, Aphrodite appeared to improve symptoms of sexual dysfunction, depression, and anxiety among females with diagnosed MDD and SSRI-induced sexual dysfunction. Further and similar studies should investigate the underlying psychophysiological mechanisms.

2023-05-09·Antibiotics (Basel, Switzerland)

Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms.

Article

作者: Alhuwaydi, Ahmed M ; Abouelkheir, Mohamed ; Ahmed, Eman Ibrahim ; Taha, Ahmed E

Reboxetine (REB) and sertraline (SER) are antidepressants. The antifungal potential of these drugs against planktonic Candida has been recently reported with limited data about their effects on Candidal biofilms. Biofilms are self-derived extracellular matrixes produced by the microbial population that is attached to biotic surfaces, such as vaginal and oral mucosa, or abiotic surfaces, such as biomedical devices, resulting in persistent fungal infections. The commonly prescribed antifungals, azoles, are usually less effective when biofilms are formed, and most of the prescribed antifungals are only fungistatic. Therefore, the current study investigates the antifungal potentials of REB and SER, alone and in combination with fluconazole (FLC) and itraconazole (ITR) against Candidal biofilms. Using proper controls, Candida species (Candida albicans, C. albicans; Candida krusei, C. krusei; and Candida glabrata, C. glabrata) were used to form biofilms in 96-well microplates. Serial dilutions corresponding to concentrations ranging from 2 to 4096 µg/mL of the target drugs (REB, SER, FLC, ITR) were prepared and added to the plates. Impairment of the biofilm biomass and biofilm metabolic viability was detected using the crystal violet (CV) assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. In the checkerboard assay, the sessile fractional inhibitory concentration index (SFICI) was calculated to evaluate the effects of drug combinations. SER was more effective in reducing the biomass than REB for C. albicans and C. glabrata, but both were equal for C. krusei. For the reduction in metabolic activity in C. albicans and C. glabrata, SER had a slight advantage over REB. In C. krusei, REB was slightly more potent. Overall, FLC and ITR were almost equal and produced more significant reductions in metabolic activity when compared to SER and REB, except for C. glabrata, where SER was almost equal to FLC. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans. Synergism was detected between REB + ITR against biofilm cells of C. krusei. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans, C. krusei, and C. glabrata. The results of the present study support the potential of SER and REB as anti-Candidal biofilm agents that are beneficial as a new antifungal to combat Candidal resistance.

2021-10-01·Journal of hepatology

Anti-epileptic drugs and hepatitis C therapy: Real-world experience

Letter

作者: Cabezas, Joaquín ; Marcos-Fosch, Cristina ; Crespo, Javier ; Buti, Maria

Direct-acting antivirals (DAAs) have significantly improved treatment of hepatitis C virus (HCV) infection, and almost all patients receiving these drugs achieve sustained virol. response (SVR).However, there is still a niche of individuals with HCV who cannot be treated because of drug-drug interactions (DDIs), one of the few remaining impediments to DAA use.DDIs with antiseizure medication (ASM) are especially important, as clin. experience has shown that in some cases these drugs cannot be discontinued or replaced by others during HCV therapy.This is a description of 5 patients with chronic HCV infection receiving ASMs who were treated with DAAs even though co-administration of these drugs is not recommended due to potential DDIs.All patients achieved an end-of-treatment response and SVR12 and no adverse events or required dose modifications were reported.Patient 1 was a 40-yr-old man on treatment with oxcarbazepine 300 mg BID for a psychotic and personality disorder; the attending psychiatrist deemed that treatment discontinuation was not feasible, as the patient's condition was extremely labile, and concomitant medications were clorazepate 50 mg daily, clotiapine 40 mg daily, levetiracetam 500 mg BID, and zuclopenthixol 25 mg QID.Patient 2 was a 39-yr-old man on treatment with oxcarbazepine 600 mg TID for epilepsy; the neurologist attempted a switch from oxcarbazepine to levetiracetam to avoid interactions with DAAs, but 1 wk later the patient experienced several complex seizures; hence, oxcarbazepine was re-started, and no concomitant medications.Patient 3 was a 54-yr-old man on treatment with phenytoin 100 mg BID for epilepsy; although the neurologist was willing to change his medication, the patient refused, and concomitant medications were dolutegravir 50 mg daily, abacavir 600 mg daily, lamivudine 300 mg daily, and clonazepam 0.5 mg daily.Patient 4 was a 38-yr-old man on treatment with oxcarbazepine 600 mg BID for a psychotic and personality disorder; psychiatrist considered that that the patient's labile condition made oxcarbazepine discontinuation unfeasible, and concomitant medications werfe clonazepam 2 mg TID, paroxetine 20 mg daily, perphenazine 8 mg daily, and quetiapine 200 mg daily.Patient 5 was a 43-yr-old man on treatment with eslicarbazepine 400 mg TID for epilepsy; the neurologist switched eslicarbazepine to brivaracetam to avoid interactions with DAAs, but eslicarbazepine had to be re-started because of adverse events, and concomitant medications were topiramate 75 mg BID, ser- traline 100 mg daily, clobazam 25 mg daily, enalapril 20 mg daily, and bisoprolol 5mg daily.This report has the shortcoming that plasma DAA concentrations and HCV RNA levels were not serially analyzed during therapy, as these are real-life patients and such determinations are not routinely done in this clin. situation.In conclusion, the cases reported here indicate promising outcomes for HCV treatment in patients receiving ASMs.DDIs, together with the known dif fi culties related to screening and linkage-to-care in some HCV-infected populations are the main obstacles we have yet to overcome to achieve the WHO HCV elimination goals.

项与枸橼酸舍曲林相关的新闻（医药）

2025-09-04

·生物制品圈

抗抑郁赛道，前赴后继

▲多重福利来袭，点击即可预约 2022年8月，60多年来全球首个采用新机制的抗抑郁口服药Auvelity （氢溴酸右美沙芬和盐酸安非他酮复方缓释片）在美国获批上市，打破了抗抑郁老药市场格局。 2023年8月，首个也是唯一一个用于成人产后抑郁症（PPD）口服治疗药物Zurzuvae（Zuranolone）在美国获批上市，拓宽了抑郁症治疗患者人群。 2025年1月，强生宣布以总交易额约为146亿美元收购Intra-Cellular Therapies，该公司核心产品为5-羟色胺2A（5-HT2A）受体拮抗剂和多巴胺受体D2调节剂Caplyta（卢美哌隆，Lumateperone），Caplyta已获FDA批准用于治疗成人精神分裂症，以及与双相I型或II型障碍相关的抑郁发作。 2025年8月，艾伯维以高达12亿美元的价格收购Gilgamesh Pharmaceuticals旗下的抗抑郁药物bretisilocin，该药物目前处于临床2期。这些新机制药物获批和重磅交易显示了制药行业对抑郁症治疗领域的重视和投入，也反映了市场对新型、更有效抑郁症药物的迫切需求。 01 抑郁症流行病学抑郁症是一种常见的精神障碍，主要表现为情绪低落、兴趣减退、思维迟缓和身体不适等症状。它不仅影响患者的生活质量，还可能对工作、学习和社交功能产生负面影响。根据2021年全球疾病负担研究，全球抑郁症发病数为3.5744亿例，患病数为3.3241亿例，伤残调整生命年（DALYs）为5633万。抑郁症在全球范围内都是一个重大的公共卫生挑战，其发病率、患病率和DALYs的年龄标准化率虽有下降趋势，但绝对病例数和年龄标准化率仍在增加[1]。重度抑郁症是美国最常见的精神障碍之一。对于某些人来说，重度抑郁症会导致严重的损伤，干扰或限制一个人进行主要生活活动的能力。 2021年，美国估计有2100万成人至少经历过一次重度抑郁发作，占所有美国成人的8.3%。其中，女性的发病率为10.3%，高于男性的6.2%，18-25岁年龄段的发病率为18.6%，是所有年龄段中最高的，在有多种（两个或以上）种族身份的人群中，重度抑郁发作的发病率最高，为13.9%（图1）[2]。图1. 2021年美国18岁或以上成年人过去一年重度抑郁发作的患病率据估计，美国有500万12至17岁的青少年至少有一次重度抑郁发作。这一数字占美国12至17岁人口的20.1%。与男性（11.5%）相比，青春期女性（29.2%）的重度抑郁发作患病率更高。重度抑郁发作的患病率在两个或两个以上种族的青少年中最高（27.2%）。图2. 2021 年美国青少年重度抑郁发作的过去一年患病率根据中国精神卫生调查（CMHS）的数据，中国抑郁症的终生患病率为6.8%，12个月患病率为3.6%。这意味着超过9500万中国人一生中曾患过抑郁症。女性抑郁症的终生患病率为8.0%，显著高于男性的5.7%[3]。 02 抑郁症发病机制到目前为止，抑郁症的发病机制吸引了世界各地越来越多的研究人员进行探索，但确切的发病机制仍不清楚。受体假说已被用于从多个角度阐明抑郁症的发病机制[1]。除了众所周知的受体，如NMDA受体、AMPA受体、糖皮质激素受体、5-HT受体、GABA受体和DA受体外，“非经典”受体，如代谢型谷氨酸受体、阿片受体和胰岛素受体，对抑郁症的发病机制也很重要（图1）。此外，大量研究表明，抑郁症的发生和发展与遗传基础密切相关，遗传基础占抑郁症风险的近 40-50%，导致抑郁症成为一种高度遗传的疾病，并受到更广泛的关注。由于抑郁症（MDD）的发病机制复杂，准确的诊断方法和药物治疗策略相对有限。为了解释抑郁症的发病机制，提出了几种假说，包括：（i）下丘脑-垂体-肾上腺（HPA）轴功能障碍假说，（ii）单胺假说，（iii）炎症假说，（iv）遗传和表观遗传异常假说，（v）大脑结构和功能重塑假说，以及（vi）社会心理假说（图3）[4]。图3. 抑郁症发病机制 HPA轴功能障碍假说认为，抑郁症的发生与HPA轴的过度激活和负反馈机制受损密切相关。这种功能障碍导致GC水平异常升高，进而影响神经递质和神经营养因子的活性，最终导致抑郁症的发生。单胺假说是解释抑郁症发病机制的经典理论之一,单胺假说认为，抑郁症的发生与大脑中单胺类神经递质的缺乏有关，主要包括5-羟色胺（5-HT，血清素）去甲肾上腺素（NE）、多巴胺（DA）等神经递质。许多抗抑郁药物的作用机制都是通过增加大脑中单胺类神经递质的水平来发挥作用。例如，选择性5-羟色胺再摄取抑制剂（SSRIs）通过抑制5-HT的再摄取，增加突触间隙中5-HT的浓度，从而改善抑郁症状。三环类抗抑郁药（TCAs）则同时抑制5-HT和NE的再摄取。这些药物的疗效支持了单胺假说。然而，没有任何一种假说能够单独充分解释抑郁症（MDD）的病理基础，而这些假说所提出的许多机制相互之间存在交互作用。近年来，在识别抑郁症的新药物疗法、诊断标准以及非药物预防措施方面取得了巨大进展，并启动了相关的临床试验。具体而言，越来越多的证据表明，星形胶质细胞功能障碍在抑郁症中起着重要作用。在实验动物中，通过药物消融内侧前额叶皮质（mPFC）中的星形胶质细胞会导致抑郁样症状，而且对抑郁症患者的尸检研究显示，其前额叶皮质（PFC）、海马和杏仁核中胶质细胞的密度降低。 03 获批的抑郁症药物全球已有多款药物上市，不过目前世界各地抗抑郁症治疗相关指南中推荐的药物治疗方案一致性差，美国常用的12种抗抑郁药包括了选择性5-羟色胺再摄取抑制剂（SSRIs）、5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRIs）以及非典型抗抑郁药。这些药物分别是：舍曲林（左洛复）、艾司西酞普兰（来士普）、曲唑酮、氟西汀（百忧解）、安非他酮（安非他酮）、度洛西汀（欣百达）、喹硫平（思瑞康）、西酞普兰（喜普妙）、文拉法辛（怡诺思）、阿立哌唑（安律凡）、帕罗西汀（帕罗西汀）和米氮平（瑞美隆）。这些药物常被用于治疗重度抑郁症及相关疾病，因为它们疗效显著且副作用各有不同，使临床医生能够根据患者个体需求调整治疗方案[5]。全球常用的抗抑郁症药物有灵北的艾司西酞普兰、辉瑞的舍曲林、艾伯维的氟伏沙明、GSK的帕罗西汀、礼来的度洛西汀和惠氏的文拉法辛等。近几年，也有一些新颖机制的抗抑郁药物获批上市。 2019年3月，艾司氯胺酮鼻喷雾剂首次获得美国FDA批准，用于治疗难治性抑郁症（TRD），需与口服抗抑郁药联合使用。艾司氯胺酮（Esketamine）是氯胺酮的右旋异构体，具有更高的效价，通过阻断NMDA受体，增加谷氨酸的释放，激活AMPA受体，促进神经营养因子（如BDNF）的产生，从而增强突触可塑性和神经再生（图4）[6]。图4. 艾司氯胺酮作用机制艾司氯胺酮的SUSTAIN-3试验结果显示：在诱导治疗期间，蒙哥马利-阿斯伯格抑郁量表（MADRS）总分有所下降，且这种下降在优化/维持治疗期间得以维持（各阶段基线至阶段终点的平均[标准差]变化：诱导期：-12.8[9.73]；优化/维持期：+0.2[9.93]）。在诱导治疗终点时，有35.6%的参与者达到缓解；在第112周和优化/维持治疗终点时，分别有48.5%和49.6%的参与者达到缓解（图5）[7]。图5. 艾司氯胺酮的SUSTAIN-3试验结果 2023年4月20日，中国国家药品监督管理局正式批准了强生公司生产的盐酸艾司氯胺酮鼻喷雾剂（商品名：速开朗）在中国上市。这是中国首个获批的具有全新作用机制和给药方式的抗抑郁药物，主要用于与口服抗抑郁药联合使用，能够快速缓解伴有急性自杀意念或行为的成人抑郁症患者的抑郁症状。 2025年1月21日，强生宣布FDA批准了SPRAVATO®（Esketamine）CIII 鼻喷雾剂的补充新药申请（sNDA），使这种创新疗法成为第一个也是唯一一个针对对至少两种口服抗抑郁药反应不足的重度抑郁症（MDD）成年人的单一疗法。 2022年8月，美国生物医药公司Axsome Therapeutics的抗抑郁口服药Auvelity获得美国FDA批准，用于治疗成年人抑郁症（MDD），成为60多年来全球首个采用新机制的抗抑郁口服药，在拥挤的抗抑郁老药市场中开辟了一个新市场。 Auvelity是一种固定剂量的复方缓释片，主要成分包括氢溴酸右美沙芬（45mg）和盐酸安非他酮（105mg），右美沙芬作为NMDA受体拮抗剂和σ-1受体激动剂，调节谷氨酸能神经传递，具有抗惊厥和神经保护作用，还能阻断血清素和多巴胺的再摄取；安非他酮抑制CYP2D6酶，延长右美沙芬的半衰期，从而增强其效果（图6）。图6. Auvelity作用机制临床试验数据显示，Auvelity治疗成人MDD患者起效迅速，治疗1周即可显著改善抑郁症状。治疗2周后，临床治愈率较安慰剂有显著提高，且持续至治疗结束。安全性结果显示Auvelity耐受性良好（图7）。图7. Auvelity的疗效 2023年8月4日，渤健和Sage Therapeutics公司共同开发的神经活性类固醇γ-氨基丁酸A型（GABAA）受体阳性别构调节剂Zurzuvae（Zuranolone）获FDA批准，成为首个也是唯一一个用于成人产后抑郁症（PPD）口服治疗药物。2025年7月24日，欧洲药品管理局（EMA）的人用药品委员会（CHMP）也推荐授予Zurzuvae上市许可。 Zurzuvae的一项临床试验（NCT04442503）研究发现，每天服用 Zurzuvae 50 mg，持续2周的女性在第15天的抑郁症状显着减轻。与安慰剂评分相比，Zurzuvae 50mg的17项汉密尔顿抑郁量表（HAMD-17）降低了-15.6（HAMD-17），安慰剂评分降低了-11.6，差异为-4.0，抑郁症状从第 3天开始改善，一直持续到第42天（图8）[8]。图8. Zurzuvae的疗效 04 在研的新机制抗抑郁药物除此之外，还有很多在研的新机制抗抑郁药物，如Osavampator、Seltorexant、GH-001、NBI-1070770和JJH201501等（图9）。图9. 部分获批和在研的抗抑郁症药物代表性药物 1.Osavampator Osavampator（NBI-1065845或者TAK-653）最初是由武田制药研发的一种AMPA受体正变构调节剂（PAM）。2020年，Neurocrine Biosciences获得了osavampator及其他六个神经精神疾病项目的独家授权，支付了1.2亿美元的首付款。根据最初的协议，武田制药有资格获得高达4.95亿美元的开发里程碑付款、高达14亿美元的商业里程碑付款，以及最高达到两位数比例的净销售额分成。2025年1月27日，武田重新谈判了这笔交易，重新获得osavampator在日本的独家权益（图10）[9]。图10. Osavampator的结构临床前研究显示：Osavampator在大鼠强迫游泳行为模型（RSBM）中，经过6天的给药后，产生了显著的抗抑郁样效应。然而，与氯胺酮不同的是，TAK-653并未在大鼠中诱导出过度运动行为，而这种行为是与人类精神分裂样副作用相关的行为指标。因此，TAK-653可能是一种具有改善安全性潜力的药物，可用于治疗包括难治性抑郁症（TRD）在内的重度抑郁症（图11）[10]。图11. Osavampator临床前研究结果 2024年4月，Neurocrine公布了osavampator在成年MDD受试者中的2期SAVITRI™研究的积极顶线数据：接受osavampator治疗的患者在第28天（主要终点）和第56天（次要终点）的蒙哥马利-阿斯伯格抑郁评分量表（MADRS）总分上均显示出统计学上显著的改善（图12）。图12. Osavampator的临床结果今年1月28日，Neurocrine宣布启动一项3期注册研究，以评估 osavampator的疗效、安全性和耐受性，用于重度抑郁症（MDD）抗抑郁药的辅助治疗[11]。 2.Seltorexant Seltorexant 是强生公司旗下杨森制药开发的一种选择性食欲素-2受体（OX2R）拮抗剂，旨在治疗伴有失眠症状的重度抑郁症（MDD）和阿尔茨海默病等神经科学领域疾病。目前强生已终止seltorexant治疗阿尔茨海默病的临床研究，但是seltorexant在治疗伴有失眠症状的重度抑郁症显示积极效果，仍在进行中。 2024年，Mesens等人在《Molecular Psychiatry》杂志上报道了Seltorexant的一项临床1b期试验（NCT03374475）结果：共有128名参与者入组，包括86名富集样本（安慰剂导入期无反应者）（图13）[12]。在第5周时，汉密尔顿抑郁量表17项（HDRS17）评分从基线的平均变化（标准差）在各组之间存在显著差异：Seltorexant 20mg组为-7.0（5.04），Seltorexant 40mg组为-5.5（4.34），安慰剂组为-4.4（3.67）（p=0.0456），这一差异归因于20mg组与安慰剂组之间的差异（p=0.0049）。在基线失眠症状较严重的患者中，Seltorexant 20mg在第5周时对抑郁严重程度的改善更为显著（名义p=0.0059）。当通过去除睡眠项目来调整HDRS评分时，20mg组的治疗益处仍然显著（名义p=0.0289）。与安慰剂组相比，20mg组的HDRS17评分变化在数值上大于40mg组，这与之前的研究数据一致，在之前的研究中，Seltorexant是作为传统抗抑郁药物的辅助药物给药的。在次要分析中，20mg组的皮质醇觉醒反应有所下降，而40mg组或安慰剂组则没有这种变化；尽管40mg组的总睡眠时间增加更多，但该组也显示出快速眼动睡眠潜伏期缩短和N1期睡眠增加，而在20mg组中则没有这种现象。这些生物标志物数据提出了可能解释Seltorexant表观曲线剂量反应关系的机制假设。图13. Seltorexant的临床1b期试验结果 2024年5月，强生宣布seltorexant在一项针对伴有失眠症状的重度抑郁症患者的III期临床试验（MDD3001）中达到了所有主要和次要终点。该研究显示，seltorexant在改善抑郁症状和减少睡眠障碍方面具有统计学意义和临床意义（图14）[13]。图14. Seltorexant的临床3期试验结果 3.GH001 GH001是由GH Research PLC开发的一种用于治疗难治性抑郁症（TRD）的药物。其主要成分是美布福汀（mefenamic acid，5-MeO-DMT），通过专有的吸入方式给药。GH001的开发旨在通过激活5-羟色胺2A受体（5-HT2A）来产生抗抑郁效果（图15）。图15. GH001临床试验进展 2025年2月，GH Research宣布GH001的一项用于难治性抑郁症（TRD）患者的随机、双盲、安慰剂对照2b期临床试验（GH001-TRD-201）达到了主要终点：GH001在第8天使蒙哥马利-阿斯伯格抑郁量表（MADRS）总分从基线显著降低15.2分，而安慰剂组增加了0.3分（差异为-15.5分，p<0.0001）。试验中的所有次要终点均达到，结果与主要终点一致。与安慰剂相比，GH001治疗在第8天使临床医生总体印象严重程度量表（CGI-S）和汉密尔顿焦虑量表（HAM-A）的评分以及生活质量问卷（Q-LES-Q-SF）的评分均显著改善，具有临床意义和统计学意义[14]。 2025年7月，GH Research宣布向FDA提交了对之前宣布的 GH001 研究性新药申请（IND）临床搁置的完整答复。他们现在已经收到了 FDA 的回复，只剩下一个保留问题。FDA要求他们提供与之前公布的大鼠呼吸道组织学结果相关的额外数据或进一步的理由。他们坚信，基于科学证据，呼吸道组织学结果是大鼠特异性的。没有与狗毒理学相关的其他请求。没有与设备相关的问题。与 FDA 就 IND 完全缓解的接触正在进行中。他们正在积极努力解决剩余的问题。 GH Research计划在2026年启动GH001的全球关键性计划，目前正在进行准备工作，包括成立指导委员会以及选择临床研究组织和研究地点。 4.Bretisilocin Bretisilocin是由生物技术公司Gilgamesh Pharmaceuticals研发的一款5-HT2A受体激动剂和5-HT释放剂，通过作用于5-HT2A受体来发挥疗效，2025年8月，艾伯维公司以12亿美元收购了该药物（图16）。图16. Gilgamesh Pharmaceuticals的研发管线与传统迷幻药物（如LSD和psilocybin）相比，Bretisilocin具有更短的半衰期，仅需约两小时即可完成治疗，且不引发幻觉。 2025年5月27日，Gilgamesh宣布了Bretisilocin的一项针对重度抑郁症患者 2a 期结果：接受两次药物治疗的患者中，94%在一个月后症状得到了显著缓解。在另一项2a期研究中，与低剂量对照组相比，蒙哥马利-奥斯伯格抑郁量表（MADRS）总分改善具有统计学显著性。第14天时，单剂量（10mg）治疗组MADRS总分较基线改变-21.6分，而低剂量（1mg）对照组改变-12.1分（p=0.003）（图17）。图17. Bretisilocin的临床试验结果 5.JJH201501 JJH201501是由吉贝尔利用其氘代药物研发技术平台研发的伏硫西汀衍生物，是一种新型的多受体作用机制的抗抑郁药，通过将伏硫西汀中甲基氢替换成氘来增强药物的稳定性，减缓代谢速度，从而达到增加药效、减少药物不良反应的目的（图18）。图18. JJH201501的研发进展 JJH201501目前已完成了I期、IIa期和IIb期临床研究。2024年5月11日，由吉贝尔药业主办的“JJH201501片Ⅲ期临床研究全国研究者启动会”在北京成功举办。目前，抗抑郁新药JJH201501正在有序开展Ⅲ期临床试验，按目前的计划，预计2025年完成Ⅲ期临床研究并提交上市申请。 6.LY03021 绿叶制药集团是一家致力于创新药物的研发、生产和销售的国际化制药公司。绿叶制药在抗抑郁症药物研发方面取得了显著进展，其核心产品若欣林®（盐酸托鲁地文拉法辛缓释片）是中国首个自主研发并拥有自主知识产权的抗抑郁1类创新药，于2022年12月获批上市（图19）。若欣林通过其独特的三重再摄取抑制作用（SNDRI），全面改善抑郁症状，尤其对快感缺失、阻滞和认知障碍等改善突出，克服了现有药物的缺陷，且不引起失眠和嗜睡，不影响性功能、体重和脂代谢。 2025年8月18日，绿叶制药集团宣布若欣林用于治疗广泛性焦虑障碍的Ⅲ期临床试验已完成患者入组，预计2025年底提交上市申请。该试验为多中心、随机、双盲、安慰剂对照研究，以评估若欣林治疗广泛性焦虑障碍的安全。 LY03021是绿叶制药自主研发的1类创新药，通过靶向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。非临床研究显示，LY03021给药后24小时即显著改善模型动物的抑郁症状，且连续用药至21天疗效稳定，具有快速起效和疗效持久的优势。 2025年8月3日，LY03021在中国开展的I期临床研究已完成首例受试者入组。图19. 绿叶制药CNS管线小结抑郁症是一种常见的心理健康障碍，对患者的身心健康和社会功能等多方面造成严重危害，传统抗抑郁症药物在治疗抑郁症方面具有重要作用，但存在起效缓慢、副作用多、治疗反应差异大等缺点。这些缺点可能影响患者的治疗依从性和康复进程，因此仍需新颖机制的抗抑郁症药物。随着抑郁症发病机制研究的深入，越来越多新颖机制的抗抑郁药物被开发，有望给患者更多的选择。主要参考文献 1.Jian Rong et.al, Global, regional and national burden of depressive disorders and attributable risk factors, from 1990 to 2021: results from the 2021 Global Burden of Disease study, The British Journal of Psychiatry, First View, pp. 1 – 10 2.https://www-nimh-nih-gov.libproxy1.nus.edu.sg/health/statistics/major-depression 3.Prof Yueqin Huang, Prof Yu Wang, Prof Hong Wang, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry. Feb 2019. 4.Lulu Cui et.al, Major depressive disorder: hypothesis, mechanism, prevention and treatment, Signal Transduction and Targeted Therapy (2024) 9:30 5.MedicineNet：What Are the Top 5 Antidepressants? 6.Piotr Kawczak, Igor Feszak et.al, Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms 7.Naim Zaki, MD et.al, Safety and efficacy with esketamine in treatment resistant depression: long-term extension study, International Journal of Neuropsychopharmacology, 2025, pyaf027 8.https://www.drugs.com/zurzuvae.html 9.Atsushi Suzuki et.al, Strictly regulated agonistdependent activation of AMPAR is the key characteristic of TAK653 for robust synaptic responses and cognitive improvement, Scientific Reports (2021) 11:14532 10.Hiroe Hara et.al, TAK-653, an AMPA receptor potentiator with minimal agonistic activity, produces an antidepressant-like effect with a favorable safety profile in rats, Pharmacology Biochemistry and Behavior Volume 211, December 2021, 173289 11.Neurocrine Biosciences Announces Initiation of Phase 3 Registrational Program for Osavampator as an Adjunctive Therapy for the Treatment of Major Depressive Disorder in Adults 12.Sofie Mesens et.al, Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial, Molecular Psychiatry (2025) 30:2427–2435 13.Seltorexant, adjunctive to antidepressants, in adults with MDD with insomnia symptoms: results of a double-blind, randomized, placebo-controlled study 14.GH Research Announces Primary Endpoint Met in Phase 2b Trial with GH001 in TRD Demonstrating -15.5 Point Placebo-adjusted MADRS Reduction 15.Gilgamesh Pharmaceuticals Announces Positive Topline Phase 2a Results for GM-2505 in Major Depressive Disorder (MDD) 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

并购临床2期上市批准

2025-03-31

·PRNewswire

Transcend Therapeutics Announces Primary Endpoint Met in IMPACT-1 Phase 2 Study of TSND-201 in PTSD

Primary endpoint met, with TSND-201 demonstrating statistically significant placebo-adjusted CAPS-5 improvement of -9.64 points on Day 64 (p = 0.011) TSND-201 demonstrated rapid improvements, with a statistically significant placebo-adjusted CAPS-5 improvement of -8.00 points on Day 10 (p = 0.012), with placebo-adjusted improvements remaining statistically significantly for the duration of the trial Robust and statistically significant improvements were noted across multiple secondary endpoints on Day 64 TSND-201 was generally safe and well tolerated, with a safety profile consistent with its non-hallucinogenic pharmacology Company plans to align with FDA on Phase 3 program for PTSD NEW YORK, March 31, 2025 /PRNewswire/ -- Transcend Therapeutics, a clinical-stage biotechnology company that develops medicines to treat neuropsychiatric diseases, today announced positive results from the IMPACT-1 study (Investigation of Methylone for Post-Traumatic Stress Disorder [PTSD]). IMPACT-1 was a randomized, double-blind, placebo-controlled, Phase 2 clinical trial evaluating TSND-201 (methylone), a rapid-acting neuroplastogen, for the treatment of PTSD. This study enrolled 65 patients with severe PTSD (Clinician-Administered PTSD Scale for DSM-5 [CAPS-5] ≥ 35), all of whom had previously tried a PTSD treatment, to receive 4 oral doses of TSND-201 or placebo, with each dose separated by one week. Patients were followed for a total of 64 days after the first dose. Continue Reading CAPS-5 Scores Over Time; * p <0.05 On the primary endpoint, change from baseline to Day 64, TSND-201 demonstrated a statistically significant placebo-adjusted CAPS-5 improvement of -9.64 points on Day 64 (-23.28 points vs. -13.64 points; p = 0.011). TSND-201 also demonstrated rapid and statistically significant improvements from baseline compared to placebo on the CAPS-5 total severity score. Starting on Day 10, TSND-201 demonstrated a statistically significant placebo-adjusted CAPS-5 improvement of -8.00 points (-17.83 points vs. -9.83 points; p = 0.012), which was durable throughout the study until Day 64. "We are encouraged by the positive Phase 2 results demonstrating TSND-201's potential as a rapid-acting and durable treatment for patients with PTSD," said Transcend Therapeutics Co-Founder and CEO Blake Mandell. "We look forward to working with the FDA to align on a Phase 3 program in PTSD." TSND-201 demonstrated statistically significant improvements on multiple secondary endpoints, including response (≥ 50% improvement from baseline on CAPS-5; 57.1% vs. 19.2%; p = 0.002), remission (≤ 11 points on the CAPS-5; 32.1% vs. 11.5%; p = 0.036), and loss of PTSD diagnosis (60.7% vs. 30.8%; p = 0.014). Treatment with TSND-201 was generally safe and well tolerated. The majority of adverse events were transient, occurring on the day of dosing and resolving the same day. The most commonly occurring adverse events in the TSND-201 group were headache, decreased appetite, nausea, dizziness, blood pressure increase, dry mouth, insomnia, muscle tightness, and feeling abnormal. One serious adverse event of seizure occurred in the TSND-201 group; the event occurred 7 days after the last dose in a patient with a history of seizure and was considered unrelated to study drug. "It has been over two decades without a new treatment for PTSD. The results of this study suggest that TSND-201 may represent a significant clinical breakthrough — demonstrating clinically meaningful efficacy with a rapid onset," commented Murray B. Stein, M.D., M.P.H., Distinguished Professor of Psychiatry and Public Health at the University of California San Diego and Staff Psychiatrist at the Veteran Affairs San Diego Healthcare System. "Rapid-acting, episodic treatments could be a paradigm shift in the treatment of PTSD, providing hope for the many patients who have struggled to find effective relief." About Transcend Therapeutics Transcend Therapeutics, founded in 2021, is a clinical-stage, neuroscience-focused company developing rapid-acting treatments for neuropsychiatric diseases. The company's mission is to develop new drugs for the millions of people for whom current psychiatric medicines have not worked. Transcend's leadership team has made pivotal contributions to 14 FDA approvals and $7B in M&A and public company value. Transcend has raised approximately $50M to date. About TSND-201 TSND-201, a rapid-acting neuroplastogen, is a proprietary formulation of methylone developed by Transcend Therapeutics. TSND-201 has well-characterized primary pharmacology, with its primary site of action at the monoamine transporters, and no activity at 5HT-2a (i.e., not hallucinogenic). Transcend is developing TSND-201 as a rapid-acting and durable treatment for PTSD and other central nervous system (CNS) indications. TSND-201 is an investigational medication. About PTSD PTSD is a mental health condition that can occur after experiencing or witnessing a life-threatening or traumatic event. Symptoms may include flashbacks, nightmares, severe anxiety, and uncontrollable thoughts about the event. PTSD impacts approximately 13 million Americans each year and it is estimated that nearly 7% of U.S. adults will be diagnosed with PTSD during their lifetime. Only two medications are FDA-approved for the treatment of PTSD (sertraline and paroxetine), yet their efficacy is modest at best. New treatments for PTSD are urgently needed. Contact: [email protected] SOURCE Transcend Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果临床2期上市批准临床3期

2024-10-14

·药通社

又一个首仿ANDA！！！

“天下武功，唯快不破”，这在当下极度内卷的仿制药立项上体现得淋漓尽致！目前大多数CXO和药企立项都有这么几个优选标准： 1、适应症范围广，市场容量大，有增长潜力； 2、收载于诊疗指南和临床路径，临床安全性有效性数据扎实，临床价值或定位明确； 3、贴合企业自身的市场优势领域； 4、原料药和辅料可及； 5、专利风险小； 6、现有产线尽可能匹配或稍作改造即可； 7、公开的信息和私下打听到的竞争家数少； 8、参比制剂明确，研发难度和投入小或适中； 9、临床只需要做BE/BA或者无需临床的项目，更是多数企业的心头好。舍曲林：两种盐型，三种剂型国庆节前药审中心就承办了这么一款首仿药：盐酸舍曲林口服浓缩液，受理号：CYHS2403263。该品种基本上就符合上述企业立项优选的大多数标准，相信有不少企业也立了项，但很可惜还是比海南斯达制药慢了些。舍曲林最早是由辉瑞公司研发的抗抑郁药物，属于一款经典的选择性5-羟色胺再摄取抑制剂(SSRI)，在国内企业20年前神奇的运作之下，已经有两种盐型，三种剂型，四个品种纳入了医保目录。【盐酸舍曲林片】相信大家对盐酸舍曲林片都很熟悉，1990年首次在英国上市，1991年美国上市。在抗抑郁药物中，有一种常见的药物——“左洛复”。左洛复的英文商品名为“Zoloft”，又名“舍曲林”，在临床中称为“盐酸舍曲林”，是美国处方量最大的抗抑郁品牌药。在我国临床中，左洛复除了被广泛用于治疗抑郁症、焦虑症、强迫症和双相情感障碍的治疗中，还常用于治疗创伤后应激障碍(PTSD)、重度抑郁症(MDD)、恐慌症、强迫症(OCD)、经前焦虑障碍(PMDD)和社交恐惧症等精神心理疾病。盐酸舍曲林片也早在4年前已经纳入第三批集采，也是目前临床使用最为广泛的剂型。【枸橼酸舍曲林片】哈尔滨健迪医药2001年按照改盐和改剂型申请新药临床，2006年申请生产，2008年批准上市，上市后十年终于进入国家医保(2017版至今)。舍曲林能够通过改盐上市成为独家品种，该盐基需要明显的临床优势。按照现行法规要求，笔者认为很难说服CDE。【盐酸舍曲林胶囊】原研除了片剂外，为满足高剂量使用需求，通过一项与片剂的PK对比研究和一项食物影响研究，于2021年美国上市了硬胶囊剂型。中国早在十几年前就有5家企业通过改变剂型（不改变给药途径，老5类）申请了上市。目前仅联环药业和四川百草通过了一致性评价。盐酸舍曲林胶囊目前竞争格局还是很温和的，是不是可以考虑立项？但是要注意：为什么CNS头部玩家京新药业不急着过评值得思考？【盐酸舍曲林分散片】最早也是哈尔滨健迪医药通过该剂型申报的，目前仅两家有分散片的批文，本身该品种原研并无分散片剂型，京新已经对照片剂剂型进行了两次BE试验，预计是要尝试申报一致性评价，但笔者认为批准的可能性存疑。【盐酸舍曲林口服浓缩液】该剂型是远早于胶囊剂上市的，上个世纪就批准了，该品种同样是通过一项与片剂的PK对比研究和一项食物影响研究。在其一项BA研究中，比较了100 mg舍曲林口服溶液与100 mg片剂在16名健康成人体内的药代动力学，Cmax的90%置信区间上限为126.4%，严格意义是不等效！与食物一起服用会导致Cmax和AUC的小幅增加。FDA审评认为其口服溶液与片剂的药代参数差异基本上没有临床意义！立项：可从剂型上做文章同一品种不同剂型，尤其还是那种同给药途径的项目——因为改变给药途径，基本都要做临床，前几个月讨论比较多的乙酰半胱氨酸注射液就是典型。相关文章： 1个月被CDE拒批5次？规格&适应症都不太可能批准！又2家被毙！乙酰半胱氨酸口服溶液全军覆没？给了一个立项的思路：一般该类型立项思路主要集中在神经精神类、呼吸系统和自身免疫类领域项目，比如由布瑞哌唑片扩展到布瑞哌唑片口溶膜和布瑞哌唑片口崩片；富马酸喹硫平片扩展到富马酸喹硫平缓释片，孟鲁司特钠片扩展到孟鲁司特钠颗粒、孟鲁司特钠咀嚼片、孟鲁司特钠口崩片；比拉斯汀片扩展到比拉斯汀口服溶液和比拉斯汀口崩片；依巴斯汀片扩展到依巴斯口服溶液等等。如果企业已经有了或者立项了一个剂型，与其在绞尽脑汁地寻找其他品种，不如将现有品种吃透。回归到这次申报的盐酸舍曲林口服浓缩液，就是一个典型案例。一个已经上市了二十多年的老药，且相同给药途径的药物早早在国内上市，可以豁免生物等效性研究的假3类项目，然而申报企业是海南斯达制药，但其并没有上市的舍曲林相关制剂。按理说，京新药业，本身就有舍曲林的片剂、胶囊和分散片的批准文号，本能就应该对舍曲林是否存在其他剂型比其他企业有天生的敏感度才对，抛开市场不谈，京新药业作为盐酸舍曲林口服浓缩液的首仿才是最合理，也是最容易的。 PS: 立项还可以从哪些方面去考量，去寻找新项目，后续咱们慢慢聊，欢迎留言。投稿/内容沟通：华籍美人（Ww_150525）近期精华文章

上市批准专利到期一致性评价

100 项与枸橼酸舍曲林相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	国家/地区	公司	日期
强迫症	中国	哈药集团三精明水药业有限公司	2008-03-18

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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


NCT02504931 (DDx, CTgov)	临床4期	酗酒 \| 创伤后应激障碍 \| 酒精相关疾病	49	Sertraline (Sertraline)	範襯艱簾鑰範獵鬱鏇淵(鑰鏇範顧壓顧獵網衊鏇) = 襯構選遞獵網遞憲膚夢願膚鹹衊鑰廠醖夢蓋衊 (淵醖觸獵鏇鬱窪膚鬱襯, 24.8) 更多	-	2018-02-27
				Placebo (Placebo)	範襯艱簾鑰範獵鬱鏇淵(鑰鏇範顧壓顧獵網衊鏇) = 壓範壓遞憲簾構憲構繭願膚鹹衊鑰廠醖夢蓋衊 (淵醖觸獵鏇鬱窪膚鬱襯, 24.1) 更多