A Randomized, Placebo-controlled, Double-blind, Phase 3 Clinical Study to Investigate the Efficacy and Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms (Hot Flashes) in Women With Stage 0 to 3 Hormone Receptor-positive Breast Cancer Who Are Receiving Adjuvant Endocrine Therapy

One of the standard treatments for women with breast cancer is hormone therapy, but this treatment can cause hot flashes. Hormone replacement therapy, or HRT, is most often prescribed for hot flashes for women in menopause but cannot be given to women on hormone therapy for breast cancer. Fezolinetant, an alternative to HRT, treats hot flashes for women in menopause. As hot flashes happen in the same way for women on hormone therapy for breast cancer, fezolinetant could help these women. In this study, women on hormone therapy for breast cancer who have moderate to severe hot flashes will take part. They will either take fezolinetant or a placebo to treat their hot flashes. The placebo looks like fezolinetant but doesn't have any medicine in it.
The main aim of this study is to confirm if women who take fezolinetant have fewer hot flashes that are less severe compared to women who take the placebo.
Women 18 years or older seeking treatment for hot flashes. They can take part in the study if they have an average of 7 or more moderate to severe hot flashes each day. They are having hormone therapy for breast cancer from stage 0 (cancer cells that have not spread to nearby tissue) up to stage 3+ (the cancer has spread from the breast to the lymph nodes near the breast or the chest wall).
The women will be assigned 1 of 2 study treatments (fezolinetant or placebo) by chance alone. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study treatments (fezolinetant or placebo). Women who take part in the study will take 1 tablet every day for 52 weeks (1 year). Each woman will be given an electronic handheld device with an app to track their hot flashes. Some women may be able to use the app on their own smartphone. In the last 10 days before their next clinic visit, the women will record information about their hot flashes. They will also use another device to answer questions about how hot flashes affect their daily life. During the study, the women will visit their study clinic about every 4 weeks for a health check. This will include some blood and urine tests. Some visits will also include a bone scan (called a DXA scan) and a liver ultrasound. Women who have a womb (uterus) will also have a test called a transvaginal ultrasound. A probe is gently placed inside the vagina. Sound waves will create a picture of the organs in the pelvis. This will allow the study doctor to look more closely at the uterus and surrounding organs. The last clinic visit will be 3 weeks after the women take their last tablet of study treatment (fezolinetant or placebo).

开始日期2024-07-31

申办/合作机构

Astellas Pharma Global Development, Inc.

NCT06385158 / Recruiting临床1期

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Oral Dose Escalation of GS1-144 Tablets and the Effects of Food on the Pharmacokinetics of GS1-144 in a Chinese Population

A Phase I clinical study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral dose escalation of GS1-144 tablets and the effects of food on the pharmacokinetics of GS1-144 in a Chinese population

开始日期2024-04-01

申办/合作机构

长春金赛药业有限责任公司

CTIS2023-504955-28-01 / Recruiting

(22423 NIRVANA) A randomized, parallel-group treatment, Phase 2, double-blind pilot study to investigate the efficacy and safety of elinzanetant compared with placebo for treatment of sleep disturbances associated with menopause - 22423

开始日期2024-03-26

申办/合作机构

Bayer Consumer Care AG

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100 项与 NK3 相关的临床结果

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100 项与 NK3 相关的转化医学

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0 项与 NK3 相关的专利（医药）

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953

项与 NK3 相关的文献（医药）

2024-10-01·PEST MANAGEMENT SCIENCE

Target‐based discovery of antagonists of the tick (Rhipicephalus microplus) kinin receptor identifies small molecules that inhibit midgut contractions

Article

作者: Baker, Dwight ; Sacchettini, James C. ; Henriques‐Santos, Bianca Monteiro ; Pietrantonio, Patricia V. ; Snavely, Thomas ; Zhou, Nian

Abstract:

BACKGROUND:

A GPCR (G protein‐coupled receptor) target‐based approach was applied to identify antagonists of the arthropod‐specific tick kinin receptor. These small molecules were expected to reproduce the detrimental phenotypic effects that had been observed in Rhipicephalus microplus females when the kinin receptor was silenced by RNA interference. Rhipicephalus microplus, the southern cattle tick, cattle fever tick, or Asian blue tick, is the vector of pathogenic microorganisms causing the deadly bovine babesiosis and anaplasmosis. The widespread resistance to acaricides in tick populations worldwide emphasizes that exploring novel targets for effective tick control is imperative.

RESULTS:

Fifty‐three structural analogs of previously identified tick kinin antagonists were screened in a ‘dual‐addition’ calcium fluorescence assay using a CHO‐K1 cell line expressing the tick kinin receptor. Seven molecules were validated as non‐cytotoxic antagonists, four of which were partial (SACC‐0428764, SACC‐0428780, SACC‐0428800, and SACC‐0428803), and three were full antagonists (SACC‐0428799, SACC‐0428801, and SACC‐0428815). Four of these antagonists (SACC‐0428764, SACC‐0428780, SACC‐0428799, and SACC‐0428815) also inhibited the tick midgut contractions induced by the myotropic kinin agonist analog 1728, verifying their antagonistic bioactivity. The small molecules were tested on recombinant human neurokinin (NK) receptors, the one most similar to the invertebrate kinin receptors. Most molecules were inhibitors of the NK1 receptor, except SACC‐0412066, a previously identified tick kinin receptor antagonist, which inhibited the NK1 receptor only at the highest concentration tested (25 μm). None of the molecules inhibited the NK3 human receptor.

CONCLUSION:

Molecules identified through this approach could be useful probes for studying the tick kinin signaling system and midgut physiology. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

2024-09-01·JOURNAL OF NEUROENDOCRINOLOGY

Restoring function to inactivating G protein‐coupled receptor variants in the hypothalamic–pituitary–gonadal axis¹

Review

作者: Radomsky, Tarryn ; Millar, Robert P. ; Anderson, Ross C. ; Newton, Claire L.

Abstract:

G protein‐coupled receptors (GPCRs) are central to the functioning of the hypothalamic–pituitary–gonadal axis (HPG axis) and include the rhodopsin‐like GPCR family members, neurokinin 3 receptor, kappa‐opioid receptor, kisspeptin 1 receptor, gonadotropin‐releasing hormone receptor, and the gonadotropin receptors, luteinizing hormone/choriogonadotropin receptor and follicle‐stimulating hormone receptor. Unsurprisingly, inactivating variants of these receptors have been implicated in a spectrum of reproductive phenotypes, including failure to undergo puberty, and infertility. Clinical induction of puberty in patients harbouring such variants is possible, but restoration of fertility is not always a realisable outcome, particularly for those patients suffering from primary hypogonadism. Thus, novel pharmaceuticals and/or a fundamental change in approach to treating these patients are required. The increasing wealth of data describing the effects of coding‐region genetic variants on GPCR function has highlighted that the majority appear to be dysfunctional as a result of misfolding of the encoded receptor protein, which, in turn, results in impaired receptor trafficking through the secretory pathway to the cell surface. As such, these intracellularly retained receptors may be amenable to ‘rescue’ using a pharmacological chaperone (PC)‐based approach. PCs are small, cell permeant molecules hypothesised to interact with misfolded intracellularly retained proteins, stabilising their folding and promoting their trafficking through the secretory pathway. In support of the use of this approach as a viable therapeutic option, it has been observed that many rescued variant GPCRs retain at least a degree of functionality when ‘rescued’ to the cell surface. In this review, we examine the GPCR PC research landscape, focussing on the rescue of inactivating variant GPCRs with important roles in the HPG axis, and describe what is known regarding the mechanisms by which PCs restore trafficking and function. We also discuss some of the merits and obstacles associated with taking this approach forward into a clinical setting.

2024-08-14·JOURNAL OF PHYSICS-CONDENSED MATTER

Superconductivity in monolayer Janus titanium-sulfur hydride (TiSH) at ambient pressure

Article

作者: Munib Ul Hassan Noor Ul Taqi, M ; Pinsook, Udomsilp

Abstract:

Janus two dimensional (2D) materials are new and novel materials. As they break out-of-plane symmetry, they possess several fascinating properties which can be applied in catalytic reactions and opto-electronics. Recent synthesis of MoSH and the prediction of phonon-mediated superconductivity have opened a new way to investigate the properties of hydrogenated Janus materials (Novoselov et al 2004 Science306 666–9; Mehta et al 2023 Solid State Commun.375 115347; Naik et al 2023 Comput. Theor. Chem.1228 114278). In this work, we performed the density functional theory calculations to demonstrate that titanium sulfur hydride (TiSH) is dynamically stable and becomes phonon-mediated superconductor with the superconducting critical temperature, Tc = 9.24 K with the corresponding value of electron–phonon coupling constant, λ = 0.71, in the weak interaction limits, under ambient conditions. Eliashberg spectral function α2F(ω) was well converged for dense grid of q1 × q2 × q3 = 12 × 12 × 1 and nk1 × nk2 × nk3 = 140 × 140 × 1. The effect of smearing broadening was also considered for determining well converged value of Tc and λ. Figure 5(b) shows that after smearing broadening of 0.02 Ry, λ shows convergent values, and subsequent changes are as low as less that 5% of the peak value. Overall, our findings predicted a new member in the 2D Janus hydride family with possible applications in 2D nanomaterials and superconducting devices applications.

115

项与 NK3 相关的新闻（医药）

2024-09-19

·安斯泰来中国

2024年服贸会：安斯泰来助力中国医药创新与高质量发展

9月12日，2024年中国国际服务贸易交易会（服贸会）在北京盛大开幕，安斯泰来再次以数字化形式参展，展示了最新创新成果，并被《中国贸易报》、《人民日报》健康客户端和《科技日报》等多家媒体关注和报道。作为一家以创新为驱动的全球制药企业，安斯泰来一直致力于将全球创新成果加速引入中国，助力“健康中国2030”目标的早日实现。以下为报道内容节选：《中国贸易报》：加强在华创新与合作，安斯泰来助力医药服务贸易健康发展 “服贸会是引领行业创新的重要平台。”2024年服贸会期间，安斯泰来相关负责人在接受《中国贸易报》记者专访时说，“我们希望通过参加服贸会，发挥跨国企业的桥梁作用，推动全球创新药物‘引进来’和中国本土创新‘走出去’，赋能中国医药行业创新发展，以更高水平的本土合作，与产业伙伴共同助力‘健康中国2030’的早日实现，推动中国医药行业可持续和高质量发展。” 记者了解到，安斯泰来1994年进入中国市场，产品管线涉及肿瘤、移植免疫、泌尿等多个领域。2019年，中国升级为安斯泰来五大全球市场之一。安斯泰来在2021年完成了在华战略布局的升级，形成了“一个总部和两个中心”的新架构。2022年安斯泰在北京线上参加服贸会。今年，安斯泰来再度借力数字化形式展示安斯泰来在华战略布局、重磅新品。据悉，安斯泰来不断加速将全球创新药物引入中国市场，填补未被满足的医疗需求。以胃癌治疗领域为例，中国每年新增确诊病例接近全球一半。自2019年起，安斯泰来中国就开始参与针对胃癌的CLDN 18.2单抗的全球多中心临床试验，并实现了安斯泰来历史上首次中国与全球同步开发与同步递交上市申请。最近一年来，安斯泰来中国接连取得了四款产品的里程碑进展，近期还实现了公司首个一期临床试验IND批准，并启动了第一家研究中心。在安斯泰来看来，当前，中国医药市场充满新机遇。“2024年《政府工作报告》将创新药列为积极培育的新兴产业之一，7月《全链条支持创新药发展实施方案》审议通过，创新药产业将迎来新的发展阶段。”安斯泰来相关负责人表示，从加速药品审评审批制度到提升新药准入速度，再到推进商业模式的数字化转型，鼓励创新政策频频出台，中国医药行业的快速发展由此获得良好的市场环境，让外资药企的创新药物从研发到上市的周期大大缩短，中国患者能够更早享受到全球领先的治疗方案。借助这些政策红利，安斯泰来将进一步扩大在中国的研发投入，推动更多具有突破性的药物和治疗方案尽早在华落地。此外，随着智慧医疗应用边界不断拓宽、人工智能（AI）不断渗透，科技助力个性化疾病管理，高科技、高效能、高质量的数智建设方式已成为未来健康产业高质量发展的驱动力。人工智能赋能药物研发，可大幅缩短研发周期，降低成本，提升成功率，安斯泰来为此一直在采取推动整个价值链的数字化转型举措。安斯泰来于2022年创建了一个集成人类、AI和机器人属性的新药发现平台Mahol-A-Ba，该平台能在较短时间开发出高质量药物。 “中国是安斯泰来的重要市场。为了更好地服务中国用户，安斯泰来探索出一条路径，即‘将前沿的技术和创新科学运用到研发中，以迅速给患者带来价值。’” 安斯泰来相关负责人表示，未来，安斯泰来将进一步深化对中国市场和中国研发土壤的耕耘，与更多中国本土企业开展合作，将立足于中国的创新内容带向全球。《人民日报》健康客户端：安斯泰来在服贸会展示胃癌靶向药等多款创新产品 9月12日，安斯泰来借力数字化形式亮相2024北京服贸会，展出创新性胃癌靶向药、靶向Nectin-4的ADC药物，以及绝经相关中度至重度血管舒缩症（VMS）非激素疗法等。靶向Nectin-4的ADC药物维恩妥尤单抗，在今年8月获批用于局部晚期或转移性尿路上皮癌患者；创新性胃癌靶向药Zolbetuximab用于一线治疗CLDN18.2阳性、HER2阴性的局部晚期不可切除或转移性胃或胃食管交界处（GEJ）腺癌患者。绝经相关中度至重度血管舒缩症状的非激素、选择性神经激肽3（NK3）受体拮抗剂药物Fezolinetant已获批落地博鳌乐城。事实上，安斯泰来开展的临床研究在较常规更早的临床研发阶段就将中国考虑纳入，同步研发、同步递交上市申请，以实现创新药物的同步上市。目前其产品管线涉及肿瘤、移植免疫、泌尿等多个领域。《科技日报》：服贸会加速健康产业数字化转型 2024年中国国际服务贸易交易会（简称“服贸会”）于9月12日在北京拉开帷幕。本届服贸会围绕服务贸易开放发展新趋势，举办了涵盖服务贸易便利化、文化和旅游融合、数字经济贸易、科技创新等热门话题的13场主题论坛，旨在推动服务贸易的高水平对外开放，深化国际交流与合作。其中，在9月12日举办的数字贸易发展趋势和前沿论坛上，与会者对数字技术和数字贸易的重点领域展开了深入讨论，引发广泛关注和热议。论坛上，国务院发展研究中心对外经济研究部与中国信息通信研究院联合发布了《数字贸易发展与合作报告2024》。该报告显示，加快数字化转型和大力发展数字贸易，已经成为各国抓住数字时代发展机遇、应对全球经济不确定性挑战的关键战略。中国蓬勃发展的数字经济和广阔的市场空间，为各类企业创造了前所未有的机遇。在健康产业领域，数字化转型正推动着新模式和新技术的应用落地，为医疗服务和社会大众健康带来新变革。对于医药企业来说，紧跟数字经济潮流，抓住数字贸易的发展机遇，已成为提升服务能力的关键。借力于数字化转型中从支付端、融资端、审评端、考核端等维度全链条助推创新药研发、生产及商业化的新政策，安斯泰来不断加速创新药物的在中国的研发与落地进程。今年，安斯泰来携数个创新药成果登场服贸会线上展，展现其在创新药领域的创新成果，领域覆盖胃癌、尿路上皮癌和前列腺癌等，其中包括有全球首个靶向Nectin-4的ADC药物，全球首个胃癌靶向Claudin18.2单抗，还有全球创新的绝经相关中度至重度血管舒缩症(VMS)非激素疗法等。在全球数字经济快速发展的背景下，服贸会不仅是服务贸易领域的创新高地，更是促进各产业与数字技术深度融合的重要平台。数字经济带来的技术创新和模式变革，正在重塑健康产业的生态格局。关于安斯泰来中国安斯泰来自1994年进入中国，始终专注于尚未满足的医疗需求，以公开、诚信和协作的方式开展业务，全心全意向中国大众提供高质量的创新药品和服务，致力于提升中国社会的健康福祉。中国是安斯泰来全球增长战略中至关重要的一部分，目前，公司在中国市场销售的产品涉及肿瘤、移植免疫、泌尿、感染等多个专业治疗领域。更多信息，请访问我们的网站www.astellas.com.cn。

临床申请临床1期

2024-09-13

·BioSpace

Astellas’ Hot Flash Drug Veozah Slapped With Another FDA Warning for Liver Injury

Astellas’ headquarters for the Americas iStock, JHVEPhoto One patient developed elevated liver blood tests after receiving Astellas Pharma’s non-hormonal small molecule blocker, leading the regulator to add a warning to the drug’s label. The FDA on Thursday added a warning to the label of Astellas Pharma ’s hot flash therapy Veozah (fezolinetant), alerting patients and prescribers to a newly documented risk of “rare but serious” liver injury. The new warning was prompted by a postmarketing review of a patient who was taking Veozah and subsequently saw spikes in liver blood test values. The patient also showed signs of liver injury after being treated for around 40 days, according to the regulator. Per Veozah’s updated label , prescribers should test their patients’ blood liver markers more frequently, including monthly screens for the first two months after initiating Veozah, followed by additional tests after three, six and nine months. Doctors and prescribers should also conduct hepatic testing before starting patients on Veozah. In case of signs that could indicate liver problems, patients should stop taking Veozah “immediately” and contact their healthcare professional, according to the FDA. Common symptoms of liver harm include fatigue, jaundice, nausea and vomiting, as well as unusual itching and light-colored stools. Despite being a hit to Veozah’s safety profile, Thursday’s label seems unlikely to substantially hurt Astellas. Jeffries analysts in a note to investors said that the new warning “strengthened Veozah’s label” and that while the additional testing requirements will put more burden on patients, they “may not have much impact on demand overall.” Administered orally, Veozah is a non-hormonal small molecule blocker of the NK3 receptor which plays a part in the signaling cascade that results in the release of specific hormones involved in the menstrual cycle. Veozah specifically acts on neurons in the brain’s thermoregulatory centers, allowing it to reduce the frequency and intensity of hot flashes and night sweats. The FDA approved Veozah in May 2023 for women in menopause. In December 2023, Astellas unveiled more Phase IIIb data for Veozah, touting statistically significant improvements in moderate to severe vasomotor symptoms in patients at 24 weeks compared with placebo. Veozah also reduced sleep disturbance in these patients. At the time, the pharma noted that these findings will help it with reimbursement negotiations in Europe. Bayer is also advancing a non-hormonal competitor to Veozah. Elinzanetant is a small molecule dual inhibitor of the NK1 and NK3 receptors, which the pharma is also positioning as a treatment for moderate to severe vasomotor symptoms in menopause. Bayer won rights to elinzanetant when it bought KaNDy Therapeutics in August 2020 for $425 million upfront . In May 2024, Bayer reported data from its pivotal Phase III OASIS 1 and OASIS 2 studies, demonstrating that elinzanetant significantly lowered the frequency of hot flashes, reduced sleep disturbances and improved menopause-related quality of life.

临床结果上市批准并购临床3期

2024-09-12

·drugs

Drug Safety Communication: FDA Adds Warning About Rare Occurrence of Serious Liver Injury with Use of Veozah (fezolinetant) for Hot Flashes Due to Menopause

Audience: Patient, Health Professional, OBGYN, Endocrinology September 12, 2024 -- The FDA is warning that Veozah ( fezolinetant ), a medicine used to treat hot flashes due to menopause, can cause rare but serious liver injury. If there are signs and symptoms suggesting liver injury, stopping the medicine could prevent worsening liver injury and potentially return liver function to normal. The FDA added a warning about the risk of liver injury to the existing warning about elevated liver function test values and required liver function testing in the prescribing information for Veozah. The FDA made this update after reviewing a post marketing report of a patient with elevated liver function test values and signs and symptoms of liver injury after taking the medicine for about 40 days. The FDA also added new recommendations for patients and health care professionals about increasing the frequency of liver function testing, adding monthly testing for the next 2 months after starting Veozah, and then at months 3, 6, and 9 of treatment as already recommended. The updated prescribing information also instructs patients to stop the medicine immediately and contact the health care professional who prescribed the medicine if signs and symptoms of liver injury occur. BACKGROUND: Veozah (fezolinetant) is a nonhormonal prescription medicine approved in May 2023 to reduce the frequency and severity of moderate to severe hot flashes caused by menopause. The medicine is in a drug class called neurokinin 3 (NK3) receptor antagonists. It works to restore the balance between estrogen hormones and a brain chemical called neurokinin B (NKB) by blocking the activities of the NK3 receptor, which plays a role in the brain’s control of body temperature. RECOMMENDATIONS: Patients and Caregivers Health Care Professionals Related Information Source: FDA Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

上市批准