A Randomized, Double-blind, Placebo-Controlled, 2-Period Crossover, Phase 2 Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral TAK-071 in Parkinson Disease Patients With Cognitive Impairment and an Elevated Risk of Falls

It is hoped that TAK-071 will help people with Parkinson's disease to walk with better balance. The main aim of the study is to check if there is a difference in how participants walk after treatment with TAK-071. Another aim is to see if it improves how participants think and remember.
At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 groups by chance.
Both groups will have 2 treatments but in a different order. The treatments are TAK-071 tablets or placebo. In this study, a placebo will look like the TAK-071 but will not have any medicine in it.
One group will take TAK-071 for 6 weeks, have at least a 3-week break, then take a placebo for 6 weeks. The other group will take a placebo for 6 weeks, have at least a 3-week break, then take TAK-071 for 6 weeks. The participants will not know the order of their 2 treatments, nor will their study doctors. This is to help make sure the results are more reliable.
The participants will visit the clinic at the beginning and end of each treatment for a check-up. 14 days after the 2nd treatment, clinic staff will telephone the participants for a final check-up.

开始日期2020-10-21

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

[+1]

NCT02918266 / Terminated临床1期

A Randomized, Double-Blind, Sponsor Unblinded, Placebo-Controlled, 5-Period Crossover, Phase 1b Study To Evaluate The Effects Of Single Oral Administration of TAK-071 On Scopolamine-Induced Cognitive Impairment In Healthy Subjects

The purpose of this study is to assess the effect of a single oral dose of TAK-071 on the attenuation of cognitive deficit induced by scopolamine as measured by Groton Maze Learning Test (GMLT) (total number of errors).

开始日期2016-11-21

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT02769065 / Terminated临床1期

A Phase 1 Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Oral Doses of TAK-071 in Healthy Subjects and Subjects With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability and Food Effect of TAK-071 in Healthy Subjects

The purpose of this study was to assess the safety, tolerability, and pharmacokinetic (PK) of TAK-071 when administered as single rising dose (SRD) and multiple rising dose (MRD) orally in healthy participants and participants with mild cognitive impairment (MCI) or mild Alzheimer disease (AD).

开始日期2016-05-05

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

100 项与 TAK-071 相关的临床结果

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100 项与 TAK-071 相关的转化医学

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100 项与 TAK-071 相关的专利（医药）

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项与 TAK-071 相关的文献（医药）

2022-02-01·British journal of clinical pharmacology2区 · 医学

Safety, pharmacokinetics and quantitative EEG modulation of TAK‐071, a novel muscarinic M1 receptor positive allosteric modulator, in healthy subjects

2区 · 医学

Article

作者: Martenyi, Ferenc ; Buhl, Derek L. ; Rosen, Laura ; Simen, Arthur A. ; Mamashli, Fahimeh ; Volfson, Dmitri ; Gevorkyan, Hakop ; Yin, Wei ; Khudyakov, Polyna

Aims:

TAK‐071 is a muscarinic M1 receptor positive allosteric modulator designed to have low cooperativity with acetylcholine. This was a first‐in‐human study to evaluate the safety, pharmacokinetics, and pharmacodynamics of TAK‐071.

Methods:

TAK‐071 was administered as single and multiple doses in a randomized, double‐blind, placebo‐controlled, parallel‐group design in healthy volunteers alone and in combination with donepezil. Laboratory, electrocardiogram (ECG) and electroencephalogram (EEG) evaluations were performed. Cerebrospinal fluid and blood samples were taken to evaluate the pharmacokinetics (PK), relative bioavailability and food effect.

Results:

TAK‐071 was safe and well tolerated, and no deaths or serious adverse events occurred. TAK‐071 demonstrated a long mean (% coefficient of variation) half‐life of 46.3 (25.2%) to 60.5 (51.5%) hours and excellent brain penetration following oral dosing. Coadministration with donepezil had no impact on the PK of either drug. There was no food effect on systemic exposure. Quantitative EEG analysis revealed that TAK‐071 40‐80 mg increased power in the 7‐9 Hz range in the posterior electrode group with eyes open and 120‐160 mg doses increased power in the 16‐18 Hz range and reduced power in the 2‐4 Hz range in central‐posterior areas with eyes open and eyes closed. Functional connectivity was significantly reduced after TAK‐071 at high doses and was enhanced with coadministration of donepezil under the eyes‐closed condition.

Conclusions:

PK and safety profiles of TAK‐071 were favorable, including those exceeding expected pharmacologically active doses based on preclinical data. When administered without donepezil TAK‐071 was largely free of cholinergic adverse effects. Further clinical evaluation of TAK‐071 is warranted.

2021-11-01·Neuroscience letters4区 · 医学

Therapeutic potential of TAK-071, a muscarinic M1 receptor positive allosteric modulator with low cooperativity, for the treatment of cognitive deficits and negative symptoms associated with schizophrenia

4区 · 医学

Article

作者: Yamada, Ryuji ; Hirakawa, Takeshi ; Kurimoto, Emi ; Kimura, Haruhide

The selective activation of the muscarinic M₁ receptor (M₁R) may be a promising approach for treating cognitive impairment associated with cholinergic dysfunction. We previously reported that low cooperativity (α-value) is associated with a favorable cholinergic side effect profile of M₁R positive allosteric modulators (M₁ PAMs), as well as being a crucial factor for the cognitive improvement observed after combining M₁ PAMs with donepezil, in rodents. In this study, we preclinically characterized TAK-071, a novel M₁ PAM with low cooperativity (α-value = 199), as a new therapy for schizophrenia. We tested TAK-071 in the offspring of polyriboinosinic-polyribocytidylic acid-treated dams, which is a maternal immune activation model of schizophrenia. TAK-071 improved sociability deficits and working memory in this model. In a genetic mouse model of schizophrenia, miR-137 transgenic (Tg) mice, TAK-071 improved deficits in working memory, recognition memory, sociability, and sensorimotor gating. Patients with schizophrenia usually take several antipsychotics to treat positive symptoms. Thus, we also investigated the combined effects of TAK-071 with currently prescribed antipsychotics. Among the 10 antipsychotics tested, only olanzapine and quetiapine showed M₁R antagonistic effects, which were counteracted by TAK-071 at possible effective concentrations for cognitive improvement in vitro. Moreover, haloperidol did not affect the ability of TAK-071 to improve working memory in miR-137 Tg mice, suggesting a low risk of losing efficacy when combined with dopamine D₂ receptor antagonists. In conclusion, TAK-071 can exert beneficial effects on social behavior and cognitive function and could be a new therapy for schizophrenia.

2021-07-01·Psychopharmacology3区 · 医学

Reduction of falls in a rat model of PD falls by the M1 PAM TAK-071

3区 · 医学

Article

作者: Sarter, Martin ; Kucinski, Aaron

RATIONALE:

In addition to the disease-defining motor symptoms, patients with Parkinson's disease (PD) exhibit gait dysfunction, postural instability, and a propensity for falls. These dopamine (DA) replacement-resistant symptoms in part have been attributed to loss of basal forebrain (BF) cholinergic neurons and, in interaction with striatal dopamine (DA) loss, to the resulting disruption of the attentional control of balance and complex movements. Rats with dual cholinergic-DA losses ("DL rats") were previously demonstrated to model PD falls and associated impairments of gait and balance.

OBJECTIVES:

We previously found that the muscarinic M1-positive allosteric modulator (PAM) TAK-071 improved the attentional performance of rats with BF cholinergic losses. Here, we tested the hypotheses that TAK-071 reduces fall rates in DL rats.

RESULTS:

Prior to DL surgery, female rats were trained to traverse a rotating straight rod as well as a rod with two zigzag segments. DL rats were refamiliarized with such traversals post-surgery and tested over 7 days on increasingly demanding testing conditions. TAK-071 (0.1, 0.3 mg/kg, p.o.) was administered prior to daily test sessions over this 7-day period. As before, DL rats fell more frequently than sham-operated control rats. Treatment of DL rats with TAK-071 reduced falls from the rotating rod and the rotating zigzag rod, specifically when the angled part of the zigzag segment, upon entering, was at a steep, near vertical angle.

CONCLUSIONS:

TAK-071 may benefit complex movement control, specifically in situations which disrupt the patterning of forward movement and require the interplay between cognitive and motor functions to modify movement based on information about the state of dynamic surfaces, balance, and gait.

项与 TAK-071 相关的新闻（医药）

2024-05-10

·药事纵横

武田2023净利润下降55%，将进行9亿美元重组

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。5月9日，武田制药公布了2023财报（2023年4月~2024年3月）：全年营收42638亿日元，同比增长5.9%；净利润为1441亿日元，同比下降54.6%。按地区收入来看，美国收入最多，达21957亿日元；其次是欧洲和加拿大，收入9668亿日元；第三是日本本土，收入4514亿日元，其他地区收入情况如下：按产品收入来看，武田收入主要来源5大板块：消化、罕见病、血液制品、神经科学和肿瘤。其中，消化领域产品收入是最主要来源，2023年收入12162亿日元，同比增长11%。其中Entyvio(维多珠单抗)是该管线的顶梁柱支柱产品，2023年销售8009亿日元，同比增长14%。但是，武田降压药“Azilva”2023年仅销售336亿日元，同比大降54%。Azilva于2012年1月在日本上市，2021年销售额达到763亿日元。2021年6月，恒瑞医药的阿齐沙坦片获批，拿下国内首仿。而武田明星产品“Vyvanse”2023年销售4232亿日元，同比下降8%。Vyvanse于2003年首次被批准用于注意力缺陷/多动障碍。其成人适应症专利已于2023年 2 月 24 日到期，儿科适应症也于2023年 8 月 24 日到期。Sandoz、Teva 和 Mylan 等公司至少有 12 款 Vyvanse 仿制药即将推出。2023年由于武田失去了Azilva 和Vyvanse 的独家经营权，导致年利润下降超50%。再加上克罗恩病干细胞疗法 Alofisel和肺癌酪氨酸激酶抑制剂 Exkivity的研究失败，于是，武田决定对公司进行重组，提高未来几年的利润率。预计2024年将产生1400亿日元（约9亿美元）的一次性重组费用。武田表示，重组将包括优化员工、削减开支、砍管线。公司的目标是从2025开始，每年将核心利润率提高 1%~2.5%，最终达到 30%。武田研发管线财报中还提到，2023年武田共有18款药物从管线中剔除，包括：肺癌产品Exkivity、阿尔茨海默氏症药物DNL-919（ATV：TREM2）、异染性脑白质营养不良酶替代疗法TAK-611、治疗恶心和呕吐的候选药物 TAK-105、治疗伴有复杂肛瘘的克罗恩病的Cx601、针对帕金森病的TAK-071、癌症疗法TAK-981、细胞疗法 TAK-007、多发性骨髓瘤和实体瘤的TAK-573、实体瘤的TAK-102/TAK-103、多发性骨髓瘤的TAK-940以及预防寨卡病毒感染的TAK-426等。与此同时，有报道称：武田将关闭其圣地亚哥研究中心（拥有340名员工），将更多资源集中在有前途的后期研发管线上。武田首席执行官 Christophe Weber表示：“展望 2024 年，预计将有多达6个项目处于III 期开发中，通过开发将推进这些有前景的疗法，同时适度增加研发投资。”虽然 Vyvanse 等药物独家经营权的丧失对武田营收造成了影响，但该公司预计，至少在 2030 年之前，该公司面临的此类风险将有限。因此，预计2025年起能够恢复收入和利润增长。参考资料：https://www.takeda.com/newsroom/newsreleases/2024/takeda-announces-fy23-full-year-results-and-fy2024-outlook-pdf/活动推荐点击图片查看详细信息

财报临床3期专利到期

2024-02-12

·药事纵横

武田再砍6条管线

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。武士刀起，管线落！在研发的道路上，杀伐决断，勇于放弃也是一种积极的策略。继去年半年报武田宣布砍掉4条管线后，近日又披露停止了6个管线项目。近期，多家全球知名药企纷纷揭晓了最新财报，除了各项财务数据备受瞩目外，其研发管线的战略调整同样引起了业界的广泛关注。尤其被终止的研发项目，它们背后的故事与经验教训对于整个行业而言都极具借鉴意义，有助于其他企业在研发道路上规避风险，少走弯路，减少不必要的探索。例如罗氏将从其研发管线中剔除5款神经学领域资产和3款肿瘤资产（包括2款死磕十多年的AD药物），旨在平衡整体投资组合价值并加速开发更有价值资产。辉瑞也砍掉3条管线，涉及到广谱抗真菌类，抗肿瘤药和1款B7H4/CD3双抗。除了罗氏、辉瑞等药企，武田制药在最新披露信息中显示，净利下降和管理层变动，也终止了6个研发项目。2023财年前三季度，武田全球总收入为3.21万亿日元（约合220亿美元），同比增长4.6%。净利润为1471亿日元，同比下降49%。该公司预计其2023财年营收将达到3.9万亿日元（合266亿美元）。武田公司表示，其利润的变化反映了仿制药的竞争、新冠肺炎疫苗收入的减少以及研发、数据和技术方面投资的增加。近期，武田在人事变动和对外合作方面也动作频频。CFO辞职，肿瘤学部门换帅首席财务官Costa Saroukos将于4月1日辞职，以便更接近他在澳大利亚的家人。他在这份工作上工作了六年，并帮助完成了制药史上最大的交易之一——2019 年以 620 亿美元收购夏尔。Takeda CEO Christophe Weber评价称其在此交易中发挥了重要作用。此外，武田还宣布前CRISPR Therapeutics公司首席医学官PK Morrow于1月29日接替ChrisArendt担任肿瘤学部门负责人。Christophe Weber, Takeda CEO在对外合作方面，今年2月初武田花费3亿美元购买Protagonist的PhIII罕见病药物。去年12月JCR Pharmaceuticals宣布武田决定停止与JCR合作，开发使用腺相关病毒（AAV）结合JCR J-Brain Cargo技术的基因疗法。近日有媒体报道，武田制药终止了六条研发管线。这些项目包括治疗伴有复杂肛瘘的克罗恩病的Cx601、针对帕金森病的TAK-071、多发性骨髓瘤和实体瘤的TAK-573、实体瘤的TAK-102/TAK-103、多发性骨髓瘤的TAK-940以及预防寨卡病毒感染的TAK-426。这些决策主要基于临床试验结果未达到预期、战略调整以及对市场需求和流行病学的评估。武田制药表示，这些举措是为了最大化公司价值和资源利用效率。具体项目和原因如下：研发总裁Andy Plump在更新研发管线时提到，武田在细胞治疗方面将聚焦通用型细胞治疗的研发，削减了其他处于I期临床试验阶段的3项CAR-T细胞治疗项目，分别为TAK-102、TAK-103和TAK-940。TAK-102和TAK-103针对实体肿瘤开发，而TAK-940则是为CD19针对多发性骨髓瘤。此外武田在本周四宣布，将于2024财年上半年在全球范围内启动其正在研究中的口服ORX2激动剂TAK-861在1型嗜睡症的全球三期临床试验，并放弃在2型嗜睡症中开发该候选药物的计划。在对112名NT1患者进行的具有主要和关键次要终点的P2b研究中取得积极结果后，武田开发了几种食欲素受体激动剂，并有望扩大特许经营权的规模。参考资料：https://assets-dam.takeda.com/image/upload/v1706756054/Global/Investor/Financial-Results/FY2023/Q3/q3_fy2023_press_release.pdf

财报基因疗法疫苗并购高管变更

2024-02-02

·FierceBiotech

Takeda drops cancer candidates, axing immunocytokine and CAR-Ts amid shifting treatment landscape

Takeda’s pipeline cull affected assets outside of oncology. Takeda’s vision of becoming a leader in oncology ran into more trouble Thursday when the drugmaker axed (PDF) a midphase immunocytokine and three early-stage CAR-T cell therapy prospects from its R&D pipeline. Under CEO Christophe Weber, Takeda has worked to establish itself as a leader in oncology. But, as the executive said on a quarterly results call with investors, the company has “had some wins ... [and] some setbacks.” The results brought news of more setbacks, with Takeda using the update to reveal it has dropped a clutch of cancer candidates led by modakafusp alfa. Formerly known as TAK-573, modakafusp alfa consists of two interferon alpha-2b molecules fused to an anti-CD38 monoclonal antibody. The idea was to activate innate and adaptive immune cells—while also directly stopping the proliferation of multiple myeloma cells—through targeted interferon signaling. Takeda began a phase 1/2a Darzalex combination trial one year ago, adding to the slate of studies run in support of the immunocytokine, but has now pulled the plug on the program. Andrew Plump, M.D., Ph.D., president of R&D at Takeda, explained the decision on the conference call with investors. “This is a strategic decision based on a number of factors, including the existing data set, the rapidly evolving multiple myeloma treatment landscape and the long development timelines,” the R&D chief said. Takeda pushed modakafusp alfa out of the door as part of a pipeline clear-out that also hit three phase 1 autologous CAR-T candidates. Two of the prospects, GPC3-targeted TAK-102 and mesothelin-directed TAK-103, were in development in solid tumors. The third asset, TAK-940, was a CD19-directed, Memorial Sloan Kettering Cancer Center-partnered program that used the 1XX domain to try to enhance efficacy. While Takeda axed a clutch of cancer candidates, Plump said the company “remains committed to oncology and will continue to develop therapies across hematologic and solid tumors.” The R&D chief highlighted the SUMO inhibitor subasumstat, a pair of STING agonists and two T-cell engagers from the Maverick Therapeutics acquisition as candidates to watch. Plump also cited the appointment of PK Morrow, who joined Takeda from CRISPR Therapeutics last month, as a boost for the oncology unit. Morrow became head of the oncology therapeutic area unit at Takeda, having previously worked as chief medical officer of CRISPR, and held various roles at Amgen. Takeda’s pipeline cull also affected assets outside of oncology. The drugmaker removed three phase 2 drug candidates, namely the rare disease asset TAK-611—which flunked a trial last year—the Parkinson’s disease prospect TAK-071 and the depression molecule TAK-041. In phase 1, Takeda axed treatments for Alzheimer’s disease and nausea as well as a Zika vaccine candidate. Amid the changes, Takeda grew its R&D spend by 7.3%, although Chief Financial Officer Costa Saroukos said that “does reflect some phasing,” and the company is still aiming for a mid single digit increase over the full year. Saroukos made the comment on what looks set to be his last quarterly results conference call as CFO of Takeda. Milano Furuta, president of Takeda’s Japan pharma business unit, is preparing to take over as CFO in April. Saroukos is leaving because “after 20 years working abroad, I’m ready to move back to Australia to be closer to my family,” the outgoing CFO told investors.

临床1期高管变更免疫疗法临床2期临床结果

100 项与 TAK-071 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
认知功能障碍	临床2期	美国	Takeda Pharmaceutical Co., Ltd.	2020-10-21
帕金森病	临床2期	美国	Takeda Pharmaceutical Co., Ltd.	2020-10-21
阿尔茨海默症	临床1期	美国	Takeda Pharmaceutical Co., Ltd.	2016-05-05
轻度认知障碍	临床1期	美国	Takeda Pharmaceutical Co., Ltd.	2016-05-05

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临床结果

适应症

分期

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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


NCT04334317 (CTgov)	临床2期	认知功能障碍 \| 帕金森病	64	TAK-071 (Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants))	繭鬱鑰夢鏇獵鏇蓋鬱鬱(遞夢醖憲簾鹽遞艱築構) = 網蓋積願築網襯壓壓網獵製淵壓壓鏇窪獵構網 (選鬱顧繭鏇糧觸顧顧糧, 艱餘廠製壓繭鏇淵齋廠 ~ 簾簾觸簾壓鹹繭積鬱顧) 更多	-	2024-05-14
				Placebo (Sentinel Cohort: Placebo (Healthy Participants))	鏇餘襯糧餘膚壓齋餘壓(鑰遞夢淵夢餘齋鹽齋築) = 衊淵壓膚壓選餘淵鹹範積膚鏇鬱製網壓廠艱糧 (夢築鹽範廠鹽膚簾鑰襯, 鬱鏇鬱廠網範衊淵糧襯 ~ 鬱鹽積築鹹蓋選選鬱簾) 更多
NCT02769065 (AAIC2017)	临床1期	阿尔茨海默症 \| 轻度认知障碍	179	TAK-071	醖願鹽壓積廠觸築餘觸(艱鬱積憲廠願製餘鹹鹽) = 廠獵憲餘艱鑰壓繭獵齋築夢鹹窪窪膚鏇積選繭 (廠蓋獵壓鏇鹹夢壓鹽鑰 )	-	2017-07-01
				T-662	醖願鹽壓積廠觸築餘觸(艱鬱積憲廠願製餘鹹鹽) = 鬱鹽網製餘壓鏇選廠夢築夢鹹窪窪膚鏇積選繭 (廠蓋獵壓鏇鹹夢壓鹽鑰 )