Imarikiren hydrochloride(Imarikiren hydrochloride) - 药物靶点：renin_在研适应症：糖尿病肾病，高血压_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Imarikiren

+ [2]

靶点

renin

作用机制

renin抑制剂(肾素抑制剂)

治疗领域

内分泌与代谢疾病泌尿生殖系统疾病心血管疾病

在研适应症

糖尿病肾病高血压

非在研适应症

白蛋白尿2型糖尿病肝病

原研机构

Takeda Pharmaceutical Co., Ltd.

在研机构

SCOHIA PHARMA, Inc.初创企业

非在研机构

Takeda Pharmaceutical Co., Ltd.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C27H42ClN5O4

InChIKeyPUXOYQIZZIWCHH-NSLUPJTDSA-N

CAS号1202269-24-6

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关联

4

项与 Imarikiren hydrochloride 相关的临床试验

NCT02367872

/ Completed临床1期

Phase I Open-label, Parallel-group, Comparative Study to Evaluate the Effects of Renal or Hepatic Impairment on TAK-272 Pharmacokinetics With a Single Oral Administration of TAK-272 in Patients With Renal or Hepatic Impairment

The purpose of this study is to examine the effects of renal and hepatic impairment on TAK-272 pharmacokinetics with a single oral administration of TAK-272 in participants with renal or hepatic impairment.

开始日期2015-03-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT02370615

/ Completed临床1期

A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of TAK-272 and the Effect of TAK-272 on the Pharmacokinetics of Digoxin or Midazolam In the Healthy Adult Participants

The purpose of this study is to evaluate the effect of repeated-dose administration of itraconazole on the pharmacokinetics of TAK-272, as well as the effect of repeated-dose administration of TAK-272 on the pharmacokinetics of digoxin or midazolam in healthy Japanese adult males.

开始日期2015-02-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT02332824

/ Completed临床2期

A Randomized, Multi-center, Double-blind, Placebo-controlled, Parallel-group Comparison, Phase 2 Study to Evaluate the Dose-response Relationship of the Efficacy and Safety of Oral Administration of TAK-272 in Patients With Type 2 Diabetes Mellitus and Microalbuminuria

The purpose of this study is to test the efficacy and safety on daily oral doses of TAK-272 5 mg, 20 mg, 40 mg and 80 mg in patients with type 2 diabetes mellitus and microalbuminuria by randomized, double-blind, placebo-controlled, parallel-group comparison in order to determine the clinical dose of TAK-272.

开始日期2014-10-16

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

100 项与 Imarikiren hydrochloride 相关的临床结果

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100 项与 Imarikiren hydrochloride 相关的转化医学

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100 项与 Imarikiren hydrochloride 相关的专利（医药）

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10

项与 Imarikiren hydrochloride 相关的文献（医药）

2020-05-01·FEBS Open Bio4区 · 生物学

Development of a novel murine heart failure model overexpressing human renin and angiotensinogen

4区 · 生物学

ArticleOA

作者: Nishimoto, Tomoyuki ; Takeyama, Michiyasu ; Kanagawa, Ray ; Yamamura, Takeshi ; Hara, Tomoya ; Murakami‐Asahina, Mirei ; Matsumoto, Hirokazu

Renin is the rate‐limiting enzyme of the renin–angiotensin system cascade, which drives the pathophysiological progression of heart failure. Species differences in the amino acid sequence of the catalytic domain of renin limit evaluations of the potency and efficacy of human renin inhibitors in animal models, and a high dose of inhibitors is usually needed to show its organ‐protective effects in rodents. In the present study, we developed a novel murine heart failure model (triple‐tg) to enable us to evaluate the cardioprotective effect of renin inhibitors at more relevant doses for humans, by cross‐breeding calsequestrin transgenic (CSQ‐tg) mice with human renin and human angiotensinogen double‐transgenic mice. The triple‐tg mice exhibited increased plasma renin activity, worsened cardiac hypertrophy, and higher mortality compared to CSQ‐tg mice. Triple‐tg mice treated with 10 mg·kg−1 of TAK‐272 (imarikiren/SCO‐272), an orally active direct renin inhibitor, exhibited improvements in heart failure phenotypes, such as cardiac hypertrophy and survival rate; however, a dose of 300 mg·kg−1 was required to improve symptoms in CSQ‐tg mice. Our results suggest that this newly generated triple‐tg heart failure model is useful to evaluate the cardioprotective effects of human renin inhibitors at clinically relevant doses, thereby minimizing the concerns of off‐target effects related to much higher drug exposure than that achieved in clinical study.

2019-05-04·Xenobiotica4区 · 医学

The effect of elevated α₁-acid glycoprotein on the pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, in rats

4区 · 医学

Article

作者: Ebihara, Takuya ; Higuchi, Tomoaki ; Tagawa, Yoshihiko ; Jinno, Fumihiro ; Yamamoto, Masami ; Shimizu, Hisao

The pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, was investigated in rats with subcutaneously injected turpentine oil, which was an inflammation animal model. Following intravenous administration of TAK-272 to the turpentine-treated rats, the systemic clearance and volume of distribution decreased with the elevated plasma α₁-acid glycoprotein (AGP) levels. The elevated plasma AGP levels were negatively correlated with the plasma unbound fraction of TAK-272 in the rats. Although the AUCs of total TAK-272 in the turpentine-treated rats were higher than those in the control rats after intravenous and oral administration, those of unbound TAK-272, which seem to directly contribute to the pharmacological effect and safety, were nearly equal between the turpentine-treated and control rats in the respective dose routes. TAK-272 has been shown to primarily bind to AGP in the human plasma. These results strongly suggested that the pharmacokinetic of TAK-272 in humans would also be affected by the variation in the plasma AGP levels and should be discussed with not only the total concentrations but also the unbound concentrations in the clinical trial for patients with elevated plasma AGP levels.

2019-03-01·Clinical Journal of the American Society of Nephrology1区 · 医学

Efficacy and Safety of Imarikiren in Patients with Type 2 Diabetes and Microalbuminuria

1区 · 医学

Article

作者: Shimizu, Kohei ; Saiki, Takuya ; Umeda, Yuusuke ; Kuroda, Shingo ; Kagawa, Tomoya ; Sano, Yuhei ; Ito, Sadayoshi

BACKGROUND AND OBJECTIVESImarikiren is a novel, potent, and selective direct renin inhibitor that has shown high oral availability during clinical development for the treatment of diabetic nephropathy. We evaluated the efficacy and safety of imarikiren in patients with type 2 diabetes mellitus and microalbuminuria.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSThis was a randomized, multicenter, placebo-controlled, double-blind, phase 2, dose-finding trial. A total of 415 patients were randomized to imarikiren 5, 20, 40, or 80 mg; placebo; or candesartan cilexetil 8 mg treatment for 12 weeks. The primary end point was change in log-transformed urine albumin-to-creatinine ratio from baseline to the end of treatment analyzed using analysis of covariance and a fixed sequence testing procedure. Secondary efficacy end points included urine albumin-to-creatinine ratio at each assessment point and remission and progression rates. Exploratory efficacy end points included eGFR and sitting BP before dosing.RESULTSChanges in the urine albumin-to-creatinine ratio from baseline to the end of treatment were 16% (placebo), -16% (imarikiren 5 mg), -27% (imarikiren 20 mg), -38% (imarikiren 40 mg), -39% (imarikiren 80 mg), and -31% (candesartan cilexetil 8 mg). Urine albumin-to-creatinine ratio reductions from baseline were statistically significant in all imarikiren groups versus placebo (P<0.001 each) as well as for candesartan cilexetil 8 mg versus placebo (P<0.001). Remission rates (urine albumin-to-creatinine ratio <30 mg/g creatinine and decreased ≥30% from baseline) were higher in all imarikiren groups versus the placebo group. Incidence of adverse events was higher in the imarikiren 80-mg group (52%) versus placebo (42%) and candesartan cilexetil (43%) groups. Incidence of adverse events for the other imarikiren groups ranged from 33% to 42%. Adverse events were mild or moderate in severity. All imarikiren doses were well tolerated.CONCLUSIONSImarikiren resulted in a dose-dependent improvement in albuminuria compared with placebo, and it was well tolerated in patients with type 2 diabetes mellitus and microalbuminuria.

100 项与 Imarikiren hydrochloride 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
糖尿病肾病	临床2期	日本	SCOHIA PHARMA, Inc.初创企业	-
高血压	临床1期	日本	SCOHIA PHARMA, Inc.初创企业	-
肝病	药物发现	日本	Takeda Pharmaceutical Co., Ltd.	2015-03-01
白蛋白尿	药物发现	日本	Takeda Pharmaceutical Co., Ltd.	2014-10-16
2型糖尿病	药物发现	日本	Takeda Pharmaceutical Co., Ltd.	2014-10-16

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临床结果

适应症

分期

评价

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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


NCT02332824 (CTgov)	临床2期	2型糖尿病 \| 白蛋白尿	415	Candesartan cilexetil Placebo (Placebo)	糧衊憲窪糧餘觸遞觸衊(廠壓夢獵淵製壓鏇願艱) = 夢遞憲選鬱膚繭鹹蓋衊鹽遞艱糧鏇蓋築鹹簾鏇 (製築鬱衊顧蓋襯獵壓廠, 夢艱膚廠鑰獵艱蓋廠夢 ~ 餘鏇鬱遞積簾觸構網遞) 更多	-	2018-08-13
				Candesartan cilexetil Placebo+TAK-272 (TAK-272 5 mg)	糧衊憲窪糧餘觸遞觸衊(廠壓夢獵淵製壓鏇願艱) = 繭繭餘鑰廠憲鑰廠積壓鹽遞艱糧鏇蓋築鹹簾鏇 (製築鬱衊顧蓋襯獵壓廠, 鏇廠鏇壓襯壓鹹襯構獵 ~ 鑰簾鹽艱艱鹹願網壓繭) 更多
NCT02367872 (CTgov)	临床1期	肝病	48	TAK-272 (Cohort 1R: Normal Renal Function)	觸遞網構鬱襯艱齋鑰範(淵淵積願選遞製淵選壓) = 蓋鑰構顧積壓壓簾膚繭憲選衊鹹築鏇鹹鏇醖鏇 (鏇夢廠獵簾壓膚蓋築鑰, 鬱簾鬱鏇簾餘簾鹹遞夢 ~ 觸繭繭艱餘繭鹽範築獵) 更多	-	2017-08-10
				TAK-272 (Cohort 2R: Mild Renal Impairment)	觸遞網構鬱襯艱齋鑰範(淵淵積願選遞製淵選壓) = 繭鏇獵製範鑰鑰淵製觸憲選衊鹹築鏇鹹鏇醖鏇 (鏇夢廠獵簾壓膚蓋築鑰, 壓憲製衊願獵築鏇夢鹽 ~ 淵糧壓繭壓鬱糧積夢遞) 更多
NCT02370615 (CTgov)	临床1期	-	34	itraconazole+TAK-272 (Cohort 1: TAK-272 + Itraconazole)	遞範鹹鑰積窪窪鹹鹹壓(憲廠艱鑰鏇夢壓網鏇襯) = 襯鹽壓糧齋鹹鹽構鏇鏇糧壓獵壓簾獵鑰觸壓願 (艱糧糧願鑰淵築廠範網, 壓鑰範壓廠窪築願齋糧 ~ 願網艱範夢憲繭壓餘範) 更多	-	2016-05-23
				TAK-272+digoxin+midazolam (Cohort 2: Midazolam + Digoxin + TAK-272)	襯憲壓鹹構繭鹽夢遞觸(範鹽憲膚築鹹窪築鏇積) = 醖壓構觸糧顧糧鬱憲窪築遞繭憲構觸鹹醖蓋蓋 (簾窪網鹹襯蓋齋顧範範, 膚艱夢築選醖選簾顧襯 ~ 窪築廠簾齋蓋築顧淵艱) 更多