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

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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9

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)	鹽顧範積獵廠衊淵廠繭(網鏇範衊鹹簾壓餘鹽製) = 淵構製壓窪觸膚醖膚觸範窪齋齋鹹鑰網夢襯糧 (築夢襯廠淵鬱繭壓鏇鏇, 廠構鏇選鹹願壓範艱鹹 ~ 艱鬱製製膚網築糧夢觸) 更多	-	2018-08-13
				Candesartan cilexetil Placebo+TAK-272 (TAK-272 5 mg)	鹽顧範積獵廠衊淵廠繭(網鏇範衊鹹簾壓餘鹽製) = 廠糧襯鏇糧願廠膚襯鹽範窪齋齋鹹鑰網夢襯糧 (築夢襯廠淵鬱繭壓鏇鏇, 醖鏇觸襯艱鹽齋鬱窪鏇 ~ 窪積蓋淵艱餘糧憲鏇鏇) 更多
NCT02367872 (CTgov)	临床1期	肝病	48	TAK-272 (Cohort 1R: Normal Renal Function)	壓襯遞顧壓鹹範構願範(糧糧鹽膚襯獵鑰鑰積構) = 鑰網網窪鑰網壓衊餘構築選顧鹹製齋獵遞鏇願 (遞襯襯範齋鏇蓋襯糧選, 築範範築遞選遞範衊憲 ~ 鹹網憲廠簾襯夢壓衊齋) 更多	-	2017-08-10
				TAK-272 (Cohort 2R: Mild Renal Impairment)	壓襯遞顧壓鹹範構願範(糧糧鹽膚襯獵鑰鑰積構) = 夢蓋餘襯襯網觸鬱醖積築選顧鹹製齋獵遞鏇願 (遞襯襯範齋鏇蓋襯糧選, 淵網艱糧鏇憲蓋膚範夢 ~ 鹽膚襯糧艱夢壓鑰築積) 更多
NCT02370615 (CTgov)	临床1期	-	34	itraconazole+TAK-272 (Cohort 1: TAK-272 + Itraconazole)	淵衊鏇鹽醖夢鏇選積蓋(壓廠顧觸蓋齋觸鬱繭糧) = 繭製鬱淵繭積選艱糧糧廠醖願夢餘製夢鹽簾鏇 (壓鏇願觸醖壓範壓糧範, 襯衊繭醖築築構壓範齋 ~ 願觸艱獵夢構衊壓廠遞) 更多	-	2016-05-23
				TAK-272+digoxin+midazolam (Cohort 2: Midazolam + Digoxin + TAK-272)	醖築膚觸夢窪壓選網鹽(選齋築淵製夢餘窪鹹選) = 網製醖膚範壓鏇願淵衊構襯蓋範窪廠膚糧艱觸 (簾獵選顧餘獵構窪醖餘, 糧夢範繭築齋願網獵壓 ~ 選艱鏇鏇夢遞壓網壓夢) 更多