Mitiperstat(Mitiperstat) - 药物靶点：MPO_在研适应症：射血分数保留型心力衰竭，慢性阻塞性肺疾病，纤维化_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

MPO

作用机制

MPO抑制剂(髓过氧物酶抑制剂)

治疗领域

心血管疾病消化系统疾病呼吸系统疾病+ [1]

在研适应症

射血分数保留型心力衰竭慢性阻塞性肺疾病纤维化+ [2]

非在研适应症-

原研机构

阿斯利康制药有限公司

在研机构

AstraZeneca PLC

非在研机构-

最高研发阶段临床2/3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C15H15ClN4OS

InChIKeyBHKKSKOHRFHHIN-MRVPVSSYSA-N

CAS号1933460-19-5

关联

18

项与 Mitiperstat 相关的临床试验

EUCTR2022-003797-23-DE

/ Not yet recruiting临床2期

Myeloperoxidase inhibition in patients with ischemic or non-ischemic cardiomyopathy and heart failure with reduced ejection fraction

开始日期2023-05-16

申办/合作机构

Philipps University of Marburg

NCT05751759

/ Recruiting临床1期

A Phase I Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Mitiperstat

This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of mitiperstat.

开始日期2023-03-20

申办/合作机构

AstraZeneca PLC

NCT05492877

/ Active, not recruiting临床2期

A Phase IIa Randomised, Double Blind, Placebo Controlled, Parallel Arm, Multi-Centre Study to Evaluate the Efficacy and Safety of Mitiperstat (AZD4831), for 12-24 Weeks, in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

This is a research study to evaluate the efficacy and safety of the investigational drug Mitiperstat (AZD4831) in adult patients with chronic obstructive pulmonary disease.

开始日期2022-11-14

申办/合作机构

AstraZeneca PLC

100 项与 Mitiperstat 相关的临床结果

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100 项与 Mitiperstat 相关的转化医学

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100 项与 Mitiperstat 相关的专利（医药）

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15

项与 Mitiperstat 相关的文献（医药）

2024-11-01·Journal of Pharmaceutical Sciences

Early clinical drug product shelf-life setting using accelerated predictive stability and metabolite data for impurity qualification: A case study

Article

作者: Leandersson, Carina ; Ottosson, Jenny E ; Ludvigsson, Jufang Wu ; Ku, Angela ; Klarqvist, Magnus ; Fransson, Magnus ; Weidolf, Lars ; Ottosson, Jenny E.

This case study demonstrates how knowledge of degradation products together with predictions can establish a lean stability strategy using the accelerated predictive stability (APS) principles. Applying all available data for AZD4831, (R)-1-(2-(1-aminoethyl)-4-chlorobenzyl)-2-thioxo-2,3-dihydro-1H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, a reliable predictive model was developed despite minor differences in technical batch tablet compositions. Early forced degradation studies were performed to map potential degradation pathways. The insights from these studies guided the design of an APS study, which in turn inform on a suitable clinical stability program, initial specification and shelf-life. The use of APS predictions of degradants as well as total impurities highlighted at an early stage, when designing the clinical stability program, the opportunity to identify which degradation product that would be shelf-life limiting. Hence, it was possible to guide the development stability activities and set an initial shelf-life of a tablet formulation. The presented study displays the importance of combining several sources of information in drug development, e.g., potential degradation pathways, accelerated stability, stability program design, metabolite data, and specification limits.

2024-11-01·Clinical Drug Investigation

Pharmacokinetics and Tolerability of the Novel Myeloperoxidase Inhibitor Mitiperstat in Healthy Japanese and Chinese Volunteers

Article

作者: Heijer, Maria ; Bhattacharya, Chandrali ; Ericsson, Hans ; Collén, Anna ; Holden, Julie ; Sunnåker, Mikael ; Garkaviy, Pavlo ; Han, David ; Aurell, Malin ; Trebski, Monika ; Nelander, Karin

BACKGROUND AND OBJECTIVEMitiperstat (AZD4831) is a novel irreversible oral myeloperoxidase inhibitor in clinical development for heart failure with preserved ejection fraction, metabolic dysfunction-associated steatohepatitis and chronic obstructive pulmonary disease. This study evaluated the pharmacokinetics, safety and tolerability of multiple ascending doses of mitiperstat in healthy male Japanese and Chinese volunteers.METHODSThree cohorts of eight Japanese participants were randomized to receive once-daily oral doses of mitiperstat 2.5, 5 or 10 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo, per cohort). One cohort of eight Chinese participants was randomized to receive mitiperstat 5 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo).RESULTSMitiperstat was rapidly absorbed, with a time to maximum plasma concentration of 1-2 h. Exposure was dose proportional over the investigated dose range, as assessed by area under the concentration-time curve and maximum and trough plasma concentrations. Steady state was reached within 10 days, and accumulation was observed, consistent with the observed long elimination half-life of mitiperstat (50.2-57.8 h). Except for a few events of maculopapular rash, mitiperstat up to 5 mg was well tolerated in participants of Japanese or Chinese origin.CONCLUSIONSThe pharmacokinetics of mitiperstat were similar among Japanese and Chinese participants. These characteristics were similar to those in a previous multiple ascending-dose study in healthy primarily white and Black/African American volunteers. Therefore, the pharmacokinetics of mitiperstat do not affect dosing regimens in these different populations.TRIAL REGISTRATIONNCT04232345 (03/01/2020).

2024-04-01·Pharmacology Research & Perspectives

The myeloperoxidase inhibitor mitiperstat (AZD4831) does not prolong the QT interval at expected therapeutic doses

Article

作者: Ericsson, Hans ; Rekić, Dinko ; Ebrahimi, Ahmad ; Sundell, Jesper ; Dota, Corina ; Sunnåker, Mikael ; Parkinson, Joanna ; Nelander, Karin

AbstractMitiperstat is a myeloperoxidase inhibitor in clinical development for treatment of patients with heart failure and preserved or mildly reduced ejection fraction, non‐alcoholic steatohepatits and chronic obstructive pulmonary disease. We aimed to assess the risk of QT‐interval prolongation with mitiperstat using concentration–QT (C‐QT) modeling. Healthy male volunteers were randomized to receive single oral doses of mitiperstat 5, 15, 45, 135, or 405 mg (n = 6 per dose) or matching placebo (n = 10) in a phase 1 study (NCT02712372). Time‐matched pharmacokinetic and digital electrocardiogram data were collected at the baseline (pre‐dose) and at 11 time‐points up to 48 h post‐dose. C‐QT analysis was prespecified as an exploratory objective. The prespecified linear mixed effects model used baseline‐adjusted QT interval corrected for the heart rate by Fridericia's formula (ΔQTcF) as a dependent variable and plasma mitiperstat concentration as an independent variable. Initial exploratory analyses indicated that all model assumptions were met (no effect on heart rate; appropriate use of QTcF; no hysteresis; linear concentration–response relationship). Model‐predicted mean baseline‐corrected and placebo‐adjusted ΔΔQTcF was +0.73 ms (90% confidence interval [CI]: −1.73, +3.19) at the highest anticipated clinical exposure (0.093 μmol/L) during treatment with mitiperstat 5 mg once daily. The upper 90% CI was below the established threshold of regulatory concern. The 16‐fold margin to the highest observed exposure was high enough to mean that a positive control was not needed. Mitiperstat is not associated with risk of QT‐interval prolongation at expected therapeutic concentrations.

100 项与 Mitiperstat 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
射血分数保留型心力衰竭	临床3期	中国台湾	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	巴西	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	美国	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	丹麦	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	俄罗斯	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	荷兰	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	瑞典	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	匈牙利	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	法国	AstraZeneca PLC	2021-06-30
射血分数保留型心力衰竭	临床3期	土耳其	AstraZeneca PLC	2021-06-30

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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


NCT04232345 (Pubmed \| Clin Drug Investig)	临床1期	-	32	Mitiperstat 2.5 mg	願襯鑰壓範餘鏇膚鹹簾(壓構遞夢鑰淵夢廠鑰膚) = a few events of maculopapular rash 鏇簾選齋鬱鏇簾繭窪膚 (壓廠鹽壓構艱憲製膚願 ) 更多	积极	2024-11-04
				Mitiperstat 5 mg
NCT03756285 (SATELLITE, CTgov)	临床2期	射血分数保留型心力衰竭	41	AZD4831 (AZD4831)	簾遞淵構製鏇廠選夢鑰(憲廠壓鏇鹽遞餘窪獵獵) = 鏇鏇廠淵蓋簾蓋製衊觸遞艱積衊醖獵糧鏇艱願 (醖襯鹹廠鬱構願製網網, 鏇襯築獵壓觸築築鹹壓 ~ 簾鹽觸選鏇衊範積窪醖) 更多	-	2021-07-19
				Placebo (Placebo)	簾遞淵構製鏇廠選夢鑰(憲廠壓鏇鹽遞餘窪獵獵) = 顧餘衊齋選繭範鹹築襯遞艱積衊醖獵糧鏇艱願 (醖襯鹹廠鬱構願製網網, 觸淵齋夢膚蓋願構鹽積 ~ 鹽鏇鏇憲衊鑰獵選餘蓋) 更多