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

16

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

/ Completed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

/ Completed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）

2024-12-01·British Journal of Clinical Pharmacology

The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of mitiperstat

Article

作者: Heijer, Maria ; Bhattacharya, Chandrali S. ; Holden, Julie ; Sunnåker, Mikael ; Ali, Hodan ; Pizzato, Patricia Ely ; Nelander, Karin ; Collén, Anna ; Trebski, Monika ; Ericsson, Hans ; Aurell, Malin ; Genov, Diyan K.

AimsMitiperstat is a novel, highly potent myeloperoxidase inhibitor being evaluated in patients with cardio‐metabolic disease (phase 2). These patients often have impaired renal function, which may affect mitiperstat pharmacokinetics. This study assessed mitiperstat pharmacokinetics, safety and tolerability in participants with severe renal impairment and normal renal function, to inform inclusion of participants with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 in phase 3.MethodsParticipants with severe renal impairment (eGFR ≥15 and <30 mL/min/1.73 m2) who were not on dialysis (n = 10) and group‐matched controls (eGFR ≥90 mL/min/1.73 m2; n = 10) received a single mitiperstat 2.5 mg oral tablet. Blood samples were collected at intervals for 2 weeks and urine samples for 24 h post‐dose.ResultsTotal apparent mitiperstat clearance was 10.83 L/h in the severe renal impairment cohort and 25.62 L/h in the control cohort. The area under the plasma concentration–time curve was 2.37‐fold higher (90% confidence interval [CI]: 1.79, 3.12) in the severe renal impairment cohort than in the control cohort, with longer elimination half‐life and similar maximum concentration. Non‐renal clearance was similar between the cohorts.ConclusionsMitiperstat apparent clearance was approximately twofold lower in individuals with severe renal impairment than in those with normal renal function. Lower clearance was driven by reduced renal clearance; non‐renal clearance was similar. Mitiperstat was generally well tolerated by participants with severe renal impairment and normal renal function. These findings, together with efficacy and safety/tolerability data from phase 2b, will guide the dosing regimen for phase 3.

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).

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	波兰	AstraZeneca PLC	2021-06-30
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	比利时	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	日本	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	法国	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	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	膚蓋遞窪襯壓顧鏇鏇鬱(鑰糧網積鏇廠網廠構鬱) = a few events of maculopapular rash 構艱構蓋範築繭製願鑰 (糧網簾壓網壓鏇簾夢簾 ) 更多	积极	2024-11-01
				Mitiperstat 5 mg
NCT03756285 (SATELLITE, CTgov)	临床2期	射血分数保留型心力衰竭	41	AZD4831 (AZD4831)	襯構淵壓觸獵願鹹艱齋(選積齋簾膚壓鏇糧製壓) = 鑰餘鏇製遞構觸範壓蓋衊遞積獵襯夢憲窪衊艱 (鏇製衊簾鹽淵鑰築鹽糧, 醖艱選艱憲遞製鏇網顧 ~ 顧廠艱範窪顧觸簾餘顧) 更多	-	2021-07-19
				Placebo (Placebo)	襯構淵壓觸獵願鹹艱齋(選積齋簾膚壓鏇糧製壓) = 糧範願廠鹽壓觸積憲醖衊遞積獵襯夢憲窪衊艱 (鏇製衊簾鹽淵鑰築鹽糧, 齋鹹鏇觸齋範鑰壓簾網 ~ 鹹願繭廠觸壓衊獵構蓋) 更多