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

分子式C15H15ClN4OS

InChIKeyBHKKSKOHRFHHIN-MRVPVSSYSA-N

CAS号1933460-19-5

关联

19

项与 Mitiperstat 相关的临床试验

EUCTR2022-003797-23-DE / Not yet recruiting临床2期IIT

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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14

项与 Mitiperstat 相关的文献（医药）

2024-09-01·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.

2024-04-01·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.

2024-01-01·Journal of Cardiac Failure

Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results

Article

作者: Erlinge, David ; Lam, Carolyn S P ; Schou, Morten ; Wijngaarden, Jan VAN ; Voors, Adriaan A ; Lindstedt, Eva-Lotte ; Shah, Sanjiv J ; Nelander, Karin ; Gustavsson, Andreas ; Lund, Lars H ; Svedlund, Sara ; Saraste, Antti ; Grove, Erik L ; Aziz, Ahmed ; Pirazzi, Carlo ; Gabrielsen, Anders ; Garkaviy, Pavlo ; Barasa, Anders ; Gan, Li-Ming

BACKGROUNDInflammation is a key driver of heart failure with preserved left ventricular ejection fraction. AZD4831 inhibits extracellular myeloperoxidase, decreases inflammation, and improves microvascular function in preclinical disease models.METHODS AND RESULTSIn this double-blind phase 2a study (Safety and Tolerability Study of AZD4831 in Patients With Heart Failure [SATELLITE]; NCT03756285), patients with symptomatic heart failure, left ventricular ejection fraction of ≥40%, and elevated B-type natriuretic peptides were randomized 2:1 to once-daily oral AZD4831 5 mg or placebo for 90 days. We aimed to assess target engagement (primary end point: myeloperoxidase specific activity) and safety of AZD4831. Owing to coronavirus disease 2019, the study was terminated early after randomizing 41 patients (median age 74.0 years, 53.7% male). Myeloperoxidase activity was decreased by more than 50% from baseline to day 30 and day 90 in the AZD4831 group, with a placebo-adjusted decreased of 75% (95% confidence interval, 48, 88, nominal P < .001). No improvements were noted in secondary or exploratory end points, apart from a trend in Kansas City Cardiomyopathy Questionnaire overall summary score. No deaths or treatment-related serious adverse events occurred. AZD4831 treatment-related adverse events were generalized maculopapular rash, pruritus, and diarrhea (all n = 1).CONCLUSIONSAZD4831 inhibited myeloperoxidase and was well tolerated in patients with heart failure and left ventricular ejection fraction of 40% or greater. Efficacy findings were exploratory owing to early termination, but warrant further clinical investigation of AZD4831.LAY SUMMARYFew treatments are available for patients with the forms of heart failure known as heart failure with preserved or mildly reduced ejection fraction. Current treatments do not target inflammation, which may play an important role in this condition. We tested a new drug called AZD4831 (mitiperstat), which decreases inflammation by inhibiting the enzyme myeloperoxidase. Among the 41 patients in our clinical trial, AZD4831 had a good safety profile and inhibited myeloperoxidase by the expected amount. Results mean we can conduct further trials to see whether AZD4831 decreases the symptoms of heart failure and improves patients' ability to participate in physical exercise.

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	加拿大	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	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	保加利亚	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


NCT03756285 (SATELLITE, CTgov)	临床2期	射血分数保留型心力衰竭	41	AZD4831 (AZD4831)	範鏇繭鏇襯鑰艱製廠鏇(築廠鹹簾鬱製築齋廠鬱) = 簾鬱蓋網鹹顧獵築鹹衊構顧構鑰夢襯壓鑰膚構 (願壓鑰壓繭繭齋憲齋鑰, 鏇構齋築夢鏇鹽餘鏇憲 ~ 築醖糧製艱艱網製齋鹽) 更多	-	2021-07-19
				Placebo (Placebo)	範鏇繭鏇襯鑰艱製廠鏇(築廠鹹簾鬱製築齋廠鬱) = 築遞廠製壓夢鹽壓鹹觸構顧構鑰夢襯壓鑰膚構 (願壓鑰壓繭繭齋憲齋鑰, 鬱網醖窪廠鹹壓齋夢襯 ~ 餘蓋積積鏇淵鏇鬱願製) 更多