AZD-4818(AZD-4818) - 药物靶点：CCR1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

CCR1

作用机制

CCR1拮抗剂(C-C趋化因子受体1型拮抗剂)

治疗领域

呼吸系统疾病

在研适应症-

非在研适应症

慢性阻塞性肺疾病

原研机构

阿斯利康制药有限公司

在研机构-

非在研机构

AstraZeneca PLC

最高研发阶段无进展临床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C27H32Cl2N2O7

InChIKeyHVTUHSABWJPWNK-SFHVURJKSA-N

CAS号1003566-93-5

关联

3

项与 AZD-4818 相关的临床试验

NCT00629239 / Completed临床2期

A 4-week Double-blind, Placebo-controlled, Randomized, Parallel Group Phase IIa Study to Assess the Tolerability/Safety and Efficacy of Inhaled AZD4818 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

The purpose of this study is to see if treatment with AZD4818 for four weeks is tolerable, safe and effective in treating COPD and, if so, how it compares with placebo.

开始日期2008-01-01

申办/合作机构

AstraZeneca PLC

NCT00687232 / Completed临床1期

A Randomised, Placebo-controlled Single-blind, Single-centre Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Inhaled Doses of AZD4818 in Healthy Japanese Male Volunteers

The purpose is to investigate safety and tolerability of single and multiple ascending inhaled doses of AZD4818 in healthy Japanese male volunteers.

开始日期2008-01-01

申办/合作机构

AstraZeneca PLC

EUCTR2007-003962-16-FI / Not yet recruitingN/A

A 4-week double-blind, placebo-controlled, randomised, parallel group phase IIa study to assess the tolerability/safety and efficacy of inhaled AZD4818 in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) - TOP

开始日期2007-12-21

申办/合作机构

AstraZeneca AB

100 项与 AZD-4818 相关的临床结果

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100 项与 AZD-4818 相关的转化医学

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100 项与 AZD-4818 相关的专利（医药）

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4

项与 AZD-4818 相关的文献（医药）

2013-12-01·Journal of Aerosol Medicine and Pulmonary Drug Delivery4区 · 医学

Validation of a General In Vitro Approach for Prediction of Total Lung Deposition in Healthy Adults for Pharmaceutical Inhalation Products

4区 · 医学

Article

作者: Borgström, Lars ; Lundbäck, Hans ; Svensson, Mårten ; Olsson, Bo

BACKGROUNDA validated method to predict lung deposition for inhaled medication from in vitro data is lacking in spite of many attempts to correlate in vitro and in vivo outcomes. By using an in vivo-like in vitro setup and analyzing inhalers from the same batches, both in vitro and in vivo, we wanted to create a situation where information from the in vitro and in vivo outcomes could be analyzed at the same time.METHODNine inhalation products containing either budesonide or AZD4818 were evaluated. These comprised two pressurized metered dose inhalers (pMDIs), a pMDI plus a spacer, four dry powder inhalers, and two dosimetric nebulizers. In vitro, an in vivo-like setup consisting of anatomically correct inlet throats were linked to a flow system that could replay actual inhalation flow profiles through the throat to a filter or to an impactor. In vivo, total lung deposition was measured in healthy adults by pharmacokinetic methods.RESULTS AND CONCLUSIONWe could show that the amount of drug escaping filtration in a realistic throat model under realistic delivery conditions predicts the typical total lung deposition in trained healthy adult subjects in the absence of significant exhaled mass. We could further show that by using combinations of throat models and flow profiles that represent realistic deviations from the typical case, variations in ex-cast deposition reflect between-subject variation in lung deposition. Further, we have demonstrated that ex-cast deposition collected either by a simple filter or by a cascade impactor operated at a fixed flow rate using a mixing inlet, to accommodate a variable flow profile through the inhaler, predicts equally well the lung deposited dose. Additionally, the ex-cast particle size distribution measured by this method may be relevant for predicting exhaled fraction and regional lung deposition by computational models.

2010-09-01·Current Topics in Medicinal Chemistry4区 · 医学

CCR1 Antagonists: What Have We Learned From Clinical Trials

4区 · 医学

Review

作者: Brown, Matthew F. ; Zwillich, Samuel H. ; Gladue, Ronald P.

The identification of chemokines and their receptors as potent mediators of leukocyte infiltration raised interest in the potential role of these proteins on disease pathogenesis. This is exemplified by the chemokine receptor, CCR1, which has been shown to be up-regulated in a number of human diseases, the implications of which have been suggested by animal models where inhibition of CCR1 or its ligands have shown beneficial effects. These data support the possibility that a CCR1 antagonist will provide therapeutic benefit to patients with inflammatory diseases. Over the last several years, several of these antagonists entered clinical trials, including CP-481,715 (Pfizer) and MLN3897 (Millennium) for rheumatoid arthritis, BX471 (Berlex / Scherring AG) for multiple sclerosis, and AZD-4818 (Astra-Zeneca) for COPD. This review will describe the evidence that supported the role of CCR1 in these diseases, the results from clinical trials, and provide perspectives on what has been learned from these trials for potential application / consideration to other studies with chemokine receptor antagonists.

2010-09-01·Respiratory Medicine3区 · 医学

Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients

3区 · 医学

Article

作者: Huib A. Kerstjens ; Leif Eriksson ; Jørgen Vestbo ; Kerstin Dahlström ; Leif Bjermer

OBJECTIVEThis study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD.METHODSThis double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300mug or placebo twice daily via Turbuhaler((R)) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured. Plasma concentrations of AZD4818 were measured after the first dose and after 2 and 4 weeks' treatment.RESULTSSixty-five patients (47 male; median age 65.6 years) received AZD4818 (n=33) or placebo (n=32). There was no statistically significant difference between AZD4818 and placebo in change from baseline to endpoint for FEV(1) (AZD4818-placebo: 0.026L, p=0.69), morning PEF (-6L/min, p=0.23), or other lung function measures. There was no difference between treatment groups in the 6-min walk test, MMRC dyspnoea index, BODE index and CCQ scores. Plasma concentrations indicated that patients were exposed to AZD4818 as expected. AZD4818 was well tolerated: 27 treatment-related adverse events (13 with AZD4818, 14 with placebo), 2 serious adverse events (both AZD4818: exacerbation [considered not treatment-related] and deep vein thrombosis [considered treatment-related]) and 11 discontinuations (7 with AZD4818).CONCLUSIONSInhaled AZD4818 was well tolerated at 300mug twice daily for 4 weeks in patients with COPD; however, there was no indication of a beneficial treatment effect despite exposure as expected. These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas.

100 项与 AZD-4818 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12002

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
慢性阻塞性肺疾病	临床2期	挪威	AstraZeneca PLC	2008-01-01
慢性阻塞性肺疾病	临床2期	芬兰	AstraZeneca PLC	2008-01-01
慢性阻塞性肺疾病	临床2期	荷兰	AstraZeneca PLC	2008-01-01
慢性阻塞性肺疾病	临床2期	丹麦	AstraZeneca PLC	2008-01-01
慢性阻塞性肺疾病	临床2期	瑞典	AstraZeneca PLC	2008-01-01