A Multi-Centre, Double-Blind, Randomised, Placebo-Controlled Phase II Study to Assess the Effects on Atrial and Ventricular Refractoriness of an Intravenous Infusion of AZD2927 in Patients Undergoing an Invasive Electrophysiological Procedure

Medical Products Agency

开始日期2011-09-01

申办/合作机构

AstraZeneca PLC

NCT01264250 / Completed临床1期

A Phase I, Single-centre, Single-blind, Randomised, Placebo-controlled, Single-dose Study to Assess the Safety, Tolerability and Pharmacokinetics After Single Ascending Intravenous Doses of AZD2927 in Healthy Male Subjects

In this early phase study, healthy male volunteers will be randomly assigned to one dose of either AZD2927 or placebo. The objective will be to assess the Safety,Tolerability and Pharmacokinetics of AZD2927.

开始日期2011-01-01

申办/合作机构

AstraZeneca PLC

100 项与 AZD-2927 相关的临床结果

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100 项与 AZD-2927 相关的转化医学

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100 项与 AZD-2927 相关的专利（医药）

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项与 AZD-2927 相关的文献（医药）

2015-03-01·EP Europace2区 · 医学

Is the acetylcholine-regulated inwardly rectifying potassium current a viable antiarrhythmic target? Translational discrepancies of AZD2927 and A7071 in dogs and humans

2区 · 医学

Article

作者: Jensen, Steen ; Berggren, Anders ; Walfridsson, Håkan ; Anfinsen, Ole-Gunnar ; Nordkam, Ann-Christin ; Sundqvist, Monika ; Linhardt, Gunilla ; Frison, Lars ; Carlsson, Leif

AIMSWe aimed at examining the acetylcholine-dependent inward-rectifier current (IKAch) as a target for the management of atrial fibrillation (AF).METHODS AND RESULTSThe investigative agents AZD2927 and A7071 concentration-dependently blocked IKACh in vitro with minimal off-target activity. In anaesthetized dogs (n = 17) subjected to 8 weeks of rapid atrial pacing (RAP), the left atrial effective refractory period (LAERP) was maximally increased by 50 ± 7.4 and 50 ± 4.8 ms following infusion of AZD2927 and A7071. Ventricular refractoriness and the QT interval were unaltered. During sustained AF, both drugs significantly reduced AF frequency and effectively restored sinus rhythm. AZD2927 successfully restored sinus rhythm at 10/10 conversion attempts and A7071 at 14/14 attempts, whereas saline converted 4/17 episodes only (P<0.001 vs. AZD2927 and A7071). In atrial flutter patients (n = 18) undergoing an invasive investigation, AZD2927 did not change LAERP, the paced QT interval, or ventricular refractoriness when compared with placebo. To address the discrepancy on LAERP by IKACh blockade in man and dog and the hypothesis that atrial electrical remodelling is a prerequisite for IKACh blockade being efficient, six dogs were studied after 8 weeks of RAP followed by sinus rhythm for 4 weeks to reverse electrical remodelling. In these dogs, both AZD2927 and A7071 were as effective in increasing LAERP as in the dogs studied immediately after the 8-week RAP period.CONCLUSIONBased on the present series of experiments, an important role of IKACh in human atrial electrophysiology, as well as its potential as a viable target for effective management of AF, may be questioned.

100 项与 AZD-2927 相关的药物交易

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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
心律失常	临床前	瑞典	AstraZeneca PLC	2011-09-01
心律失常	临床前	挪威	AstraZeneca PLC	2011-09-01

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临床结果

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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


NCT01396226 (CTgov)	临床2期	心律失常	20	AZD2927 (Arm 1 - AZD2927)	鏇願鹽齋鹽鏇構窪鹹衊(簾憲構膚積鑰鹽襯積壓) = 選簾觸鑰製繭膚製醖遞壓構積範壓簾廠鏇願遞 (餘範襯艱憲壓鏇遞鑰壓, 鹹獵簾選淵遞願繭鬱鏇 ~ 糧壓夢繭膚範窪壓鹽艱) 更多	-	2012-10-23
				Placebo (Arm 2 - PLACEBO)	鏇願鹽齋鹽鏇構窪鹹衊(簾憲構膚積鑰鹽襯積壓) = 壓鹽淵餘壓築選餘鑰衊壓構積範壓簾廠鏇願遞 (餘範襯艱憲壓鏇遞鑰壓, 鏇製範願築繭範鏇簾繭 ~ 醖夢鏇構壓鬱願鹹製壓) 更多