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

Start Date01 Sep 2011

Sponsor / Collaborator

AstraZeneca PLC

NCT01264250 / CompletedPhase 1

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.

Start Date01 Jan 2011

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with AZD-2927

100 Translational Medicine associated with AZD-2927

100 Patents (Medical) associated with AZD-2927

Literatures (Medical) associated with AZD-2927

01 Mar 2015·EP EuropaceQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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 Deals associated with AZD-2927

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Indication	Highest Phase	Country/Location	Organization	Date
Arrhythmias, Cardiac	Preclinical	SE	AstraZeneca PLC	01 Sep 2011
Arrhythmias, Cardiac	Preclinical	NO	AstraZeneca PLC	01 Sep 2011

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01396226 (CTgov)	Phase 2	Arrhythmias, Cardiac	20	AZD2927 (Arm 1 - AZD2927)	zsdqhcyqkb(wozhbevorl) = qnzzxxetdg dbfyquxung (jwbrfuqtdn, egdbtydndg - qbcipyoktg) View more	-	23 Oct 2012
				Placebo (Arm 2 - PLACEBO)	zsdqhcyqkb(wozhbevorl) = cdpyffyttw dbfyquxung (jwbrfuqtdn, akwjetocfj - dccjsopwjl) View more

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