A Multi-centre Study Comparing the Effects of AZD2927 and Placebo on the Electrical Activity in the Heart in Patients

Study Overview
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Brief Summary
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Medical Products Agency

Detailed Description
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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. The study has an adaptive design. In the 1st dose group the planned number of randomised patients is 24. The tentative number of randomised patients in the optional 2nd dose group is 12, 24 or 36 and thus a total maximum of 60 patients will be randomised in the study.

Official Title
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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

Conditions
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Arrhythmia

Intervention / Treatment
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* Drug: AZD2927
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or postmenopausal female, aged 20 to 80 years inclusive, clinical indication for catheter ablation of atrial flutter, history of paroxysmal atrial flutter, with or without paroxysmal AF. Single episodes of persistent atrial flutter or AF requiring cardioversion do not exclude the patient from the study, sinus rhythm at randomisation, adequate anticoagulation or antithrombotic treatment according to ESC guidelines 2010 or national guideline, Exclusion Criteria: cardioversion within 14 days before randomisation, history of stroke or transient ischaemic attack (TIA). History of significant head trauma, epilepsy or other disorders increasing the risk for seizures, QTcF >450 ms or <350 ms measured in sinus rhythm at randomisation, history and/or signs of clinically significant sinus node dysfunction. Sinus bradycardia (50 beats per minute or less) at randomisation, personal or family history of Torsades de Pointes (TdP), any other polymorphic ventricular tachycardia, long QT syndrome, short QT syndrome, Brugada syndrome, or personal history of sustained (>30 s) monomorphic ventricular tachycardia.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>A single dose of AZD2927 administered as an iv infusion | Drug: AZD2927<br>* A single dose of AZD2927 administered as an iv infusion<br>|
| Placebo Comparator: 2<br>A single dose of placebo administered as an iv infusion | Drug: Placebo<br>* A single dose of placebo administered as an iv infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Atrial Effective Refractory Period | Change in LAERP from before IP infusion to 1st and 2nd assessments during IP infusion | Baseline to last assessment during IP infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventricular Effective Refractory Period | Change in VERP from before IP infusion to 1st and 2nd assessments during IP infusion | Baseline to last assessment during IP infusion | 
| Paced QT Interval | Change in CS Paced QT interval (P600 MS) from before and after IP infusion during electrophysiological measurements | Baseline to last assessment during IP infusion | 
| Atrio-ventricular Effective Refractory Period | Change from observation before IP infusion to during 1st and 2nd LAERP Mean | Baseline to last assessment during IP infusion | 
| PA Interval | Reflects intra-atrial conduction and is defined as the interval from the onset of the P wave in the surface ECG to the onset of atrial activation (A) in the His bundle electrogram. Change from observation before IP infusion to 30 min after IP start | Baseline to last assessment during IP infusion | 
| AH Interval | Change from observation before IP infusion to 30 mins after IP start. AH interval- the conduction time from the low right atrium at the inter-atrial septum through the AV node to the His bundle, ie, intra-nodal conduction time. | Baseline to last assessment during IP infusion | 
| HV Interval | Change from observation before IP infusion to 30 mins after IP start. HV interval - represents conduction time from the proximal His bundle to the ventricular myocardium, ie, infra-nodal conduction time. | Baseline to last assessment during IP infusion | 
| PR Interval | Interval from the onset of the P-wave to the start of the QRS complex. Change from observation before IP infusion to 6 to 8 hours and 20 to 24 hours after IP infusion | Baseline to last assessment during IP infusion | 
| QRS Duration | Change from observation before IP infusion to 6 to 8 hours and 20 to 24 hours after IP infusion | Baseline to last assessment during IP infusion | 
| RR Interval | Change from observation before IP infusion to 6 to 8 hours and 20 to 24 hours after IP infusion | Baseline to last assessment during IP infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IKACh, Atrial refractoriness, cardiac electrophysiology