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

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

Study Overview

• Status: Completed
• Conditions: Arrhythmia
• Intervention / Treatment: Drug: AZD2927; Drug: Placebo

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • Research Site
• Sweden
  • Linköping, Sweden
    • Research Site
  • Stockholm, Sweden
    • Research Site
  • Umeå, Sweden
    • Research Site
  • Örebro, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; A single dose of AZD2927 administered as an iv infusion	Drug: AZD2927; A single dose of AZD2927 administered as an iv infusion
Placebo Comparator: 2; A single dose of placebo administered as an iv infusion	Drug: Placebo; A single dose of placebo administered as an iv infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Stefan C Carlsson, MD, PHD, AstraZeneca; Principal Investigator: Hakan Walfridsson, MD, PHD, University Hospital Linkoping Sweden

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: July 13, 2011
• First Submitted That Met QC Criteria: July 15, 2011
• First Posted (Estimate): July 18, 2011

Study Record Updates

• Last Update Posted (Estimate): November 27, 2012
• Last Update Submitted That Met QC Criteria: November 22, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Atrial refractoriness; cardiac electrophysiology; IKACh
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac
• Other Study ID Numbers: D4120C00002; 2011-001716-59 (EudraCT Number)