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

• Ventricular Effective Refractory Period [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  Change in VERP from before IP infusion to 1st and 2nd assessments during IP infusion
• Paced QT Interval [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  Change in CS Paced QT interval (P600 MS) from before and after IP infusion during electrophysiological measurements
• Atrio-ventricular Effective Refractory Period [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  Change from observation before IP infusion to during 1st and 2nd LAERP Mean
• PA Interval [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  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
• AH Interval [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  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.
• HV Interval [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  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.
• PR Interval [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  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
• QRS Duration [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  Change from observation before IP infusion to 6 to 8 hours and 20 to 24 hours after IP infusion
• RR Interval [ Time Frame: Baseline to last assessment during IP infusion ] [ Designated as safety issue: No ]
  Change from observation before IP infusion to 6 to 8 hours and 20 to 24 hours after IP infusion

• To evaluate the effects of AZD2927 on VERP, paced QT interval and other EP and ECG variables by assessment of PA interval; AH interval; HV interval;AVERP(L), PR (PQ) interval, QRS duration, paced QT interval, RR interval [ Time Frame: Each patient's change from predose to the protocol times where assessments are scheduled on day 1 of the patient's hospital stay day. ] [ Designated as safety issue: Yes ]
• To assess the safety and tolerability of AZD2927 by assessment of AEs, ECG (including HR), BP, physical examination, weight and laboratory variables [ Time Frame: Patients will be followed during their whole participation in the study, a time period between 7-35 days. ] [ Designated as safety issue: Yes ]
• To describe the PK of AZD2927 by assessment of plasma concentration of AZD2927 [ Time Frame: During day 1 at the patient's hospital stay (i.e. 1 day) ] [ Designated as safety issue: No ]
• To describe the AZD2927 PK/PD relationship for LAERP, VERP and paced QT interval by assessment of population PK/PD variables, eg, Emax, EC50 or slope depending upon shape of the model [ Time Frame: During day 1 at the patient's hospital stay (i.e. 1 day) ] [ Designated as safety issue: No ]

Medical Products Agency

• 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.

• Drug: AZD2927
  A single dose of AZD2927 administered as an iv infusion
• Drug: Placebo
  A single dose of placebo administered as an iv infusion

• Experimental: 1
  A single dose of AZD2927 administered as an iv infusion
  Intervention: Drug: AZD2927
• Placebo Comparator: 2
  A single dose of placebo administered as an iv infusion
  Intervention: Drug: Placebo

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.