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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01396226

Enrollment

Registered

2011-07-18

Start date

2011-09-30

Completion date

2012-01-31

Last updated

2012-11-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arrhythmia

Keywords

Atrial refractoriness, cardiac electrophysiology, IKACh

Brief summary

Medical Products Agency

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.

Interventions

DRUGAZD2927

A single dose of AZD2927 administered as an iv infusion

DRUGPlacebo

A single dose of placebo administered as an iv infusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

20 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Paced QT Interval	Baseline to last assessment during IP infusion	Change in CS Paced QT interval (P600 MS) from before and after IP infusion during electrophysiological measurements
Atrio-ventricular Effective Refractory Period	Baseline to last assessment during IP infusion	Change from observation before IP infusion to during 1st and 2nd LAERP Mean
PA Interval	Baseline to last assessment during IP infusion	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	Baseline to last assessment during IP infusion	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.
Ventricular Effective Refractory Period	Baseline to last assessment during IP infusion	Change in VERP from before IP infusion to 1st and 2nd assessments during IP infusion
PR Interval	Baseline to last assessment during IP infusion	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	Baseline to last assessment during IP infusion	Change from observation before IP infusion to 6 to 8 hours and 20 to 24 hours after IP infusion
RR Interval	Baseline to last assessment during IP infusion	Change from observation before IP infusion to 6 to 8 hours and 20 to 24 hours after IP infusion
HV Interval	Baseline to last assessment during IP infusion	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.

Countries

Norway, Sweden

Participant flow

Recruitment details

The study had enrolled 20 patients. A total of 18 patients were randomised of which 12 patients received AZD2927. All patients who received treatment completed the study.

Participants by arm

Arm	Count
AZD2927 AZD2927 solution for infusion	12
PLACEBO Placebo solution for infusion	6
Total	18

Baseline characteristics

Characteristic	AZD2927	PLACEBO	Total
Age Continuous	57.9 Years STANDARD_DEVIATION 7.7	63.8 Years STANDARD_DEVIATION 8.3	59.9 Years STANDARD_DEVIATION 8.2
Race/Ethnicity, Customized White	12 Participants	6 Participants	18 Participants
Sex: Female, Male Female	1 Participants	1 Participants	2 Participants
Sex: Female, Male Male	11 Participants	5 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	2 / 12	1 / 6
serious Total, serious adverse events	0 / 12	0 / 6