E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003119 |
E.1.2 | Term | Arrhythmia |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the effects of AZD2927, compared to baseline, on the left atrial effective refractory period (LAERP), in patients undergoing an invasive electrophysiological (EP) procedure. |
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E.2.2 | Secondary objectives of the trial |
· To evaluate the effects of AZD2927, compared to baseline, on the ventricular effective refractory period (VERP), paced QT interval and other EP and electrocardiographic (ECG) variables in patients undergoing an invasive EP procedure
· To assess the safety and tolerability of AZD2927
· To describe the pharmacokinetics of AZD2927
· To describe the AZD2927 pharmacokinetic (PK)/pharmacodynamic (PD) relationship for LAERP, VERP and paced QT interval
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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 (bpm) 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change in the left atrial effective refractory period (LAERP) by assessment of LAERP |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Each patient’s change in LAERP from the mean at predose to the mean during investigational product infusion |
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E.5.2 | Secondary end point(s) |
1)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
2)To assess the safety and tolerability of AZD2927 by assessment of AEs, ECG (including HR), BP, physical examination, weight and laboratory variables
3)To describe the PK of AZD2927 by assessment of plasma concentration of AZD2927
4)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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1)Each patient's change from predose to the protocol times where assessments are scheduled
2)During the study
3)In hospital period
4)In hospital period |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |