E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Heart Failure and left ventricular systolic dysfunction at risk for ventricular arrhythmia |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Heart Failure and left ventricular systolic dysfunction at risk for ventricular arrhythmia |
|
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049694 |
E.1.2 | Term | Left ventricular dysfunction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007558 |
E.1.2 | Term | Cardiac failure chronic |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047281 |
E.1.2 | Term | Ventricular arrhythmia |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 |
To evaluate the anti-arrhythmic efficacy of S 44121 versus placebo administered orally for a total of 12 weeks in patients with chronic heart failure (CHF) and left ventricular systolic dysfunction who received an implanted cardioverter defibrillator (ICD) for primary or secondary prevention of ventricular arrhyhthmia. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety profile of S 44121. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients.
- Aged between 18 and 80 years (inclusive).
- ICD for primary or secondary prevention of ventricular arrhythmia for at least 3 months before selection.
- Symptomatic CHF for at least 6 months before selection.
- NYHA functional class I, II or III.
- Ischemic disease or idiopathic dilated cardiomyopathy as main cause for CHF.
- Treatment with a beta-blocker for at least 3 months before selection.
- An average number of at least 100 premature ventricular complexes (PVCs) per hour on a 48-hour Holter ECG recording.
- LVEF ≤ 40% at echocardiographic examination.
- Sinus or atrial rhythm (paced or spontaneous). |
|
E.4 | Principal exclusion criteria |
- Unstable condition within 4 weeks before selection.
- Recent (less than 3 months before selection) myocardial infarction, unstable angina or coronary revascularisation.
- History of stroke or cerebral transient ischemic attack within 3 months before selection.
- Severe primary aortic or mitral stenosis or regurgitation.
- Congenital heart disease.
- Hypertrophic obstructive cardiomyopathy.
- Cardiac resynchronisation therapy (CRT) started within 3 months before selection.
- Episode of reverted ventricular fibrillation or Torsade de Pointes within 4 weeks before selection.
- Atrio-ventricular block of second or third degree.
- Corrected QT interval duration (Bazett’s formula) > 480 ms. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Average rate of PVCs per hour during 48 hours Holter ECG recording. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Holter-based ECG parametres at the W000 (48h), and W012 (48h) visits. |
|
E.5.2 | Secondary end point(s) |
- Average rate of PVCs per hour during 24 hours Holter ECG recording,
- Occurence of individual cardiac arrhythmias as recorded on the Holter ECG,
- Occurence of ventricular tachycardia, ventricular fibrillation, and appropriate electrical ICD-based therapies as recorded on the ICD. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Holter-based ECG parameters at the W001 (24h), W004 (24h), and, ICD-based ECG parameters at W000, W012 and W014 visits. |
|
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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
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 | 4 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Canada |
Korea, Republic of |
Singapore |
Taiwan |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
Last Visit of the Last Patient as stated in the protocol. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |