E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic heart failure and left ventricular dysfunction |
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E.1.1.1 | Medical condition in easily understood language |
Chronic heart failure and left ventricular dysfunction |
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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 | 14.1 |
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 |
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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 |
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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 |
- Evaluation of the effects on cardiac function and NT-proBNP. |
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E.2.2 | Secondary objectives of the trial |
- Evaluation of the safety profile. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients superior or equal to 18 years and less or equal to 80 years.
- Symptomatic chronic heart failure for at least 6 months before selection.
- NYHA functional class II or III.
- Ischemic disease or idiopathic dilated cardiomyopathy as main cause for CHF.
- Left ventricular systolic dysfunction as evidenced by a LVEF less or equal to 40 % as measured within 6 months before selection.
- ACE inhibitor and/or an ARB treatment for at least 3 months before selection.
- NT-proBNP plasma concentration superior or equal to 400 pg/mL or BNP plasma concentration superior or equal to 100 pg/mL.
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E.4 | Principal exclusion criteria |
- Treatment with a beta-blocker within 2 months before selection.
- Unstable condition within the previous 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 the previous 3 months before selection.
- Severe aortic or mitral stenosis, severe aortic regurgitation, or severe mitral regurgitation.
- Congenital heart disease.
- Hypertrophic obstructive cardiomyopathy.
- Pericardial disease.
- Atrio-ventricular block of second or third degree.
- Corrected QT interval duration (Bazett’s formula) > 480 ms.
- Family history of long QT syndrome or congenital long QT syndrome.
- Serum creatinine > 200 micromoles/L (> 2.26 mg/dL).
- ALAT or ASAT > 3 times the upper limit of normal values.
- Serum total calcium < 2.1 mmol/L or > 2.6 mmol/L.
- Blood hemoglobin lower than 110 g/L (in males) or lower than 100 g/L (in females).
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E.5 End points |
E.5.1 | Primary end point(s) |
- Echocardiographic parameters.
- NT-proBNP plasma concentrations. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Echocardiographic parameters at the selection, W000, W004, W008 and W012 visits,
- NT-proBNP plasma concentrations before W000 visit, and at W001, W004, W008 and W012 visits. |
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E.5.2 | Secondary end point(s) |
- Clinical safety measurements (12-lead resting ECG, physical examination, adverse events, blood clinical laboratory parameters) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-12-lead resting ECG, physical examination and adverse events at selection, W000, W001, W004, W008, and W012 visits.
-blood clinical parameters before W000 visit and at W001, W004, W008 and W012 visits. |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
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 | 5 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Estonia |
Germany |
Italy |
Latvia |
Poland |
Portugal |
Romania |
Russian Federation |
Ukraine |
United Kingdom |
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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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Last Visit of Last Patient as stated in the protocol. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
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 |