E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hypertensive patients of either sex aged 40-69 years |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10057166 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10047065 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10047065 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10047065 |
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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 |
Primary objective The primary objective of the study is to assess the effects of a 24-week treatment period with the two investigational medicinal products (IMPs) combinations on arterial stiffness (aortic pulse wave velocity, PWV). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives The secondary objectives of the study are to assess the effects of a 24-week treatment period with the two IMPs combinations on the following parameters: Parameters of pressure wave reflection (augmentation index - AIx) and central arterial pressure; Endothelial function: flow mediated dilation (FMD) of brachial artery; Sitting blood pressure and heart rate measured at clinics; 24-hour blood pressure monitoring (ABPM); Adverse events and adverse drug reactions: Metabolic effects (lipid and glucose profile, insulin-resistance); ECG parameters; Routine laboratory parameters (haematology, blood chemistry and urinalysis). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be enrolled at Visit 1 into the run-in period if they meet all the following criteria: 1. Men or post-menopausal women that express their willing to participate in the study by signing the informed consent; 2. Subjects aged 40-69 years (inclusive); 3. Medical history of arterial hypertension not controlled with ACE-inhibitors given as monotherapy. 4. Subjects satisfying any 3 of the following 5 criteria of metabolic syndrome, defined according to the criteria of the American Heart Association (Grundy et al, 2005): Elevated waist circumference (&#8805; 102 cm in men and &#8805; 88 cm in women); Elevated triglycerides (&#8805; 150 mg/dl): Reduced HDL cholesterol (< 40 mg/dl in men and < 50 mg/dl in women); Elevated blood pressure (SBP &#8805; 130 mmHg or DBP &#8805; 85 mmHg); Elevated fasting plasma glucose (FPG &#8805; 100 mg/dl) or drug treatment for elevated glucose levels; 5. Patients co-operative attitude and able to adhere to study protocol procedures and timelines. At visit 2 (end of run-in), after 4 weeks of treatment with Enalapril 20 mg once daily, patients will be randomised in the treatment phase if they meet the following criteria: 6. SBP 140-159 mmHg and DBP 90-99 mmHg. |
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E.4 | Principal exclusion criteria |
Patients will not be enrolled at Visit 1 into the run-in period if they meet any of the following criteria: 1. History of major cardiovascular events (i.e. myocardial infarction, angina, congestive heart failure) or cerebrovascular events (stroke, transient ischemic attacks); 2. Clinically significant cardiac arrhythmias (e.g. atrial fibrillation, atrial-ventricular block); 3. Blood creatinine levels > 1.2 mg/dl in women or > 1.3 mg/dl in men; 4. Albumin/Creatinine ratio in urines > 300 mg/g; 5. Concomitant diabetes mellitus (i.e. FPG > 126 mg/dl) or concomitant oral antidiabetic therapy; 6. Concomitant dyslipidemias treated with statines therapy; 7. Severe anaemia, defined as haemoglobin levels &#8804; 10 g/dl; 8. History of other clinically significant cardiac, renal, neurologic, hepatic or endocrine diseases whose sequelae and/or treatments could interfere with the results of the present study; 9. Any other clinically significant abnormalities, as judged by the Investigator, in laboratory tests (haematology, blood chemistry) performed at the screening visit; 10. History of malignancy in the past 3 years; 11. History of alcohol or drug abuse; 12. Allergy, sensitivity or intolerance to study drug and/or study drug formulation ingredients; 13. Patients with metabolic or major psychiatric disorders that, in the view of the investigator, could compromise the patients participation in the study; 14. Patients unable to give a valid informed consent; 15. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study; 16. Patients who received any investigational new drug within the last 12 weeks; 17. Patients who have been previously enrolled in this study; 18. Employees of the investigator or study centre (i.e., principal investigator, sub-investigator, study coordinators, other study staff, employees, or contractors of each), with direct involvement in the proposed study or other studies under the direction of that investigator and/or study centre, as well as family members of the employees or the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable of the study is the change from baseline to the end of treatment of the aortic PWV (m/sec) measured at the end of the 24 weeks of treatment. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
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 | Information not present in EudraCT |
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
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |