E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Microcirculatory Endothelial Function, Arterial Stiffness And Wave Reflection |
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MedDRA Classification |
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 assess the effects of 7 days treatment of Nebivolol and Carvedilol on the skin microvascular endothelial function, arterial stiffness and wave reflection to the aorta in healthy volunteers.
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to evaluate the role of the EDHF (endothelium derived hyperpolarizing factor) pathway in the beneficial microvascular endothelial effects of Nebivolol and Carvedilol.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male volunteers • ≥ 18 year old at the randomisation visit and ≤ 75 year old • Normotensive volunteers : SBP <140mm Hg and DBP < 90 • Caucasians volunteers • Given informed consent • Normal sinus rhythm with FC >60 BPM
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E.4 | Principal exclusion criteria |
• Cardiovascular disease (such as unstable angina, sick sinus syndrome, heart failure with LVEF < 50%, valvular disease, unstable ischemic heart disease, antecedent of ventricular arrhythmia, syncope, branch block on the ECG, …) if clinically significant, at the discretion of the Investigator • Myocardial infarction or cerebrovascular event within the previous 3 months • Use of any medication during the trial • Use of non ocular β-blockers within the previous month • Chronic obstructive pulmonary disease (COPD) or bronchial asthma • Severe peripheral vascular disease • Diabetes mellitus type 1 or type 2 • serum creatinine >2.5 mg/dl • Creatinine clearance< 50 ml/ min • Disabling or terminal illness • History of sensitivity or significant adverse reactions to β-blocker therapy • Severe obesity (Body Mass Index>35 kg/m²) • Cannabis or other drug abuse • Use of anti-inflammatory drugs within the past 2 weeks even topically apply • Excessive use of Alcohol (at the discretion of the Investigator)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to assess the effects of 7 days treatment of Nebivolol and Carvedilol on the skin microvascular endothelial function, arterial stiffness and wave reflection to the aorta in healthy volunteers. This primary objective will be assessed through the endpoints: • Skin microvascular blood flow after Acetylcholine iontophoresis on skin pretreated with intradermal injection of saline: (Endothelial dependent vasodilatation, Nebivolol versus Carvedilol effect compared to baseline). • Skin microvascular blood flow after Nitroprusside iontophoresis on skin pretreated with intradermal injection of saline (Endothelial independent vasodilatation, Nebivolol versus Carvedilol effect compared to baseline). • Pulse wave velocity (Nebivol versus Carvedilol effect compared to baseline). • Aortic augmentation Index (Nebivolol versus Carvedilol effect compared to baseline).
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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 | No |
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) | 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 | 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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | 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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28 days after the last visit of the last subject undergoing the trial, when a phone call will be done to exclude any possible adverse event during the follow-up period. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |