E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Isolated Systolic Hypertension |
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E.1.1.1 | Medical condition in easily understood language |
Isolated raised systolic bloodpressure |
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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 | LLT |
E.1.2 | Classification code | 10050591 |
E.1.2 | Term | Isolated systolic hypertension |
E.1.2 | System Organ Class | 100000004866 |
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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 |
To demonstrate the superiority of the combination Nebivolol plus HCTZ versus Irbesartan plus HCTZ in term of SBP reduction after 12 weeks of treatment in elderly patients with isolated systolic ypertension. |
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E.2.2 | Secondary objectives of the trial |
To investigate the tolerability of the combination Nebivolol plus HCTZ versus Irbesartan plus HCTZ. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female aged at least 60 years;
• Office systolic blood pressure >140 mmHg and office diastolic blood pressure ≤ 90 mmHg;
• Willing to give written informed consent.
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E.4 | Principal exclusion criteria |
· Systolic blood pressure equal to or greater than 180 mmHg at the end of washout (visit 2) or run-in period (visit 3b);
· Differences >20mmHg for SBP and >10mmHg for DBP on 3 consecutive readings at baseline
· Current treatment with more than 2 antihypertensive agents within the last 6 months;
· History of stroke, myocardial infarction, PCI or coronary bypass surgery within the last 12 months
· Symptomatic lower limb ischemia i.e. claudicatio intermittens
· Secondary hypertension (i.e.renovascular, adrenal, endocrine, tumor ..);
· Serum creatinine > 150 μmol/L
· Hepatic impairment defined as ASAT or ALAT >2 x upper normal limit;
· Chronic administration of any medication known to affect blood pressure.
· bradycardia (heart rate < 60 bpm prior to start therapy).
· Acute heart failure, cardiogenic shock or episodes of heart failure decompensation requiring i.v. inotropic therapy;
· Clinically significant ECG abnormalities at baseline.
· Any other medical or mental condition or laboratory abnormality that makes the patient unsuitable for the study in the opinion of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be the change from baseline (Day 0) to the end of treatment (Day +84) in systolic blood pressure. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
· To investigate the tolerability of the combination Nebivolol plus HCTZ versus Irbesartan plus HCTZ.
· Furthermore secondary efficacy criteria:
· Percentage of normalized patients (mean SBP ≤ 140 mmHg) at the end of treatment (Day +84);
· Percentage of responding patients (decrease of mean SBP ≥ 20 mmHg) at the end of treatment
(Day +84);
· Change from baseline to the end of treatment (Day +84) in the 24-hour mean SBP, measured by ABPM;
· Change from baseline to the end of treatment (Day +84) in the 24-hour mean DBP, measured
by ABPM;
· Change from baseline to the end of treatment (Day +84) in SBP in the last six hours of the 24-
hour dose period (as measured by 24-hour ABPM);
· Change from baseline to the end of treatment (Day +84) in DBP in the last six hours of the 24-
hour dose period (as measured by 24-hour ABPM);
· Change from baseline to the end of treatment (Day +84) in SBP and DBP for other time intervals [i.e. daytime mean (06:00-00:00), and night-time mean (00:00-6:00)] (as measured by 24-hour ABPM).
· Change from baseline to the end of treatment (Day +84) in arterial stiffness/distensibility
· To investigate the effect of Nebivolol + HCTZ as compared to Irbesartan + HCTZ on the arterial stiffness parameters (details in section 24.2 (Appendix 2). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Irbesartan/hydrochlorothiazide |
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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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 14 |