E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncontrolled hypertension (UHT, i.e. blood pressure ≥ 150/90, or ≥ 150/85 mm Hg in diabetic patients) despite treatment with at least two
different classes of antihypertensive medications. |
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E.1.1.1 | Medical condition in easily understood language |
Poorly regulated high blood pressure (blood pressure ≥ 150/90, or ≥ 150/85 mm Hg in diabetic patients) despite treatment with at least two different kinds of blood pressure lowering medications. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 |
To demonstrate safety and to determine most effective dose of subcutaneous nesiritide in patients with UHT. |
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E.2.2 | Secondary objectives of the trial |
To improve renal function, reduce dosage and/or number of required conventional antihypertensive medications, and suppress aldosterone release. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Ambulatory with UHT (ie. SBP/DBP ≥ 150/90 mm Hg, or SBP/DBP ≥ 150/85 mm Hg for diabetic patients ) despite treatment with ≥ 2 antihypertensive
drugs belonging to different classes. 24-hour ambulatory blood pressure measurement (ABPM) at screening confirming UHT (average day-time SBP > 135 and/or DBP >85 mmHg) to exclude "white coat syndrome". |
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E.4 | Principal exclusion criteria |
Secondary hypertension, estimated glomerular filtration rate (eGFR) < 30 mL/min, heart failure (Ejection Fraction < 40%). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main purpose of this study is to determine a safe and tolerable dose yielding an acceptable acute BP response during 6 hours compared to placebo. An acceptable acute BP response is defined as a reduction of SBP ≥ 10 mm Hg and/or reduction of DBP ≥ 5 mm Hg. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The main statistical analysis is planned when all the participants have completed the treatment phase. |
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E.5.2 | Secondary end point(s) |
Suppression of aldosterone. Improvement of renal function (by eGFR). Effects on 24-h water and electrolyte excretion. Effects on the endogenous natriuretic peptides system. Change in heart rate variability. Reduced number or dosage of standard anti-hypertensive medications during BNP administration compared to baseline and placebo. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The main statistical analysis is planned when all the participants have completed the treatment phase. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
New indication (UHT) and new administration route (subcutaneous) than currently used |
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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 | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |