E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic heart failure with worsening of symptoms like shortness of breath at rest or minimal exertion |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
|
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 assess the effects of i.v. infusion of RLX030 compared to placebo on renal blood flow in patients with chronic heart failure.
-To assess the effects of i.v. infusion of RLX030 compared to placebo on glomerular filtration rate in patients with chronic heart failure.
|
|
E.2.2 | Secondary objectives of the trial |
- To assess the effects of i.v. infusion of RLX030 compared to placebo on diuresis and fractional sodium clearance in patients with chronic heart failure.
- To assess the effects of RLX030 administered as i.v. infusion on central aortic systolic pressure and radial arterial pulse waveform in patients with chronic heart failure.
- To assess the pharmacokinetics of RLX030 administered as i.v. infusion in patients with chronic heart failure.
- To assess the overall safety and tolerability of RLX030 administered as i.v. infusion in patients with chronic heart failure.
-To assess the effects of RLX030 30μg/kg/day
compared to placebo on ECG intervals |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Chronic heart failure
- On optimal standard therapy including a stable dose of loop diuretics
- Reduced systolic function (LVEF ≤ 45%)
- BNP ≥ 100 pg/mL or NT-pro-BNP of ≥ 400 pg/mL
- NYHA Class II or III
- Worsening symptoms, e.g. fatigue and dyspnea
- Impaired renal function defined as an estimated glomerular filtration |
|
E.4 | Principal exclusion criteria |
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
- Women of child-bearing potential unless they are using effective methods of contraception
- Pregnant or nursing (lactating) women
- Systolic blood pressure < 110 mm Hg
- Current use of NSAIDs
- Significant liver impairment
- Significant lung impairment
- Significant heart valve dysfunction or arrythmias
- Myocaridal infarction or acute coronary syndrome within the last 45 days
- History of hypersensitivity to iodine or shellfish
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Renal Blood flow (RBF),
- Glomerular Filtration rate (GFR)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline, at 2, 4, 6, 8, 20, 22, 24, 26, and 28 hours after start of infusion of study drug |
|
E.5.2 | Secondary end point(s) |
a. non-invasive measurement of central aortic systolic pressure and radial arterial pulse waveform
b. Pharmacokinetics
c. Selected biomarkers
d. Safety and tolerability
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
a. At baseline, at 2, 4, 6, 8, 20, 22, 24, 26, and 28 hours after start of infusion of study drug
b. At baseline, at 10, 30 minutes, and 2, 8, 20, 22, 24, 28 and 48 hours after start of infusion of study drug
c. At baseline and at 8, 24, and 48 hours after start of infusion of study drug
d. Safety biochemistry and hematology samples taken at baseline and at 8, 20, and 24 hours after start of infusion of study drug and whenever clinically indicated. Blood pressure measured together with central aortic systolic pressure (see. a.) and ECG taken at baseline and at 8, 20, 24, and 48 hours after start of infusion of study drug
|
|
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 | No |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Germany |
Netherlands |
Poland |
United States |
|
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
|
Last patient’s last visit |
|
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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |