| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Subacute decompensated chronic heart failure NYHA Class III-IV | |
| 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 investigate the effect of ZP120 on: Diuresis | |
| E.2.2 | Secondary objectives of the trial | 1) Glomerular filtration rate,
2)Renal excretion of sodium and potassium,
3) Blood pressure
4) Renal blood flow (non-invasive),
5) Dyspnea severity,
6) Need for rescue medication,
7) Living with Heart Failure Questionnaire (LWHF)
8) Kinetics of ZP120 (end of infusion on each dose level),
9) Safety and tolerability parametres,
10) Assessment of: U-Osmolality, U-AQP2, P-Reinin, P-Angiotensin, P-Aldosteron, P-Vasopressin and P-h-BNP | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | 1) Age 18 years or more,
2) A diagnosis of chronic symptomatic congestive heart failure (CHF symptoms and objective evidence of LVD) treated with furosemide and other evidence based treatments for chronic heart failure (NYHA class II-IV),
3) Objective signs of LVD corresponding to a LVEF less than or equal to 45%, determined by echocardiography or radionucleide cardiography within the last year, explaining the heart failure symptoms,
4) Symptoms and objective evidence or signs of cardiac decompensation requiring hospitalization for treatment:
a. Worsening heart failure symptoms within the last week (current NYHA class III-IV),
b. Evidence or clinical signs of abnormal fluid accumulation: A weight gain of greater than or equal to 2.5 kg within the previous 2 days, and one or more of the following: peripheral edema, ascites, hepatic congestion, or pulmonary congestion, pleural effusion,
5) Fertile women with a negative pregnancy test. Fertile women and male patients must be willing to use an approved method of contraception until the Follow-up Visit on Day 7
6) Ability to understand and willing to sign Informed Consent Form | |
| E.4 | Principal exclusion criteria | 1) Significant aortic and mitral valve stenosis requiring surgical correction
2) Acute grade 3 mitral valve insufficiency, e.g. corda rupture
3) History of or clinically significant evidence of any severe disease other than heart failure that preclude participation and complicate the evaluation of study results: Hepatic disease (ASAT, ALAT Alkaline Phosphatase, LDH, bilirubin > 3 times ULN or Albumin < 3 times LLN), renal disease (GFR less than or equal to 25 ml/min based on calculated creatinine clearance, poorly controlled diabetics (fasting blood glucose >12 mmol/l), cancer
4) Unstable angina, cardiogenic shock
5) Myocardial infarction within the last week
6) Pulmonary embolism
7) Cardiac surgery within the last month or acutely required PCI
8) Participation in another study evaluating an experimental compound within the last 30 days
9) Previous treatment with ZP120
10) Consumption of alcohol within 24 hours prior to ZP120 / placebo dosing
11) Inability or unwillingness to provide informed consent
12) Treatment with thiazides
13) BMI outside range of 20-35 kg/m2 (BMI equal to 20 and 35 kg/m2 is accepted)
14) Body weight above 120 kg
15) Any other condition or therapy, which in the opinion of the Principal Investigator would make the patient unsuitable for this study | |
| E.5 End points |
| E.5.1 | Primary end point(s) | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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.8.3 | 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.8.5 | 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 | Information not present in EudraCT |
| 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 visit of last patient | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
