E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Failure of the heart to fill with or eject blood |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 |
The objective of the study is to investigate the safety and tolerability of the partial adenosine A1 agonist BAY 1067197 on top of standard therapy in patients with chronic heart failure.
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the pharmacokinetics and hemodynamic response to a single oral dose of BAY 1067197. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Stable systolic heart failure (heart failure with reduced ejection fraction, HFrEF; NYHA I-III) in sinus rhythm with a documented EF ≤45% within the last 3 months
•Stable standard HF therapy including intermediate to high dose β-blocker with either ≥ 95 mg metoprolol succinate (controlled release tablet), ≥ 5mg Bisoprolol (IR-tablet) or ≥5mg Nebivolol (IR tablet) for at least 4 weeks. Additional intake of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers and optional aldosterone-receptor antagonists, diuretics or digitalis is allowed
•Men or confirmed postmenopausal women (defined as being amenorrheic for longer than 2 years with an appropriate clinical profile, e.g. age appropriate and a history of vasomotor symptoms) or women without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy (documented by medical report verification). Men enrolled in this study must agree to use adequate barrier birth control measures during the treatment period of the study and for 12 weeks after receiving the investigational medicinal product (IMP)
•Male patients must agree not to act as sperm donor for 12 weeks after dosing
•Age: 18 to 75 years (inclusive) at the first screening visit
•Ethnicity: White
•Body mass index (BMI): above/equal 18.0 and below/equal 29.9 kg/m²
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E.4 | Principal exclusion criteria |
•Biventricular pacing/active CRT device
•Dependency on pacemaker or ICD device with pacemaker dependency (a paced ventricular rhythm > 5% of heart activity)
•A history of relevant diseases of vital organs other than the heart, of the central nervous system or other organs
•Known hypersensitivity to the study preparations (active substances or excipients of the preparations) or to any other β-blocker
•Current or history of AV-Block > I°
•Unstable condition, indicated by requirement of IV drug (diuretic, inotrope, etc.) or NYHA IV
•Acute Coronary Syndrome (defined as unstable angina [UA], non-ST elevation myocardial infarction [NSTEMI], ST elevation myocardial infarction [STEMI]) within 3 months prior to first study drug administration
•History of asthma or COPD ≥ GOLD II and/or allergic asthma
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of patients with occurrence of AV-Block > I° up to 48 hours |
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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) |
Pharmacokinetic profile determined by tmax up to 24 hours
Pharmacokinetic profile determined by t1/2 up to 22 days
Heart rate at multiple time points up to 24 hours
Blood pressure at multiple time points up to 24 hours
Number of participants with adverse events as a measure of safety and tolerability up to 48 hours |
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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 | No |
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) | 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 | No |
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 | No |
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 | 1 |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 15 |