E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stable chronic heart failure subjects with left ventricular systolic dysfunction and mild (Part A) or moderate (Part B) chronic kidney disease |
|
E.1.1.1 | Medical condition in easily understood language |
BAY94-8862 dose finding trial in subjects with chronic heart failure and mild (Part A) or moderate (Part B) chronic kidney disease |
|
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 | 10007541 - Cardiac disorders |
|
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 |
Part A
The safety and tolerability of 3 oral doses of BAY 94 8862 given once daily over 4 weeks in a randomized, placebo-controleld, double-blind study in subjects with chronic heart failure (CHF) with left ventricular systolic dysfunction (LVSD) and mild chronic kidney disease (CKD) (60 mL/min/7.73 m2 => eGFR <90 mL/min/1.73 m2). the effects on serum potassium, the effects of these doses on the change in biomarkers of renal function, eGFR using the Modification of Diet in Renal Disease Study Group (MDRD) formula, albuminuria, and pharmacokinetics of BAY 94 8862 and its metabolites in plasma after multiple oral doses.
Part B
To investigate the change of serum potassium after treatment with 4 oral dosages of BAY 94 8862 given once or twice daily over 4 weeks in a randomized, placebo-controlled, double-blind study design versus placebo in subjects with CHF with LVSD adn moderate CKD (30 mL/min/1.73 m2=<eGFR=<60 mL/min/1.73 m2). |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives of Part B of the study are:
To investigate the change of serum potassium after treatment with 4 oral dosages of BAY 94 8862 given once or twice daily over 4 weeks versus the active comparator spironolactone in subjects with CHF with LVSD and moderate CKD (30 mL/min/1.73 m2 =< eGFR =<60 mL/min/1.73 m2).
To assess safety and tolerability of these doses, the effect on cardiac function by changes in concentrations of various biomarkers, and the change in biomarkers of renal function, eGFR (MDRD), and albuminuria. In addition, pharmacokinetics of BAY 94 8862 and its metabolites in plasma after multiple oral doses will be assessed.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men aged 18 years and older or postmenopausal women aged 55 years and older or women aged 18 years and older without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy
2. Clinical diagnosis of CHF (chronic heart failure), either ischemic or non-ischemic, NYHA (New York Heart Association) class II - III, treated with evidenced-based therapy for CHF, e.g. beta-blockers and ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blocker) as well as diuretics, unless contraindicated or not tolerated
3. Known kidney damage for >/= 3 months, as defined by structural or functional abnormalities of the kidney, and
-- Part A: 60 mL/min/1.73 m2 </= eGFR (estimated Glomerular Filtration Rate) < 90 mL/min/1.73 m2 (MDRD, Modification of Diet in Renal Disease) at the screening visit
-- Part B: 30 mL/min/1.73 m2 </= eGFR <= 60 mL/min/1.73 m2 (MDRD) at the screening visit
4. Serum potassium </= 4.8 mmol/L at the screening visit
5. Systolic blood pressure >/= 90 mmHg without signs or symptoms of hypotension at the screening visit
|
|
E.4 | Principal exclusion criteria |
1. Known hypersensitivity to the study drug (active substance or excipients) or spironolactone and respective excipients (Part B only)
2. Subjects with anuria, acute renal failure, or Addison’s disease
3. Acute coronary syndrome or unstable coronary artery disease within 30 days prior to randomization
4. Valvular heart disease requiring surgical intervention during the course of the study
5. History of hospitalization for hyperkalemia or acute renal failure induced by previous aldosterone antagonist treatment
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in serum potassium |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Change in serum magnesium , change in blood pressure, change in heart rate |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 8, Day 15, Day 22, Day 29 |
|
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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Austria |
Belgium |
Czech Republic |
Denmark |
Finland |
Germany |
Israel |
Norway |
Poland |
Sweden |
|
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 last treatment |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 7 |