Primary objective of the study is• To investigate efficacy and safety of different oraldoses of BAY94-8862 given once daily over 90 daysThe secondary objectives are:•To assess the effects of these doses on a compositeendpoint of death from any cause…
ID
Source
Brief title
Condition
- Heart failures
- Diabetic complications
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Relative decrease in N-terminal prohormone B-type natriuretic peptide
(NT-proBNP). From baseline to 90 days.
Secondary outcome
Change in blood potassium From baseline
to 90 days
Change in blood pressure From
baseline to 90 days
Change in heart rate From
baseline to 90 days
Number of participants with adverse events as a
measure of safety and tolerability Up to 120
days
Background summary
Current treatment for Congestive Heart Failure (HF) consists of
angiotensin-converting enzyme inhibitors,
angiotensin receptor blockers and beta-blockers.
Despite their use, aldosterone and cortisol levels remain inappropriately
elevated in patients with signs and
symptoms of worsening chronic heart failure (WCHF).
This may contribute to cardio-renal dysfunction. The deleterious neurohormonal
profile and the observation
that mineralocorticoid receptor antagonists (MRAs) significantly reduce
morbidity and mortality in HF has
prompted studying the utility of MRAs in WCHF. BAY94-8862 is a novel
non-steroidal MRA. Safety and efficacy
of different oral doses of BAY94-8862 will be investigated in subjects with
WCHF and either type 2
diabetes mellitus with or without chronic kidney disease (CKD) or moderate CKD
alone in comparison to
eplerenone.
Study objective
Primary objective of the study is
• To investigate efficacy and safety of different oral
doses of BAY94-8862 given once daily over 90 days
The secondary objectives are:
•To assess the effects of these doses on a composite
endpoint of death from any cause, CV hospitalizations,
or emergency presentations for WCHF until Visit 9 (Day
90±2)
•To assess the effects of these doses on BNP, and NT
proBNP at Visit 5 (Day 30±2), Visit 7 (Day 60±2), and
Visit 9 (Day 90±2)
• To assess the change in health-related quality of life
from baseline to Visit 5 (Day 30±2) and Visit 9 (Day
90±2) assessed by the Kansas City Cardiomyopathy
Questionnaire and EQ-5D-3L
Study design
Multi-center, randomized, adaptive, double-blind, double-dummy,
comparator-controlled parallel-group design.
Intervention
2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg BAY 94-8862 once daily
will be compared to eplerenone 25 mg every other day, 25 mg once daily, or
50 mg once daily for safety, tolerability, effects on cardiac function by
changes in concentrations of various biomarkers; pharmacokinetics of
BAY 94-8862 and health-related quality of life (HRQoL) will be assessed.
Study burden and risks
Up to 10 study visits in 120 days. (3/9 visits may possibly occur whilst
hospitalised).
Blood samples at each study visit.
Two questionnaires to complete at 4 visits. EQ-5D-3L - 2 pages in length and
KCCQ consists of 23 items.
Physical Examination at 4 visits.
ECG assessment at 8 visits.
Some patients may need to stop current medication before entering the study.
BAY94-8862 may have some therapeutic benefit, however this cannot be
guaranteed. Patients are at risk
of experiencing side effects.
Energieweg 1
Mijdrecht 3641RT
NL
Energieweg 1
Mijdrecht 3641RT
NL
Listed location countries
Age
Inclusion criteria
• Men and women aged 18 years and older. The lower age limit may be higher if legally requested in the participating country
• Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active. Adequate contraception is defined as a combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices)
• Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous diuretics at hospital;• Subjects with clinical diagnosis of CHF either ischemic or non ischemic, NYHA functional class II -IV;• Subjects with type 2 diabetes mellitus ;and / or;Subjects with 30 mL/min/1.73m2 < or = eGFR < or = 60 mL/min/1.73m2 (MDRD)(23) at screening ;• Left ventricular ejection fraction (LVEF) < or = 40%;• Blood potassium <= 5.0 mmol/L at screening ;• Systolic blood pressure > or = 90 mmHg without signs and symptoms of hypotension at the screening visit
Exclusion criteria
• Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis;• Acute coronary syndrome (ACS) in the last 30 days prior to screening ;• Cardiogenic shock;• Valvular heart disease requiring surgical intervention during the course of the study;• Stroke or transient ischemic cerebral attack in the last 3 months prior to the screening visit;• Concomitant treatment with any MRA, renin inhibitor, or potassium-sparing diuretic
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002627-15-NL |
| ClinicalTrials.gov | NCT01807221 |
| CCMO | NL44105.042.13 |