chronic heart failure with preserved ejection fraction (LVEF equal or above 45%) MedDRA version: 19.1 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: BAY 1067197 hydrochloride film coated tablet 5 mg
Product Code: BAY 1067197 hydrochloride film coated tablet 5 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: neladenoson
Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women aged 45 years and older 2. Diagnosis of chronic heart failure (CHF), NYHA class II-IV (without evidence of a non-cardiac explanation for dyspnea), LVEF = 45% assessed by any imaging modality (e.g. echocardiography, cardiac magnetic resonance, cine levocardiography) within the previous 6 months with no significant change in clinical status suggesting potential for deterioration in ejection fraction. 3. In the 6 months prior to run-in: a) Requirement of treatment with a diuretic AND b) Elevated natriuretic peptides, defined as one of: o BNP = 75 pg/mL or NT-proBNP = 300 pg/mL (sinus rhythm) o BNP = 200 pg/mL or NT-proBNP = 900 pg/mL (atrial fibrillation) AND c) At least one of the following: o LA enlargement (LA diameter = 3.9 cm, LA volume = 55 mL, LAVI = 29 mL/m2, or LAA = 20 cm2) (assessed by local imaging) o LV hypertrophy (septal or posterior wall thickness = 1.1 cm) (local imaging) o Elevated filling pressures (invasive assessment) at rest (PAWP = 20 mmHg or LVEDP = 15 mmHg) or with exercise (PAWP = 25 mmHg) (historical records) 4. 6MWD = 100 m and = 550 m at Visit 2 (baseline) 5. Written informed consent signed before any study-specific procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 230
Exclusion criteria
Exclusion criteria: 1. Acute decompensated heart failure (defined as acute exacerbation of HF that may require IV therapy with diuretics, vasodilators or inotropic drugs and?/?or mechanical support) within the past 4 weeks 2. Initiation or dose modification of cardiovascular pharmacological therapy within the past 2 weeks (dose modification of pre-existing diuretic?/?anticoagulant medication is allowed based on patient-specific needs) 3. Inability to exercise: wheelchair?/?scooter?/?walker dependent; dependent on supplemental oxygen 4. HF is not the primary factor limiting activity as indicated by the patient affirming #1, #2 or #3 of the following questionnaire: My ability to be active is most limited by: #1 - Joint, foot, leg, hip or back pain #2 - Unsteadiness or dizziness impairing daily mobility #3 - Lifestyle, weather, or I just don’t like to be active 5. Previous diagnosis of HFrEF (LVEF ?100 beats/minute prior to randomization 12. Known clinically relevant ventricular arrhythmias (sustained ventricular tachycardia, ventricular flutter or fibrillation) within 3 months prior to randomization based on either medical history or device generated data (if applicable) 13. Clinically relevant permanent or intermittent AV-block > grade II in patients without a permanent pacemaker or ICD?/?CRTD 14. Severe uncorrected valvular heart disease 15. Listing for heart transplantation and?/?or anticipated implantation of a ventricular assist device 16. Severe pulmonary disease with any of the following: o Requirement of continuous (home) oxygen or o History of chronic obstructive pulmonary disease = GOLD III o Use of systemic corticosteroids 17. Asthma bronchiale with any of the following: o Symptoms not well-controlled within the past 6 months or o Ever intubated or in an intensive care unit for asthma 18. Anemia with hemoglobin 45 kg/m2 at randomization 20. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 calculated by Modification of Diet in Renal Disease (MDRD) formula within 3 months prior to randomization (see Appendix 16.1). If several values are available the latest result should be used. 21. Hepatic insufficiency classified as Child-Pugh B or C (see Appendix 16.2), or any of the following: o Primary biliary cirrhosis (PBC) o Primary sclerosing cholangitis o PBC-autoimmune hepatitis overlap syndrome 22. Concomitant use of any of the following therapy that cannot be di
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Find the optimal dose of neladenoson bialanate for the Phase III trial by detecting and characterizing a significant dose-response relationship in the primary efficacy endpoint, absolute change from baseline in 6-minute walking distance (6MWD) at 20 weeks, in patients with chronic heart failure with preserved ejection fraction (HFpEF), and by characterizing the safety, tolerability, pharmacokinetic and pharmacodynamic effects of the compound when given in addition to appropriate therapy for specific co-morbidities;Secondary Objective: An exploratory objective is to further assess pharmacokinetic parameters and blood and urine biomarkers.;Primary end point(s): Absolute change from baseline in 6MWD after 20 weeks of treatment;Timepoint(s) of evaluation of this end point: at the end of the study, no formal interim analysis is planned | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Activity (e.g. duration, intensity) reported values and absolute change from baseline at 20 weeks • NT-proBNP (pg/mL), measured values (log transformed) and absolute?/?relative change from baseline at 20 weeks to assess elevated filling pressures • High sensitivity troponin T (hs-TNT; ng/L), measured values (log transformed) and absolute?/?relative change from baseline at 20 weeks as a biomarker of myocardial injury • KCCQ, as described in protocol Section 9.4.6.1, measured values and absolute?/?relative change from baseline ;Timepoint(s) of evaluation of this end point: at the end of the study, no formal interim analysis is planned | — |
Countries
Austria, Belgium, Bulgaria, Germany, Greece, Israel, Italy, Japan, Poland, Portugal, Spain, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer AG
Outcome results
None listed