Study to research BAY 1021189 in patients with worsening heart failure with reduced ejection fraction

• Register: EUCTR
• Last refreshed on: 18 January 2016
• Main ID: EUCTR2013-002287-11-CZ
• Date of registration: 03/09/2013
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: Study to research BAY 1021189 in patients with worsening heart failure with reduced ejection fraction
• Scientific title: A randomized parallel-group, placebo-controlled, double-blind, multi-center dose finding phase II trial exploring the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the oral sGC stimulator BAY 1021189 over 12 weeks in patients with worsening heart failure and reduced ejection fraction. - SOCRATES-REDUCED
• Date of first enrolment: 12/12/2013
• Target sample size: 410
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002287-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, China, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent signed before any study-specific procedure
2. Ability to understand and follow study-related instructions
3. Worsening chronic heart failure requiring hospitalization (or IV diuretic treatment for HF without hospitalization) with initiation of study treatment after clinical stabilization:

Diagnostic methods:
- History of chronic HF: NYHA class II-IV =30 days before hospitalization (or before IV diuretic treatment for HF without hospitalization)
- Worsening HF at hospitalization (or at the time of IV diuretic treatment for HF without hospitalization)
- NT-proBNP =1000 or BNP =300 pg/mL in sinus rhythm, or NT-proBNP =1600 or BNP =500 pg/mL in A. fib. in local routine labs, and
- Symptoms and signs of congestion (clinical or radiographic signs in routine chest x-ray demonstrating pleural effusion, pulmonary congestion (redistribution, interstitial or alveolar edema), or cardiomegaly

- Clinical stabilization defined by
- no IV vasodilator for >24h and no IV diuretic for >12h before randomization and
- SBP =110 and <160, and resting HR =50 and <100 bpm at randomization

- LVEF <45% by echocardiography at randomization

4. Ability to understand and follow study-related instructions
5. Men or confirmed postmenopausal women or women without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy. Men enrolled in this study must agree to use adequate barrier birth control measures during the treatment period of the study.

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 82
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 328

Exclusion criteria:
1. Legal lower age limitations for adults (country specific)
2. IV inotropes at any time after hospitalization
3. Concurrent of anticipated nitrate use (all routes, incl. prn) for the treatment of ischemic heart disease or HF, including:
- subjects tolerant of and treated with isosorbide dinitrate/hydralazine therapy for chronic HFrEF according to guideline recommendations
- subjects requiring nitrates as anti-anginal therapy in addition or alternatively to beta-blockers
4. Cardiac comorbidity (either of the following):
- Specific HF etiologies, including:
- Hypertrophic cardiomyopathy with LV outflow tract obstruction; or
- Pericardial disease, such as constrictive pericarditis; or
- Infiltrative or inflammatory myocardial disease such as acute myocarditis, amyloidosis, sarcoidosis; or
- Valvular heart disease: (severe aortic or mitral regurgitation, moderate or severe aortic stenosis, any mitral stenosis requiring surgical repair, active endocarditis)
- Acute coronary syndrome, including unstable angina, NSTEMI or STEMI, or CABG within 60 days prior to randomization, or indication for PCI or CABG
- Significant cardiac ischemia in a stress test within a year of enrollment without revascularization since
- Symptomatic carotid stenosis, or transient ischemic attack or stroke within 30 days prior to randomization
- New initiation of cardiac resynchronization therapy within 60 days prior to randomization
- Listing for heart transplantation and/or anticipated/implanted ventricular assist device
- Complex congenital heart disease
5. Non-cardiac comorbidity, indicated by either of the following at the time of randomization
- Glomerular filtration rate <30 ml/min/1.73 m2 calculated by Modification of Diet in Renal Disease [MDRD] formula
- Hepatic insufficiency classified as Child-Pugh B or C
- Morbid obesity with a BMI >40 kg/m²
- Malignancy or other non-cardiac condition limiting life expectancy to <1 year, per physician judgment
- Severe pulmonary disease with either requirement of continuous home oxygen or recent bronchial artery embolization for massive hemoptysis
- Subjects with allergies, intolerance or hypersensitivity to investigational drug or any of the excipients
- Medical condition or history thereof that in the opinion of the investigator would impair the ability to complete the planned study procedures
6. Concomitant Treatment with a PDE5 inhibitor or sGC stimulator
7. Participation in another clinical study or treatment with another investigational product =30 days prior to randomization


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Heart failure
MedDRA version: 17.1 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849

Intervention(s)

Product Name: BAY 1021189 1.25 mg coated tablet
Product Code: BAY 1021189
Pharmaceutical Form: Coated tablet
Current Sponsor code: BAY102189
Other descriptive name: BAY 1021189
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.25-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Product Name: BAY 1021189 tablet 5 mg
Product Code: BAY 1021189
Pharmaceutical Form: Coated tablet
Current Sponsor code: BAY 1021189
Other descriptive name: BAY 1021189
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12 of treatment.

Secondary Objective: N/A

Primary end point(s): 1. Change from baseline to week 12 in log-transformed NT-proBNP

Main Objective: To find the optimal dose of BAY 1021189 for Phase III that can be given in addition to standard diuretic and comorbidity treatment by characterizing the safety, tolerability, pharmacodynamic effects, and pharmacokinetics, and detecting a significant dose-response relationship in the primary endpoint change in NT-proBNP at 12 weeks in patients with worsening chronic heart failure with reduced ejection fraction.

Secondary Outcome(s)

Secondary end point(s): 1. Changes in heart structure/function as measured by echocardiography
2. Changes in biomarkers
3. Changes to blood pressure & heart rate
4. Changes in health-related quality of life
5. Hospitalisations and death from cardiovascular causes
6. Change in NYHA function class
7. Incidence (new or recurrence) of atrial fibrillation
8. Changes in background heart failure therapies
9. Change in Composite Congestion Score
10. Incidence of ICD / CRT-D interventions

Timepoint(s) of evaluation of this end point: 1. From baseline to 12 weeks
2. From baseline to 12 weeks
3. From baseline to 12 weeks
4. From baseline to 12 weeks
5. From baseline to 16 weeks
6. From baseline to 12 weeks
7. From baseline to 16 weeks
8. From baseline to 12 weeks
9. From baseline to 12 weeks
10. From baseline to 12 weeks

Secondary ID(s)

BAY1021189/15371

Source(s) of Monetary Support

Bayer HealthCare AG