Clinical Trials List
Protocol NumberBAY 1021189 / 15371
2013-10-31 - 2015-06-30
Phase II
Terminated4
Study ended1
ICD-10I50.9
Heart failure, unspecified
ICD-9428.9
Heart failure, unspecified
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 BAY1021189 Over 12 Weeks in Patients With Worsening Heart Failure With Reduced Ejection Fraction (HFrEF)
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Trial Applicant
BAYER TAIWAN COMPANY LTD.
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Sponsor
Bayer AG.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- JYH-MING JIMMY JUANG Division of Cardiovascular Diseases
- LIAN-YU LIN Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 林幸榮 Division of Cardiovascular Diseases
- Kang-Ling Wang Division of Cardiovascular Diseases
- Tse-Min Lu Division of Cardiovascular Diseases
- Wen-Chung Yu Division of Cardiovascular Diseases
- Shih-Hsien Sung Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Study ended
Co-Principal Investigator
- 顏學偉 Division of Cardiovascular Diseases
- Ye-Hsu Lu Division of Cardiovascular Diseases
- 鄭凱鴻 Division of Cardiovascular Diseases
- Chun-Yuan Chu Division of Cardiovascular Diseases
- 溫文才 Division of Cardiovascular Diseases
- Cheng-An Chiu Division of Cardiovascular Diseases
- Tsung-Hsien Lin Division of Cardiovascular Diseases
- 朱志生 Division of Cardiovascular Diseases
- Po-Chao Hsu Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Worsening Heart Failure With Reduced Ejection Fraction (HFrEF)
Objectives
Objective of the study is to find the optimal dose of the once daily oral soluble guanylate cyclase stimulator (sGC) BAY1021189 for Phase III that can be given in addition to standard therapy for heart failure with reduced ejection fraction (HFrEF).
Test Drug
BAY 1021189 immediate-release (IR) tablet
Active Ingredient
BAY 1021189
Dosage Form
Oral
Dosage
1.25 mg /2.5 mg / 5 mg / 10 mg
Endpoints
Primary Outcome Measures :
Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12 [ Time Frame: Baseline, Week 12 ]
Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.
Other Outcome Measures:
Changes in Heart Function as Measured by Echocardiography, Left Ventricular End-Diastolic Volume (LVEDV), and Left Ventricular End-Systolic Volume (LVESV) From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
Left Ventricular End-Diastolic Volume (LVEDV) and Left ventricular end-systolic volume (LVESV) are measured echocardiography parameter. These are acquired during a non-invasive echocardiography examination.
Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
The left ventricular ejection fraction work index (LVEF) is a calculated echocardiography parameter. LVEF is derived from the directly measured parameters left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These 2 parameters are acquired during a noninvasive echocardiography examination. Formula: LVEF = 100*(LVEDV - LVESV)/LVEDV.
Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12 [ Time Frame: Baseline, Week 12 ]
Blood pressure was measured by monitor measurements after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.
Change From Baseline in Heart Rate to Week 12 [ Time Frame: Baseline, Week 12 ]
Heart rate was measured after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed.
Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality) [ Time Frame: Baseline until 16 weeks ]
Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.
Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy [ Time Frame: Baseline upto 16 weeks ]
ICD / CRT with defibrillation therapy (CRT-D) included previous appropriate interventions such as shocks or anti-tachycardic pacing (ATP) when diagnostic of sustained ventricular tachycardias in pre defined rapid zone.
Number of Subjects With Treatment-Emergent Adverse Events [ Time Frame: From the start of study treatment upto 5 days after the last dose of study drug ]
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; and another medically important serious event as judged by the investigator. AEs are considered to be treatment-emergent if they have started or worsened after first application of study drug up to 5 days after end of treatment with study drug.
Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL) [ Time Frame: Baseline, Week 12 ]
Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL) [ Time Frame: Baseline, Week 12 ]
TIMP-4: tissue inhibitor of matrix metalloproteinases 4
Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL) [ Time Frame: Baseline, Week 12 ]
cGMP: cyclic guanosine monophosphate
Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L) [ Time Frame: Baseline, Week 12 ]
PIIINP: pro-collagen III N-terminal peptide
Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL) [ Time Frame: Baseline, Week 12 ]
GDF-15: growth differentiation factor 15
Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL) [ Time Frame: Baseline, Week 12 ]
ST2: suppression of tumorigenicity 2
Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL) [ Time Frame: Baseline, Week 12 ]
Gal-3: Galectin-3
Change From Baseline in Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) to Week 12 [ Time Frame: Baseline, Week 12 ]
Log-Transformed N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a circulating plasma biomarker of cardiovascular function and prognosis in heart failure.
Other Outcome Measures:
Changes in Heart Function as Measured by Echocardiography, Left Ventricular End-Diastolic Volume (LVEDV), and Left Ventricular End-Systolic Volume (LVESV) From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
Left Ventricular End-Diastolic Volume (LVEDV) and Left ventricular end-systolic volume (LVESV) are measured echocardiography parameter. These are acquired during a non-invasive echocardiography examination.
Changes in Heart Function as Measured by Echocardiography, Left Ventricular Ejection Fraction (LVEF), From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
The left ventricular ejection fraction work index (LVEF) is a calculated echocardiography parameter. LVEF is derived from the directly measured parameters left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These 2 parameters are acquired during a noninvasive echocardiography examination. Formula: LVEF = 100*(LVEDV - LVESV)/LVEDV.
Change From Baseline in Systolic and Diastolic Blood Pressure to Week 12 [ Time Frame: Baseline, Week 12 ]
Blood pressure was measured by monitor measurements after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart).The changes in blood pressure were recorded and the mean of the three measurements was analyzed.
Change From Baseline in Heart Rate to Week 12 [ Time Frame: Baseline, Week 12 ]
Heart rate was measured after 10 minutes resting in a supine position (3 measurements taken approximately 2 minutes apart). The changes in heart rate were recorded and the mean of the three measurements was analyzed.
Number of Subjects With Clinical Events (Heart Failure [HF] Hospitalization and Cardio-Vascular [CV] Mortality) [ Time Frame: Baseline until 16 weeks ]
Clinical events (heart failure and mortality) were analyzed as CV death, and HF hospitalization at specified time points.
Number of Subjects With Implantable Cardioverter Defibrillators Cardiac Resynchronization Therapy With Defibrillation (ICD/CRT-D) Therapy [ Time Frame: Baseline upto 16 weeks ]
ICD / CRT with defibrillation therapy (CRT-D) included previous appropriate interventions such as shocks or anti-tachycardic pacing (ATP) when diagnostic of sustained ventricular tachycardias in pre defined rapid zone.
Number of Subjects With Treatment-Emergent Adverse Events [ Time Frame: From the start of study treatment upto 5 days after the last dose of study drug ]
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; and another medically important serious event as judged by the investigator. AEs are considered to be treatment-emergent if they have started or worsened after first application of study drug up to 5 days after end of treatment with study drug.
Change in Biomarkers From Baseline to Week 12: Osteopontin (ng/mL) [ Time Frame: Baseline, Week 12 ]
Change in Biomarkers From Baseline to Week 12: TIMP-4 (pg/mL) [ Time Frame: Baseline, Week 12 ]
TIMP-4: tissue inhibitor of matrix metalloproteinases 4
Change in Biomarkers From Baseline to Week 12: cGMP (Pmol/mL) [ Time Frame: Baseline, Week 12 ]
cGMP: cyclic guanosine monophosphate
Change in Biomarkers From Baseline to Week 12: PIIINP (mcg/L) [ Time Frame: Baseline, Week 12 ]
PIIINP: pro-collagen III N-terminal peptide
Change in Biomarkers From Baseline to Week 12: GDF-15 (pg/mL) [ Time Frame: Baseline, Week 12 ]
GDF-15: growth differentiation factor 15
Change in Biomarkers From Baseline to Week 12: ST2 (pg/mL) [ Time Frame: Baseline, Week 12 ]
ST2: suppression of tumorigenicity 2
Change in Biomarkers From Baseline to Week 12: Gal-3 (μg/mL) [ Time Frame: Baseline, Week 12 ]
Gal-3: Galectin-3
Inclution Criteria
Inclusion Criteria:
Worsening chronic heart failure (WCHF) requiring hospitalization (or intravenous diuretic treatment for HF without hospitalization) with initiation of study treatment after clinical stabilization
Left ventricular ejection fraction (LVEF) <45% by echocardiography at randomization
Worsening chronic heart failure (WCHF) requiring hospitalization (or intravenous diuretic treatment for HF without hospitalization) with initiation of study treatment after clinical stabilization
Left ventricular ejection fraction (LVEF) <45% by echocardiography at randomization
Exclusion Criteria
Exclusion Criteria:
Intravenous inotropes at any time after hospitalization
Intravenous inotropes at any time after hospitalization
The Estimated Number of Participants
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Taiwan
24 participants
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Global
513 participants
