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Trial record 2 of 2 for:    neladenoson bialanate | Cardiac Failure | Italy

A Trial to Study Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction (PANTHEON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02992288
Recruitment Status : Completed
First Posted : December 14, 2016
Results First Posted : April 23, 2019
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Heart Failure
Interventions Drug: Neladenoson bialanate (BAY1067197)
Drug: Placebo
Enrollment 427
Recruitment Details Study was conducted at multiple centers in 11 countries between 22 February 2017 (first participant first visit) and 16 May 2018 (last participant last visit).
Pre-assignment Details Overall, 462 participants were screened. Of them, 35 participants did not complete screening due to unmet eligibility criteria, consent withdrawal, adverse events and other unspecified reasons. In total, 427 participants were randomized and 426 participants received study treatment.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Period Title: Overall Study
Started 106 37 70 73 69 72
Treated 106 37 70 72 69 72
Completed 89 32 63 64 61 59
Not Completed 17 5 7 9 8 13
Reason Not Completed
Adverse Event             8             2             2             2             2             7
Non-compliance with study drug             0             1             1             0             1             0
Physician Decision             3             0             1             0             0             1
Death             2             0             2             1             2             0
Lost to Follow-up             0             0             0             1             0             0
Protocol Violation             0             0             0             0             0             1
Withdrawal by Subject             4             2             1             5             3             4
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg Total
Hide Arm/Group Description Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Total of all reporting groups
Overall Number of Baseline Participants 106 37 70 73 69 72 427
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
66.9  (9.4) 66.6  (10.5) 66.4  (11.2) 68.1  (10.0) 67.6  (9.8) 67.5  (10.0) 67.2  (10.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Female
18
  17.0%
9
  24.3%
11
  15.7%
14
  19.2%
12
  17.4%
7
   9.7%
71
  16.6%
Male
88
  83.0%
28
  75.7%
59
  84.3%
59
  80.8%
57
  82.6%
65
  90.3%
356
  83.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Hispanic or Latino
1
   0.9%
0
   0.0%
1
   1.4%
1
   1.4%
2
   2.9%
0
   0.0%
5
   1.2%
Not Hispanic or Latino
105
  99.1%
37
 100.0%
69
  98.6%
72
  98.6%
66
  95.7%
72
 100.0%
421
  98.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
1
   0.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
6
   5.7%
3
   8.1%
3
   4.3%
5
   6.8%
3
   4.3%
5
   6.9%
25
   5.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   1.9%
2
   5.4%
2
   2.9%
2
   2.7%
2
   2.9%
2
   2.8%
12
   2.8%
White
98
  92.5%
32
  86.5%
65
  92.9%
66
  90.4%
64
  92.8%
65
  90.3%
390
  91.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Left ventricular ejection fraction (LVEF)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of LVEF
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
28.24  (10.67) 26.22  (7.99) 27.58  (8.92) 29.70  (10.87) 29.87  (11.54) 26.24  (8.92) 28.18  (10.17)
[1]
Measure Description: Left ventricular ejection fraction (LVEF) is defined as the fraction of blood being pumped out of the left ventricle of the heart with each contraction.
New York Heart Association (NYHA) Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Class I
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Class II
62
  58.5%
23
  62.2%
38
  54.3%
44
  60.3%
49
  71.0%
49
  68.1%
265
  62.1%
Class III/IV
44
  41.5%
14
  37.8%
31
  44.3%
29
  39.7%
20
  29.0%
23
  31.9%
161
  37.7%
[1]
Measure Description: NYHA classifies the extent of heart failure as Class I: Cardiac disease without resulting limitation of physical activity, Class II: Cardiac disease resulting in slight limitation of physical activity, Class III: Cardiac disease resulting in marked limitation of physical activity and Class IV: Cardiac disease resulting in inability to carry out any physical activity without discomfort.
N-terminal pro-hormone b-type natriuretic peptide (NT-proBNP)  
Median (Full Range)
Unit of measure:  Picograms per milliliter (pg/mL)
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
2111.00
(78.0 to 30428.0)
2071.00
(155.0 to 17760.0)
2063.00
(25.5 to 49896.0)
1894.50
(56.0 to 13294.0)
2084.00
(406.0 to 24551.0)
2419.00
(60.0 to 13387.0)
2085.00
(25.5 to 49896.0)
Medical history: Chronic heart failure etiology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Ischemic
65
  61.3%
25
  67.6%
45
  64.3%
50
  68.5%
37
  53.6%
42
  58.3%
264
  61.8%
Non-ischemic
41
  38.7%
12
  32.4%
24
  34.3%
23
  31.5%
32
  46.4%
30
  41.7%
162
  37.9%
Missing
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Medical history: Atrial fibrillation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
With Atrial fibrillation
44
  41.5%
14
  37.8%
27
  38.6%
26
  35.6%
27
  39.1%
33
  45.8%
171
  40.0%
Without Atrial fibrillation
62
  58.5%
23
  62.2%
43
  61.4%
47
  64.4%
42
  60.9%
39
  54.2%
256
  60.0%
Medication of interest: Beta-blocker  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Beta-blocker
103
  97.2%
37
 100.0%
66
  94.3%
70
  95.9%
67
  97.1%
69
  95.8%
412
  96.5%
Not used at baseline
3
   2.8%
0
   0.0%
4
   5.7%
3
   4.1%
2
   2.9%
3
   4.2%
15
   3.5%
Medication of interest: Angiotensin-converting enzyme inhibitor  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Angiotensin-converting enzyme inhibitor
58
  54.7%
19
  51.4%
41
  58.6%
41
  56.2%
36
  52.2%
45
  62.5%
240
  56.2%
Not used at baseline
48
  45.3%
18
  48.6%
29
  41.4%
32
  43.8%
33
  47.8%
27
  37.5%
187
  43.8%
Medication of interest: Angiotensin receptor blocker  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Angiotensin receptor blocker
15
  14.2%
6
  16.2%
11
  15.7%
14
  19.2%
9
  13.0%
9
  12.5%
64
  15.0%
Not used at baseline
91
  85.8%
31
  83.8%
59
  84.3%
59
  80.8%
60
  87.0%
63
  87.5%
363
  85.0%
Medication of interest: Angiotensin receptor-neprilysin inhibitor  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Angiotensin receptor-neprilysin inhibitor
20
  18.9%
7
  18.9%
9
  12.9%
9
  12.3%
12
  17.4%
12
  16.7%
69
  16.2%
Not used at baseline
86
  81.1%
30
  81.1%
61
  87.1%
64
  87.7%
57
  82.6%
60
  83.3%
358
  83.8%
Medication of interest: Mineralocorticoid receptor antagonist  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 37 participants 70 participants 73 participants 69 participants 72 participants 427 participants
Mineralocorticoid receptor antagonist
93
  87.7%
33
  89.2%
56
  80.0%
60
  82.2%
56
  81.2%
57
  79.2%
355
  83.1%
Not used at baseline
13
  12.3%
4
  10.8%
14
  20.0%
13
  17.8%
13
  18.8%
15
  20.8%
72
  16.9%
1.Primary Outcome
Title Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) (%) at Week 20 Measured by Echocardiography
Hide Description Left ventricular ejection fraction (LVEF) was measured by echocardiography. Mean and standard deviation were reported.
Time Frame Baseline, Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol set (PPS) included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline LVEF values not due to cardiovascular (CV) death or heart failure (HF) hospitalization or with other major protocol deviation were excluded from PPS LVEF set.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 47 19 35 47 40 38
Mean (Standard Deviation)
Unit of Measure: Percentage of LVEF
-2.19  (8.39) 2.59  (8.48) -3.01  (10.43) 0.13  (8.74) -2.45  (10.54) 1.53  (10.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2297
Comments Linear dose-response shape: The multiple comparison procedures (MCP) approach was applied to calculate the adjusted one-sided one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4409
Comments Sigmoidal Emax 1 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2842
Comments Sigmoidal Emax 2 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2534
Comments Emax dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3842
Comments Quadratic dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
2.Primary Outcome
Title Absolute Change From Baseline in Log-transformed NT-pro B-type Natriuretic Peptide (BNP) at Week 20
Hide Description NT-pro b-type Natriuretic Peptide (BNP) was measured. Mean and standard deviation were reported.
Time Frame Baseline, Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
PPS included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline BNP value not due to CV death or HF hospitalization or with other major protocol deviation were excluded from the PPS BNP.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 82 29 58 59 53 56
Mean (Standard Deviation)
Unit of Measure: log picograms per milliliter
-0.07  (0.70) -0.24  (0.90) -0.07  (0.52) -0.07  (0.56) 0.07  (0.55) -0.08  (0.79)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8966
Comments Linear dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9233
Comments Sigmoidal Emax 1 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9296
Comments Sigmoidal Emax 2 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7357
Comments Emax dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9083
Comments Quadratic dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
3.Secondary Outcome
Title Change From Baseline in Left Ventricular End-Systolic Volume (LVESV) at Week 20
Hide Description LVESV was defined as the volume of blood in the left ventricle at the end of contraction, or systole and the beginning of filling or diastole. Mean and standard deviation were reported.
Time Frame Baseline, Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
PPS included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline LVEF values not due to CV death or HF hospitalization or with other major protocol deviation were excluded from PPS LVEF set.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 47 19 35 47 40 38
Mean (Standard Deviation)
Unit of Measure: Milliliters (mL)
-5.44  (33.29) -21.41  (48.13) -2.82  (35.12) -4.32  (29.73) -3.12  (33.96) -15.16  (39.65)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4596
Comments Linear dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7859
Comments Sigmoidal Emax1 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5562
Comments Sigmoidal Emax2 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5338
Comments Emax dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7303
Comments Quadratic dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
4.Secondary Outcome
Title Change From Baseline in Left Ventricular End-Diastolic Volume (LVEDV) at Week 20
Hide Description LVEDV was defined as the volume of blood in the left ventricle at end load or filling in diastole or the amount of blood in the ventricles just before systole. Mean and standard deviation were reported.
Time Frame Baseline, Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
PPS included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline LVEF values not due to CV death or HF hospitalization or with other major protocol deviation were excluded from PPS LVEF set.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 47 19 35 47 40 38
Mean (Standard Deviation)
Unit of Measure: Milliliters (mL)
-13.16  (40.23) -21.65  (61.96) -12.44  (39.84) -5.92  (30.89) -11.17  (42.32) -19.69  (48.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5703
Comments Linear dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8253
Comments Sigmoidal Emax1 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6506
Comments Sigmoidal Emax2 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6923
Comments Emax dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8036
Comments Quadratic dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
5.Secondary Outcome
Title Change From Baseline in High Sensitivity Troponin T (Hs-TNT) at Week 20
Hide Description High sensitivity troponin T (hs-TNT) was measured. Mean and standard deviation were reported.
Time Frame Baseline, Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
PPS included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline BNP value not due to CV death or HF hospitalization or with other major protocol deviation were excluded from the PPS BNP.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 82 29 58 59 53 56
Mean (Standard Deviation)
Unit of Measure: Picograms per milliliter (pg/mL)
0.13  (9.98) 6.46  (33.04) 3.77  (22.32) 7.43  (37.79) 2.59  (12.90) 7.03  (24.81)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9955
Comments Linear dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9946
Comments Sigmoidal Emax1 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9913
Comments Sigmoidal Emax2 dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9982
Comments Emax dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Neladenoson Bialanate 5 mg, Neladenoson Bialanate 10 mg, Neladenoson Bialanate 20 mg, Neladenoson Bialanate 30 mg, Neladenoson Bialanate 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9959
Comments Quadratic dose-response shape: The MCP approach was applied to calculate the adjusted one-sided p-values of the contrast test.
Method MCP-Mod method
Comments Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques under model uncertainty.
6.Secondary Outcome
Title Number of Participants With Composite Efficacy Outcome
Hide Description Composite efficacy outcome was the first occurrence of CV death, HF hospitalization or urgent visit for HF. Number of participants with composite efficacy outcome were reported.
Time Frame Baseline up to Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
PPS included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline BNP value not due to CV death or HF hospitalization or with other major protocol deviation were excluded from the PPS BNP.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 82 29 58 59 53 56
Measure Type: Count of Participants
Unit of Measure: Participants
10
  12.2%
4
  13.8%
10
  17.2%
9
  15.3%
7
  13.2%
8
  14.3%
7.Secondary Outcome
Title Number of Participants With Cardiovascular (CV) Mortality
Hide Description Cardiovascular (CV) mortality was assessed. Number of participants with CV mortality were reported.
Time Frame Baseline up to Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
PPS included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline BNP value not due to CV death or HF hospitalization or with other major protocol deviation were excluded from the PPS BNP.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 82 29 58 59 53 56
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.2%
1
   3.4%
3
   5.2%
1
   1.7%
2
   3.8%
1
   1.8%
8.Secondary Outcome
Title Number of Participants With Heart Failure (HF) Hospitalization and Urgent Visits for Heart Failure (HF)
Hide Description Number of participants with HF hospitalization and urgent visits for HF were reported.
Time Frame Baseline up to Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
PPS included all participants without validity findings affecting efficacy evaluation. The participants with invalid/missing baseline or missing post-baseline BNP value not due to CV death or HF hospitalization or with other major protocol deviation were excluded from the PPS BNP.
Arm/Group Title Placebo Neladenoson Bialanate 5 mg Neladenoson Bialanate 10 mg Neladenoson Bialanate 20 mg Neladenoson Bialanate 30 mg Neladenoson Bialanate 40 mg
Hide Arm/Group Description:
Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 5 milligrams (mg) of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
Overall Number of Participants Analyzed 82 29 58 59 53 56
Measure Type: Count of Participants
Unit of Measure: Participants
10
  12.2%
4
  13.8%
9
  15.5%
8
  13.6%
5
   9.4%
8
  14.3%
Time Frame From start of study drug administration up to 26 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Neladenoson Bialanate 5mg Neladenoson Bialanate 10mg Neladenoson Bialanate 20mg Neladenoson Bialanate 30mg Neladenoson Bialanate 40mg
Hide Arm/Group Description Participants received placebo matched to neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 5 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 10 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 20 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 30 mg of neladenoson bialanate tablets orally once daily for 20 weeks. Participants received 40 mg of neladenoson bialanate tablets orally once daily for 20 weeks.
All-Cause Mortality
Placebo Neladenoson Bialanate 5mg Neladenoson Bialanate 10mg Neladenoson Bialanate 20mg Neladenoson Bialanate 30mg Neladenoson Bialanate 40mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/106 (7.55%)      1/37 (2.70%)      5/70 (7.14%)      1/72 (1.39%)      2/69 (2.90%)      2/72 (2.78%)    
Hide Serious Adverse Events
Placebo Neladenoson Bialanate 5mg Neladenoson Bialanate 10mg Neladenoson Bialanate 20mg Neladenoson Bialanate 30mg Neladenoson Bialanate 40mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/106 (29.25%)      13/37 (35.14%)      28/70 (40.00%)      22/72 (30.56%)      28/69 (40.58%)      26/72 (36.11%)    
Blood and lymphatic system disorders             
Anaemia * 1  2/106 (1.89%)  2 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 2/69 (2.90%)  2 2/72 (2.78%)  2
Cardiac disorders             
Acute myocardial infarction * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 1/69 (1.45%)  1 0/72 (0.00%)  0
Angina pectoris * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Angina unstable * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 1/69 (1.45%)  1 0/72 (0.00%)  0
Atrial fibrillation * 1  2/106 (1.89%)  3 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 3/72 (4.17%)  3
Atrial flutter * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 2/70 (2.86%)  2 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Atrial tachycardia * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Atrioventricular block complete * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 2/70 (2.86%)  2 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Cardiac arrest * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Cardiac failure * 1  15/106 (14.15%)  20 7/37 (18.92%)  8 12/70 (17.14%)  14 6/72 (8.33%)  10 10/69 (14.49%)  17 11/72 (15.28%)  16
Cardiac failure acute * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 1/72 (1.39%)  1 0/69 (0.00%)  0 1/72 (1.39%)  1
Cardiac failure chronic * 1  5/106 (4.72%)  8 1/37 (2.70%)  1 2/70 (2.86%)  2 3/72 (4.17%)  7 2/69 (2.90%)  2 0/72 (0.00%)  0
Cardiac failure congestive * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Cardio-respiratory arrest * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Cardiogenic shock * 1  3/106 (2.83%)  3 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Coronary artery disease * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Low cardiac output syndrome * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 1/72 (1.39%)  1
Mitral valve incompetence * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Myocardial infarction * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Myocardial ischaemia * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Right ventricular failure * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Tachycardia * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Ventricular fibrillation * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Ventricular tachycardia * 1  1/106 (0.94%)  1 1/37 (2.70%)  1 2/70 (2.86%)  2 1/72 (1.39%)  1 1/69 (1.45%)  1 0/72 (0.00%)  0
Cardiac ventricular thrombosis * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Acute left ventricular failure * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Endocrine disorders             
Hyperthyroidism * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Gastrointestinal disorders             
Ascites * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Diarrhoea * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Gastric haemorrhage * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Gastrointestinal haemorrhage * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Ileus * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  2
Upper gastrointestinal haemorrhage * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Large intestinal haemorrhage * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  2
General disorders             
Chest pain * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Sudden death * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 1/72 (1.39%)  1 1/69 (1.45%)  1 0/72 (0.00%)  0
Oedema due to cardiac disease * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Hepatobiliary disorders             
Hepatic function abnormal * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Jaundice * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Immune system disorders             
Hypersensitivity * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Infections and infestations             
Infection * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 1/72 (1.39%)  2
Peritonitis * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Pneumonia * 1  2/106 (1.89%)  2 0/37 (0.00%)  0 1/70 (1.43%)  1 2/72 (2.78%)  2 1/69 (1.45%)  1 1/72 (1.39%)  1
Pneumonia legionella * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Septic shock * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Serratia sepsis * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Injury, poisoning and procedural complications             
Fall * 1  1/106 (0.94%)  2 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Hip fracture * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Joint dislocation * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Rib fracture * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Traumatic fracture * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Lower limb fracture * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Post-traumatic pain * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Toxicity to various agents * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Craniocerebral injury * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Investigations             
Arteriogram coronary * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Blood pressure decreased * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Device function test * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Metabolism and nutrition disorders             
Diabetes mellitus * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Hyperkalaemia * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Hypokalaemia * 1  2/106 (1.89%)  3 0/37 (0.00%)  0 1/70 (1.43%)  1 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Pain in extremity * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Cervix carcinoma * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Chronic lymphocytic leukaemia * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Rectal adenocarcinoma * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Renal cancer metastatic * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Prostate cancer * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Nervous system disorders             
Dizziness * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 1/72 (1.39%)  1
Paraparesis * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Presyncope * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Seizure * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Syncope * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Product Issues             
Device failure * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Psychiatric disorders             
Confusional state * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Delirium * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Renal and urinary disorders             
Renal failure * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 2/72 (2.78%)  2
Renal impairment * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 2/70 (2.86%)  2 1/72 (1.39%)  1 2/69 (2.90%)  2 3/72 (4.17%)  3
Chronic kidney disease * 1  2/106 (1.89%)  2 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 2/72 (2.78%)  2
Acute kidney injury * 1  2/106 (1.89%)  2 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 1/69 (1.45%)  1 2/72 (2.78%)  2
Reproductive system and breast disorders             
Benign prostatic hyperplasia * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Chronic obstructive pulmonary disease * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Dyspnoea * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 1/70 (1.43%)  1 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Dyspnoea exertional * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Pleural effusion * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Pulmonary congestion * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Respiratory failure * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Sleep apnoea syndrome * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Surgical and medical procedures             
Atrial septal defect repair * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Cardiac pacemaker insertion * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Cardiac pacemaker replacement * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Implantable defibrillator insertion * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 2/70 (2.86%)  2 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Ventricular assist device insertion * 1  1/106 (0.94%)  2 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Implantable defibrillator replacement * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 0/72 (0.00%)  0
Cardiac resynchronisation therapy * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 0/70 (0.00%)  0 1/72 (1.39%)  1 1/69 (1.45%)  1 0/72 (0.00%)  0
Colectomy * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Vascular disorders             
Aortic aneurysm * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 0/69 (0.00%)  0 1/72 (1.39%)  1
Hypotension * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 1/70 (1.43%)  1 1/72 (1.39%)  1 1/69 (1.45%)  1 1/72 (1.39%)  1
Peripheral ischaemia * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
Thrombosis * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 1/69 (1.45%)  1 0/72 (0.00%)  0
1
Term from vocabulary, MedDRA (21.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Neladenoson Bialanate 5mg Neladenoson Bialanate 10mg Neladenoson Bialanate 20mg Neladenoson Bialanate 30mg Neladenoson Bialanate 40mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/106 (22.64%)      10/37 (27.03%)      15/70 (21.43%)      18/72 (25.00%)      24/69 (34.78%)      19/72 (26.39%)    
Cardiac disorders             
Cardiac failure * 1  9/106 (8.49%)  9 2/37 (5.41%)  2 2/70 (2.86%)  2 1/72 (1.39%)  1 3/69 (4.35%)  3 3/72 (4.17%)  6
Gastrointestinal disorders             
Abdominal pain * 1  1/106 (0.94%)  1 2/37 (5.41%)  2 1/70 (1.43%)  1 1/72 (1.39%)  3 0/69 (0.00%)  0 0/72 (0.00%)  0
Nausea * 1  1/106 (0.94%)  2 0/37 (0.00%)  0 0/70 (0.00%)  0 0/72 (0.00%)  0 2/69 (2.90%)  2 5/72 (6.94%)  5
General disorders             
Asthenia * 1  1/106 (0.94%)  2 0/37 (0.00%)  0 1/70 (1.43%)  1 2/72 (2.78%)  2 4/69 (5.80%)  4 0/72 (0.00%)  0
Fatigue * 1  2/106 (1.89%)  2 2/37 (5.41%)  2 1/70 (1.43%)  1 2/72 (2.78%)  2 1/69 (1.45%)  1 0/72 (0.00%)  0
Infections and infestations             
Urinary tract infection * 1  1/106 (0.94%)  1 0/37 (0.00%)  0 1/70 (1.43%)  1 0/72 (0.00%)  0 0/69 (0.00%)  0 4/72 (5.56%)  4
Metabolism and nutrition disorders             
Hyperglycaemia * 1  2/106 (1.89%)  2 2/37 (5.41%)  2 0/70 (0.00%)  0 1/72 (1.39%)  1 0/69 (0.00%)  0 0/72 (0.00%)  0
Nervous system disorders             
Dizziness * 1  3/106 (2.83%)  3 0/37 (0.00%)  0 1/70 (1.43%)  1 2/72 (2.78%)  2 4/69 (5.80%)  4 4/72 (5.56%)  4
Headache * 1  3/106 (2.83%)  3 1/37 (2.70%)  1 2/70 (2.86%)  2 0/72 (0.00%)  0 6/69 (8.70%)  8 1/72 (1.39%)  1
Renal and urinary disorders             
Renal impairment * 1  6/106 (5.66%)  7 1/37 (2.70%)  1 0/70 (0.00%)  0 4/72 (5.56%)  4 6/69 (8.70%)  6 7/72 (9.72%)  7
Respiratory, thoracic and mediastinal disorders             
Dyspnoea * 1  0/106 (0.00%)  0 0/37 (0.00%)  0 3/70 (4.29%)  3 4/72 (5.56%)  6 3/69 (4.35%)  3 3/72 (4.17%)  3
Vascular disorders             
Hypotension * 1  0/106 (0.00%)  0 1/37 (2.70%)  1 5/70 (7.14%)  6 4/72 (5.56%)  4 3/69 (4.35%)  3 2/72 (2.78%)  2
1
Term from vocabulary, MedDRA (21.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 30 days but less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer
Phone: 1-888-8422937
EMail: clinical-trials-contact@bayer.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02992288    
Other Study ID Numbers: 15128
2016-003839-38 ( EudraCT Number )
First Submitted: December 12, 2016
First Posted: December 14, 2016
Results First Submitted: March 11, 2019
Results First Posted: April 23, 2019
Last Update Posted: April 23, 2019