Heart Failure
Conditions
Keywords
Chronic Heart Failure, Heart Failure with Preserved Ejection Fraction
Brief summary
The objective of the study is to find the optimal dose of once daily oral neladenoson bialanate (BAY1067197) when given in addition to appropriate therapy for specific comorbidities.
Interventions
5 mg orally once daily for 20 weeks
DRUGPlacebo
Orally once daily for 20 weeks
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women aged 45 years and older * Diagnosis of chronic heart failure, NYHA (New York Heart Association) class II-IV, LVEF (left ventricular ejection fraction) ≥ 45% and elevated NT-proBNP
Exclusion criteria
* Acute decompensated heart failure within the past 4 weeks * Inability to exercise * Previous diagnosis of HFrEF (heart failure with reduced ejection fraction) (LVEF \< 40%)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Baseline, and up to 20 weeks of treatment | The 6MWD test is designed to evaluate a subject's exercise capacity while performing an everyday activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Baseline, and up to 20 weeks of treatment | AVIVO™ Mobile Patient Management System, a wearable wireless device worn by the subject, was used to monitor subjects' cardiovascular status. The patient's everyday physical activity e.g. duration, intensity, was also tracked by the AVIVO device. For Activity Intensity, the Unit of Measure is percentage of maximum activity, and length of intervals is daily. |
| Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Baseline, and up to 20 weeks of treatment | NT-proBNP = N-terminal pro-hormone b-type natriuretic peptide |
| Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Baseline, and up to 20 weeks of treatment | High sensitivity troponin T (hs-TNT) was measured |
| Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Baseline, and up to 20 weeks of treatment | The KCCQ is the leading health-related quality-of-life measure for patients with chronic heart failure (CHF). It is a 23-item questionnaire that independently measures the impact of patient's heart failure (HF), or its treatment, on 7 distinct domains: 1) Symptom Frequency 2) Symptom Burden 3) Physical Limitation 4) Quality of Life 5) Social Limitations 6) Self-efficacy 7) Symptoms Stability. Overall summary score= mean score of (symptom frequency + symptom burden+ physical limitation + quality of life + social limitation); scores on a scale of 0 to 100, higher scores means better outcome; Physical Limitation: scores on a scale of 0 to 100, higher scores means better outcome; Total symptom score=mean score of (symptom frequency + symptom burden): scores on a scale of 0 to 100, higher scores means better outcome. Positive change means improvement and negative change means deterioration. |
Countries
Austria, Belgium, Bulgaria, Germany, Greece, Israel, Italy, Japan, Poland, Portugal, Spain, United States
Participant flow
Recruitment details
The study was conducted at 76 study centers in 12 countries, between 10 May 2017 (first patient first visit) and 20 June 2018 (last patient last visit)
Pre-assignment details
A total of 339 subjects entered the screening period, of whom 34 withdrew before randomization. The remaining 305 subjects were randomized and received at least one dose of study drug
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks | 76 |
| Neladenoson Bialanate 5 mg Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks | 27 |
| Neladenoson Bialanate 10 mg Subjects received 10 mg of neladenoson bialanate tablets orally for 20 weeks | 50 |
| Neladenoson Bialanate 20 mg Subjects received 20 mg of neladenoson bialanate tablets orally for 20 weeks | 51 |
| Neladenoson Bialanate 30 mg Subjects received 30 mg of neladenoson bialanate tablets orally for 20 weeks | 50 |
| Neladenoson Bialanate 40 mg Subjects received 40 mg of neladenoson bialanate tablets orally for 20 weeks | 51 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 4 | 6 | 1 |
| Overall Study | Death | 1 | 0 | 2 | 0 | 1 | 0 |
| Overall Study | Non-compliance | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Neladenoson Bialanate 40 mg | Neladenoson Bialanate 30 mg | Neladenoson Bialanate 20 mg | Neladenoson Bialanate 10 mg | Neladenoson Bialanate 5 mg |
|---|---|---|---|---|---|---|---|
| 6MWD | 322.8 meter STANDARD_DEVIATION 97.1 | 321.5 meter STANDARD_DEVIATION 101 | 347.2 meter STANDARD_DEVIATION 94.5 | 321.1 meter STANDARD_DEVIATION 93.4 | 324.5 meter STANDARD_DEVIATION 105 | 295.8 meter STANDARD_DEVIATION 110.4 | 311.6 meter STANDARD_DEVIATION 108.2 |
| Age, Continuous | 73.1 Years STANDARD_DEVIATION 8 | 73.6 Years STANDARD_DEVIATION 8.6 | 73.7 Years STANDARD_DEVIATION 8.3 | 76 Years STANDARD_DEVIATION 9.4 | 71.4 Years STANDARD_DEVIATION 6.8 | 73.5 Years STANDARD_DEVIATION 9.9 | 74.3 Years STANDARD_DEVIATION 9.3 |
| eGFR | 62.0 mL/min/1.73 square meter STANDARD_DEVIATION 17.9 | 59.1 mL/min/1.73 square meter STANDARD_DEVIATION 18.9 | 60.0 mL/min/1.73 square meter STANDARD_DEVIATION 17.5 | 57.5 mL/min/1.73 square meter STANDARD_DEVIATION 18.2 | 57.1 mL/min/1.73 square meter STANDARD_DEVIATION 17.3 | 61.0 mL/min/1.73 square meter STANDARD_DEVIATION 24.2 | 52.6 mL/min/1.73 square meter STANDARD_DEVIATION 17.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 300 Participants | 50 Participants | 50 Participants | 51 Participants | 49 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| LVEF | 57.09 percentage of blood ejected STANDARD_DEVIATION 8.68 | 56.09 percentage of blood ejected STANDARD_DEVIATION 10.5 | 52.3 percentage of blood ejected STANDARD_DEVIATION 12.76 | 59.43 percentage of blood ejected STANDARD_DEVIATION 8.72 | 57.3 percentage of blood ejected STANDARD_DEVIATION 10.4 | 53.78 percentage of blood ejected STANDARD_DEVIATION 11.6 | 56.54 percentage of blood ejected STANDARD_DEVIATION 9.62 |
| Medical history: Atrial fibrillation | 28 Participants | 116 Participants | 21 Participants | 20 Participants | 19 Participants | 18 Participants | 10 Participants |
| Medical history: diabetes | 36 Participants | 129 Participants | 21 Participants | 22 Participants | 20 Participants | 23 Participants | 7 Participants |
| Medical history: hypertension | 66 Participants | 269 Participants | 42 Participants | 46 Participants | 45 Participants | 45 Participants | 25 Participants |
| NT-proBNP | 882.0 pg/ml | 869.0 pg/ml | 886.5 pg/ml | 626.0 pg/ml | 834.5 pg/ml | 1000.0 pg/ml | 1013.0 pg/ml |
| NYHA class II | 61 Participants | 232 Participants | 39 Participants | 31 Participants | 41 Participants | 37 Participants | 23 Participants |
| NYHA class III/IV | 15 Participants | 73 Participants | 12 Participants | 19 Participants | 10 Participants | 13 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 33 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 267 Participants | 45 Participants | 45 Participants | 45 Participants | 44 Participants | 24 Participants |
| Sex: Female, Male Female | 36 Participants | 160 Participants | 29 Participants | 32 Participants | 21 Participants | 26 Participants | 16 Participants |
| Sex: Female, Male Male | 40 Participants | 145 Participants | 22 Participants | 18 Participants | 30 Participants | 24 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 76 | 0 / 27 | 2 / 50 | 1 / 51 | 1 / 50 | 1 / 51 |
| other Total, other adverse events | 24 / 76 | 13 / 27 | 14 / 50 | 22 / 51 | 17 / 50 | 24 / 51 |
| serious Total, serious adverse events | 21 / 76 | 9 / 27 | 11 / 50 | 11 / 51 | 14 / 50 | 16 / 51 |
Outcome results
Primary
Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment
The 6MWD test is designed to evaluate a subject's exercise capacity while performing an everyday activity.
Time frame: Baseline, and up to 20 weeks of treatment
Population: Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure, and it also included subjects who were censored due to cardiovascular (CV) death or hospitalization for heart failure (HF) that prevented assessment of efficacy at 20 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Value at baseline | 329 meter | Standard Deviation 95 |
| Placebo | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Change from baseline to Week 20 | 1.89 meter | Standard Deviation 49.5 |
| Neladenoson Bialanate 5 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Value at baseline | 306 meter | Standard Deviation 117 |
| Neladenoson Bialanate 5 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Change from baseline to Week 20 | 24.8 meter | Standard Deviation 72.4 |
| Neladenoson Bialanate 10 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Value at baseline | 300 meter | Standard Deviation 109 |
| Neladenoson Bialanate 10 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Change from baseline to Week 20 | 27.2 meter | Standard Deviation 90 |
| Neladenoson Bialanate 20 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Value at baseline | 328 meter | Standard Deviation 105 |
| Neladenoson Bialanate 20 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Change from baseline to Week 20 | 14.6 meter | Standard Deviation 54.1 |
| Neladenoson Bialanate 30 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Value at baseline | 321 meter | Standard Deviation 101 |
| Neladenoson Bialanate 30 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Change from baseline to Week 20 | 16.3 meter | Standard Deviation 55.4 |
| Neladenoson Bialanate 40 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Value at baseline | 363 meter | Standard Deviation 83 |
| Neladenoson Bialanate 40 mg | Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment | Change from baseline to Week 20 | 10.7 meter | Standard Deviation 60.2 |
p-value: 0.6232MCP-Mod method
p-value: 0.5183MCP-Mod method
p-value: 0.33MCP-Mod method
p-value: 0.0918MCP-Mod method
p-value: 0.2701MCP-Mod method
Secondary
Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity
AVIVO™ Mobile Patient Management System, a wearable wireless device worn by the subject, was used to monitor subjects' cardiovascular status. The patient's everyday physical activity e.g. duration, intensity, was also tracked by the AVIVO device. For Activity Intensity, the Unit of Measure is percentage of maximum activity, and length of intervals is daily.
Time frame: Baseline, and up to 20 weeks of treatment
Population: Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Value at visit Baseline | 2.83 percentage of maximum activity | Standard Deviation 1.03 |
| Placebo | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Change from baseline at Week 20 | -0.19 percentage of maximum activity | Standard Deviation 0.58 |
| Neladenoson Bialanate 5 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Change from baseline at Week 20 | -0.25 percentage of maximum activity | Standard Deviation 0.51 |
| Neladenoson Bialanate 5 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Value at visit Baseline | 2.76 percentage of maximum activity | Standard Deviation 0.72 |
| Neladenoson Bialanate 10 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Value at visit Baseline | 2.83 percentage of maximum activity | Standard Deviation 0.95 |
| Neladenoson Bialanate 10 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Change from baseline at Week 20 | -0.12 percentage of maximum activity | Standard Deviation 0.58 |
| Neladenoson Bialanate 20 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Value at visit Baseline | 2.51 percentage of maximum activity | Standard Deviation 0.91 |
| Neladenoson Bialanate 20 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Change from baseline at Week 20 | -0.08 percentage of maximum activity | Standard Deviation 0.67 |
| Neladenoson Bialanate 30 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Value at visit Baseline | 2.61 percentage of maximum activity | Standard Deviation 0.94 |
| Neladenoson Bialanate 30 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Change from baseline at Week 20 | -0.18 percentage of maximum activity | Standard Deviation 0.57 |
| Neladenoson Bialanate 40 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Change from baseline at Week 20 | -0.14 percentage of maximum activity | Standard Deviation 0.57 |
| Neladenoson Bialanate 40 mg | Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity | Value at visit Baseline | 2.43 percentage of maximum activity | Standard Deviation 0.57 |
Secondary
Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score
The KCCQ is the leading health-related quality-of-life measure for patients with chronic heart failure (CHF). It is a 23-item questionnaire that independently measures the impact of patient's heart failure (HF), or its treatment, on 7 distinct domains: 1) Symptom Frequency 2) Symptom Burden 3) Physical Limitation 4) Quality of Life 5) Social Limitations 6) Self-efficacy 7) Symptoms Stability. Overall summary score= mean score of (symptom frequency + symptom burden+ physical limitation + quality of life + social limitation); scores on a scale of 0 to 100, higher scores means better outcome; Physical Limitation: scores on a scale of 0 to 100, higher scores means better outcome; Total symptom score=mean score of (symptom frequency + symptom burden): scores on a scale of 0 to 100, higher scores means better outcome. Positive change means improvement and negative change means deterioration.
Time frame: Baseline, and up to 20 weeks of treatment
Population: Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Baseline | 69.19 scores on a scale | Standard Deviation 18.02 |
| Placebo | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Change from baseline | 3.38 scores on a scale | Standard Deviation 13.55 |
| Placebo | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Baseline | 69.07 scores on a scale | Standard Deviation 19.43 |
| Placebo | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Change from baseline | 2.18 scores on a scale | Standard Deviation 17.54 |
| Placebo | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Baseline | 76.78 scores on a scale | Standard Deviation 19.64 |
| Placebo | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Change from baseline | 2.96 scores on a scale | Standard Deviation 15.85 |
| Neladenoson Bialanate 5 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Change from baseline | 7.04 scores on a scale | Standard Deviation 17.24 |
| Neladenoson Bialanate 5 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Change from baseline | 1.40 scores on a scale | Standard Deviation 17.62 |
| Neladenoson Bialanate 5 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Change from baseline | 5.82 scores on a scale | Standard Deviation 17.51 |
| Neladenoson Bialanate 5 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Baseline | 64.75 scores on a scale | Standard Deviation 23.99 |
| Neladenoson Bialanate 5 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Baseline | 63.18 scores on a scale | Standard Deviation 25.24 |
| Neladenoson Bialanate 5 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Baseline | 72.25 scores on a scale | Standard Deviation 21.73 |
| Neladenoson Bialanate 10 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Change from baseline | 0.14 scores on a scale | Standard Deviation 19.08 |
| Neladenoson Bialanate 10 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Baseline | 68.99 scores on a scale | Standard Deviation 23.13 |
| Neladenoson Bialanate 10 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Change from baseline | -1.34 scores on a scale | Standard Deviation 22.56 |
| Neladenoson Bialanate 10 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Baseline | 68.03 scores on a scale | Standard Deviation 22.79 |
| Neladenoson Bialanate 10 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Baseline | 66.42 scores on a scale | Standard Deviation 21.21 |
| Neladenoson Bialanate 10 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Change from baseline | -1.33 scores on a scale | Standard Deviation 20.61 |
| Neladenoson Bialanate 20 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Change from baseline | 0.92 scores on a scale | Standard Deviation 14.65 |
| Neladenoson Bialanate 20 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Change from baseline | 3.73 scores on a scale | Standard Deviation 13.03 |
| Neladenoson Bialanate 20 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Baseline | 69.35 scores on a scale | Standard Deviation 22.64 |
| Neladenoson Bialanate 20 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Change from baseline | 3.56 scores on a scale | Standard Deviation 14.04 |
| Neladenoson Bialanate 20 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Baseline | 69.99 scores on a scale | Standard Deviation 20.18 |
| Neladenoson Bialanate 20 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Baseline | 64.57 scores on a scale | Standard Deviation 20.73 |
| Neladenoson Bialanate 30 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Baseline | 63.67 scores on a scale | Standard Deviation 17.76 |
| Neladenoson Bialanate 30 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Baseline | 68.00 scores on a scale | Standard Deviation 20.09 |
| Neladenoson Bialanate 30 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Change from baseline | 0.27 scores on a scale | Standard Deviation 14.83 |
| Neladenoson Bialanate 30 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Baseline | 64.53 scores on a scale | Standard Deviation 22.47 |
| Neladenoson Bialanate 30 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Change from baseline | -3.75 scores on a scale | Standard Deviation 22.1 |
| Neladenoson Bialanate 30 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Change from baseline | 2.54 scores on a scale | Standard Deviation 16.79 |
| Neladenoson Bialanate 40 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Change from baseline | 2.17 scores on a scale | Standard Deviation 17.32 |
| Neladenoson Bialanate 40 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Physical Limitation Score Baseline | 63.12 scores on a scale | Standard Deviation 23.44 |
| Neladenoson Bialanate 40 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Baseline | 71.03 scores on a scale | Standard Deviation 18.8 |
| Neladenoson Bialanate 40 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Total Symptom Score Change from baseline | 2.62 scores on a scale | Standard Deviation 16.04 |
| Neladenoson Bialanate 40 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Change from baseline | 2.25 scores on a scale | Standard Deviation 14.25 |
| Neladenoson Bialanate 40 mg | Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score | Overall Summary Score Baseline | 64.65 scores on a scale | Standard Deviation 18.07 |
Secondary
Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks
High sensitivity troponin T (hs-TNT) was measured
Time frame: Baseline, and up to 20 weeks of treatment
Population: Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Value at baseline | 2.92 log(pg/mL) |
| Placebo | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.00 log(pg/mL) |
| Neladenoson Bialanate 5 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.02 log(pg/mL) |
| Neladenoson Bialanate 5 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Value at baseline | 3.25 log(pg/mL) |
| Neladenoson Bialanate 10 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Value at baseline | 2.95 log(pg/mL) |
| Neladenoson Bialanate 10 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.00 log(pg/mL) |
| Neladenoson Bialanate 20 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Value at baseline | 2.76 log(pg/mL) |
| Neladenoson Bialanate 20 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.12 log(pg/mL) |
| Neladenoson Bialanate 30 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Value at baseline | 2.73 log(pg/mL) |
| Neladenoson Bialanate 30 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.13 log(pg/mL) |
| Neladenoson Bialanate 40 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.01 log(pg/mL) |
| Neladenoson Bialanate 40 mg | Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks | Value at baseline | 2.76 log(pg/mL) |
Secondary
Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks
NT-proBNP = N-terminal pro-hormone b-type natriuretic peptide
Time frame: Baseline, and up to 20 weeks of treatment
Population: Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Value at baseline | 6.80 log (pg/ml) |
| Placebo | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | -0.07 log (pg/ml) |
| Neladenoson Bialanate 5 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Value at baseline | 6.78 log (pg/ml) |
| Neladenoson Bialanate 5 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.08 log (pg/ml) |
| Neladenoson Bialanate 10 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Value at baseline | 6.81 log (pg/ml) |
| Neladenoson Bialanate 10 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.13 log (pg/ml) |
| Neladenoson Bialanate 20 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Value at baseline | 6.73 log (pg/ml) |
| Neladenoson Bialanate 20 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.06 log (pg/ml) |
| Neladenoson Bialanate 30 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Value at baseline | 6.68 log (pg/ml) |
| Neladenoson Bialanate 30 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.09 log (pg/ml) |
| Neladenoson Bialanate 40 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Value at baseline | 6.64 log (pg/ml) |
| Neladenoson Bialanate 40 mg | Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks | Absolute change from baseline to Week 20 | 0.19 log (pg/ml) |