Coronary Artery Disease
Conditions
Keywords
coronary artery disease
Brief summary
This was a mechanistic study in patients with coronary artery disease on the effects of Serelaxin on micro- and macrovascular function.
Detailed description
double blind, randomized, parallel group, placebo controlled study
Interventions
DRUGSerelaxin
Serelaxin solution diluted in 5% glucose volume/volume (v/v) solution
OTHERPlacebo
5% v/v glucose solution
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
double blind, randomized, parallel group, placebo controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients ≥18 years of age, with body weight \<160 kg. * Patients with proven obstructive coronary artery disease, determined either by functional (e.g. treadmill testing) or non-invasive clinical imaging assessments (e.g. stress-echo, PET or SPECT myocardial perfusion), or invasive coronary angiography or by CT coronary angiography at any point in time in patients with or without mild left ventricular systolic dysfunction (LVSD)
Exclusion criteria
* Previous treatment with serelaxin (also known as: RLX030, relaxin) * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. * Current or planned dialysis. * Impaired renal function during screening defined as an estimated glomerular filtration rate (eGFR) at screening and prior to treatment of \<30 mL/min/1.73 m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation due to potential issue with administration of GdDTPA used as the MRI contrast agent. * Sick-Sinus-Syndrome * Current or history of pulmonary edema, including suspected sepsis. * restrictive, or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function) * Known significant valvular disease (including any of the following: severe aortic stenosis \[AVA \< 1.0 or peak gradient \> 50 on prior or current echocardiogram\], severe aortic regurgitation, or severe mitral stenosis). * Clinical diagnosis of acute coronary syndrome (ACS) including unstable angina within 30 days prior to screening as determined by both clinical and enzymatic criteria * Troponin elevation and dynamics indicative of ACS at any time between screening and randomization. * Previous myocardial infarction within 3 months of screening * History of Coronary Artery Bypass Graft (CABG) surgery * Heart failure due to significant arrhythmias (including any of the following: ventricular tachycardia, bradyarrhythmias with ventricular rate \< 45 beats per minute or any second or third degree AV block or atrial fibrillation/flutter with ventricular response of \> 120 beats per minute) * Any surgical or medical condition which in the opinion of the investigator may place the patient at higher risk from his/her participation in the study (e.g., history of poor tolerance of adenosine or 3 vessel coronary disease) * Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points | baseline to Day 3 | Global MPRI (Myocardial Perfusion Reserve Index) is defined as ratio between mean global myocardial blood flow values at rest and during adenosine stress with Mid Perfusion Reserve Index or Midl PRI (Mid Perfusion Reserve Index) which is defined as ratio between mid myocardial blood flow values at rest and during adenosine stress |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Aortic Velocity | At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion | Summary table for measurements of arterial velocity from cardiac MRI - Mean (SD) \[n\] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device |
| Change From Baseline in Augmentation Index Measured From Sphygmocor Device | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion | Summary of values and change from baseline in augmentation index by time and treatment The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance |
| Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion | The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included The augmentation index is a ratio calculated from the blood pressure waveform, it is a measure of wave reflection and arterial stiffness. Augmentation index is commonly accepted as a measure of the enhancement (augmentation) of central aortic pressure by a reflected pulse wave |
| Change From Baseline in Aortic Distensibility Measured by MRI | At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion | Measurements of arterial stiffness from cardiac MRI - Mean (SD) \[n\] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device. (mmHg-1) |
| Serum Concentration of Serelaxin | Day1, Day 2, Day 3 and Day 30 after the start of infusion | Summary statistics of serelaxin serum PK concentrations Blood samples were taken to measure serelaxin concentration |
| Serum Concentration of Antibodies to Serelaxin | From pre-dose on Day 1 until Day 30 after the start of drug infusion | Frequency and percentage of anti-Serelaxin antibodies Blood samples were taken to measure antibodies to serelaxin concentration at Pre-dose on Day 1, and at Day 30 after the start of the 48h drug infusion |
| Systemic Clearance of Serelaxin | From pre-dose on Day 1 until 48h after the start of drug infusion | Systemic clearance was estimated using the rate of serelaxin infusion and the steady state concentration |
| Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion | Pulse wave velocity was assessed by the SphygmoCor device |
Countries
United Kingdom
Participant flow
Recruitment details
Out of the total 63 participants screened, 62 were randomized. 4 of the randomized participants did not receive study drug, and 58 did receive study drug
Pre-assignment details
Of the 58 participants in the safety analysis set, 56 completed the treatment and follow-up period as planned (i.e. Day 30 and Day 180).
Participants by arm
| Arm | Count |
|---|---|
| Serelaxin Serelaxin was administered at a dose of 30 μg/kg/24h by intravenous infusion for 48 hours | 30 |
| Placebo Placebo was administered by intravenous infusion for 48 hours | 28 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
Baseline characteristics
| Characteristic | Serelaxin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 6.42 | 60.1 Years STANDARD_DEVIATION 7.05 | 61.4 Years STANDARD_DEVIATION 6.79 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 27 Participants | 26 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 30 | 18 / 28 |
| serious Total, serious adverse events | 5 / 30 | 7 / 28 |
Outcome results
Primary
Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points
Global MPRI (Myocardial Perfusion Reserve Index) is defined as ratio between mean global myocardial blood flow values at rest and during adenosine stress with Mid Perfusion Reserve Index or Midl PRI (Mid Perfusion Reserve Index) which is defined as ratio between mid myocardial blood flow values at rest and during adenosine stress
Time frame: baseline to Day 3
Population: The Pharmacodynamic (PD) analysis set included all patients with available PD data who received any study drug and experienced no protocol deviations with relevant impact on PD data.~Participants who did not receive study drug as per study protocol, i.e. a reduced infusion rate, were excluded from this analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin | Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points | Global Myocardial Perfusion Reserve Index (MPRI) | -0.244 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points | Mid Perfusion Reserve Index | -0.264 ratio |
| Placebo | Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points | Global Myocardial Perfusion Reserve Index (MPRI) | -0.133 ratio |
| Placebo | Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points | Mid Perfusion Reserve Index | -0.075 ratio |
Comparison: SAP for Global Myocardial Perfusion Reserve Index (MPRI)p-value: 0.43895% CI: [-0.399, 0.176]ANCOVA
Secondary
Change From Baseline in Aortic Distensibility Measured by MRI
Measurements of arterial stiffness from cardiac MRI - Mean (SD) \[n\] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device. (mmHg-1)
Time frame: At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion
Population: PD Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin | Change From Baseline in Aortic Distensibility Measured by MRI | Ascending Aorta Distensibility, Day 0 | 0.0017 mmHg-1 | Standard Deviation 0.00158 |
| Serelaxin | Change From Baseline in Aortic Distensibility Measured by MRI | Ascending Aorta Distensibility, Day 47 | 0.0015 mmHg-1 | Standard Deviation 0.00124 |
| Serelaxin | Change From Baseline in Aortic Distensibility Measured by MRI | Descending Aorta Distensibility, Day 0 | 0.0023 mmHg-1 | Standard Deviation 0.00146 |
| Serelaxin | Change From Baseline in Aortic Distensibility Measured by MRI | Descending Aorta Distensibility, Day 47 | 0.0023 mmHg-1 | Standard Deviation 0.00118 |
| Placebo | Change From Baseline in Aortic Distensibility Measured by MRI | Descending Aorta Distensibility, Day 47 | 0.0023 mmHg-1 | Standard Deviation 0.00142 |
| Placebo | Change From Baseline in Aortic Distensibility Measured by MRI | Ascending Aorta Distensibility, Day 0 | 0.0014 mmHg-1 | Standard Deviation 0.00192 |
| Placebo | Change From Baseline in Aortic Distensibility Measured by MRI | Descending Aorta Distensibility, Day 0 | 0.0019 mmHg-1 | Standard Deviation 0.00221 |
| Placebo | Change From Baseline in Aortic Distensibility Measured by MRI | Ascending Aorta Distensibility, Day 47 | 0.0015 mmHg-1 | Standard Deviation 0.00134 |
Secondary
Change From Baseline in Aortic Velocity
Summary table for measurements of arterial velocity from cardiac MRI - Mean (SD) \[n\] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device
Time frame: At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion
Population: PD Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin | Change From Baseline in Aortic Velocity | Peak Flow Velocity (cm/s), Day 0 (n=24, 24) | 127.981 cm/s | Standard Deviation 60.7571 |
| Serelaxin | Change From Baseline in Aortic Velocity | Peak Flow Velocity (cm/s), Day 47 (n=23, 25) | 127.981 cm/s | Standard Deviation 60.7571 |
| Placebo | Change From Baseline in Aortic Velocity | Peak Flow Velocity (cm/s), Day 0 (n=24, 24) | 106.557 cm/s | Standard Deviation 38.9573 |
| Placebo | Change From Baseline in Aortic Velocity | Peak Flow Velocity (cm/s), Day 47 (n=23, 25) | 106.557 cm/s | Standard Deviation 38.9573 |
Secondary
Change From Baseline in Augmentation Index Measured From Sphygmocor Device
Summary of values and change from baseline in augmentation index by time and treatment The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance
Time frame: Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
Population: PD Analysis Set For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 1, 2h (n=23,25) | -4.12 ratio | Standard Deviation 11.441 |
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 1, 6h (n=24,26) | -2.99 ratio | Standard Deviation 9.066 |
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 2, 24h (n=24,25) | -0.82 ratio | Standard Deviation 8.173 |
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 3, 47h (n=23,25) | 3.51 ratio | Standard Deviation 10.608 |
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 3, 50h (n=22, 24) | -0.67 ratio | Standard Deviation 13.034 |
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 3, 54h (n=22,25) | -1.37 ratio | Standard Deviation 12.253 |
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 30 (n=25, 26) | -0.83 ratio | Standard Deviation 11.462 |
| Serelaxin | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 180 (n=24,25) end of study | 0.24 ratio | Standard Deviation 6.885 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 180 (n=24,25) end of study | 0.54 ratio | Standard Deviation 11.795 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 1, 2h (n=23,25) | -2.48 ratio | Standard Deviation 11.56 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 3, 50h (n=22, 24) | -3.81 ratio | Standard Deviation 9.397 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 1, 6h (n=24,26) | -0.58 ratio | Standard Deviation 9.551 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 30 (n=25, 26) | 0.58 ratio | Standard Deviation 12.124 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 2, 24h (n=24,25) | 0.22 ratio | Standard Deviation 9.906 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 3, 54h (n=22,25) | -0.48 ratio | Standard Deviation 11.748 |
| Placebo | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | DAY 3, 47h (n=23,25) | 0.22 ratio | Standard Deviation 12.057 |
Secondary
Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis
Pulse wave velocity was assessed by the SphygmoCor device
Time frame: Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
Population: The Pharmacodynamic (PD) analysis set included all patients with available PD data who received any study drug and experienced no protocol deviations with relevant impact on PD data. Any patients who had a reduced flow rate of infusion were excluded from this analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 1, 0hrs (n=25,26) | 7.453 meters/second | Standard Deviation 2.0541 |
| Serelaxin | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 2, 24hrs (n=19,24) | 7.051 meters/second | Standard Deviation 1.879 |
| Serelaxin | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 3, 47hrs (n=22,23) | 7.195 meters/second | Standard Deviation 1.9164 |
| Serelaxin | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 30, 0hrs (n=23, 24) | 7.989 meters/second | Standard Deviation 1.8151 |
| Serelaxin | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 3, 47hrs (n=23,25) | 29.57 meters/second | Standard Deviation 9.751 |
| Serelaxin | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 180 EOS (n=23,24) | 8.335 meters/second | Standard Deviation 2.1087 |
| Placebo | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 3, 47hrs (n=23,25) | 26.04 meters/second | Standard Deviation 10.039 |
| Placebo | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 1, 0hrs (n=25,26) | 8.166 meters/second | Standard Deviation 1.9515 |
| Placebo | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 30, 0hrs (n=23, 24) | 8.463 meters/second | Standard Deviation 2.4437 |
| Placebo | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 2, 24hrs (n=19,24) | 7.677 meters/second | Standard Deviation 2.1361 |
| Placebo | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 180 EOS (n=23,24) | 8.844 meters/second | Standard Deviation 2.1739 |
| Placebo | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | DAY 3, 47hrs (n=22,23) | 8.264 meters/second | Standard Deviation 2.4964 |
Secondary
Serum Concentration of Antibodies to Serelaxin
Frequency and percentage of anti-Serelaxin antibodies Blood samples were taken to measure antibodies to serelaxin concentration at Pre-dose on Day 1, and at Day 30 after the start of the 48h drug infusion
Time frame: From pre-dose on Day 1 until Day 30 after the start of drug infusion
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Serelaxin | Serum Concentration of Antibodies to Serelaxin | DAY 1 NEGATIVE | 100 percentage of participants |
| Serelaxin | Serum Concentration of Antibodies to Serelaxin | DAY 1 POSITIVE | 0 percentage of participants |
| Serelaxin | Serum Concentration of Antibodies to Serelaxin | DAY 30 NEGATIVE | 100 percentage of participants |
| Serelaxin | Serum Concentration of Antibodies to Serelaxin | DAY 30 POSITIVE | 0 percentage of participants |
| Placebo | Serum Concentration of Antibodies to Serelaxin | DAY 30 POSITIVE | 0 percentage of participants |
| Placebo | Serum Concentration of Antibodies to Serelaxin | DAY 1 NEGATIVE | 100 percentage of participants |
| Placebo | Serum Concentration of Antibodies to Serelaxin | DAY 30 NEGATIVE | 100 percentage of participants |
| Placebo | Serum Concentration of Antibodies to Serelaxin | DAY 1 POSITIVE | 0 percentage of participants |
Secondary
Serum Concentration of Serelaxin
Summary statistics of serelaxin serum PK concentrations Blood samples were taken to measure serelaxin concentration
Time frame: Day1, Day 2, Day 3 and Day 30 after the start of infusion
Population: Pharmacokinetic Analysis Set~The PK analysis set includes all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no protocol deviations with relevant impact on PK data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin | Serum Concentration of Serelaxin | DAY 1, 0hrs (n=30) | 0.637 pg/mL | Standard Deviation 3.49 |
| Serelaxin | Serum Concentration of Serelaxin | DAY 2, 24hrs, (n=26) | 27600 pg/mL | Standard Deviation 79000 |
| Serelaxin | Serum Concentration of Serelaxin | DAY 3, 48hrs (n=22) | 26300 pg/mL | Standard Deviation 48000 |
| Serelaxin | Serum Concentration of Serelaxin | DAY 3, 50 hrs (n=21) | 7940 pg/mL | Standard Deviation 8450 |
| Serelaxin | Serum Concentration of Serelaxin | DAY 3, 54hrs, (n=22) | 3960 pg/mL | Standard Deviation 3140 |
| Serelaxin | Serum Concentration of Serelaxin | DAY 30 (n=30) | 0.00 pg/mL | Standard Deviation 0 |
Secondary
Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance
The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included The augmentation index is a ratio calculated from the blood pressure waveform, it is a measure of wave reflection and arterial stiffness. Augmentation index is commonly accepted as a measure of the enhancement (augmentation) of central aortic pressure by a reflected pulse wave
Time frame: Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
Population: PD Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 1, 2h (n=23,25) | -4.088 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 1, 6h (n=24,26) | -3.277 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 2, 24h (n=24,25) | -0.774 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 3, 47h (n=23,25) | 3.488 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 3, 50h (n=22, 24) | -0.764 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 3, 54h (n=22,25) | -1.737 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 30 (n=25, 26) | -0.979 ratio |
| Serelaxin | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 180 (n=24,25) end of study | 0.234 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 180 (n=24,25) end of study | 0.284 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 1, 2h (n=23,25) | -1.970 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 3, 50h (n=22, 24) | -4.015 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 1, 6h (n=24,26) | -0.394 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 30 (n=25, 26) | 0.776 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 2, 24h (n=24,25) | 0.070 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 3, 54h (n=22,25) | -0.753 ratio |
| Placebo | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | DAY 3, 47h (n=23,25) | 0.035 ratio |
Secondary
Systemic Clearance of Serelaxin
Systemic clearance was estimated using the rate of serelaxin infusion and the steady state concentration
Time frame: From pre-dose on Day 1 until 48h after the start of drug infusion
Population: Pharmacokinetic Analysis Set~The PK analysis set includes all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no protocol deviations with relevant impact on PK data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Serelaxin | Systemic Clearance of Serelaxin | 107 mL/hr/kg | Standard Deviation 80.6 |