Acute Heart Failure
Conditions
Keywords
Acute heart failure, RELAX-AHF-PEDIATRIC PK, AHF
Brief summary
The purpose of the study was to evaluate the safety, tolerability and pharmacokinetics of an intravenous infusion of serelaxin on top of standard of care therapy, in pediatric patients with acute heart failure (AHF)
Detailed description
The study was terminated early and the pediatric development of serelaxin in the treatment of acute heart failure (AHF) discontinued, following the results of the phase III study RELAX-AHF-2 (CRLX030A2301/NCT01870778) study in adult patients with AHF. Whilst no new safety concerns associated with serelaxin were observed, the study in adults did not meet either of its primary endpoints
Interventions
DRUGSerelaxin
Serelaxin was administered intravenously for up to 48 hours.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria: * Body weight ≥2.5 kg to ≤120 kg * Hospitalized in an intensive care unit or step-down unit with the following: * \- Signs and symptoms of acute heart failure of any etiology * \- Stable dose of vasoactive and/or inotropic drugs * \- For non-surgical patients echocardiographic evidence of reduced ventricular function (ejection fraction \<50% or fractional shortening \<28%) * Systolic blood pressure (SBP) ≥25th percentile SBP for age and gender. Key
Exclusion criteria
* Moderate to severe left ventricular outflow tract, mitral stenosis, or aortic arch obstruction * Single ventricle physiology * Fixed pulmonary hypertension * Blood lactate levels \>5 mmol/L at screening * Birth \< 36 weeks post-conceptual age (for patients \<1year old) * Confirmed or clinically suspected systemic infection or severe localized infection * Dyspnea or acute lung injury primarily due to non-cardiac causes * Patients with severe renal impairment, those known to have significant renal disease and those having renal replacement therapy * High use of inotropic and/or vasoactive agents at screening * Electrocardiographic abnormalities * Solid organ transplant recipient within 1 year of transplantation or one who presents with severe organ rejection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | through 28 days + 30 days SAE follow up after completion or discontinuation from the study | Number of patients with treatment emergent adverse events (including confirmed systolic blood pressure decreases and worsening heart failure), serious adverse events and death were reported. |
| Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28 | Pharmacokinetic (PK) concentration was presented as the surrogate for PK parameters, the original primary endpoint, due to the unavailability of the PK parameters Css and CL. Serelaxin concentration was determined in serum by a validated Enzyme Linked ImmunoSorbent Assay (ELISA) based upon the commercially available kit from R&D Systems (Catalogue No. DRL200). The ELISA method used a monoclonal antibody specific for human H2 relaxin as the capture reagent and an enzyme-linked polyclonal antibody specific for human. |
| Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28 | Pharmacokinetic (PK) concentration was presented as the surrogate for PK parameters, the original primary endpoint, due to the unavailability of the PK parameters Css and CL. Serelaxin concentration was determined in serum by a validated Enzyme Linked ImmunoSorbent Assay (ELISA) based upon the commercially available kit from R&D Systems (Catalogue No. DRL200). The ELISA method used a monoclonal antibody specific for human H2 relaxin as the capture reagent and an enzyme-linked polyclonal antibody specific for human. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for High Dose (10-30-100 ug/kg/Day) | Day 1: hour 0 and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | This analysis includes central venous and arterial oxygen saturation measurement, yielding a calculation of the arterio-venous oxygen extraction, where available at each time point. If no arterial access was available, then arterial oxygen saturation measurement data were obtained using a pulse oximeter. The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | This analysis includes central venous and arterial oxygen saturation measurement, yielding a calculation of the arterio-venous oxygen extraction, where available at each time point. If no arterial access was available, then arterial oxygen saturation measurement data were obtained using a pulse oximeter. The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Change From Baseline in Mean Left Arterial Pressure for Low Dose (3-10-30 ug/kg/Day) | baseline, prior to each dose escalation, and at 24 hr. post end of infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. |
| Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
| Change From Baseline in Mean Left Arterial Pressure for High Dose (10 -30-100 ug/kg/Day) | baseline, prior to each dose escalation, and at 24 hr. post end of infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. |
| Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day3: 24 hours post infusion | The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points |
Countries
Germany, Switzerland, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 18 patients were assigned to study treatment. 6 patients were identified with GCP violations; hence, only 12 patients were included in disposition.
Participants by arm
| Arm | Count |
|---|---|
| Serelaxin: Cohort 1 Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours. In Cohort 1, patients in age group of 6 to \<18 years were enrolled either into a low-dose or a high-dose group. During this 48-hour treatment period, the serelaxin dose rates to be administered were 3 μg/kg/day, 10 μg/kg/day and 30 μg/kg/day in the low -dose group; 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day in the high-dose group. Both the low-dose and high- dose groups were planned to receive equal number of patients. | 8 |
| Serelaxin: Cohort 2 Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours. In Cohort 2, patients in age group of 1 to \<6 years were enrolled either into a low-dose or a high-dose group. During this 48-hour treatment period, the serelaxin dose rates to be administered were 3 μg/kg/day, 10 μg/kg/day and 30 μg/kg/day in the low -dose group; 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day in the high-dose group. Both the low-dose and high- dose groups were planned to receive equal number of patients. | 3 |
| Serelaxin: Cohort 3 Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours. In Cohort 3, patients in age group of 1 month to \<1 year were enrolled either into a low-dose or a high-dose group. During this 48-hour treatment period, the serelaxin dose rates to be administered were 3 μg/kg/day, 10 μg/kg/day and 30 μg/kg/day in the low -dose group; 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day in the high-dose group. In this cohort, high- dose group was planned to receive twice the number of patients in low-dose group. | 1 |
| Total | 12 |
Baseline characteristics
| Characteristic | Serelaxin: Cohort 1 | Serelaxin: Cohort 2 | Serelaxin: Cohort 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 11.1 Years STANDARD_DEVIATION 3.23 | 2.7 Years STANDARD_DEVIATION 1.53 | 0.7 Years | 8.1 Years STANDARD_DEVIATION 5.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 1 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 6 / 8 | 3 / 3 | 0 / 1 |
| serious Total, serious adverse events | 3 / 8 | 1 / 3 | 0 / 1 |
Outcome results
Primary
Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death
Number of patients with treatment emergent adverse events (including confirmed systolic blood pressure decreases and worsening heart failure), serious adverse events and death were reported.
Time frame: through 28 days + 30 days SAE follow up after completion or discontinuation from the study
Population: All appropriately consented enrolled subjects who were exposed to study drug regardless of the exposure and have at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Serelaxin: Cohort 1 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | at least one Adverse Event | 6 Patients |
| Serelaxin: Cohort 1 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | Serious Adverse Event | 3 Patients |
| Serelaxin: Cohort 1 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
| Serelaxin: Cohort 2 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | Serious Adverse Event | 1 Patients |
| Serelaxin: Cohort 2 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | at least one Adverse Event | 3 Patients |
| Serelaxin: Cohort 2 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
| Serelaxin: Cohort 3 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | Serious Adverse Event | 0 Patients |
| Serelaxin: Cohort 3 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | Death | 0 Patients |
| Serelaxin: Cohort 3 | Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death | at least one Adverse Event | 0 Patients |
Primary
Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day)
Pharmacokinetic (PK) concentration was presented as the surrogate for PK parameters, the original primary endpoint, due to the unavailability of the PK parameters Css and CL. Serelaxin concentration was determined in serum by a validated Enzyme Linked ImmunoSorbent Assay (ELISA) based upon the commercially available kit from R&D Systems (Catalogue No. DRL200). The ELISA method used a monoclonal antibody specific for human H2 relaxin as the capture reagent and an enzyme-linked polyclonal antibody specific for human.
Time frame: at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28
Population: No data available for Cohort 2 and 3
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 1 hour 0 during infusion | NA ng/mL | — |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 3 hour 56 post infusion | 2.576 ng/mL | Geometric Coefficient of Variation 78.318 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 14 hour 312 post infusion | NA ng/mL | — |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 1 hour 2 during infusion | 2.388 ng/mL | Geometric Coefficient of Variation 47.476 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 1 hour 16 during infusion | 4.004 ng/mL | Geometric Coefficient of Variation 29.713 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 1 hour 22 during infusion | 9.774 ng/mL | Geometric Coefficient of Variation 44.219 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 32 during infusion | 10.472 ng/mL | Geometric Coefficient of Variation 45.06 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 40 during infusion | 35.515 ng/mL | Geometric Coefficient of Variation 36.868 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 48 during infusion | 39.777 ng/mL | Geometric Coefficient of Variation 39.452 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 3 hour 48.5 post infusion | 27.818 ng/mL | Geometric Coefficient of Variation 25.738 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 3 hour 52 post infusion | 7.014 ng/mL | Geometric Coefficient of Variation 64.862 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day) | Day 28 hour 648 post infusion | NA ng/mL | — |
Primary
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Pharmacokinetic (PK) concentration was presented as the surrogate for PK parameters, the original primary endpoint, due to the unavailability of the PK parameters Css and CL. Serelaxin concentration was determined in serum by a validated Enzyme Linked ImmunoSorbent Assay (ELISA) based upon the commercially available kit from R&D Systems (Catalogue No. DRL200). The ELISA method used a monoclonal antibody specific for human H2 relaxin as the capture reagent and an enzyme-linked polyclonal antibody specific for human.
Time frame: at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 40 during infusion | 7.891 ng/mL | Geometric Coefficient of Variation 49.702 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 48 during infusion | 6.315 ng/mL | Geometric Coefficient of Variation 60.265 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 22 during infusion | 2.868 ng/mL | Geometric Coefficient of Variation 23.134 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 52 post infusion | 1.751 ng/mL | Geometric Coefficient of Variation 26.134 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 2 during infusion | 0.514 ng/mL | Geometric Coefficient of Variation 23.6 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 56 post infusion | 0.420 ng/mL | Geometric Coefficient of Variation 42.285 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 32 during infusion | 3.208 ng/mL | Geometric Coefficient of Variation 32.74 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 16 during infusion | 0.795 ng/mL | Geometric Coefficient of Variation 66.578 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 48.5 post infusion | 5.107 ng/mL | Geometric Coefficient of Variation 39.153 |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day28 hour 648 n=2,1,0 post infusion | NA ng/mL | — |
| Serelaxin: Cohort 1 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 0 during infusion | 0.083 ng/mL | — |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 40 during infusion | 5.513 ng/mL | Geometric Coefficient of Variation 17.664 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 16 during infusion | 0.772 ng/mL | Geometric Coefficient of Variation 41.016 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 48 during infusion | 5.365 ng/mL | Geometric Coefficient of Variation 16.148 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 2 during infusion | 0.375 ng/mL | Geometric Coefficient of Variation 176.043 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 0 during infusion | NA ng/mL | — |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 52 post infusion | 0.956 ng/mL | Geometric Coefficient of Variation 12.016 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 48.5 post infusion | 3.999 ng/mL | Geometric Coefficient of Variation 22.826 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 22 during infusion | 2.183 ng/mL | Geometric Coefficient of Variation 11.69 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 56 post infusion | 0.416 ng/mL | Geometric Coefficient of Variation 59.458 |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day28 hour 648 n=2,1,0 post infusion | NA ng/mL | — |
| Serelaxin: Cohort 2 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 32 during infusion | 2.155 ng/mL | Geometric Coefficient of Variation 13.492 |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 56 post infusion | 0.470 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 2 during infusion | 1.250 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 16 during infusion | 0.571 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 22 during infusion | 3.810 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 32 during infusion | NA ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 40 during infusion | 0.236 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 2 hour 48 during infusion | 9.010 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 48.5 post infusion | 66.600 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 3 hour 52 post infusion | 2.440 ng/mL | — |
| Serelaxin: Cohort 3 | Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day | Day 1 hour 0 during infusion | NA ng/mL | — |
Secondary
Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day) | Day 1 our 16 | -0.100 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 32 | 0.200 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 48 | -0.300 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day) | Baseline | 1.300 mmol/L |
Secondary
Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | -3.200 mmol/L | — |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | -3.100 mmol/L | — |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | -3.100 mmol/L | — |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Baseline | 3.900 mmol/L | — |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | -1.100 mmol/L | — |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | -0.900 mmol/L | — |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Baseline | 2.560 mmol/L | Standard Deviation 1.0748 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | -0.500 mmol/L | — |
Secondary
Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day) | Baseline | 1.200 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day) | Day 1 our 16 | -0.600 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 48 | -0.200 mmol/L |
Secondary
Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 3 24 hours post infusion | -0.222 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | -0.222 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | 0.111 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Baseline | 1.110 mmol/L |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | 0.333 mmol/L |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Baseline | 2.000 mmol/L |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | 0 mmol/L |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | 0 mmol/L |
Secondary
Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day)
This analysis includes central venous and arterial oxygen saturation measurement, yielding a calculation of the arterio-venous oxygen extraction, where available at each time point. If no arterial access was available, then arterial oxygen saturation measurement data were obtained using a pulse oximeter. The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day) | Baseline | 97.2 percentage of oxygen saturation | Standard Deviation 2.56 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day) | Day 1 our 16 | -0.2 percentage of oxygen saturation | Standard Deviation 3.87 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 32 | -0.2 percentage of oxygen saturation | Standard Deviation 2.32 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 48 | -0.2 percentage of oxygen saturation | Standard Deviation 2.14 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day) | Day 3 24 hours post infusion | -0.2 percentage of oxygen saturation | Standard Deviation 1.92 |
Secondary
Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day)
This analysis includes central venous and arterial oxygen saturation measurement, yielding a calculation of the arterio-venous oxygen extraction, where available at each time point. If no arterial access was available, then arterial oxygen saturation measurement data were obtained using a pulse oximeter. The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 3 - 24 hours post infusion | -5.0 percentage of oxygen saturation | Standard Deviation 4.24 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | -4.5 percentage of oxygen saturation | Standard Deviation 2.12 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Baseline | 99.5 percentage of oxygen saturation | Standard Deviation 0.71 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | -4.5 percentage of oxygen saturation | Standard Deviation 0.71 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | -3.0 percentage of oxygen saturation | Standard Deviation 1.41 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | -2.0 percentage of oxygen saturation | Standard Deviation 3 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 3 - 24 hours post infusion | 1.7 percentage of oxygen saturation | Standard Deviation 1.53 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | -0.3 percentage of oxygen saturation | Standard Deviation 1.53 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | 1.3 percentage of oxygen saturation | Standard Deviation 1.53 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Baseline | 94.0 percentage of oxygen saturation | Standard Deviation 6.56 |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 3 - 24 hours post infusion | -3.0 percentage of oxygen saturation | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Baseline | 100.0 percentage of oxygen saturation | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | -3.0 percentage of oxygen saturation | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | -2.0 percentage of oxygen saturation | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | 0.0 percentage of oxygen saturation | — |
Secondary
Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day) | Baseline | 2.2 mL/kg/hour | Standard Deviation 2.48 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day) | Day 1 our 16 | -0.8 mL/kg/hour | Standard Deviation 2.59 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 32 | 0.0 mL/kg/hour | Standard Deviation 5.1 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 48 | -0.4 mL/kg/hour | Standard Deviation 2.7 |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day) | Day 3 24 hours post infusion | -2.0 mL/kg/hour | Standard Deviation 2.71 |
Secondary
Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Baseline | 2.0 mL/kg/hour | — |
| Serelaxin: Cohort 1 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | -1.0 mL/kg/hour | — |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 3 24 hours post infusion | 1.5 mL/kg/hour | Standard Deviation 2.12 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Baseline | 1.3 mL/kg/hour | Standard Deviation 1.53 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | 0.7 mL/kg/hour | Standard Deviation 1.15 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | 3.7 mL/kg/hour | Standard Deviation 4.73 |
| Serelaxin: Cohort 2 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | 0.0 mL/kg/hour | Standard Deviation 2 |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 1 our 16 | 0.0 mL/kg/hour | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | 0.0 mL/kg/hour | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Baseline | 1.0 mL/kg/hour | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 3 24 hours post infusion | 0.0 mL/kg/hour | — |
| Serelaxin: Cohort 3 | Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | -1.0 mL/kg/hour | — |
Secondary
Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day) | Baseline | 4.0 mmHg |
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day) | Day 1 hour 16 | 2.0 mmHg |
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 32 | 3.0 mmHg |
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day) | Day 2 hour 48 | 1.0 mmHg |
Secondary
Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day) | Baseline | 9.0 mmHg |
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day) | Day 1 hour 16 | -1.0 mmHg |
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 | 2.0 mmHg |
| Serelaxin: Cohort 1 | Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 | 2.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day) | Baseline | 14.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day) | Day 1 hour 16 | 2.0 mmHg |
Secondary
Change From Baseline in Mean Left Arterial Pressure for High Dose (10 -30-100 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study.
Time frame: baseline, prior to each dose escalation, and at 24 hr. post end of infusion
Population: No data available
Secondary
Change From Baseline in Mean Left Arterial Pressure for Low Dose (3-10-30 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study.
Time frame: baseline, prior to each dose escalation, and at 24 hr. post end of infusion
Population: No data available
Secondary
Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for High Dose (10-30-100 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Population: no data available for any time points
Secondary
Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day)
The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points
Time frame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day3: 24 hours post infusion
Population: participants with available data differed across time points
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 diastolic | 11.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 48 systolic | 6.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Baseline diastolic | 14.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Baseline systolic | 20.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Day 1 hour 16 diastolic | -2.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Day 1 hour 16 systolic | 3.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 diastolic | 0.0 mmHg |
| Serelaxin: Cohort 2 | Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day) | Day 2 hour 32 systolic | -2.0 mmHg |