Trial Outcomes & Findings for Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure (NCT NCT02151383)
NCT ID: NCT02151383
Last Updated: 2019-06-25
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
through 28 days + 30 days SAE follow up after completion or discontinuation from the study
Results posted on
2019-06-25
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
3
|
1
|
|
Overall Study
Low-dose
|
2
|
3
|
1
|
|
Overall Study
High-dose
|
6
|
0
|
0
|
|
Overall Study
COMPLETED
|
8
|
3
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure
Baseline characteristics by cohort
| Measure |
Serelaxin: Cohort 1
n=8 Participants
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.
|
Serelaxin: Cohort 2
n=3 Participants
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.
|
Serelaxin: Cohort 3
n=1 Participants
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.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
11.1 Years
STANDARD_DEVIATION 3.23 • n=5 Participants
|
2.7 Years
STANDARD_DEVIATION 1.53 • n=7 Participants
|
0.7 Years
STANDARD_DEVIATION NA • n=5 Participants
|
8.1 Years
STANDARD_DEVIATION 5.17 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: through 28 days + 30 days SAE follow up after completion or discontinuation from the studyPopulation: All appropriately consented enrolled subjects who were exposed to study drug regardless of the exposure and have at least one post-baseline safety assessment.
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.
Outcome measures
| Measure |
Serelaxin: Cohort 3
n=1 Participants
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.
|
Serelaxin: Cohort 1
n=8 Participants
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.
|
Serelaxin: Cohort 2
n=3 Participants
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.
|
|---|---|---|---|
|
Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death
Serious Adverse Event
|
0 Patients
|
3 Patients
|
1 Patients
|
|
Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death
at least one Adverse Event
|
0 Patients
|
6 Patients
|
3 Patients
|
|
Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death
Death
|
0 Patients
|
0 Patients
|
0 Patients
|
PRIMARY outcome
Timeframe: 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 28Population: participants with available data differed across time points
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.
Outcome measures
| Measure |
Serelaxin: Cohort 3
n=1 Participants
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.
|
Serelaxin: Cohort 1
n=2 Participants
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.
|
Serelaxin: Cohort 2
n=2 Participants
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.
|
|---|---|---|---|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 3 hour 52 post infusion
|
2.440 ng/mL
|
1.751 ng/mL
Geometric Coefficient of Variation 26.134
|
0.956 ng/mL
Geometric Coefficient of Variation 12.016
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 1 hour 0 during infusion
|
NA ng/mL
Geometric Coefficient of Variation NA
All outcome value(s) = 0. Therefore, Geometric mean and CV% geo-mean are not populated.
|
0.083 ng/mL
Geometric Coefficient of Variation NA
CV% geo-mean is derived as a function of log-transformed data. At least one patient had an outcome value = 0, causing the logarithm of the outcome value and thus CV% geo-mean undefined (note: logarithm of data can only be defined for a value \> 0)
|
NA ng/mL
Geometric Coefficient of Variation NA
All outcome value(s) = 0. Therefore, Geometric mean and CV% geo-mean are not populated.
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 1 hour 2 during infusion
|
1.250 ng/mL
|
0.514 ng/mL
Geometric Coefficient of Variation 23.600
|
0.375 ng/mL
Geometric Coefficient of Variation 176.043
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 1 hour 16 during infusion
|
0.571 ng/mL
|
0.795 ng/mL
Geometric Coefficient of Variation 66.578
|
0.772 ng/mL
Geometric Coefficient of Variation 41.016
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 1 hour 22 during infusion
|
3.810 ng/mL
|
2.868 ng/mL
Geometric Coefficient of Variation 23.134
|
2.183 ng/mL
Geometric Coefficient of Variation 11.690
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 2 hour 32 during infusion
|
NA ng/mL
Geometric Coefficient of Variation NA
All outcome value(s) = 0. Therefore, Geometric mean and CV% geo-mean are not populated
|
3.208 ng/mL
Geometric Coefficient of Variation 32.740
|
2.155 ng/mL
Geometric Coefficient of Variation 13.492
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 2 hour 40 during infusion
|
0.236 ng/mL
|
7.891 ng/mL
Geometric Coefficient of Variation 49.702
|
5.513 ng/mL
Geometric Coefficient of Variation 17.664
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 2 hour 48 during infusion
|
9.010 ng/mL
|
6.315 ng/mL
Geometric Coefficient of Variation 60.265
|
5.365 ng/mL
Geometric Coefficient of Variation 16.148
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 3 hour 48.5 post infusion
|
66.600 ng/mL
|
5.107 ng/mL
Geometric Coefficient of Variation 39.153
|
3.999 ng/mL
Geometric Coefficient of Variation 22.826
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day 3 hour 56 post infusion
|
0.470 ng/mL
|
0.420 ng/mL
Geometric Coefficient of Variation 42.285
|
0.416 ng/mL
Geometric Coefficient of Variation 59.458
|
|
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Day28 hour 648 n=2,1,0 post infusion
|
—
|
NA ng/mL
Geometric Coefficient of Variation NA
All outcome value(s) = 0. Therefore, Geometric mean and CV% geo-mean are not populated
|
NA ng/mL
All outcome value(s) = 0. Therefore, Geometric mean and CV% geo-mean are not populated
|
PRIMARY outcome
Timeframe: 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 28Population: No data available for Cohort 2 and 3
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.
Outcome measures
| Measure |
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.
|
Serelaxin: Cohort 1
n=6 Participants
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.
|
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.
|
|---|---|---|---|
|
Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day)
Day 1 hour 0 during infusion
|
—
|
NA ng/mL
Geometric Coefficient of Variation NA
At least one outcome value = 0. Geometric mean is calculated based on the logarithm of the outcome values, and is not populated if any outcome value = 0. CV is not available due to insufficient number of patients with measurement
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 45.060
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day)
Day 14 hour 312 post infusion
|
—
|
NA ng/mL
Geometric Coefficient of Variation NA
At least one outcome value = 0. Geometric mean is calculated based on the logarithm of the outcome values, and is not populated if any outcome value=0.Geometric CV cannot be calculated due to insufficient number of participants with events
|
—
|
|
Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day)
Day 28 hour 648 post infusion
|
—
|
NA ng/mL
Geometric Coefficient of Variation NA
At least one outcome value = 0. Geometric mean is calculated based on the logarithm of the outcome values, and is not populated if any outcome value = 0. Geometric CV cannot be calculated due to insufficient number of participants with events
|
—
|
SECONDARY outcome
Timeframe: baseline, prior to each dose escalation, and at 24 hr. post end of infusionPopulation: No data available
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, prior to each dose escalation, and at 24 hr. post end of infusionPopulation: No data available
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
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.
|
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.
|
Serelaxin: Cohort 2
n=1 Participants
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.
|
|---|---|---|---|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
SECONDARY outcome
Timeframe: Day 1: hour 0 and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: no data available for any time points
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
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
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.
|
Serelaxin: Cohort 1
n=1 Participants
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.
|
Serelaxin: Cohort 2
n=1 Participants
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.
|
|---|---|---|---|
|
Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)
Baseline
|
—
|
9.0 mmHg
|
14.0 mmHg
|
|
Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)
Day 1 hour 16
|
—
|
-1.0 mmHg
|
2.0 mmHg
|
|
Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)
Day 2 hour 32
|
—
|
2.0 mmHg
|
—
|
|
Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)
Day 2 hour 48
|
—
|
2.0 mmHg
|
—
|
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
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.
|
Serelaxin: Cohort 1
n=1 Participants
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.
|
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.
|
|---|---|---|---|
|
Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day)
Day 2 hour 32
|
—
|
3.0 mmHg
|
—
|
|
Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day)
Baseline
|
—
|
4.0 mmHg
|
—
|
|
Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day)
Day 1 hour 16
|
—
|
2.0 mmHg
|
—
|
|
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 outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionThis 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
Outcome measures
| Measure |
Serelaxin: Cohort 3
n=1 Participants
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.
|
Serelaxin: Cohort 1
n=2 Participants
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.
|
Serelaxin: Cohort 2
n=3 Participants
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.
|
|---|---|---|---|
|
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
|
99.5 percentage of oxygen saturation
Standard Deviation 0.71
|
94.0 percentage of oxygen saturation
Standard Deviation 6.56
|
|
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
|
-4.5 percentage of oxygen saturation
Standard Deviation 0.71
|
-2.0 percentage of oxygen saturation
Standard Deviation 3.00
|
|
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
|
-4.5 percentage of oxygen saturation
Standard Deviation 2.12
|
1.3 percentage of oxygen saturation
Standard Deviation 1.53
|
|
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
|
-3.0 percentage of oxygen saturation
Standard Deviation 1.41
|
-0.3 percentage of oxygen saturation
Standard Deviation 1.53
|
|
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
|
-5.0 percentage of oxygen saturation
Standard Deviation 4.24
|
1.7 percentage of oxygen saturation
Standard Deviation 1.53
|
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
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.
|
Serelaxin: Cohort 1
n=6 Participants
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.
|
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.
|
|---|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
Serelaxin: Cohort 3
n=1 Participants
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.
|
Serelaxin: Cohort 1
n=2 Participants
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.
|
Serelaxin: Cohort 2
n=3 Participants
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.
|
|---|---|---|---|
|
Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day)
Baseline
|
1.0 mL/kg/hour
|
2.0 mL/kg/hour
|
1.3 mL/kg/hour
Standard Deviation 1.53
|
|
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
|
—
|
1.5 mL/kg/hour
Standard Deviation 2.12
|
|
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
|
-1.0 mL/kg/hour
|
0.7 mL/kg/hour
Standard Deviation 1.15
|
|
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
|
—
|
3.7 mL/kg/hour
Standard Deviation 4.73
|
|
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
|
—
|
0.0 mL/kg/hour
Standard Deviation 2.00
|
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
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.
|
Serelaxin: Cohort 1
n=6 Participants
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.
|
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.
|
|---|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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 5.10
|
—
|
|
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 2.70
|
—
|
|
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 outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
Serelaxin: Cohort 3
n=1 Participants
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.
|
Serelaxin: Cohort 1
n=2 Participants
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.
|
Serelaxin: Cohort 2
n=3 Participants
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.
|
|---|---|---|---|
|
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
|
2.560 mmol/L
Standard Deviation 1.0748
|
|
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
|
-0.500 mmol/L
|
|
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
|
-1.100 mmol/L
|
|
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
|
-0.900 mmol/L
|
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
Serelaxin: Cohort 3
n=1 Participants
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.
|
Serelaxin: Cohort 1
n=2 Participants
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.
|
Serelaxin: Cohort 2
n=3 Participants
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.
|
|---|---|---|---|
|
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
Standard Deviation NA
Standard deviation cannot be calculated due to insufficient number of patients with measurement
|
—
|
|
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
|
0 mmol/L
|
|
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
|
2.000 mmol/L
|
|
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
|
0 mmol/L
|
|
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
|
—
|
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
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.
|
Serelaxin: Cohort 1
n=1 Participants
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.
|
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.
|
|---|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusionPopulation: participants with available data differed across time points
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
Outcome measures
| Measure |
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.
|
Serelaxin: Cohort 1
n=2 Participants
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.
|
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.
|
|---|---|---|---|
|
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
|
—
|
|
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
Standard Deviation NA
Standard deviation cannot be calculated due to insufficient number of patients with measurement
|
—
|
|
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
Standard Deviation NA
Not available due to insufficient number of patients with measurement
|
—
|
Adverse Events
Serelaxin: Cohort 1
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serelaxin: Cohort 2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serelaxin: Cohort 3
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Serelaxin: Cohort 1
n=8 participants at risk
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.
|
Serelaxin: Cohort 2
n=3 participants at risk
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.
|
Serelaxin: Cohort 3
n=1 participants at risk
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.
|
|---|---|---|---|
|
Cardiac disorders
Atrial thrombosis
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
25.0%
2/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Vascular disorders
Hypotension
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Vascular disorders
Vena cava thrombosis
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
Other adverse events
| Measure |
Serelaxin: Cohort 1
n=8 participants at risk
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.
|
Serelaxin: Cohort 2
n=3 participants at risk
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.
|
Serelaxin: Cohort 3
n=1 participants at risk
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.
|
|---|---|---|---|
|
Cardiac disorders
Supraventricular extrasystoles
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Cardiac disorders
Tachycardia
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Cardiac disorders
Ventricular tachycardia
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
General disorders
Non-cardiac chest pain
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Infections and infestations
Pneumonia viral
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Injury, poisoning and procedural complications
Procedural pain
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Investigations
Blood pressure systolic decreased
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Investigations
Cardioactive drug level increased
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Metabolism and nutrition disorders
Hypochloraemia
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Nervous system disorders
Headache
|
25.0%
2/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Psychiatric disorders
Insomnia
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
33.3%
1/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Skin and subcutaneous tissue disorders
Skin oedema
|
12.5%
1/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
|
Vascular disorders
Hypotension
|
25.0%
2/8 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/3 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
0.00%
0/1 • Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow-up (i.e. approximately 28 days) for the participants per protocol
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER