Septic Shock
Conditions
Keywords
V1a agonist
Brief summary
The purpose of this trial was to examine the safety and tolerability, pharmacokinetics of FE 202158 and to assess whether it can stabilize blood pressure and reduce vascular (blood vessel) leakage. FE 202158 had previously been tested in healthy volunteers.
Detailed description
This was a multi-centre, double-blind, randomized, placebo-controlled, parallel group trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of FE 202158 (using three ascending doses) in patients with vasodilatory hypotension in early septic shock, when given as continuous infusion for up to 7 days. The trial comprised of three treatment arms where FE 202158 was administered in 1.25 ng, 2.5 ng and 3.75 ng dose, respectively. A placebo arm was also included in the trial where patients received isotonic saline. Efficacy of FE 202158 was determined by evaluating its ability to maintain mean arterial pressure (MAP) \>60 mmHg and its modulating effect on inflammatory markers. Effects of FE 202158 on other variables like vital signs, morbidity, mortality and pulmonary function were also determined.
Interventions
DRUGFE 202158 1.25
FE 202158 at dose 1.25 ng/kg/min infused.
DRUGFE 202158 2.5
FE 202158 at dose 2.5 ng/kg/min infused.
DRUGFE 202158 3.75
FE 202158 at dose 3.75 ng/kg/min infused.
OTHERPlacebo
Isotonic saline infused.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form by the patient or a legal representative according to local regulations * Man or woman 18 years of age or older * Proven or suspected infection * Low blood pressure * Signs of decreased circulation in the tissues * Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from the day of informed consent to one week after the end of infusion of study medication.
Exclusion criteria
* Present or a history (within the last 5 years) of acute coronary syndrome (myocardial infarction or unstable angina). Patients who have been asymptomatic for 6 months after coronary revascularisation are eligible. * Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test. * Known or suspected cardiac failure * Pregnancy or breastfeeding * Any cause of hypotension other than early septic shock * Use of vasopressin or terlipressin for blood pressure support during the current hospital admission * Proven or suspected acute mesenteric ischemia, as judged by the investigator * Known episode of septic shock within 1 month prior to randomisation * Underlying chronic heart disease * Traumatic brain injury * Present hospitalisation with burn injury * Symptomatic peripheral vascular disease including Raynaud's syndrome * Previously randomized in this trial * Intake of an investigational drug within the last 3 months (or longer if judged by the Investigator to possibly influence the outcome of the current study) * Known participation in another clinical trial * Considered by the investigator to be unsuitable to participate in the trial for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 1 up to Day 7 | Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 1 up to Day 7 | Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Cumulative Dose of Open Label NE. | Day 1 up to Day 7 | Cumulative Dose of Open Label NE over 7 days. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Infusion Rates of Open Label NE. | Day 1 up to Day 7 | Mean open label NE infusion rate within each predefined time period. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter in Patients : Initial Elimination Half-life | Day 1 up to Day 7 | PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| PK Parameter in Patients : Terminal Elimination Half-life | Day 1 up to Day 7 | PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in C-reactive Protein (CRP) | Day 1 up to Day 7 | The change from Baseline in CRP levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | At Day 1, Day 2, Day 4, and Day 7 | The change from Baseline in TNF-alpha levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in Interleukin-6 (IL-6) | At Day 1, Day 2, Day 4, and Day 7 | The change from Baseline in IL-6 levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in Interleukin-10 (IL-10) | At Day 1, Day 2, Day 4, and Day 7 | The change from Baseline in IL-10 levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | At Day 1, Day 2, Day 4, and Day 7 | The change from Baseline in IL-1R levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in Heart Rate | Day 1 up to Day 7 | The change from Baseline in heart rate was analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in Fluid Balance | Day 1 up to Day 7 | The change from Baseline in fluid balance were analysed and presented as per the planned time points. The fluid balance was adjusted for length of time interval and weight. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration | Day 1 up to Day 7 | PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 up to Day 7 | Change from Baseline in PaO2/FiO2 was observed at each time-point. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 up to Day 7 | Change from Baseline in tidal volume was observed at each time-point. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 up to Day 7 | Change from Baseline in arterial blood gas (lactate) was observed at each time-point. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Days Alive and Free of Any Organ Dysfunction at Day 7 | At Day 7 | Percentage of days alive and free of any organ dysfunction (i.e. no. of days divided by 7). The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Percentage of Patients Alive and Free of All Vasopressors | At Day 7, Day 14 and Day 28 | Percentage of patients alive and free of all vasopressors was assessed on Days 7, 14, and 28. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Percentage of Days Alive and Free of Dialysis | At Day 7, Day 14 and Day 28 | Percentage of days alive and free of dialysis was assessed on Days 7, 14, and 28. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Percentage of Days Alive and Free of Ventilation | At Day 7 | Percentage of days alive and free of ventilation was assessed on Days 7, 14, and 28. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Mortality | At Day 1, 7, 14, and 28 | Mortality was assessed as percentage of patients dead at pre-specified time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| Incidence of Abnormal Changes in ECG | Day 1 up to Day 7 | The number of patients having abnormal changes in ECG variables during the trial period was presented. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| SOFA Score | Day 1 up to Day 7, Day 14 and Day 29 | The SOFA score, is used to track a patient's status during the stay in an intensive care unit. This scoring system is used to determine the extent of a person's organ function or rate of failure. The scoring system comprise of scores for six different system: Respiratory System; Nervous System; Cardiovascular System; Liver; Coagulation; and Renal System. Score for each system ranges from 0-4 (0=normal, 4=worst). Total SOFA score is a sum of the individual system score and range from 0 to 24, 0 being the better and 24 being the worst patient status. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| PK Parameter in Patients : Time to Steady State | Day 1 up to Day 7 | PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| PK Parameter in Patients : Clearance | Day 1 up to Day 7 | PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
| PK Parameter in Patients : Steady State Volume of Distribution | Day 1 up to Day 7 | PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome. |
Countries
Belgium, Canada, Denmark, United States
Participant flow
Recruitment details
Total 55 patients were screened and 53 were randomized. One patient randomized to placebo died before dosing, and one patient randomized to 2.5 ng/kg/min was erroneously dosed with placebo.
Participants by arm
| Arm | Count |
|---|---|
| FE 202158 1.25 Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min.
FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use. | 10 |
| FE 202158 2.5 Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min.
FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use. | 19 |
| FE 202158 3.75 Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 3.75 ng/kg/min.
FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use. | 2 |
| PLCBO Patients in the arm received an intravenous infusion for up to 7 days of placebo. | 21 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 | 2 | 4 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | FE 202158 1.25 | Total | PLCBO | FE 202158 3.75 | FE 202158 2.5 |
|---|---|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 19.6 | 60.4 years STANDARD_DEVIATION 17.1 | 63.2 years STANDARD_DEVIATION 18 | 69 years STANDARD_DEVIATION 12.7 | 57.1 years STANDARD_DEVIATION 15.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 51 Participants | 20 Participants | 2 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 50 Participants | 20 Participants | 2 Participants | 18 Participants |
| Sequential Organ Failure Assessment (SOFA) Score | 9.3 Score on a scale STANDARD_DEVIATION 2.16 | 10.5 Score on a scale STANDARD_DEVIATION 3.31 | 10.4 Score on a scale STANDARD_DEVIATION 3.46 | 12 Score on a scale STANDARD_DEVIATION 0 | 11.2 Score on a scale STANDARD_DEVIATION 3.73 |
| Sex: Female, Male Female | 7 Participants | 23 Participants | 6 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 29 Participants | 15 Participants | 1 Participants | 10 Participants |
| Weight | 64.8 Kilogram STANDARD_DEVIATION 14.3 | 77.8 Kilogram STANDARD_DEVIATION 22.2 | 75.1 Kilogram STANDARD_DEVIATION 15.3 | 77.5 Kilogram STANDARD_DEVIATION 17.7 | 87.6 Kilogram STANDARD_DEVIATION 28.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 10 | 14 / 19 | 0 / 2 | 13 / 21 |
| serious Total, serious adverse events | 2 / 10 | 2 / 19 | 2 / 2 | 6 / 21 |
Outcome results
Primary
Cumulative Dose of Open Label NE.
Cumulative Dose of Open Label NE over 7 days. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Full Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 4 - 96 hours | 465 µg/kg | Standard Deviation 507 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 2 - 36 hours | 282 µg/kg | Standard Deviation 206 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 1 - 1 hour | 14.3 µg/kg | Standard Deviation 11.6 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 5 - 108 hours | 349 µg/kg | Standard Deviation 342 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 2 - 48 hours | 349 µg/kg | Standard Deviation 303 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 6 - 144 hours | 421 µg/kg | Standard Deviation 519 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 4 - 84 hours | 443 µg/kg | Standard Deviation 471 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 3 - 60 hours | 389 µg/kg | Standard Deviation 377 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 1 - 6 hours | 75.8 µg/kg | Standard Deviation 60.4 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 3 - 72 hours | 420 µg/kg | Standard Deviation 432 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 7 - 168 hours | 477 µg/kg | Standard Deviation 673 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 6 - 132 hours | 404 µg/kg | Standard Deviation 474 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 1 - 12 hours | 130 µg/kg | Standard Deviation 96.3 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 7 - 156 hours | 444 µg/kg | Standard Deviation 582 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 5 - 120 hours | 374 µg/kg | Standard Deviation 410 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 1 - 24 hours | 211 µg/kg | Standard Deviation 147 |
| FE 202158 1.25 | Cumulative Dose of Open Label NE. | Day 1 - 3 hours | 40.5 µg/kg | Standard Deviation 35 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 4 - 84 hours | 169 µg/kg | Standard Deviation 395 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 5 - 108 hours | 186 µg/kg | Standard Deviation 452 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 1 - 1 hour | 13.1 µg/kg | Standard Deviation 12.6 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 1 - 3 hours | 30 µg/kg | Standard Deviation 33.1 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 1 - 6 hours | 46.9 µg/kg | Standard Deviation 59.4 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 1 - 12 hours | 66.5 µg/kg | Standard Deviation 102 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 1 - 24 hours | 101 µg/kg | Standard Deviation 193 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 2 - 36 hours | 122 µg/kg | Standard Deviation 253 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 2 - 48 hours | 138 µg/kg | Standard Deviation 297 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 3 - 60 hours | 150 µg/kg | Standard Deviation 334 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 3 - 72 hours | 160 µg/kg | Standard Deviation 364 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 4 - 96 hours | 179 µg/kg | Standard Deviation 430 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 5 - 120 hours | 193 µg/kg | Standard Deviation 467 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 6 - 132 hours | 200 µg/kg | Standard Deviation 495 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 6 - 144 hours | 217 µg/kg | Standard Deviation 563 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 7 - 156 hours | 236 µg/kg | Standard Deviation 643 |
| FE 202158 2.5 | Cumulative Dose of Open Label NE. | Day 7 - 168 hours | 245 µg/kg | Standard Deviation 678 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 1 - 1 hour | 19.2 µg/kg | Standard Deviation 14.6 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 4 - 96 hours | 707 µg/kg | Standard Deviation 674 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 1 - 12 hours | 206 µg/kg | Standard Deviation 159 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 7 - 168 hours | 824 µg/kg | Standard Deviation 897 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 5 - 120 hours | 749 µg/kg | Standard Deviation 757 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 1 - 6 hours | 110 µg/kg | Standard Deviation 84 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 7 - 156 hours | 798 µg/kg | Standard Deviation 853 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 6 - 132 hours | 767 µg/kg | Standard Deviation 793 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 1 - 3 hours | 57.2 µg/kg | Standard Deviation 44 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 5 - 108 hours | 728 µg/kg | Standard Deviation 713 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 3 - 60 hours | 606 µg/kg | Standard Deviation 509 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 6 - 144 hours | 782 µg/kg | Standard Deviation 823 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 3 - 72 hours | 646 µg/kg | Standard Deviation 567 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 2 - 48 hours | 554 µg/kg | Standard Deviation 445 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 2 - 36 hours | 477 µg/kg | Standard Deviation 363 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 4 - 84 hours | 680 µg/kg | Standard Deviation 623 |
| PLCBO | Cumulative Dose of Open Label NE. | Day 1 - 24 hours | 360 µg/kg | Standard Deviation 270 |
Primary
Infusion Rates of Open Label NE.
Mean open label NE infusion rate within each predefined time period. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 5 - 108 hours | 0.0 µg/kg/min | Standard Deviation 0 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 2 - 48 hours | 0.08 µg/kg/min | Standard Deviation 0.16 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 1 - 3 hours | 0.22 µg/kg/min | Standard Deviation 0.19 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 1 - 1 hour | 0.24 µg/kg/min | Standard Deviation 0.19 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 3 - 60 hours | 0.03 µg/kg/min | Standard Deviation 0.05 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 6 - 144 hours | 0.03 µg/kg/min | Standard Deviation 0.08 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 4 - 96 hours | 0.03 µg/kg/min | Standard Deviation 0.07 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 3 - 72 hours | 0.04 µg/kg/min | Standard Deviation 0.08 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 1 - 12 hours | 0.13 µg/kg/min | Standard Deviation 0.11 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 4 - 84 hours | 0.03 µg/kg/min | Standard Deviation 0.07 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 7 - 168 hours | 0.05 µg/kg/min | Standard Deviation 0.15 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 6 - 132 hours | 0.02 µg/kg/min | Standard Deviation 0.05 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 1 - 24 hours | 0.09 µg/kg/min | Standard Deviation 0.08 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 7 - 156 hours | 0.04 µg/kg/min | Standard Deviation 0.12 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 5 - 120 hours | 0.02 µg/kg/min | Standard Deviation 0.07 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 2 - 36 hours | 0.10 µg/kg/min | Standard Deviation 0.12 |
| FE 202158 1.25 | Infusion Rates of Open Label NE. | Day 1 - 6 hours | 0.18 µg/kg/min | Standard Deviation 0.15 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 4 - 96 hours | 0.01 µg/kg/min | Standard Deviation 0.05 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 1 - 1 hour | 0.22 µg/kg/min | Standard Deviation 0.21 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 1 - 3 hours | 0.11 µg/kg/min | Standard Deviation 0.17 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 1 - 6 hours | 0.09 µg/kg/min | Standard Deviation 0.15 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 1 - 12 hours | 0.06 µg/kg/min | Standard Deviation 0.14 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 1 - 24 hours | 0.04 µg/kg/min | Standard Deviation 0.11 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 2 - 36 hours | 0.02 µg/kg/min | Standard Deviation 0.07 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 2 - 48 hours | 0.02 µg/kg/min | Standard Deviation 0.06 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 3 - 60 hours | 0.02 µg/kg/min | Standard Deviation 0.06 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 3 - 72 hours | 0.01 µg/kg/min | Standard Deviation 0.04 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 4 - 84 hours | 0.02 µg/kg/min | Standard Deviation 0.06 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 5 - 108 hours | 0.01 µg/kg/min | Standard Deviation 0.01 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 5 - 120 hours | 0.01 µg/kg/min | Standard Deviation 0.04 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 6 - 132 hours | 0.01 µg/kg/min | Standard Deviation 0.04 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 6 - 144 hours | 0.03 µg/kg/min | Standard Deviation 0.13 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 7 - 156 hours | 0.02 µg/kg/min | Standard Deviation 0.08 |
| FE 202158 2.5 | Infusion Rates of Open Label NE. | Day 7 - 168 hours | 0.02 µg/kg/min | Standard Deviation 0.05 |
| PLCBO | Infusion Rates of Open Label NE. | Day 1 - 3 hours | 0.31 µg/kg/min | Standard Deviation 0.24 |
| PLCBO | Infusion Rates of Open Label NE. | Day 5 - 108 hours | 0.04 µg/kg/min | Standard Deviation 0.08 |
| PLCBO | Infusion Rates of Open Label NE. | Day 1 - 24 hours | 0.19 µg/kg/min | Standard Deviation 0.17 |
| PLCBO | Infusion Rates of Open Label NE. | Day 7 - 168 hours | 0.01 µg/kg/min | Standard Deviation 0.03 |
| PLCBO | Infusion Rates of Open Label NE. | Day 5 - 120 hours | 0.03 µg/kg/min | Standard Deviation 0.07 |
| PLCBO | Infusion Rates of Open Label NE. | Day 1 - 12 hours | 0.26 µg/kg/min | Standard Deviation 0.2 |
| PLCBO | Infusion Rates of Open Label NE. | Day 7 - 156 hours | 0.02 µg/kg/min | Standard Deviation 0.06 |
| PLCBO | Infusion Rates of Open Label NE. | Day 6 - 132 hours | 0.02 µg/kg/min | Standard Deviation 0.06 |
| PLCBO | Infusion Rates of Open Label NE. | Day 1 - 6 hours | 0.28 µg/kg/min | Standard Deviation 0.22 |
| PLCBO | Infusion Rates of Open Label NE. | Day 1 - 1 hour | 0.32 µg/kg/min | Standard Deviation 0.24 |
| PLCBO | Infusion Rates of Open Label NE. | Day 3 - 72 hours | 0.05 µg/kg/min | Standard Deviation 0.1 |
| PLCBO | Infusion Rates of Open Label NE. | Day 6 - 144 hours | 0.02 µg/kg/min | Standard Deviation 0.06 |
| PLCBO | Infusion Rates of Open Label NE. | Day 4 - 84 hours | 0.04 µg/kg/min | Standard Deviation 0.11 |
| PLCBO | Infusion Rates of Open Label NE. | Day 3 - 60 hours | 0.07 µg/kg/min | Standard Deviation 0.11 |
| PLCBO | Infusion Rates of Open Label NE. | Day 2 - 48 hours | 0.08 µg/kg/min | Standard Deviation 0.13 |
| PLCBO | Infusion Rates of Open Label NE. | Day 4 - 96 hours | 0.03 µg/kg/min | Standard Deviation 0.1 |
| PLCBO | Infusion Rates of Open Label NE. | Day 2 - 36 hours | 0.13 µg/kg/min | Standard Deviation 0.14 |
Primary
Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE
Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Full Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 202158 1.25 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 4 - 96 hrs | 100.0 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 2 - 48 hrs | 100.0 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 1 - 12 hrs | 100.0 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 1 - 24 hrs | 87.5 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 7 - 168 hrs | 62.5 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 2 - 48 hrs | 100.0 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 1 - 12 hrs | 100.0 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 1 - 24 hrs | 100.0 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 4 - 96 hrs | 100.0 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 7 - 168 hrs | 100.0 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 7 - 168 hrs | 100.0 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 4 - 96 hrs | 100.0 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 1 - 12 hrs | 94.7 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 2 - 48 hrs | 100.0 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE | Day 1 - 24 hrs | 100.0 Percentage of patients |
Primary
Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Full Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 202158 1.25 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 4 - 96 hrs | 75.0 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 2 - 48 hrs | 55.6 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 1 - 12 hrs | 0.0 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 1 - 24 hrs | 10.0 Percentage of patients |
| FE 202158 1.25 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 7 - 168 hrs | 62.5 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 2 - 48 hrs | 66.7 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 1 - 12 hrs | 47.1 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 1 - 24 hrs | 68.8 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 4 - 96 hrs | 66.7 Percentage of patients |
| FE 202158 2.5 | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 7 - 168 hrs | 80.0 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 7 - 168 hrs | 100.0 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 4 - 96 hrs | 70.6 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 1 - 12 hrs | 0.0 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 2 - 48 hrs | 38.9 Percentage of patients |
| PLCBO | Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) | Day 1 - 24 hrs | 20.0 Percentage of patients |
Secondary
Change From Baseline in Arterial Blood Gas (Lactate)
Change from Baseline in arterial blood gas (lactate) was observed at each time-point. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 5 - 108 hours | -0.633 mmol/L | Standard Deviation 0.963 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 48 hours | -0.722 mmol/L | Standard Deviation 1.11 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 6 hours | 0 mmol/L | Standard Deviation 0.482 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 4 - 96 hours | -0.671 mmol/L | Standard Deviation 0.948 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 54 hours | -0.788 mmol/L | Standard Deviation 1.22 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 24 hours | -0.9 mmol/L | Standard Deviation 1.06 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 4 - 84 hours | -0.5 mmol/L | Standard Deviation 1.07 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 60 hours | -0.163 mmol/L | Standard Deviation 1.13 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 7 - 168 hours | -0.533 mmol/L | Standard Deviation 2.2 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 72 hours | -0.643 mmol/L | Standard Deviation 1.03 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 66 hours | -0.371 mmol/L | Standard Deviation 1.08 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 6 - 144 hours | -1.03 mmol/L | Standard Deviation 1.01 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 30 hours | -0.975 mmol/L | Standard Deviation 1.09 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 7 - 156 hours | -0.56 mmol/L | Standard Deviation 0.783 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 6 - 132 hours | -0.717 mmol/L | Standard Deviation 0.768 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 36 hours | -0.744 mmol/L | Standard Deviation 1.01 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 18 hours | -0.525 mmol/L | Standard Deviation 0.932 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 5 - 120 hours | -0.6 mmol/L | Standard Deviation 1 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 42 hours | -0.844 mmol/L | Standard Deviation 0.958 |
| FE 202158 1.25 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 12 hours | -0.489 mmol/L | Standard Deviation 0.857 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 6 - 144 hours | -1.28 mmol/L | Standard Deviation 1.84 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 6 hours | -0.367 mmol/L | Standard Deviation 1.03 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 12 hours | -0.833 mmol/L | Standard Deviation 1.53 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 18 hours | -1.01 mmol/L | Standard Deviation 1.66 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 24 hours | -1.01 mmol/L | Standard Deviation 1.93 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 30 hours | -1.33 mmol/L | Standard Deviation 2.5 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 36 hours | -1.45 mmol/L | Standard Deviation 2.57 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 42 hours | -1.57 mmol/L | Standard Deviation 2.84 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 48 hours | -1.68 mmol/L | Standard Deviation 2.84 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 54 hours | -1.6 mmol/L | Standard Deviation 1.99 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 60 hours | -1.15 mmol/L | Standard Deviation 1.65 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 66 hours | -1.01 mmol/L | Standard Deviation 1.84 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 72 hours | -1.27 mmol/L | Standard Deviation 1.92 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 4 - 84 hours | -0.975 mmol/L | Standard Deviation 1.76 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 4 - 96 hours | -0.52 mmol/L | Standard Deviation 0.902 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 5 - 108 hours | -1.37 mmol/L | Standard Deviation 2.07 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 5 - 120 hours | -1.06 mmol/L | Standard Deviation 1.89 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 6 - 132 hours | -1.26 mmol/L | Standard Deviation 1.87 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 7 - 156 hours | -2.17 mmol/L | Standard Deviation 3.44 |
| FE 202158 2.5 | Change From Baseline in Arterial Blood Gas (Lactate) | Day 7 - 168 hours | -1.6 mmol/L | Standard Deviation 1.92 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 12 hours | -0.0444 mmol/L | Standard Deviation 0.912 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 4 - 96 hours | -1.34 mmol/L | Standard Deviation 1.47 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 42 hours | -0.917 mmol/L | Standard Deviation 1.11 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 7 - 168 hours | -1.34 mmol/L | Standard Deviation 1.62 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 5 - 108 hours | -1.21 mmol/L | Standard Deviation 1.51 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 36 hours | -0.683 mmol/L | Standard Deviation 1.19 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 7 - 156 hours | -1.3 mmol/L | Standard Deviation 1.36 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 5 - 120 hours | -1.38 mmol/L | Standard Deviation 1.5 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 30 hours | -0.647 mmol/L | Standard Deviation 1.12 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 6 hours | -0.0278 mmol/L | Standard Deviation 0.647 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 6 - 132 hours | -1.23 mmol/L | Standard Deviation 1.27 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 24 hours | -0.533 mmol/L | Standard Deviation 1.13 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 66 hours | -1.15 mmol/L | Standard Deviation 1.39 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 60 hours | -0.925 mmol/L | Standard Deviation 1.4 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 1 - 18 hours | -0.3 mmol/L | Standard Deviation 0.974 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 72 hours | -0.879 mmol/L | Standard Deviation 1.45 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 3 - 54 hours | -1.11 mmol/L | Standard Deviation 1.33 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 6 - 144 hours | -1.12 mmol/L | Standard Deviation 0.946 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 4 - 84 hours | -1.12 mmol/L | Standard Deviation 1.36 |
| PLCBO | Change From Baseline in Arterial Blood Gas (Lactate) | Day 2 - 48 hours | -0.888 mmol/L | Standard Deviation 1.29 |
Secondary
Change From Baseline in C-reactive Protein (CRP)
The change from Baseline in CRP levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in C-reactive Protein (CRP) | Day 1 (0-24 hours) | 9.81 mg/L | Standard Deviation 42.2 |
| FE 202158 1.25 | Change From Baseline in C-reactive Protein (CRP) | Day 2 (24-48 hours) | -16.2 mg/L | Standard Deviation 89.4 |
| FE 202158 1.25 | Change From Baseline in C-reactive Protein (CRP) | Day 4 (72-96 hours) | -95.8 mg/L | Standard Deviation 97.1 |
| FE 202158 1.25 | Change From Baseline in C-reactive Protein (CRP) | Day 7 (144-168 hours) | -93.3 mg/L | Standard Deviation 58 |
| FE 202158 2.5 | Change From Baseline in C-reactive Protein (CRP) | Day 7 (144-168 hours) | -211.0 mg/L | Standard Deviation 223 |
| FE 202158 2.5 | Change From Baseline in C-reactive Protein (CRP) | Day 1 (0-24 hours) | -4.84 mg/L | Standard Deviation 38.5 |
| FE 202158 2.5 | Change From Baseline in C-reactive Protein (CRP) | Day 4 (72-96 hours) | -176 mg/L | Standard Deviation 208 |
| FE 202158 2.5 | Change From Baseline in C-reactive Protein (CRP) | Day 2 (24-48 hours) | -52.4 mg/L | Standard Deviation 70.1 |
| PLCBO | Change From Baseline in C-reactive Protein (CRP) | Day 7 (144-168 hours) | -141 mg/L | Standard Deviation 221 |
| PLCBO | Change From Baseline in C-reactive Protein (CRP) | Day 2 (24-48 hours) | -5.63 mg/L | Standard Deviation 118 |
| PLCBO | Change From Baseline in C-reactive Protein (CRP) | Day 4 (72-96 hours) | -71.8 mg/L | Standard Deviation 97.5 |
| PLCBO | Change From Baseline in C-reactive Protein (CRP) | Day 1 (0-24 hours) | 32.7 mg/L | Standard Deviation 63.8 |
Secondary
Change From Baseline in Fluid Balance
The change from Baseline in fluid balance were analysed and presented as per the planned time points. The fluid balance was adjusted for length of time interval and weight. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 5 - 96-108 hours | -4.3 mL/hour/kg | Standard Deviation 6.08 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 2 - 42-48 hours | -3.82 mL/hour/kg | Standard Deviation 6.66 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 1 - 0-6 hours | -2.11 mL/hour/kg | Standard Deviation 6.99 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 4 - 84-96 hours | -4.01 mL/hour/kg | Standard Deviation 6.08 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 3 - 48-54 hours | -3.2 mL/hour/kg | Standard Deviation 6.26 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 1 - 18-24 hours | -3.49 mL/hour/kg | Standard Deviation 6.78 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 4 - 72-84 hours | -4.82 mL/hour/kg | Standard Deviation 6.47 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 3 - 54-60 hours | -4.42 mL/hour/kg | Standard Deviation 7.6 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 7 - 156-168 hours | -5.38 mL/hour/kg | Standard Deviation 6.09 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 3 - 66-72 hours | -4.64 mL/hour/kg | Standard Deviation 6.71 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 3 - 60-66 hours | -4.31 mL/hour/kg | Standard Deviation 6.68 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 6 - 132-144 hours | -5.41 mL/hour/kg | Standard Deviation 6.62 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 2 - 24-30 hours | -3.49 mL/hour/kg | Standard Deviation 5.56 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 7 - 144-156 hours | -5.56 mL/hour/kg | Standard Deviation 6.34 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 6 - 120-132 hours | -4.17 mL/hour/kg | Standard Deviation 6.19 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 2 - 30-36 hours | -3.42 mL/hour/kg | Standard Deviation 5.63 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 1 - 12-18 hours | -3.66 mL/hour/kg | Standard Deviation 6.68 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 5 - 108-120 hours | -4.12 mL/hour/kg | Standard Deviation 5.99 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 2 - 36-42 hours | -3.34 mL/hour/kg | Standard Deviation 6.09 |
| FE 202158 1.25 | Change From Baseline in Fluid Balance | Day 1 - 0-12 hours | -3.56 mL/hour/kg | Standard Deviation 6.34 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 6 - 132-144 hours | -2.99 mL/hour/kg | Standard Deviation 3.17 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 1 - 0-6 hours | -0.0513 mL/hour/kg | Standard Deviation 3.08 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 1 - 0-12 hours | -0.889 mL/hour/kg | Standard Deviation 3.29 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 1 - 12-18 hours | -1.41 mL/hour/kg | Standard Deviation 3.11 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 1 - 18-24 hours | -1.47 mL/hour/kg | Standard Deviation 3.45 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 2 - 24-30 hours | -1.75 mL/hour/kg | Standard Deviation 3.1 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 2 - 30-36 hours | -0.963 mL/hour/kg | Standard Deviation 3.82 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 2 - 36-42 hours | -1.82 mL/hour/kg | Standard Deviation 3.36 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 2 - 42-48 hours | -2.18 mL/hour/kg | Standard Deviation 3.51 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 3 - 48-54 hours | -1.97 mL/hour/kg | Standard Deviation 3.68 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 3 - 54-60 hours | -2.85 mL/hour/kg | Standard Deviation 3.52 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 3 - 60-66 hours | -2.86 mL/hour/kg | Standard Deviation 3.33 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 3 - 66-72 hours | -2.75 mL/hour/kg | Standard Deviation 3.76 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 4 - 72-84 hours | -2.52 mL/hour/kg | Standard Deviation 3.36 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 4 - 84-96 hours | -2.4 mL/hour/kg | Standard Deviation 3.55 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 5 - 96-108 hours | -2.84 mL/hour/kg | Standard Deviation 4.08 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 5 - 108-120 hours | -3.3 mL/hour/kg | Standard Deviation 3.84 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 6 - 120-132 hours | -3.04 mL/hour/kg | Standard Deviation 3.86 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 7 - 144-156 hours | -2.37 mL/hour/kg | Standard Deviation 3.1 |
| FE 202158 2.5 | Change From Baseline in Fluid Balance | Day 7 - 156-168 hours | -2.85 mL/hour/kg | Standard Deviation 3.13 |
| PLCBO | Change From Baseline in Fluid Balance | Day 1 - 0-12 hours | -0.578 mL/hour/kg | Standard Deviation 2.2 |
| PLCBO | Change From Baseline in Fluid Balance | Day 4 - 84-96 hours | -2.67 mL/hour/kg | Standard Deviation 3.58 |
| PLCBO | Change From Baseline in Fluid Balance | Day 2 - 36-42 hours | -2.54 mL/hour/kg | Standard Deviation 3.48 |
| PLCBO | Change From Baseline in Fluid Balance | Day 7 - 156-168 hours | -2.6 mL/hour/kg | Standard Deviation 2.46 |
| PLCBO | Change From Baseline in Fluid Balance | Day 5 - 96-108 hours | -2.62 mL/hour/kg | Standard Deviation 3.2 |
| PLCBO | Change From Baseline in Fluid Balance | Day 2 - 30-36 hours | -1.47 mL/hour/kg | Standard Deviation 3.04 |
| PLCBO | Change From Baseline in Fluid Balance | Day 7 - 144-156 hours | -2.8 mL/hour/kg | Standard Deviation 2.69 |
| PLCBO | Change From Baseline in Fluid Balance | Day 5 - 108-120 hours | -2.22 mL/hour/kg | Standard Deviation 2.78 |
| PLCBO | Change From Baseline in Fluid Balance | Day 2 - 24-30 hours | -0.905 mL/hour/kg | Standard Deviation 2.68 |
| PLCBO | Change From Baseline in Fluid Balance | Day 1 - 0-6 hours | -0.477 mL/hour/kg | Standard Deviation 2.03 |
| PLCBO | Change From Baseline in Fluid Balance | Day 6 - 120-132 hours | -2.67 mL/hour/kg | Standard Deviation 3.45 |
| PLCBO | Change From Baseline in Fluid Balance | Day 1 - 18-24 hours | -0.119 mL/hour/kg | Standard Deviation 2.95 |
| PLCBO | Change From Baseline in Fluid Balance | Day 3 - 60-66 hours | -2.21 mL/hour/kg | Standard Deviation 2.54 |
| PLCBO | Change From Baseline in Fluid Balance | Day 3 - 54-60 hours | -2.91 mL/hour/kg | Standard Deviation 2.55 |
| PLCBO | Change From Baseline in Fluid Balance | Day 1 - 12-18 hours | -0.98 mL/hour/kg | Standard Deviation 2.42 |
| PLCBO | Change From Baseline in Fluid Balance | Day 3 - 66-72 hours | -2.54 mL/hour/kg | Standard Deviation 2.79 |
| PLCBO | Change From Baseline in Fluid Balance | Day 3 - 48-54 hours | -1.93 mL/hour/kg | Standard Deviation 2.59 |
| PLCBO | Change From Baseline in Fluid Balance | Day 6 - 132-144 hours | -2.87 mL/hour/kg | Standard Deviation 3.19 |
| PLCBO | Change From Baseline in Fluid Balance | Day 4 - 72-84 hours | -2.35 mL/hour/kg | Standard Deviation 3.28 |
| PLCBO | Change From Baseline in Fluid Balance | Day 2 - 42-48 hours | -2.01 mL/hour/kg | Standard Deviation 3.52 |
Secondary
Change From Baseline in Heart Rate
The change from Baseline in heart rate was analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 33 hours | -9.3 Beats per minute | Standard Deviation 13.9 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 6 hours | -4.9 Beats per minute | Standard Deviation 6.06 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 9 hours | -7.2 Beats per minute | Standard Deviation 7.02 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 12 hours | -7.6 Beats per minute | Standard Deviation 10.4 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 15 hours | -8.6 Beats per minute | Standard Deviation 7.76 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 18 hours | -7.22 Beats per minute | Standard Deviation 9.58 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 21 hours | -10 Beats per minute | Standard Deviation 9.31 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 24 hours | -7.44 Beats per minute | Standard Deviation 17.9 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 27 hours | -7.6 Beats per minute | Standard Deviation 14.5 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 30 hours | -10.3 Beats per minute | Standard Deviation 14.4 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 1 - 3 hours | -5.7 Beats per minute | Standard Deviation 8.06 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 36 hours | -6.9 Beats per minute | Standard Deviation 15.5 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 39 hours | -6.7 Beats per minute | Standard Deviation 12.8 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 42 hours | -6 Beats per minute | Standard Deviation 12.4 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 45 hours | -1.9 Beats per minute | Standard Deviation 8.91 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 2 - 48 hours | -9.9 Beats per minute | Standard Deviation 13.8 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 51 hours | -10.2 Beats per minute | Standard Deviation 8.53 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 54 hours | -6.11 Beats per minute | Standard Deviation 10.1 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 57 hours | -3.67 Beats per minute | Standard Deviation 10.4 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 60 hours | -1.6 Beats per minute | Standard Deviation 7.96 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 63 hours | -6.78 Beats per minute | Standard Deviation 10.6 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 66 hours | -5.11 Beats per minute | Standard Deviation 10.9 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 69 hours | -9.44 Beats per minute | Standard Deviation 11.9 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 3 - 72 hours | -11.9 Beats per minute | Standard Deviation 10.5 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 4 - 78 hours | -2.11 Beats per minute | Standard Deviation 20.9 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 4 - 84 hours | -2.4 Beats per minute | Standard Deviation 16.8 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 4 - 90 hours | -7.38 Beats per minute | Standard Deviation 15.3 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 4 - 96 hours | -2.56 Beats per minute | Standard Deviation 22.3 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 5 - 102 hours | 4.63 Beats per minute | Standard Deviation 23.2 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 5 - 108 hours | 2.11 Beats per minute | Standard Deviation 15.7 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 5 - 114 hours | 1.25 Beats per minute | Standard Deviation 18.9 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 5 - 120 hours | 4.11 Beats per minute | Standard Deviation 18.1 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 6 - 126 hours | -0.714 Beats per minute | Standard Deviation 13 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 6 - 132 hours | 1.13 Beats per minute | Standard Deviation 14.8 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 6 - 138 hours | -3 Beats per minute | Standard Deviation 9.92 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 6 - 144 hours | 1.38 Beats per minute | Standard Deviation 8.19 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 7 - 150 hours | 0.2 Beats per minute | Standard Deviation 13.4 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 7 - 156 hours | 6 Beats per minute | Standard Deviation 20.2 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 7 - 162 hours | 6.33 Beats per minute | Standard Deviation 22 |
| FE 202158 1.25 | Change From Baseline in Heart Rate | Day 7 - 168 hours | 8.17 Beats per minute | Standard Deviation 13.7 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 42 hours | -11.3 Beats per minute | Standard Deviation 16.5 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 5 - 120 hours | -7.15 Beats per minute | Standard Deviation 17.4 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 45 hours | -9.11 Beats per minute | Standard Deviation 14.1 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 48 hours | -7.39 Beats per minute | Standard Deviation 13 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 7 - 156 hours | -4.58 Beats per minute | Standard Deviation 19.9 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 51 hours | -8.06 Beats per minute | Standard Deviation 16.7 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 6 - 126 hours | -5.79 Beats per minute | Standard Deviation 20.2 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 54 hours | -10.5 Beats per minute | Standard Deviation 18.1 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 57 hours | -6.87 Beats per minute | Standard Deviation 21.8 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 60 hours | -8.25 Beats per minute | Standard Deviation 22.3 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 6 - 132 hours | -9.93 Beats per minute | Standard Deviation 16.7 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 63 hours | -10.3 Beats per minute | Standard Deviation 22.6 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 66 hours | -9.63 Beats per minute | Standard Deviation 19.4 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 7 - 168 hours | -6.27 Beats per minute | Standard Deviation 21.3 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 69 hours | -4.64 Beats per minute | Standard Deviation 24.6 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 6 - 138 hours | -10.6 Beats per minute | Standard Deviation 14.6 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 3 - 72 hours | -10.7 Beats per minute | Standard Deviation 19.8 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 4 - 78 hours | -10.1 Beats per minute | Standard Deviation 18.9 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 7 - 162 hours | -3.5 Beats per minute | Standard Deviation 19.1 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 4 - 84 hours | -12.5 Beats per minute | Standard Deviation 17.6 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 6 - 144 hours | -10.7 Beats per minute | Standard Deviation 17.3 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 4 - 90 hours | -10.6 Beats per minute | Standard Deviation 19.2 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 3 hours | -11.0 Beats per minute | Standard Deviation 14.1 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 6 hours | -11.9 Beats per minute | Standard Deviation 14.9 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 4 - 96 hours | -12.2 Beats per minute | Standard Deviation 16.1 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 9 hours | -11.6 Beats per minute | Standard Deviation 17.3 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 12 hours | -11.5 Beats per minute | Standard Deviation 13.8 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 15 hours | -13.2 Beats per minute | Standard Deviation 15.5 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 5 - 102 hours | -9.38 Beats per minute | Standard Deviation 19.8 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 18 hours | -6.26 Beats per minute | Standard Deviation 19.1 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 21 hours | -9.79 Beats per minute | Standard Deviation 14.8 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 7 - 150 hours | -6 Beats per minute | Standard Deviation 22.3 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 1 - 24 hours | -2.95 Beats per minute | Standard Deviation 25.1 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 5 - 108 hours | -10.5 Beats per minute | Standard Deviation 15.9 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 27 hours | -9.16 Beats per minute | Standard Deviation 19.3 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 30 hours | -13.1 Beats per minute | Standard Deviation 17.4 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 33 hours | -11.1 Beats per minute | Standard Deviation 15 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 5 - 114 hours | -10.3 Beats per minute | Standard Deviation 16.7 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 36 hours | -9.47 Beats per minute | Standard Deviation 16 |
| FE 202158 2.5 | Change From Baseline in Heart Rate | Day 2 - 39 hours | -9.21 Beats per minute | Standard Deviation 18.4 |
| PLCBO | Change From Baseline in Heart Rate | Day 4 - 90 hours | -4.18 Beats per minute | Standard Deviation 31 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 42 hours | -9.5 Beats per minute | Standard Deviation 24.4 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 33 hours | -10.5 Beats per minute | Standard Deviation 22.2 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 3 hours | -4.9 Beats per minute | Standard Deviation 14.3 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 45 hours | -6.5 Beats per minute | Standard Deviation 28.1 |
| PLCBO | Change From Baseline in Heart Rate | Day 5 - 120 hours | -5.06 Beats per minute | Standard Deviation 28.1 |
| PLCBO | Change From Baseline in Heart Rate | Day 6 - 144 hours | 1.28 Beats per minute | Standard Deviation 18.6 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 48 hours | -8.9 Beats per minute | Standard Deviation 25 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 24 hours | -2.37 Beats per minute | Standard Deviation 29.4 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 6 hours | -6.55 Beats per minute | Standard Deviation 13.1 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 51 hours | -9.11 Beats per minute | Standard Deviation 27.9 |
| PLCBO | Change From Baseline in Heart Rate | Day 7 - 168 hours | -6.94 Beats per minute | Standard Deviation 15.6 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 39 hours | -7.2 Beats per minute | Standard Deviation 25.7 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 54 hours | -9.94 Beats per minute | Standard Deviation 27 |
| PLCBO | Change From Baseline in Heart Rate | Day 6 - 126 hours | -4.19 Beats per minute | Standard Deviation 24.4 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 9 hours | -5.35 Beats per minute | Standard Deviation 17.7 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 57 hours | -7.94 Beats per minute | Standard Deviation 28.6 |
| PLCBO | Change From Baseline in Heart Rate | Day 7 - 156 hours | -8.83 Beats per minute | Standard Deviation 15.2 |
| PLCBO | Change From Baseline in Heart Rate | Day 4 - 96 hours | -7.78 Beats per minute | Standard Deviation 28 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 60 hours | -9.4 Beats per minute | Standard Deviation 25.5 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 27 hours | -5.4 Beats per minute | Standard Deviation 27.9 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 12 hours | -8.45 Beats per minute | Standard Deviation 16.3 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 63 hours | -10.6 Beats per minute | Standard Deviation 24.7 |
| PLCBO | Change From Baseline in Heart Rate | Day 6 - 132 hours | -4.22 Beats per minute | Standard Deviation 24.7 |
| PLCBO | Change From Baseline in Heart Rate | Day 7 - 162 hours | -11.5 Beats per minute | Standard Deviation 15.9 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 66 hours | -10.9 Beats per minute | Standard Deviation 25 |
| PLCBO | Change From Baseline in Heart Rate | Day 5 - 108 hours | -6.05 Beats per minute | Standard Deviation 27.8 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 15 hours | -4.5 Beats per minute | Standard Deviation 18.5 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 69 hours | -8.35 Beats per minute | Standard Deviation 26.2 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 36 hours | -9.05 Beats per minute | Standard Deviation 26.7 |
| PLCBO | Change From Baseline in Heart Rate | Day 2 - 30 hours | -7.35 Beats per minute | Standard Deviation 22.9 |
| PLCBO | Change From Baseline in Heart Rate | Day 3 - 72 hours | -8.41 Beats per minute | Standard Deviation 28.7 |
| PLCBO | Change From Baseline in Heart Rate | Day 6 - 138 hours | -6.4 Beats per minute | Standard Deviation 23.6 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 18 hours | -6.95 Beats per minute | Standard Deviation 18.8 |
| PLCBO | Change From Baseline in Heart Rate | Day 4 - 78 hours | -7.06 Beats per minute | Standard Deviation 29.7 |
| PLCBO | Change From Baseline in Heart Rate | Day 5 - 102 hours | -9.65 Beats per minute | Standard Deviation 28.4 |
| PLCBO | Change From Baseline in Heart Rate | Day 7 - 150 hours | -1.88 Beats per minute | Standard Deviation 28.2 |
| PLCBO | Change From Baseline in Heart Rate | Day 4 - 84 hours | -9.5 Beats per minute | Standard Deviation 27 |
| PLCBO | Change From Baseline in Heart Rate | Day 1 - 21 hours | -3.2 Beats per minute | Standard Deviation 22.9 |
| PLCBO | Change From Baseline in Heart Rate | Day 5 - 114 hours | -6.12 Beats per minute | Standard Deviation 30.3 |
Secondary
Change From Baseline in Interleukin-10 (IL-10)
The change from Baseline in IL-10 levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 1, Day 2, Day 4, and Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in Interleukin-10 (IL-10) | Day 1 (0-24 hours) | -19.2 ng/L | Standard Deviation 54.6 |
| FE 202158 1.25 | Change From Baseline in Interleukin-10 (IL-10) | Day 2 (24-48 hours) | -34 ng/L | Standard Deviation 70.4 |
| FE 202158 1.25 | Change From Baseline in Interleukin-10 (IL-10) | Day 4 (72-96 hours) | -31.9 ng/L | Standard Deviation 95.2 |
| FE 202158 1.25 | Change From Baseline in Interleukin-10 (IL-10) | Day 7 (144-168 hours) | 8 ng/L | Standard Deviation 24.3 |
| FE 202158 2.5 | Change From Baseline in Interleukin-10 (IL-10) | Day 7 (144-168 hours) | -91.7 ng/L | Standard Deviation 220 |
| FE 202158 2.5 | Change From Baseline in Interleukin-10 (IL-10) | Day 1 (0-24 hours) | -58.3 ng/L | Standard Deviation 179 |
| FE 202158 2.5 | Change From Baseline in Interleukin-10 (IL-10) | Day 4 (72-96 hours) | -92.3 ng/L | Standard Deviation 213 |
| FE 202158 2.5 | Change From Baseline in Interleukin-10 (IL-10) | Day 2 (24-48 hours) | -78.9 ng/L | Standard Deviation 189 |
| PLCBO | Change From Baseline in Interleukin-10 (IL-10) | Day 7 (144-168 hours) | -52.8 ng/L | Standard Deviation 97.1 |
| PLCBO | Change From Baseline in Interleukin-10 (IL-10) | Day 2 (24-48 hours) | -43 ng/L | Standard Deviation 76.1 |
| PLCBO | Change From Baseline in Interleukin-10 (IL-10) | Day 4 (72-96 hours) | -56.6 ng/L | Standard Deviation 84.5 |
| PLCBO | Change From Baseline in Interleukin-10 (IL-10) | Day 1 (0-24 hours) | -25.8 ng/L | Standard Deviation 51.7 |
Secondary
Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist
The change from Baseline in IL-1R levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 1, Day 2, Day 4, and Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 1 (0-24 hours) | 0.763 µg/L | Standard Deviation 5.39 |
| FE 202158 1.25 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 2 (24-48 hours) | -3.65 µg/L | Standard Deviation 9.89 |
| FE 202158 1.25 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 4 (72-96 hours) | -6.38 µg/L | Standard Deviation 12 |
| FE 202158 1.25 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 7 (144-168 hours) | -3.5 µg/L | Standard Deviation 5.72 |
| FE 202158 2.5 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 7 (144-168 hours) | -5.3 µg/L | Standard Deviation 10.4 |
| FE 202158 2.5 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 1 (0-24 hours) | -3.71 µg/L | Standard Deviation 7.61 |
| FE 202158 2.5 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 4 (72-96 hours) | -6.44 µg/L | Standard Deviation 12 |
| FE 202158 2.5 | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 2 (24-48 hours) | -4.77 µg/L | Standard Deviation 10.7 |
| PLCBO | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 7 (144-168 hours) | -3.9 µg/L | Standard Deviation 8.35 |
| PLCBO | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 2 (24-48 hours) | -3.84 µg/L | Standard Deviation 7.86 |
| PLCBO | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 4 (72-96 hours) | -4.51 µg/L | Standard Deviation 8.63 |
| PLCBO | Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist | Day 1 (0-24 hours) | -3.28 µg/L | Standard Deviation 5.79 |
Secondary
Change From Baseline in Interleukin-6 (IL-6)
The change from Baseline in IL-6 levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 1, Day 2, Day 4, and Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in Interleukin-6 (IL-6) | Day 1 (0-24 hours) | -329 ng/L | Standard Deviation 736 |
| FE 202158 1.25 | Change From Baseline in Interleukin-6 (IL-6) | Day 2 (24-48 hours) | -720 ng/L | Standard Deviation 1178 |
| FE 202158 1.25 | Change From Baseline in Interleukin-6 (IL-6) | Day 4 (72-96 hours) | -794 ng/L | Standard Deviation 1206 |
| FE 202158 1.25 | Change From Baseline in Interleukin-6 (IL-6) | Day 7 (144-168 hours) | -883 ng/L | Standard Deviation 1559 |
| FE 202158 2.5 | Change From Baseline in Interleukin-6 (IL-6) | Day 7 (144-168 hours) | -1184 ng/L | Standard Deviation 1801 |
| FE 202158 2.5 | Change From Baseline in Interleukin-6 (IL-6) | Day 1 (0-24 hours) | -524 ng/L | Standard Deviation 2255 |
| FE 202158 2.5 | Change From Baseline in Interleukin-6 (IL-6) | Day 4 (72-96 hours) | -1209 ng/L | Standard Deviation 1844 |
| FE 202158 2.5 | Change From Baseline in Interleukin-6 (IL-6) | Day 2 (24-48 hours) | -888 ng/L | Standard Deviation 1798 |
| PLCBO | Change From Baseline in Interleukin-6 (IL-6) | Day 7 (144-168 hours) | -814 ng/L | Standard Deviation 1823 |
| PLCBO | Change From Baseline in Interleukin-6 (IL-6) | Day 2 (24-48 hours) | -398 ng/L | Standard Deviation 2101 |
| PLCBO | Change From Baseline in Interleukin-6 (IL-6) | Day 4 (72-96 hours) | -1140 ng/L | Standard Deviation 1944 |
| PLCBO | Change From Baseline in Interleukin-6 (IL-6) | Day 1 (0-24 hours) | -529 ng/L | Standard Deviation 1750 |
Secondary
Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha
The change from Baseline in TNF-alpha levels were analysed and presented as per the planned time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 1, Day 2, Day 4, and Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 1 (0-24 hours) | -0.75 ng/L | Standard Deviation 2.37 |
| FE 202158 1.25 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 2 (24-48 hours) | -0.75 ng/L | Standard Deviation 2.37 |
| FE 202158 1.25 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 4 (72-96 hours) | -0.833 ng/L | Standard Deviation 2.5 |
| FE 202158 1.25 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 7 (144-168 hours) | -1.25 ng/L | Standard Deviation 3.06 |
| FE 202158 2.5 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 7 (144-168 hours) | 1.14 ng/L | Standard Deviation 4.28 |
| FE 202158 2.5 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 1 (0-24 hours) | -0.194 ng/L | Standard Deviation 0.825 |
| FE 202158 2.5 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 4 (72-96 hours) | 0.75 ng/L | Standard Deviation 3 |
| FE 202158 2.5 | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 2 (24-48 hours) | 0.0 ng/L | Standard Deviation 0 |
| PLCBO | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 7 (144-168 hours) | 0.25 ng/L | Standard Deviation 0.845 |
| PLCBO | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 2 (24-48 hours) | 0.0 ng/L | Standard Deviation 0 |
| PLCBO | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 4 (72-96 hours) | -0.125 ng/L | Standard Deviation 0.559 |
| PLCBO | Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha | Day 1 (0-24 hours) | -0.125 ng/L | Standard Deviation 0.559 |
Secondary
Days Alive and Free of Any Organ Dysfunction at Day 7
Percentage of days alive and free of any organ dysfunction (i.e. no. of days divided by 7). The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | Days Alive and Free of Any Organ Dysfunction at Day 7 | 5.38 Percentage of days | Standard Deviation 10.7 |
| FE 202158 2.5 | Days Alive and Free of Any Organ Dysfunction at Day 7 | 3.8 Percentage of days | Standard Deviation 11.4 |
| PLCBO | Days Alive and Free of Any Organ Dysfunction at Day 7 | 0.0 Percentage of days | Standard Deviation 0 |
Secondary
Incidence of Abnormal Changes in ECG
The number of patients having abnormal changes in ECG variables during the trial period was presented. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QT interval >=450 msec | 3 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | PQ interval <=120 msec | 1 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QTcF >=450 msec | 1 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QT interval >=480 msec | 1 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | Heart rate >=100 beats per minute | 5 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QT interval >=60 msec increase from Baseline | 5 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QT interval >=500 msec | 0 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QTcF >=500 msec | 0 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QT interval >=30 msec increase from Baseline | 7 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | PQ interval >=220 msec | 0 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QTcF >=60 msec increase from Baseline | 2 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | Heart rate <=50 beats per minute | 0 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QRS interval >=120 msec | 2 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QTcF >=30 msec increase from Baseline | 3 Number of patients |
| FE 202158 1.25 | Incidence of Abnormal Changes in ECG | QTcF >=480 msec | 0 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QTcF >=480 msec | 3 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | Heart rate <=50 beats per minute | 1 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | Heart rate >=100 beats per minute | 11 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | PQ interval <=120 msec | 6 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | PQ interval >=220 msec | 0 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QRS interval >=120 msec | 2 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QT interval >=450 msec | 4 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QT interval >=480 msec | 2 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QT interval >=500 msec | 2 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QT interval >=30 msec increase from Baseline | 15 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QT interval >=60 msec increase from Baseline | 13 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QTcF >=450 msec | 9 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QTcF >=500 msec | 2 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QTcF >=30 msec increase from Baseline | 14 Number of patients |
| FE 202158 2.5 | Incidence of Abnormal Changes in ECG | QTcF >=60 msec increase from Baseline | 9 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QT interval >=450 msec | 8 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QTcF >=30 msec increase from Baseline | 11 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QTcF >=450 msec | 10 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QRS interval >=120 msec | 4 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | PQ interval >=220 msec | 1 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QTcF >=480 msec | 7 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | PQ interval <=120 msec | 5 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | Heart rate <=50 beats per minute | 4 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QTcF >=500 msec | 6 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QT interval >=500 msec | 3 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | Heart rate >=100 beats per minute | 8 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QT interval >=30 msec increase from Baseline | 14 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QT interval >=480 msec | 6 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QTcF >=60 msec increase from Baseline | 9 Number of patients |
| PLCBO | Incidence of Abnormal Changes in ECG | QT interval >=60 msec increase from Baseline | 12 Number of patients |
Secondary
Mortality
Mortality was assessed as percentage of patients dead at pre-specified time points. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 1, 7, 14, and 28
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 202158 1.25 | Mortality | At Day 1 | 0.0 Percentage of patients |
| FE 202158 1.25 | Mortality | At Day 7 | 20.0 Percentage of patients |
| FE 202158 1.25 | Mortality | At Day 14 | 40.0 Percentage of patients |
| FE 202158 1.25 | Mortality | At Day 28 | 50.0 Percentage of patients |
| FE 202158 2.5 | Mortality | At Day 28 | 5.3 Percentage of patients |
| FE 202158 2.5 | Mortality | At Day 1 | 0.0 Percentage of patients |
| FE 202158 2.5 | Mortality | At Day 14 | 0.0 Percentage of patients |
| FE 202158 2.5 | Mortality | At Day 7 | 0.0 Percentage of patients |
| PLCBO | Mortality | At Day 28 | 21.1 Percentage of patients |
| PLCBO | Mortality | At Day 7 | 0.0 Percentage of patients |
| PLCBO | Mortality | At Day 14 | 0.0 Percentage of patients |
| PLCBO | Mortality | At Day 1 | 0.0 Percentage of patients |
Secondary
Percentage of Days Alive and Free of Dialysis
Percentage of days alive and free of dialysis was assessed on Days 7, 14, and 28. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 7, Day 14 and Day 28
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Percentage of Days Alive and Free of Dialysis | Day 14 | 55.1 Percentage of days | Standard Deviation 45 |
| FE 202158 1.25 | Percentage of Days Alive and Free of Dialysis | Day 7 | 53.9 Percentage of days | Standard Deviation 43.4 |
| FE 202158 1.25 | Percentage of Days Alive and Free of Dialysis | Day 28 | 50.5 Percentage of days | Standard Deviation 43.9 |
| FE 202158 2.5 | Percentage of Days Alive and Free of Dialysis | Day 7 | 79.7 Percentage of days | Standard Deviation 36.4 |
| FE 202158 2.5 | Percentage of Days Alive and Free of Dialysis | Day 14 | 80.1 Percentage of days | Standard Deviation 33.4 |
| FE 202158 2.5 | Percentage of Days Alive and Free of Dialysis | Day 28 | 78.5 Percentage of days | Standard Deviation 35.4 |
| PLCBO | Percentage of Days Alive and Free of Dialysis | Day 7 | 83.2 Percentage of days | Standard Deviation 24.1 |
| PLCBO | Percentage of Days Alive and Free of Dialysis | Day 28 | 88.6 Percentage of days | Standard Deviation 19.8 |
| PLCBO | Percentage of Days Alive and Free of Dialysis | Day 14 | 87.6 Percentage of days | Standard Deviation 16.9 |
Secondary
Percentage of Days Alive and Free of Ventilation
Percentage of days alive and free of ventilation was assessed on Days 7, 14, and 28. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | Percentage of Days Alive and Free of Ventilation | 31.3 Percentage of days | Standard Deviation 37.5 |
| FE 202158 2.5 | Percentage of Days Alive and Free of Ventilation | 53.8 Percentage of days | Standard Deviation 38.9 |
| PLCBO | Percentage of Days Alive and Free of Ventilation | 23.1 Percentage of days | Standard Deviation 34.8 |
Secondary
Percentage of Patients Alive and Free of All Vasopressors
Percentage of patients alive and free of all vasopressors was assessed on Days 7, 14, and 28. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: At Day 7, Day 14 and Day 28
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 202158 1.25 | Percentage of Patients Alive and Free of All Vasopressors | Day 14 | 40.0 Percentage of patients |
| FE 202158 1.25 | Percentage of Patients Alive and Free of All Vasopressors | Day 7 | 60.0 Percentage of patients |
| FE 202158 1.25 | Percentage of Patients Alive and Free of All Vasopressors | Day 28 | 50.0 Percentage of patients |
| FE 202158 2.5 | Percentage of Patients Alive and Free of All Vasopressors | Day 14 | 89.5 Percentage of patients |
| FE 202158 2.5 | Percentage of Patients Alive and Free of All Vasopressors | Day 7 | 57.9 Percentage of patients |
| FE 202158 2.5 | Percentage of Patients Alive and Free of All Vasopressors | Day 28 | 82.4 Percentage of patients |
| PLCBO | Percentage of Patients Alive and Free of All Vasopressors | Day 7 | 73.7 Percentage of patients |
| PLCBO | Percentage of Patients Alive and Free of All Vasopressors | Day 28 | 83.3 Percentage of patients |
| PLCBO | Percentage of Patients Alive and Free of All Vasopressors | Day 14 | 94.7 Percentage of patients |
Secondary
Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration | 0.50 ng/mL | Standard Deviation 0.13 |
| FE 202158 2.5 | Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration | 0.99 ng/mL | Standard Deviation 0.32 |
Secondary
PK Parameter in Patients : Clearance
PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | PK Parameter in Patients : Clearance | 10.0 Litre/hour | Standard Deviation 2.8 |
| FE 202158 2.5 | PK Parameter in Patients : Clearance | 13.1 Litre/hour | Standard Deviation 2.9 |
Secondary
PK Parameter in Patients : Initial Elimination Half-life
PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | PK Parameter in Patients : Initial Elimination Half-life | 0.18 Hour | Standard Deviation 0.09 |
| FE 202158 2.5 | PK Parameter in Patients : Initial Elimination Half-life | 0.17 Hour | Standard Deviation 0.06 |
Secondary
PK Parameter in Patients : Steady State Volume of Distribution
PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | PK Parameter in Patients : Steady State Volume of Distribution | 25.5 Litre | Standard Deviation 10.6 |
| FE 202158 2.5 | PK Parameter in Patients : Steady State Volume of Distribution | 31.2 Litre | Standard Deviation 14.7 |
Secondary
PK Parameter in Patients : Terminal Elimination Half-life
PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | PK Parameter in Patients : Terminal Elimination Half-life | 2.5 Hour | Standard Deviation 1.1 |
| FE 202158 2.5 | PK Parameter in Patients : Terminal Elimination Half-life | 2.7 Hour | Standard Deviation 1.2 |
Secondary
PK Parameter in Patients : Time to Steady State
PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 202158 1.25 | PK Parameter in Patients : Time to Steady State | 7.6 Hour | Standard Deviation 2.8 |
| FE 202158 2.5 | PK Parameter in Patients : Time to Steady State | 7.0 Hour | Standard Deviation 2.3 |
Secondary
Pulmonary Function : Change From Baseline in PaO2/FiO2
Change from Baseline in PaO2/FiO2 was observed at each time-point. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 4 - 96 hours | 96.1 Ratio | Standard Deviation 97.2 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 48 hours | 16.2 Ratio | Standard Deviation 74.3 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 6 hours | -1.7 Ratio | Standard Deviation 80.3 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 4 - 84 hours | 61.4 Ratio | Standard Deviation 115 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 54 hours | 24.8 Ratio | Standard Deviation 137 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 6 - 144 hours | 42.8 Ratio | Standard Deviation 69.3 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 72 hours | 51.7 Ratio | Standard Deviation 120 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 60 hours | 118 Ratio | Standard Deviation 172 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 24 hours | -4.22 Ratio | Standard Deviation 84.4 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 66 hours | 64.7 Ratio | Standard Deviation 131 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 12 hours | 22.8 Ratio | Standard Deviation 95.3 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 6 - 132 hours | 123 Ratio | Standard Deviation 154 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 30 hours | 54.3 Ratio | Standard Deviation 142 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 7 - 168 hours | 117 Ratio | Standard Deviation 255 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 5 - 120 hours | 63.7 Ratio | Standard Deviation 130 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 36 hours | 15.8 Ratio | Standard Deviation 112 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 7 - 156 hours | 37.6 Ratio | Standard Deviation 68.3 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 5 - 108 hours | 123 Ratio | Standard Deviation 233 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 42 hours | 28.6 Ratio | Standard Deviation 137 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 18 hours | 12.1 Ratio | Standard Deviation 86.7 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 18 hours | -17.6 Ratio | Standard Deviation 94 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 6 hours | 1.35 Ratio | Standard Deviation 85.2 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 12 hours | -11.9 Ratio | Standard Deviation 61.9 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 24 hours | 34.8 Ratio | Standard Deviation 144 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 30 hours | -16.5 Ratio | Standard Deviation 116 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 36 hours | 6.89 Ratio | Standard Deviation 115 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 42 hours | -1.27 Ratio | Standard Deviation 118 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 48 hours | 10.3 Ratio | Standard Deviation 105 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 54 hours | 49.5 Ratio | Standard Deviation 81.1 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 60 hours | 9.8 Ratio | Standard Deviation 106 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 66 hours | 6.38 Ratio | Standard Deviation 70.1 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 72 hours | 74.2 Ratio | Standard Deviation 89.8 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 4 - 84 hours | 7.54 Ratio | Standard Deviation 85.4 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 7 - 156 hours | 40.9 Ratio | Standard Deviation 83.8 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 4 - 96 hours | 65.5 Ratio | Standard Deviation 112 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 5 - 108 hours | 30.1 Ratio | Standard Deviation 49.3 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 5 - 120 hours | 5.89 Ratio | Standard Deviation 58.3 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 6 - 132 hours | 7.17 Ratio | Standard Deviation 89.6 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 6 - 144 hours | 30.2 Ratio | Standard Deviation 83.7 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 7 - 168 hours | 59 Ratio | Standard Deviation 68.1 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 42 hours | 14.6 Ratio | Standard Deviation 123 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 6 - 144 hours | -19.6 Ratio | Standard Deviation 114 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 4 - 96 hours | 22.9 Ratio | Standard Deviation 128 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 36 hours | 39.8 Ratio | Standard Deviation 100 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 12 hours | 7.32 Ratio | Standard Deviation 72.3 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 5 - 108 hours | 38.4 Ratio | Standard Deviation 115 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 30 hours | 12.4 Ratio | Standard Deviation 96.1 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 7 - 156 hours | -19.1 Ratio | Standard Deviation 151 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 5 - 120 hours | 51.8 Ratio | Standard Deviation 132 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 24 hours | -3.68 Ratio | Standard Deviation 92.8 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 60 hours | 50 Ratio | Standard Deviation 108 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 6 hours | -7.06 Ratio | Standard Deviation 99.9 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 66 hours | 17.7 Ratio | Standard Deviation 120 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 54 hours | 19.4 Ratio | Standard Deviation 129 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 6 - 132 hours | 40.3 Ratio | Standard Deviation 133 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 3 - 72 hours | 21.8 Ratio | Standard Deviation 119 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 2 - 48 hours | 8.24 Ratio | Standard Deviation 135 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 1 - 18 hours | 9.21 Ratio | Standard Deviation 88.5 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 4 - 84 hours | 44.1 Ratio | Standard Deviation 97.9 |
| PLCBO | Pulmonary Function : Change From Baseline in PaO2/FiO2 | Day 7 - 168 hours | -30.2 Ratio | Standard Deviation 105 |
Secondary
Pulmonary Function : Change From Baseline in Tidal Volume
Change from Baseline in tidal volume was observed at each time-point. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7
Population: The analysis population consist of Safety Analysis Set, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 4 - 96 hours | -0.528 mL/kg | Standard Deviation 1.62 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 42 hours | -0.478 mL/kg | Standard Deviation 1.13 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 7 - 156 hours | 0.483 mL/kg | Standard Deviation 1.13 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 4 - 84 hours | 0.966 mL/kg | Standard Deviation 2.44 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 48 hours | -0.604 mL/kg | Standard Deviation 1.52 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 18 hours | 0.171 mL/kg | Standard Deviation 0.957 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 72 hours | -0.23 mL/kg | Standard Deviation 1.49 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 54 hours | -0.118 mL/kg | Standard Deviation 1.86 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 7 - 168 hours | -0.0667 mL/kg | Standard Deviation 1.1 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 66 hours | -0.01 mL/kg | Standard Deviation 1.37 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 60 hours | -0.214 mL/kg | Standard Deviation 1.1 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 6 - 132 hours | -0.298 mL/kg | Standard Deviation 1.41 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 24 hours | -1.1 mL/kg | Standard Deviation 1.16 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 6 - 144 hours | -0.458 mL/kg | Standard Deviation 1.09 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 5 - 120 hours | -0.338 mL/kg | Standard Deviation 2.24 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 30 hours | -0.81 mL/kg | Standard Deviation 1.15 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 12 hours | -0.208 mL/kg | Standard Deviation 0.708 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 5 - 108 hours | 0.633 mL/kg | Standard Deviation 1.93 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 36 hours | -0.208 mL/kg | Standard Deviation 1.24 |
| FE 202158 1.25 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 6 hours | -0.533 mL/kg | Standard Deviation 0.666 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 6 - 132 hours | 0.462 mL/kg | Standard Deviation 1.86 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 7 - 156 hours | -0.733 mL/kg | Standard Deviation 1.32 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 6 hours | 0.196 mL/kg | Standard Deviation 0.736 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 12 hours | 0.256 mL/kg | Standard Deviation 0.794 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 18 hours | 0.141 mL/kg | Standard Deviation 0.539 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 24 hours | 0.285 mL/kg | Standard Deviation 1.02 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 30 hours | 0.34 mL/kg | Standard Deviation 1.46 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 36 hours | 0.145 mL/kg | Standard Deviation 0.734 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 42 hours | 0.298 mL/kg | Standard Deviation 1.21 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 48 hours | 0.532 mL/kg | Standard Deviation 1.31 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 54 hours | 0.163 mL/kg | Standard Deviation 1.19 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 60 hours | 0.62 mL/kg | Standard Deviation 1.69 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 66 hours | 0.628 mL/kg | Standard Deviation 1.25 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 72 hours | 1.48 mL/kg | Standard Deviation 3.19 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 4 - 84 hours | 0.466 mL/kg | Standard Deviation 1.89 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 4 - 96 hours | -0.313 mL/kg | Standard Deviation 0.864 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 5 - 108 hours | 0.207 mL/kg | Standard Deviation 1.39 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 5 - 120 hours | -0.412 mL/kg | Standard Deviation 0.709 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 6 - 144 hours | 0.292 mL/kg | Standard Deviation 2.69 |
| FE 202158 2.5 | Pulmonary Function : Change From Baseline in Tidal Volume | Day 7 - 168 hours | -0.438 mL/kg | Standard Deviation 1.37 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 6 hours | -0.0189 mL/kg | Standard Deviation 1.91 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 4 - 84 hours | -0.844 mL/kg | Standard Deviation 2.03 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 36 hours | -0.223 mL/kg | Standard Deviation 1.64 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 7 - 168 hours | -2.19 mL/kg | Standard Deviation 2.93 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 4 - 96 hours | -1.16 mL/kg | Standard Deviation 2.44 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 30 hours | -0.0259 mL/kg | Standard Deviation 2.11 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 6 - 144 hours | -0.823 mL/kg | Standard Deviation 1.71 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 5 - 108 hours | -0.723 mL/kg | Standard Deviation 2.14 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 24 hours | 0 mL/kg | Standard Deviation 1.64 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 7 - 156 hours | -2.14 mL/kg | Standard Deviation 2.53 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 5 - 120 hours | -0.613 mL/kg | Standard Deviation 1.73 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 18 hours | -0.26 mL/kg | Standard Deviation 1.17 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 60 hours | -0.951 mL/kg | Standard Deviation 1.57 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 54 hours | -0.859 mL/kg | Standard Deviation 1.84 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 1 - 12 hours | -0.24 mL/kg | Standard Deviation 1.37 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 66 hours | -0.592 mL/kg | Standard Deviation 1.98 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 48 hours | -0.538 mL/kg | Standard Deviation 2.02 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 6 - 132 hours | -0.746 mL/kg | Standard Deviation 1.41 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 3 - 72 hours | -0.348 mL/kg | Standard Deviation 1.78 |
| PLCBO | Pulmonary Function : Change From Baseline in Tidal Volume | Day 2 - 42 hours | -1.19 mL/kg | Standard Deviation 1.33 |
Secondary
SOFA Score
The SOFA score, is used to track a patient's status during the stay in an intensive care unit. This scoring system is used to determine the extent of a person's organ function or rate of failure. The scoring system comprise of scores for six different system: Respiratory System; Nervous System; Cardiovascular System; Liver; Coagulation; and Renal System. Score for each system ranges from 0-4 (0=normal, 4=worst). Total SOFA score is a sum of the individual system score and range from 0 to 24, 0 being the better and 24 being the worst patient status. The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.
Time frame: Day 1 up to Day 7, Day 14 and Day 29
Population: The analysis population consist of FAS, which comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 202158 1.25 | SOFA Score | Day 7 (144-168 hours) | 4.63 Score on a scale | Standard Deviation 3.7 |
| FE 202158 1.25 | SOFA Score | Day 3 (48-72 hours) | 7.6 Score on a scale | Standard Deviation 3.53 |
| FE 202158 1.25 | SOFA Score | Day 14 | 5.0 Score on a scale | Standard Deviation 4.36 |
| FE 202158 1.25 | SOFA Score | Day 28 | 1.75 Score on a scale | Standard Deviation 2.36 |
| FE 202158 1.25 | SOFA Score | Day 4 (72-96 hours) | 6.8 Score on a scale | Standard Deviation 3.91 |
| FE 202158 1.25 | SOFA Score | Day 1 (0-24 hours) | 8.7 Score on a scale | Standard Deviation 2.45 |
| FE 202158 1.25 | SOFA Score | Day 5 (96-120 hours) | 6.6 Score on a scale | Standard Deviation 4.2 |
| FE 202158 1.25 | SOFA Score | Day 2 (24-48 hours) | 8.0 Score on a scale | Standard Deviation 3.5 |
| FE 202158 1.25 | SOFA Score | Day 6 (120-144 hours) | 5.22 Score on a scale | Standard Deviation 3.35 |
| FE 202158 2.5 | SOFA Score | Day 5 (96-120 hours) | 7.06 Score on a scale | Standard Deviation 3.49 |
| FE 202158 2.5 | SOFA Score | Day 7 (144-168 hours) | 5.93 Score on a scale | Standard Deviation 3.65 |
| FE 202158 2.5 | SOFA Score | Day 4 (72-96 hours) | 7.5 Score on a scale | Standard Deviation 3.91 |
| FE 202158 2.5 | SOFA Score | Day 6 (120-144 hours) | 6.63 Score on a scale | Standard Deviation 3.32 |
| FE 202158 2.5 | SOFA Score | Day 14 | 4.27 Score on a scale | Standard Deviation 3.82 |
| FE 202158 2.5 | SOFA Score | Day 3 (48-72 hours) | 8.32 Score on a scale | Standard Deviation 3.64 |
| FE 202158 2.5 | SOFA Score | Day 2 (24-48 hours) | 8.68 Score on a scale | Standard Deviation 3.07 |
| FE 202158 2.5 | SOFA Score | Day 28 | 2.7 Score on a scale | Standard Deviation 2.63 |
| FE 202158 2.5 | SOFA Score | Day 1 (0-24 hours) | 11.9 Score on a scale | Standard Deviation 3.43 |
| PLCBO | SOFA Score | Day 28 | 2.11 Score on a scale | Standard Deviation 0.93 |
| PLCBO | SOFA Score | Day 1 (0-24 hours) | 10.5 Score on a scale | Standard Deviation 3.22 |
| PLCBO | SOFA Score | Day 3 (48-72 hours) | 8.2 Score on a scale | Standard Deviation 2.57 |
| PLCBO | SOFA Score | Day 4 (72-96 hours) | 8.05 Score on a scale | Standard Deviation 2.82 |
| PLCBO | SOFA Score | Day 5 (96-120 hours) | 7.44 Score on a scale | Standard Deviation 2.77 |
| PLCBO | SOFA Score | Day 6 (120-144 hours) | 7.06 Score on a scale | Standard Deviation 3.02 |
| PLCBO | SOFA Score | Day 7 (144-168 hours) | 7.18 Score on a scale | Standard Deviation 2.65 |
| PLCBO | SOFA Score | Day 14 | 3.53 Score on a scale | Standard Deviation 1.81 |
| PLCBO | SOFA Score | Day 2 (24-48 hours) | 9.0 Score on a scale | Standard Deviation 2.83 |