Trial Outcomes & Findings for Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA (NCT NCT03119701)

NCT ID: NCT03119701

Last Updated: 2021-01-14

Results Overview

Number of fatalities

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: Day 30
• Results posted on: 2021-01-14

Participant Flow

Participant milestones

Measure	FP-1201-lyo 10 µg FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
6-day Dosing STARTED	29	11
6-day Dosing COMPLETED	22	8
6-day Dosing NOT COMPLETED	7	3
Mid-term (Final) Follow-up at D90 STARTED	25	10
Mid-term (Final) Follow-up at D90 COMPLETED	22	9
Mid-term (Final) Follow-up at D90 NOT COMPLETED	3	1

Reasons for withdrawal

Measure	FP-1201-lyo 10 µg FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
6-day Dosing Death	4	1
6-day Dosing Adverse Event	3	0
6-day Dosing Physician Decision	0	1
6-day Dosing Withdrawal by Subject	0	1
Mid-term (Final) Follow-up at D90 Death	3	1

Baseline Characteristics

Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA

Baseline characteristics by cohort

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for Investigational drug.	Total n=38 Participants Total of all reporting groups
Age, Customized < 70 years	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Age, Customized 70-80 years	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Age, Customized > 80 years	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	11 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	11 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Finland	23 participants n=5 Participants	8 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Lithuania	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Estonia	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Baseline Height	172.3 centimetres STANDARD_DEVIATION 6.34 • n=5 Participants	177.5 centimetres STANDARD_DEVIATION 7.59 • n=7 Participants	173.8 centimetres STANDARD_DEVIATION 7.05 • n=5 Participants
Baseline Weight	82.0 kilograms STANDARD_DEVIATION 16.14 • n=5 Participants	95.9 kilograms STANDARD_DEVIATION 21.21 • n=7 Participants	86.0 kilograms STANDARD_DEVIATION 18.58 • n=5 Participants

PRIMARY outcome

Timeframe: Day 30

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Number of fatalities

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality	6 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 90

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Number of fatalities

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality	7 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 30

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Number of ventilator free days. VFDs to Day 30 were defined as the number of calendar days after initiating unassisted breathing (UAB) to Day 30 from first treatment, assuming that a patient survives at least 48 consecutive hours after initiating UAB. Patients who die without initiating UAB were assigned a VFD value of zero.

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)	25.0 days Interval 0.0 to 30.0	29.0 days Interval 0.0 to 29.0

SECONDARY outcome

Timeframe: Day 30 and Day 90

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that had sufficient data to allow for calculation of the outcome measure.

Number of days receiving hemodialysis. There were only few reported values other than zero.

Outcome measures

Measure	FP-1201-lyo 10 µg n=21 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=9 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis Day 30	0.9 days Standard Deviation 4.15	0.0 days Standard Deviation 0.00
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis Day 90	0.6 days Standard Deviation 2.68	0.0 days Standard Deviation 0.00

SECONDARY outcome

Timeframe: Day 30

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Organ failure free days were defined as the number of days in the first 30 days after the first dose of study medication that the patient was alive and free of organ failure with a SOFA score of zero for the following six organ parameters: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. It is graded from 0 to 4 according to the degree of dysfunction/ failure (higher scores indicate more severe organ failure). Patients who died without achieving a SOFA score of zero was assigned an organ failure free days value of zero.

Note: the information for organ failure free days has been only collected when the patients have been in the Intensive Care Unit (ICU). As ICU free days have been reported in a separate variable, it was decided that presented information will be kept, without trying to conduct imputation.

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score	0.0 days Standard Deviation 0.00	0.0 days Standard Deviation 0.00

SECONDARY outcome

Timeframe: Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The number of participants analyzed reflects the number of patients that were alive and had sufficient data to allow for calculation of the outcome measure.

Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter.

Outcome measures

Measure	FP-1201-lyo 10 µg n=19 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=9 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 6	11.4 mmHg Standard Deviation 5.29	15.0 mmHg Standard Deviation 0
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 1	15.4 mmHg Standard Deviation 12.37	10.3 mmHg Standard Deviation 4.80
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 2	12.2 mmHg Standard Deviation 3.58	12.1 mmHg Standard Deviation 6.01
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 3	13.1 mmHg Standard Deviation 4.62	10.3 mmHg Standard Deviation 5.35
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 4	11.4 mmHg Standard Deviation 6.60	8.6 mmHg Standard Deviation 5.32
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 5	10.5 mmHg Standard Deviation 3.14	12.5 mmHg Standard Deviation 5.45
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 9	11.0 mmHg Standard Deviation 5.48	—
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) Day 13	10.8 mmHg Standard Deviation 4.49	—

SECONDARY outcome

Timeframe: Day 30

Population: At the Baseline Visit, 2 patients in the FP-1201-lyo treatment group and 1 patient in the placebo treatment group were not tested for anti-drug antibodies.

IFN beta-1a neutralizing antibodies immune response. Blood samples for the NAbs assessments were collected at Day 0 pre-dose (baseline) and at Day 30.

Outcome measures

Measure	FP-1201-lyo 10 µg n=25 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=10 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples Baseline	0 Participants	0 Participants
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples Day 30	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 90

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

Scale gives the degree of disability or dependence in the daily activities. Single mRS value is applied for every patient based on patient or caregiver interview. The scale runs from 0-6, from perfect health without symptoms to death. Pre-operation Baseline Visit mRS value is collected for reference.

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). No symptoms - 0	5 Participants	2 Participants
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). No significant disability - 1	5 Participants	5 Participants
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). Slight disability - 2	3 Participants	1 Participants
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). Moderate disability - 3	2 Participants	0 Participants
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). Moderately severe disability - 4	3 Participants	0 Participants
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). Severe disability - 5	2 Participants	1 Participants
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). Death - 6	7 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 0 to Day 30

Population: The Full Analysis Set for Safety (FAS-S) consisted of all randomised patients receiving study treatment and comprised the analysis set on which the evaluation of safety is based.

Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.

Outcome measures

Measure	FP-1201-lyo 10 µg n=29 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters Serious TEAEs	26 Events	5 Events
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters TEAEs Leading to Study Product Discontinuation	7 Events	1 Events
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters TEAEs Leading to Death	7 Events	1 Events
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters Severe TEAEs	28 Events	2 Events
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters Product-related TEAEs	17 Events	1 Events

SECONDARY outcome

Timeframe: Day 30 or Day 90

Population: The Full Analysis Set for Efficacy (FAS-E). As the study was discontinued, analyses were performed on the available data gathered thus far.

Economic measurement:

• Length of ICU stay, in terms of ICU free days at D30
• Length of hospital stay, in terms of hospital free days at D90
• Length of stay at another health care facility at D90
• The number of days on hemodialysis at D30 and at D90
• The number of organ failure free days at D30
• The number of ventilation free days at D30

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days ICU free days at Day 30	16.8 days Standard Deviation 12.39	21.9 days Standard Deviation 11.06
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days Days in hospital at Day 90	18.1 days Standard Deviation 9.84	13.8 days Standard Deviation 9.97
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days Days in another facility at Day 90	11.8 days Standard Deviation 23.79	7.0 days Standard Deviation 19.80
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days Days on hemodialysis at Day 30	0.9 days Standard Deviation 4.15	0.0 days Standard Deviation 0.00
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days Days on hemodialysis at Day 90	0.6 days Standard Deviation 2.68	0.0 days Standard Deviation 0.00
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days Organ failure free days at Day 30	0.0 days Standard Deviation 0.00	0.0 days Standard Deviation 0.00
Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days Ventilation free days at Day 30	20.6 days Standard Deviation 10.62	25.1 days Standard Deviation 8.85

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 up to Day 13

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.

Concentration of Myxovirus Resistant Protein A (MxA)

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Baseline	3.5 ng/mL Interval 2.4 to 5.1	6.0 ng/mL Interval 3.3 to 11.0
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 1	15.0 ng/mL Interval 10.2 to 22.1	5.1 ng/mL Interval 2.8 to 9.3
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 2	19.8 ng/mL Interval 13.5 to 29.1	3.8 ng/mL Interval 2.1 to 7.0
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 3	21.2 ng/mL Interval 14.3 to 31.4	3.3 ng/mL Interval 1.8 to 6.2
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 4	36.4 ng/mL Interval 24.4 to 54.2	4.1 ng/mL Interval 2.2 to 7.7
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 5	48.3 ng/mL Interval 32.3 to 72.3	3.1 ng/mL Interval 1.6 to 5.8
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 6	50.4 ng/mL Interval 33.9 to 75.1	3.6 ng/mL Interval 1.9 to 6.8
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 9	14.3 ng/mL Interval 9.5 to 21.5	4.8 ng/mL Interval 2.4 to 9.7
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker Day 13	3.9 ng/mL Interval 2.5 to 5.9	8.7 ng/mL Interval 3.7 to 20.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 up to Day 13

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.

CD73 (ecto-5'-nucleotidase enzyme) concentration

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Baseline	2.1 ng/mL Interval 1.8 to 2.5	2.2 ng/mL Interval 1.7 to 2.9
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 1	2.0 ng/mL Interval 1.7 to 2.4	2.2 ng/mL Interval 1.6 to 2.8
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 2	2.2 ng/mL Interval 1.8 to 2.6	2.2 ng/mL Interval 1.7 to 3.0
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 3	2.0 ng/mL Interval 1.7 to 2.4	2.3 ng/mL Interval 1.7 to 3.1
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 4	2.3 ng/mL Interval 1.9 to 2.8	2.6 ng/mL Interval 1.9 to 3.5
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 5	3.0 ng/mL Interval 2.4 to 3.6	3.5 ng/mL Interval 2.6 to 4.8
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 6	3.8 ng/mL Interval 3.2 to 4.6	3.8 ng/mL Interval 2.7 to 5.2
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 9	3.9 ng/mL Interval 3.2 to 4.8	3.8 ng/mL Interval 2.6 to 5.4
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples Day 13	2.9 ng/mL Interval 2.3 to 3.6	2.7 ng/mL Interval 1.7 to 4.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 up to Day 13

Population: The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.

IL-6 concentration.

Outcome measures

Measure	FP-1201-lyo 10 µg n=27 Participants FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 Participants FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples Baseline	328.9 pg/mL Interval 223.8 to 483.3	378.9 pg/mL Interval 207.3 to 692.6
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples Day 1	493.1 pg/mL Interval 335.5 to 724.5	460.2 pg/mL Interval 251.8 to 841.0
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples Day 3	181.4 pg/mL Interval 122.0 to 270.0	130.7 pg/mL Interval 69.8 to 244.8
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples Day 6	164.1 pg/mL Interval 108.1 to 249.2	79.1 pg/mL Interval 39.8 to 157.1
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples Day 9	107.9 pg/mL Interval 69.9 to 166.5	74.5 pg/mL Interval 34.4 to 161.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 up to Day 13

Population: Data were not collected or analyzed due to the small groups and interference of corticosteroids it was not meaningful to perform the analyzes.

HGF concentration.

Outcome measures

Outcome data not reported

Adverse Events

FP-1201-lyo 10 µg

Serious events: 13 serious events

Other events: 27 other events

Deaths: 7 deaths

FP-1201-lyo Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 2 deaths

Serious adverse events

Measure	FP-1201-lyo 10 µg n=29 participants at risk FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 participants at risk FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Cardiac disorders Myocardial ischaemia	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Gastric ulcer haemorrhage	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Gastrointestinal necrosis	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Intestinal ischaemia	10.3% 3/29 • Number of events 3 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Large intestine perforation	10.3% 3/29 • Number of events 3 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
General disorders Condition aggravated	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
General disorders Multiple organ dysfunction syndrome	13.8% 4/29 • Number of events 4 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Immune system disorders Anaphylactic reaction	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Pneumonia	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Sepsis	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Septic shock	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Post procedural haemorrhage	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Sternal fracture	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Nervous system disorders Ischaemic cerebral infarction	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Nervous system disorders Paraplegia	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Nervous system disorders Spinal epidural haematoma	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Renal and urinary disorders Renal failure	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Respiratory disorder	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)

Other adverse events

Measure	FP-1201-lyo 10 µg n=29 participants at risk FP-1201-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon Beta-1a: investigational drug.	FP-1201-lyo Placebo n=11 participants at risk FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection Placebo: placebo for investigational drug.
Infections and infestations Postoperative wound infection	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Pyelonephritis	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Urinary tract infection	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Abdominal wound dehiscence	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Anaemia postoperative	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Periprocedural myocardial infarction	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Post procedural constipation	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Post procedural haemorrhage	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Post procedural oedema	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Postoperative delirium	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Procedural pain	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Injury, poisoning and procedural complications Wound secretion	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Alanine aminotransferase increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Aspartate aminotransferase increased	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Blood alkaline phosphatase increased	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Blood bilirubin increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Blood calcium decreased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Blood creatine increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Blood potassium decreased	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Blood pressure increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Blood sodium increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations C-reactive protein increased	10.3% 3/29 • Number of events 3 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Haemoglobin decreased	13.8% 4/29 • Number of events 4 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Hepatic enzyme increased	10.3% 3/29 • Number of events 3 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Inflammatory marker increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Intra-abdominal pressure increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Liver function test abnormal	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Neutrophil count increased	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations Urine output decreased	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Investigations White blood cell count increased	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Metabolism and nutrition disorders Hyperglycaemia	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Metabolism and nutrition disorders Hypokalaemia	10.3% 3/29 • Number of events 3 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Musculoskeletal and connective tissue disorders Soft tissue necrosis	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Nervous system disorders Akathisia	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Psychiatric disorders Agitation	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Psychiatric disorders Anxiety	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Psychiatric disorders Confusional state	13.8% 4/29 • Number of events 4 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	18.2% 2/11 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Psychiatric disorders Delirium	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Psychiatric disorders Disorientation	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Psychiatric disorders Restlessness	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Psychiatric disorders Sleep disorder	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Renal and urinary disorders Acute kidney injury	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Renal and urinary disorders Oliguria	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Renal and urinary disorders Renal failure	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Aspiration	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Bronchospasm	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Emphysema	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Lung infiltration	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Vascular disorders Embolism arterial	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Vascular disorders Hypertension	13.8% 4/29 • Number of events 4 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	18.2% 2/11 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Vascular disorders Hypotension	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Vascular disorders Hypovolaemic shock	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Vascular disorders Peripheral ischaemia	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Blood and lymphatic system disorders Anaemia	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Blood and lymphatic system disorders Leukocytosis	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Blood and lymphatic system disorders Thrombocytopenia	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Cardiac disorders Atrial fibrillation	17.2% 5/29 • Number of events 5 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	27.3% 3/11 • Number of events 4 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Cardiac disorders Cardiac failure congestive	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Cardiac disorders Tachycardia	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Cardiac disorders Tachycardia paroxysmal	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Eye disorders Eye irritation	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Constipation	10.3% 3/29 • Number of events 3 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Diarrhoea	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Ileus	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Gastrointestinal disorders Nausea	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
General disorders Chills	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
General disorders Pain	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
General disorders Pyrexia	20.7% 6/29 • Number of events 6 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
General disorders Systemic inflammatory response syndrome	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Hepatobiliary disorders Hepatic failure	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Candida infection	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Catheter site infection	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Clostridium difficile colitis	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Device related infection	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Fungal skin infection	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Infection	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Influenza	0.00% 0/29 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	9.1% 1/11 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Lung infection	3.4% 1/29 • Number of events 1 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
Infections and infestations Pneumonia	6.9% 2/29 • Number of events 2 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)	0.00% 0/11 • The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90. The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)

Additional Information

Chief Medical Officer

Faron Pharmaceuticals Ltd

Phone: +3584005529411

Email: medical@faron.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER