Trial Outcomes & Findings for Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS) (NCT NCT02622724)

NCT ID: NCT02622724

Last Updated: 2020-03-30

Results Overview

VFDsurv is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFDsurv) within 28 days among survivors. Ventilator-free days (VFDs) correspond to those days when unassisted breathing (UAB) was possible for a complete calendar day. UAB was defined as: spontaneously breathing with face mask, nasal prong oxygen or room air, T-piece breathing, tracheostomy mask breathing, CPAP less than or equal to 5 cmH2O without pressure support or intermittent mandatory ventilation assistance, use of CPAP or BIPAP solely for sleep apnoea management. A patient was reported as ventilator-free after 2 consecutive calendar days of unassisted breathing (a VFD value of 0 is assigned to patients who die without initiating UAB or who require more than 28 days of mechanical ventilation. All patients who die before Day28 are assigned a VFDsurv value of -1).

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 301 participants
• Primary outcome timeframe: Day 28
• Results posted on: 2020-03-30

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	Placebo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Overall Study STARTED	144	152
Overall Study Subjects Randomised	146	155
Overall Study Short-Term Follow-Up (Day 28)	105	115
Overall Study Long-Term Follow-Up (Day 90)	96	101
Overall Study Long-Term Follow-Up (Day 180)	73	74
Overall Study COMPLETED	51	49
Overall Study NOT COMPLETED	93	103

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	Placebo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Overall Study Death	51	53
Overall Study Lost to Follow-UP, withdrawal of consent	4	7
Overall Study Early termination of study	38	43

Baseline Characteristics

Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS)

Baseline characteristics by cohort

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug	Total n=296 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	89 Participants n=5 Participants	101 Participants n=7 Participants	190 Participants n=5 Participants
Age, Categorical >=65 years	55 Participants n=5 Participants	51 Participants n=7 Participants	106 Participants n=5 Participants
Age, Continuous	58.3 years STANDARD_DEVIATION 17.2 • n=5 Participants	58.4 years STANDARD_DEVIATION 14.0 • n=7 Participants	58.4 years STANDARD_DEVIATION 15.6 • n=5 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	61 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	91 Participants n=7 Participants	193 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian/Alaskan	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Arab	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian-Other	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other or not reported	35 Participants n=5 Participants	36 Participants n=7 Participants	71 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	99 Participants n=5 Participants	106 Participants n=7 Participants	205 Participants n=5 Participants
Region of Enrollment Belgium	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment Czechia	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Finland	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Italy	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Region of Enrollment United Kingdom	25 Participants n=5 Participants	29 Participants n=7 Participants	54 Participants n=5 Participants
Region of Enrollment France	54 Participants n=5 Participants	58 Participants n=7 Participants	112 Participants n=5 Participants
Region of Enrollment Germany	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Spain	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28

Population: Full Analysis Set (FAS), 296 subjects.

VFDsurv is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFDsurv) within 28 days among survivors. Ventilator-free days (VFDs) correspond to those days when unassisted breathing (UAB) was possible for a complete calendar day. UAB was defined as: spontaneously breathing with face mask, nasal prong oxygen or room air, T-piece breathing, tracheostomy mask breathing, CPAP less than or equal to 5 cmH2O without pressure support or intermittent mandatory ventilation assistance, use of CPAP or BIPAP solely for sleep apnoea management. A patient was reported as ventilator-free after 2 consecutive calendar days of unassisted breathing (a VFD value of 0 is assigned to patients who die without initiating UAB or who require more than 28 days of mechanical ventilation. All patients who die before Day28 are assigned a VFDsurv value of -1).

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28	10 Days Interval -1.0 to 26.0	8.5 Days Interval -1.0 to 26.0

SECONDARY outcome

Timeframe: At Day 28

Population: Full Analysis Set (FAS) defined as all randomised subjects that received atleast one dose of study drug.

Fatalities, mortality all-causes from randomisation up to Day 28

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Efficacy Endpoint: All-cause Mortality	26.4 percentage of subjects Interval 19.0 to 34.0	23 percentage of subjects Interval 17.0 to 31.0

SECONDARY outcome

Timeframe: Up to Day 28

Population: Full Analysis Set

All-cause mortality for subjects who died in Intensive Care Units up to Day 28.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Efficacy Endpoint: Mortality in ICU	25.7 percentage of subjects Interval 19.0 to 34.0	23.0 percentage of subjects Interval 17.0 to 31.0

SECONDARY outcome

Timeframe: Up to Day 28

Population: Full Analysis Set

This is the number of subjects who died in hospital (i.e. outside of Intensive Care Units) up to Day 28.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Efficacy Endpoint: Mortality in Hospital	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 28 or last day in intensive care unit [ICU] if patient has left the ICU earlier than Day 28

Population: Full Analysis Set

The total number of days free of organ failure by Sequential Organ Failure Assessment (SOFA) methodology. Overall, the median number of days free of organ failure was 0 days in both the treatment groups.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Other Secondary Efficacy Endpoints: Days Free of Organ Failure	0 Days Interval 0.0 to 28.0	0 Days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: Day 28

Population: Full Analysis Set

Days without renal support (any renal support was documented). Overall, the median number of days free of renal support was 28 days in the active group and 27 days in the placebo group.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Other Secondary Efficacy Endpoints: Days Free of Renal Support	28 Days Interval 0.0 to 28.0	27 Days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: Day 28

Population: Full Analysis Set

Days without vasoactive support. The vasoactive support included catecholamine and non-catecholamine vasopressors, inotropes and vasodilating agents.

Overall, the median number of days free of vasoactive support was 20 days in the active group and 21 days in the placebo group.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support	20 Days Interval 0.0 to 28.0	21 Days Interval 1.0 to 28.0

SECONDARY outcome

Timeframe: Day 28

Population: Full Analysis Set

The total number of days free of mechanical ventilation has been derived from the Patient Status report recorded on each day during the 28-day period. Patients who died during this period have been assigned a value of zero. This variable differs from the calculated "Ventilation Free Days (VFD) endpoint, which contribute to the VDFsurv primary efficacy endpoint as it require additional conditions of unassisted breathing (UAB) to be met.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation	10 Days Interval 0.0 to 26.0	9 Days Interval 0.0 to 26.0

SECONDARY outcome

Timeframe: Day 28

Population: Full Analysis Set

Number of Intensive Care Unit free days up to Day 28, i.e. the patient is no longer receiving care in ICU. Patients who die during this period have been assigned a value of zero for the number of ICU care free days.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Other Secondary Efficacy Endpoints: Number of ICU-free Days	6 Days Interval 0.0 to 24.0	3.5 Days Interval 0.0 to 24.0

SECONDARY outcome

Timeframe: Day 28

Population: Full Analysis Set

Hospitalisation days (including the stay at Intensive Care Units). Patients who died during this period have been assigned a value of 28 for the number of days in ICU or in hospital.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Other Secondary Efficacy Endpoints: Number of Days in Hospital	28 Days Interval 8.0 to 28.0	28 Days Interval 8.0 to 28.0

SECONDARY outcome

Timeframe: AEs up to Day 28, only related after Day 28 and deaths up to Day 360

Population: The analysis population included all participants who were randomized and received at least 1 dose of study treatment.

Adverse events (AE) up to Day 28. Per protocol, AEs occurring after Day 28 if the investigator considered a causal relationship with the study drug as well as all deaths up to Day 360 were reported. Treatment-emergent AEs (TEAEs) were defined as AEs that begins or worsens in intensity after at least one dose of study drug has been administered. Serious AEs (SAEs) were defined as any untoward medical occurrence that at any dose resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was an important medical event.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Evaluation of Safety: Adverse Events and Deaths Subjects with SAE	77 Participants	77 Participants
Evaluation of Safety: Adverse Events and Deaths Death	51 Participants	53 Participants
Evaluation of Safety: Adverse Events and Deaths Subjects with TEAE	130 Participants	132 Participants
Evaluation of Safety: Adverse Events and Deaths Subjects with AE considered related to study drug	41 Participants	33 Participants

SECONDARY outcome

Timeframe: Baseline and Day 28 (or last day in intensive care unit [ICU] or at withdrawal, if earlier)

Population: Full Analysis Set, the subjects who had laboratory evaluation done. Subjects were analysed for IFN beta NAbs only if BAbs were present.

The immunological response to FP-1201-lyo was assessed by monitoring presence of anti-drug binding antibodies (BAbs) and neutralising antibodies (NAbs) to IFN beta-1a on pre-dose Day 1 and at Day 28, the last day in ICU or early termination (if earlier). The BAbs were determined first, and if present, the NAbs were also determined. Presence of BAbs and NAbs were summarised categorically, using positive/negative classification.

Outcome measures

Measure	FP-1201-lyo 10 μg n=142 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	Placebo n=148 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a Presence of BAbs to IFN β-1a at baseline	2 Participants	2 Participants
Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a Presence of BAbs to IFN β-1a at Day28	0 Participants	1 Participants
Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a Presence of NAbs to IFN β-1a at baseline	1 Participants	0 Participants
Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a Presence of NAbs to IFN β-1a at Day28	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to Day 14

Population: Subjects from Full Analysis Set population for whom samples were available; analysis of last observation performed.

Evaluation of MxA biomarker change from baseline to D14 between treatments arms over time.

Outcome measures

Measure	FP-1201-lyo 10 μg n=137 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	Placebo n=143 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Efficacy Endpoint: Evaluation of Pharmacodynamic (PD) Using Myxovirus Resistance Protein A (MxA) Biomarker	31.8 ng/ml Standard Deviation 63.3	7.8 ng/ml Standard Deviation 28.8

SECONDARY outcome

Timeframe: Change from baseline to Day 180

Population: Subjects from Full Analysis Set population who completed QoL questionnaire at Baseline and Day 180.

Quality of Life was assessed through EQ-5D-3L (EuroQol 5-Dimensions 3-Levels questionnaire). An EQ Visual Analogue Scale (VAS) total score (ranging from 0-100) was measured (0= Worst imaginable health state, 100= Best imaginable health state). The EQ-5D-3L VAS scores are numerically summarised as change from pre-dose (Day 1) to long term follow-up (Day 180 visit).

Outcome measures

Measure	FP-1201-lyo 10 μg n=53 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	Placebo n=43 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Long-term Efficacy Endpoint: Change in Quality of Life From Baseline to Day 180	-10 change score on a scale Interval -55.0 to 70.0	-5 change score on a scale Interval -60.0 to 91.0

SECONDARY outcome

Timeframe: Day 180

Population: Full Analysis Set

Measuring FEV1 (forced expiratory volume in 1 second) assessed pulmonary function (airway obstruction, bronchoconstriction or bronchodilation). FEV1 is the volume exhaled during the first second of a forced expiratory manoeuvre, starting from the level of total lung capacity.

Outcome measures

Measure	FP-1201-lyo 10 μg n=48 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	Placebo n=45 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Long-term Efficacy Endpoints Relating to Respiratory Functioning (FEV1)	81.2 %FEV1 Standard Deviation 21.1	79.5 %FEV1 Standard Deviation 29.6

SECONDARY outcome

Timeframe: Day 180

Population: All subjects in Full Analysis Set population who performed atleast one 6MWT test at Day 180 visit. Furthest distance walked during the two tests was analysed using an ANOVA model.

The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % conf.interval) for the overall treatment difference was analysed.

Outcome measures

Measure	FP-1201-lyo 10 μg n=48 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	Placebo n=45 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Long-term Efficacy Endpoints Relating to Neurological Functioning (6MWT)	449 maximum distance walked (meters) Standard Deviation 174	424 maximum distance walked (meters) Standard Deviation 156

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Safety Population - no statistical analyses were made for vital signs.

Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.

No statistical analyses were made for vital signs.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Evaluation of Safety: Vital Signs - Heart Rate Heart Rate, bpm : Pre-Dose	93.4 bpm Standard Deviation 22.2	94.8 bpm Standard Deviation 22.5
Evaluation of Safety: Vital Signs - Heart Rate Heart Rate, bpm : LOP	92.5 bpm Standard Deviation 18.3	92.7 bpm Standard Deviation 19.0

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Safety Population - no statistical analyses were made for vital signs.

Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.

No statistical analyses were made for vital signs.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Evaluation of Safety: Vital Signs - Body Temperature Body Temperature, degrees C : Pre-Dose	37.1 degrees Celsius Standard Deviation 1.1	37.2 degrees Celsius Standard Deviation 1.1
Evaluation of Safety: Vital Signs - Body Temperature Body Temperature, degrees C : LOP	36.9 degrees Celsius Standard Deviation 0.9	36.8 degrees Celsius Standard Deviation 0.7

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Safety Population - no statistical analyses were made for vital signs.

Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.

No statistical analyses were made for vital signs.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Evaluation of Safety: Vital Signs - Blood Pressure Systolic Blood Pressure, mmHg: Pre-Dose	114.6 mmHg Standard Deviation 20.4	110.2 mmHg Standard Deviation 18.0
Evaluation of Safety: Vital Signs - Blood Pressure Systolic Blood Pressure, mmHg : LOP	124.3 mmHg Standard Deviation 22.8	120.3 mmHg Standard Deviation 26.2
Evaluation of Safety: Vital Signs - Blood Pressure Diastolic Blood Pressure, mmHg : Pre-Dose	58.9 mmHg Standard Deviation 12.9	55.6 mmHg Standard Deviation 9.7
Evaluation of Safety: Vital Signs - Blood Pressure Diastolic Blood Pressure, mmHg : LOP	65.1 mmHg Standard Deviation 14.8	62.6 mmHg Standard Deviation 13.8
Evaluation of Safety: Vital Signs - Blood Pressure Mean Arterial Pressure, mmHg : Pre-Dose	76.5 mmHg Standard Deviation 13.9	73.6 mmHg Standard Deviation 11.2
Evaluation of Safety: Vital Signs - Blood Pressure Mean Arterial Pressure, mmHg : LOP	82.7 mmHg Standard Deviation 15.5	80.8 mmHg Standard Deviation 16.6

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Last Observation Performed (D28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Safety population - no statistical analyses were made

Physical examination data (covering the major body systems; general appearance, head [ear, nose and throat], cardiovascular, eyes, respiratory, abdomen, urogenital, musculoskeletal, neurological, lymph nodes and skin) were categorized as "normal"; "abnormal, not clinically significant;" "abnormal, clinically significant" or "not done". Physical examinations were performed at Screening, then at the Last day in ICU and Day 28 (Out of ICU) or Early Termination, from which the last observation performed is derived. The changes from baseline to the last observations performed are categorized as "no change", "change clinically significant"; "change not clinically significant", "not done".

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Evaluation of Safety: Physical Examination Urogenital · Not done	32 Participants	38 Participants
Evaluation of Safety: Physical Examination Musculoskeletal · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Lymph nodes · Not done	39 Participants	39 Participants
Evaluation of Safety: Physical Examination Lymph nodes · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Skin · Change, Clinically Significant	3 Participants	8 Participants
Evaluation of Safety: Physical Examination Urogenital · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Musculoskeletal · No change	59 Participants	63 Participants
Evaluation of Safety: Physical Examination General Appearance · No change	59 Participants	66 Participants
Evaluation of Safety: Physical Examination Musculoskeletal · Change, Clinically Significant	11 Participants	8 Participants
Evaluation of Safety: Physical Examination General Appearance · Change, Clinically Significant	8 Participants	9 Participants
Evaluation of Safety: Physical Examination General Appearance · Change, Not Clinically Significant	8 Participants	8 Participants
Evaluation of Safety: Physical Examination General Appearance · Not done	33 Participants	34 Participants
Evaluation of Safety: Physical Examination General Appearance · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Ear, Nose and Throat · No change	67 Participants	75 Participants
Evaluation of Safety: Physical Examination Ear, Nose and Throat · Change, Clinically Significant	2 Participants	1 Participants
Evaluation of Safety: Physical Examination Ear, Nose and Throat · Change, Not Clinically Significant	5 Participants	6 Participants
Evaluation of Safety: Physical Examination Ear, Nose and Throat · Not done	34 Participants	35 Participants
Evaluation of Safety: Physical Examination Ear, Nose and Throat · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Eyes · No change	70 Participants	76 Participants
Evaluation of Safety: Physical Examination Eyes · Change, Clinically Significant	1 Participants	1 Participants
Evaluation of Safety: Physical Examination Eyes · Change, Not Clinically Significant	2 Participants	3 Participants
Evaluation of Safety: Physical Examination Eyes · Not done	35 Participants	36 Participants
Evaluation of Safety: Physical Examination Eyes · Not available/pt died	36 Participants	36 Participants
Evaluation of Safety: Physical Examination Respiratory · No change	27 Participants	30 Participants
Evaluation of Safety: Physical Examination Respiratory · Change, Clinically Significant	30 Participants	28 Participants
Evaluation of Safety: Physical Examination Respiratory · Change, Not Clinically Significant	21 Participants	26 Participants
Evaluation of Safety: Physical Examination Respiratory · Not done	30 Participants	33 Participants
Evaluation of Safety: Physical Examination Respiratory · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Abdomen · No change	65 Participants	70 Participants
Evaluation of Safety: Physical Examination Abdomen · Change, Clinically Significant	3 Participants	2 Participants
Evaluation of Safety: Physical Examination Abdomen · Change, Not Clinically Significant	9 Participants	10 Participants
Evaluation of Safety: Physical Examination Abdomen · Not done	31 Participants	35 Participants
Evaluation of Safety: Physical Examination Abdomen · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Urogenital · No change	67 Participants	72 Participants
Evaluation of Safety: Physical Examination Urogenital · Change, Clinically Significant	3 Participants	3 Participants
Evaluation of Safety: Physical Examination Urogenital · Change, Not Clinically Significant	6 Participants	4 Participants
Evaluation of Safety: Physical Examination Musculoskeletal · Change, Not Clinically Significant	5 Participants	9 Participants
Evaluation of Safety: Physical Examination Musculoskeletal · Not done	33 Participants	37 Participants
Evaluation of Safety: Physical Examination Neurological · No change	49 Participants	55 Participants
Evaluation of Safety: Physical Examination Neurological · Change, Clinically Significant	18 Participants	14 Participants
Evaluation of Safety: Physical Examination Neurological · Change, Not Clinically Significant	8 Participants	13 Participants
Evaluation of Safety: Physical Examination Neurological · Not done	33 Participants	34 Participants
Evaluation of Safety: Physical Examination Neurological · Not available/pt died	36 Participants	36 Participants
Evaluation of Safety: Physical Examination Lymph nodes · No change	69 Participants	78 Participants
Evaluation of Safety: Physical Examination Lymph nodes · Change, Clinically Significant	0 Participants	0 Participants
Evaluation of Safety: Physical Examination Lymph nodes · Change, Not Clinically Significant	0 Participants	0 Participants
Evaluation of Safety: Physical Examination Skin · No change	64 Participants	64 Participants
Evaluation of Safety: Physical Examination Skin · Change, Not Clinically Significant	5 Participants	8 Participants
Evaluation of Safety: Physical Examination Skin · Not done	36 Participants	37 Participants
Evaluation of Safety: Physical Examination Skin · Not available/pt died	36 Participants	35 Participants
Evaluation of Safety: Physical Examination Cardiovascular · No change	56 Participants	60 Participants
Evaluation of Safety: Physical Examination Cardiovascular · Change, Clinically Significant	9 Participants	8 Participants
Evaluation of Safety: Physical Examination Cardiovascular · Change, Not Clinically Significant	8 Participants	12 Participants
Evaluation of Safety: Physical Examination Cardiovascular · Not done	33 Participants	37 Participants
Evaluation of Safety: Physical Examination Cardiovascular · Not available/pt died	38 Participants	35 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Safety Population -no statistical analyses were made

Laboratory safety assessments of biochemistry, haematology and urinalysis were performed daily during the stay at ICU. Laboratory data were classified according to normal ranges as out of range (OOR; not clinically significant), OOR (clinically significant), or OOR (clinically significant and an AE). Laboratory test results were summarised by actual results by baseline and last observation period.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Evaluation of Safety: Laboratory Results Platelets, LOP · Normal	76 Participants	65 Participants
Evaluation of Safety: Laboratory Results Platelets, LOP · Not available/pt died	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Leucocytes, Pre-Dose · Normal	40 Participants	58 Participants
Evaluation of Safety: Laboratory Results Leucocytes, Pre-Dose · OOR (CS)	32 Participants	36 Participants
Evaluation of Safety: Laboratory Results Leucocytes, LOP · OOR (CS)	15 Participants	21 Participants
Evaluation of Safety: Laboratory Results Leucocytes, LOP · OOR (CS+AE)	3 Participants	4 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, Pre-Dose · OOR (NCS)	32 Participants	45 Participants
Evaluation of Safety: Laboratory Results Creatinine, LOP · OOR (CS+AE)	5 Participants	1 Participants
Evaluation of Safety: Laboratory Results Creatinine, LOP · Not available/pt died	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Bilirubin, Pre-Dose · Not available/pt died	10 Participants	7 Participants
Evaluation of Safety: Laboratory Results AST, Pre-Dose · OOR (CS)	18 Participants	14 Participants
Evaluation of Safety: Laboratory Results ALT, LOP · OOR (CS+AE)	10 Participants	8 Participants
Evaluation of Safety: Laboratory Results ALT, LOP · Not available/pt died	2 Participants	1 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, Pre-Dose · Normal	22 Participants	30 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, Pre-Dose · OOR (NCS)	103 Participants	107 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, Pre-Dose · OOR (CS)	19 Participants	14 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, Pre-Dose · Not available/pt died	0 Participants	1 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, LOP · Normal	17 Participants	18 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, LOP · OOR (NCS)	100 Participants	117 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, LOP · OOR (CS)	23 Participants	16 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, LOP · OOR (CS+AE)	3 Participants	1 Participants
Evaluation of Safety: Laboratory Results Haemoglobin, LOP · Not available/pt died	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Platelets, Pre-Dose · Normal	85 Participants	91 Participants
Evaluation of Safety: Laboratory Results Platelets, Pre-Dose · OOR (NCS)	43 Participants	42 Participants
Evaluation of Safety: Laboratory Results Platelets, Pre-Dose · OOR (CS)	16 Participants	17 Participants
Evaluation of Safety: Laboratory Results Platelets, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Platelets, Pre-Dose · Not available/pt died	0 Participants	2 Participants
Evaluation of Safety: Laboratory Results Platelets, LOP · OOR (NCS)	52 Participants	72 Participants
Evaluation of Safety: Laboratory Results Platelets, LOP · OOR (CS)	10 Participants	10 Participants
Evaluation of Safety: Laboratory Results Platelets, LOP · OOR (CS+AE)	5 Participants	5 Participants
Evaluation of Safety: Laboratory Results Leucocytes, Pre-Dose · OOR (NCS)	72 Participants	56 Participants
Evaluation of Safety: Laboratory Results Leucocytes, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Leucocytes, Pre-Dose · Not available/pt died	0 Participants	2 Participants
Evaluation of Safety: Laboratory Results Leucocytes, LOP · Normal	72 Participants	57 Participants
Evaluation of Safety: Laboratory Results Leucocytes, LOP · OOR (NCS)	52 Participants	70 Participants
Evaluation of Safety: Laboratory Results Leucocytes, LOP · Not available/pt died	2 Participants	0 Participants
Evaluation of Safety: Laboratory Results Albumin, Pre-Dose · Normal	17 Participants	17 Participants
Evaluation of Safety: Laboratory Results Albumin, Pre-Dose · OOR (NCS)	83 Participants	106 Participants
Evaluation of Safety: Laboratory Results Albumin, Pre-Dose · OOR (CS)	20 Participants	14 Participants
Evaluation of Safety: Laboratory Results Albumin, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Albumin, Pre-Dose · Not available/pt died	24 Participants	15 Participants
Evaluation of Safety: Laboratory Results Albumin, LOP · Normal	26 Participants	25 Participants
Evaluation of Safety: Laboratory Results Albumin, LOP · OOR (NCS)	97 Participants	117 Participants
Evaluation of Safety: Laboratory Results Albumin, LOP · OOR (CS)	18 Participants	9 Participants
Evaluation of Safety: Laboratory Results Albumin, LOP · OOR (CS+AE)	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Albumin, LOP · Not available/pt died	2 Participants	1 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, Pre-Dose · Normal	59 Participants	62 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, Pre-Dose · OOR (CS)	19 Participants	11 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, Pre-Dose · OOR (CS+AE)	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, Pre-Dose · Not available/pt died	33 Participants	34 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, LOP · Normal	82 Participants	93 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, LOP · OOR (NCS)	45 Participants	45 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, LOP · OOR (CS)	11 Participants	8 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, LOP · OOR (CS+AE)	2 Participants	0 Participants
Evaluation of Safety: Laboratory Results Creatine Kinase, LOP · Not available/pt died	4 Participants	6 Participants
Evaluation of Safety: Laboratory Results Creatinine, Pre-Dose · Normal	78 Participants	72 Participants
Evaluation of Safety: Laboratory Results Creatinine, Pre-Dose · OOR (NCS)	41 Participants	50 Participants
Evaluation of Safety: Laboratory Results Creatinine, Pre-Dose · OOR (CS)	23 Participants	28 Participants
Evaluation of Safety: Laboratory Results Creatinine, Pre-Dose · OOR (CS+AE)	2 Participants	0 Participants
Evaluation of Safety: Laboratory Results Creatinine, Pre-Dose · Not available/pt died	0 Participants	2 Participants
Evaluation of Safety: Laboratory Results Creatinine, LOP · Normal	69 Participants	73 Participants
Evaluation of Safety: Laboratory Results Creatinine, LOP · OOR (NCS)	56 Participants	64 Participants
Evaluation of Safety: Laboratory Results Creatinine, LOP · OOR (CS)	13 Participants	14 Participants
Evaluation of Safety: Laboratory Results Glucose, Pre-Dose · Normal	56 Participants	53 Participants
Evaluation of Safety: Laboratory Results Glucose, Pre-Dose · OOR (NCS)	76 Participants	85 Participants
Evaluation of Safety: Laboratory Results Glucose, Pre-Dose · OOR (CS)	11 Participants	10 Participants
Evaluation of Safety: Laboratory Results Glucose, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Glucose, Pre-Dose · Not available/pt died	1 Participants	4 Participants
Evaluation of Safety: Laboratory Results Glucose, LOP · Normal	65 Participants	74 Participants
Evaluation of Safety: Laboratory Results Glucose, LOP · OOR (NCS)	71 Participants	75 Participants
Evaluation of Safety: Laboratory Results Glucose, LOP · OOR (CS)	7 Participants	3 Participants
Evaluation of Safety: Laboratory Results Glucose, LOP · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Glucose, LOP · Not available/pt died	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Bilirubin, Pre-Dose · Normal	88 Participants	106 Participants
Evaluation of Safety: Laboratory Results Bilirubin, Pre-Dose · OOR (NCS)	37 Participants	33 Participants
Evaluation of Safety: Laboratory Results Bilirubin, Pre-Dose · OOR (CS)	9 Participants	6 Participants
Evaluation of Safety: Laboratory Results Bilirubin, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Bilirubin, LOP · Normal	114 Participants	121 Participants
Evaluation of Safety: Laboratory Results Bilirubin, LOP · OOR (NCS)	19 Participants	23 Participants
Evaluation of Safety: Laboratory Results Bilirubin, LOP · OOR (CS)	4 Participants	3 Participants
Evaluation of Safety: Laboratory Results Bilirubin, LOP · OOR (CS+AE)	6 Participants	5 Participants
Evaluation of Safety: Laboratory Results Bilirubin, LOP · Not available/pt died	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results AST, Pre-Dose · Normal	57 Participants	52 Participants
Evaluation of Safety: Laboratory Results AST, Pre-Dose · OOR (NCS)	50 Participants	70 Participants
Evaluation of Safety: Laboratory Results AST, Pre-Dose · OOR (CS+AE)	2 Participants	0 Participants
Evaluation of Safety: Laboratory Results AST, Pre-Dose · Not available/pt died	17 Participants	16 Participants
Evaluation of Safety: Laboratory Results AST, LOP · Normal	67 Participants	76 Participants
Evaluation of Safety: Laboratory Results AST, LOP · OOR (NCS)	54 Participants	56 Participants
Evaluation of Safety: Laboratory Results AST, LOP · OOR (CS)	8 Participants	11 Participants
Evaluation of Safety: Laboratory Results AST, LOP · OOR (CS+AE)	11 Participants	7 Participants
Evaluation of Safety: Laboratory Results AST, LOP · Not available/pt died	4 Participants	2 Participants
Evaluation of Safety: Laboratory Results ALT, Pre-Dose · Normal	86 Participants	92 Participants
Evaluation of Safety: Laboratory Results ALT, Pre-Dose · OOR (NCS)	37 Participants	43 Participants
Evaluation of Safety: Laboratory Results ALT, Pre-Dose · OOR (CS)	9 Participants	9 Participants
Evaluation of Safety: Laboratory Results ALT, Pre-Dose · OOR (CS+AE)	2 Participants	0 Participants
Evaluation of Safety: Laboratory Results ALT, Pre-Dose · Not available/pt died	10 Participants	8 Participants
Evaluation of Safety: Laboratory Results ALT, LOP · Normal	72 Participants	85 Participants
Evaluation of Safety: Laboratory Results ALT, LOP · OOR (NCS)	52 Participants	46 Participants
Evaluation of Safety: Laboratory Results ALT, LOP · OOR (CS)	8 Participants	12 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, Pre-Dose · Normal	90 Participants	97 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, Pre-Dose · OOR (NCS)	44 Participants	47 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, Pre-Dose · OOR (CS)	8 Participants	7 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, Pre-Dose · Not available/pt died	2 Participants	1 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, LOP · Normal	89 Participants	105 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, LOP · OOR (NCS)	47 Participants	41 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, LOP · OOR (CS)	7 Participants	6 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, LOP · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Bicarbonate, LOP · Not available/pt died	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Urine Protein, Pre-Dose · Normal	52 Participants	54 Participants
Evaluation of Safety: Laboratory Results Urine Protein, Pre-Dose · OOR (NCS)	67 Participants	73 Participants
Evaluation of Safety: Laboratory Results Urine Protein, Pre-Dose · OOR (CS)	5 Participants	7 Participants
Evaluation of Safety: Laboratory Results Urine Protein, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Urine Protein, Pre-Dose · Not available/pt died	20 Participants	18 Participants
Evaluation of Safety: Laboratory Results Urine Protein, LOP · Normal	66 Participants	84 Participants
Evaluation of Safety: Laboratory Results Urine Protein, LOP · OOR (NCS)	63 Participants	53 Participants
Evaluation of Safety: Laboratory Results Urine Protein, LOP · OOR (CS)	10 Participants	7 Participants
Evaluation of Safety: Laboratory Results Urine Protein, LOP · OOR (CS+AE)	0 Participants	1 Participants
Evaluation of Safety: Laboratory Results Urine Protein, LOP · Not available/pt died	5 Participants	7 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, Pre-Dose · Normal	114 Participants	123 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, Pre-Dose · OOR (NCS)	9 Participants	7 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, Pre-Dose · OOR (CS)	0 Participants	3 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, Pre-Dose · Not available/pt died	21 Participants	19 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, LOP · Normal	128 Participants	135 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, LOP · OOR (NCS)	9 Participants	10 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, LOP · OOR (CS)	1 Participants	0 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, LOP · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Urine Glucose, LOP · Not available/pt died	6 Participants	7 Participants
Evaluation of Safety: Laboratory Results Urine Blood, Pre-Dose · Normal	48 Participants	53 Participants
Evaluation of Safety: Laboratory Results Urine Blood, Pre-Dose · OOR (NCS)	67 Participants	75 Participants
Evaluation of Safety: Laboratory Results Urine Blood, Pre-Dose · OOR (CS)	10 Participants	8 Participants
Evaluation of Safety: Laboratory Results Urine Blood, Pre-Dose · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Urine Blood, Pre-Dose · Not available/pt died	19 Participants	16 Participants
Evaluation of Safety: Laboratory Results Urine Blood, LOP · Normal	57 Participants	58 Participants
Evaluation of Safety: Laboratory Results Urine Blood, LOP · OOR (NCS)	73 Participants	77 Participants
Evaluation of Safety: Laboratory Results Urine Blood, LOP · OOR (CS)	9 Participants	10 Participants
Evaluation of Safety: Laboratory Results Urine Blood, LOP · OOR (CS+AE)	0 Participants	0 Participants
Evaluation of Safety: Laboratory Results Urine Blood, LOP · Not available/pt died	5 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Costs items from hospitals were not collected.

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Costs items from hospitals were not collected.

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Costs items from hospitals were not collected.

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Costs items from hospitals were not collected

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Costs items from hospitals were not collected

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Population: Costs items from hospitals were not collected.

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 90 days

Population: Full Analysis Set (discontinued not included).

Composite endpoint including mortality and days free of mechanical ventilation (VFDsurv) within 90 days among survivors. Ventilation Free Survival at Day 90 has been classified as Dead, Alive but on a ventilator and Alive and breathing unassisted

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90 Dead	47 Participants	48 Participants
Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90 Alive-on ventilator	6 Participants	10 Participants
Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90 Alive-breathing unassisted	90 Participants	91 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Day 14

Population: Subjects from Full Analysis Set population for whom samples were available; analysis of last observation performed.

Evaluation of Cluster of differentiation 73 (CD73) change from baseline to D14 between treatments arms over time.

Outcome measures

Measure	FP-1201-lyo 10 μg n=141 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	Placebo n=148 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Change in the Treatment-specific Exploratory Biomarker Cluster of Differentiation 73 (CD73) Concentration	6.2 ng/ml Standard Deviation 8.9	6.1 ng/ml Standard Deviation 7.9

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to Day 14

Population: Subjects from Full Analysis Set population for whom samples were available; analysis of last observation performed.

Evaluation of potential inflammatory markers (PIMs) change from baseline to D14 between treatments arms over time. Potential biomarkers included IL-1ra, IL-6, FGF basic, IP-10 and TNF-α.

Outcome measures

Measure	FP-1201-lyo 10 μg n=142 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	Placebo n=149 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Changes in Levels of Potential Inflammatory Markers (PIMs) IL-1ra	1830 pg/mL Standard Deviation 5252	1699 pg/mL Standard Deviation 4565
Changes in Levels of Potential Inflammatory Markers (PIMs) IL-6	63 pg/mL Standard Deviation 298	88 pg/mL Standard Deviation 584
Changes in Levels of Potential Inflammatory Markers (PIMs) FGF basic	37 pg/mL Standard Deviation 17	38 pg/mL Standard Deviation 20
Changes in Levels of Potential Inflammatory Markers (PIMs) IP-10	1938 pg/mL Standard Deviation 3543	1762 pg/mL Standard Deviation 3894
Changes in Levels of Potential Inflammatory Markers (PIMs) TNF-α	68 pg/mL Standard Deviation 60	81 pg/mL Standard Deviation 148

OTHER_PRE_SPECIFIED outcome

Timeframe: Anytime from baseline to Day 28

Population: Only subjects with consent for a genetic sample were analysed. Carriers of the C-allele were analysed in biomarker responders compared to biomarker non-responders. 5 and 6 subjects failed to provide genotype information in analyses for responder and non-responders, respectively.

An optional genetic sample was analysed for subjects based on a separate consent. A carrier frequency was analysed for a C/T polymorphism (rs9984723) located in the 3'PRIME_UTR/intron region of IFNAR2-gene, which encodes the beta chain for the IFN-alpha/beta receptor and encompasses a regulatory motif for the glucocorticoid receptor. Biomarker responders were defined by a 3-fold elevation in MxA and a 2-fold in CD73 in comparison to baseline.

Outcome measures

Measure	FP-1201-lyo 10 μg n=38 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	Placebo n=79 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Pharmacogenetic Analysis C-allele carrier	21 Participants	26 Participants
Pharmacogenetic Analysis C-allele non-carrier	12 Participants	47 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 360 /termination of study

Population: Full Analysis Set, but the study was terminated early. The mortality numbers include 3 study subjects who had SAEs with an onset before the first dose of IMP and who subsequently died.

Fatalities; as the study was terminated early, the assessment time point for mortality at Day 360 was not reached. Therefore only the overall mortality at study termination is presented.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Exploratory, Extended Long-term Follow-up: Overall Mortality at Day 360	51 Participants	53 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Change from baseline to Day 360

Population: Subjects from Full Analysis Set population who completed QoL questionnaire at Baseline and Day 360. As the study was terminated early, only a limited amount of data were available at the post-baseline time point.

Quality of Life was assessed through EQ-5D-3L (EuroQol 5-Dimensions 3-Levels questionnaire). An EQ Visual Analogue Scale (VAS) total score (ranging from 0-100) was measured (0= Worst imaginable health state, 100= Best imaginable health state). The EQ-5D-3L VAS scores are numerically summarised as change from pre-dose (Day 1) to extended long term follow-up (Day 360 visit).

Outcome measures

Measure	FP-1201-lyo 10 μg n=37 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	Placebo n=33 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Extended Long-term Follow-up Exploratory Endpoint: Change in Quality of Life From Baseline to Day 360	0 change score on a scale Interval -59.0 to 35.0	0 change score on a scale Interval -80.0 to 86.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 360

Population: All subjects in Full Analysis Set population who performed atleast one 6MWT test at Day 360, before the study was early terminated.

The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % confidence intervals) for the overall treatment difference was analysed.

Outcome measures

Measure	FP-1201-lyo 10 μg n=32 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	Placebo n=31 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Neurological Functioning (6MWT) at Extended Long-term Follow-up	475 maximal distance walked (meters) Standard Deviation 119	453 maximal distance walked (meters) Standard Deviation 190

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 360

Population: Subjects from Full Analysis Set population attending Day 360 visit.

Measuring FEV1 (forced expiratory volume in 1 second) assessed pulmonary function (airway obstruction, bronchoconstriction or bronchodilation). FEV1 is the volume exhaled during the first second of a forced expiratory manoeuvre, starting from the level of total lung capacity.

Outcome measures

Measure	FP-1201-lyo 10 μg n=33 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	Placebo n=27 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Extended Long-term Follow-up Endpoint: Respiratory Functioning (FEV1) at Day 360	69.4 %FEV1 Standard Deviation 31.8	72.0 %FEV1 Standard Deviation 28.5

POST_HOC outcome

Timeframe: Day 28

Population: Subjects who received at least 1 dose of concomitant glucocorticoids during days 0-28

The overall use of concomitant glucocorticoids treatment in both study treatment groups (active and placebo) were analysed.

Outcome measures

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 Participants Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Post-Hoc Analyses Related to the Use of Concomitant Glucocorticoids Medications and Mortality at D28 Use of concomitant glucocorticoids	54.1 percentage of participants	64.5 percentage of participants
Post-Hoc Analyses Related to the Use of Concomitant Glucocorticoids Medications and Mortality at D28 Mortality, with concomitant glucocorticoids	39.7 percentage of participants	27.6 percentage of participants
Post-Hoc Analyses Related to the Use of Concomitant Glucocorticoids Medications and Mortality at D28 Mortality, without concomitant glucocorticoids	10.6 percentage of participants	14.8 percentage of participants

Adverse Events

FP-1201-lyo 10 μg

Serious events: 77 serious events

Other events: 109 other events

Deaths: 51 deaths

Placebo

Serious events: 77 serious events

Other events: 110 other events

Deaths: 53 deaths

Serious adverse events

Measure	FP-1201-lyo 10 μg n=144 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	Placebo n=152 participants at risk Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	5.9% 9/152 • Number of events 9 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOXIA	2.8% 4/144 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.9% 6/152 • Number of events 6 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE RESPIRATORY DISTRESS SYNDROME	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	4.6% 7/152 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LARYNGEAL OEDEMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMOMEDIASTINUM	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMOTHORAX	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMORRHAGE INTRACRANIAL	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE PULMONARY OEDEMA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMOPTYSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FIBROSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISTRESS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE RESPIRATORY FAILURE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CHRONIC RESPIRATORY FAILURE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EPISTAXIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMONIA ASPIRATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 THROMBOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TRACT CONGESTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MULTI-ORGAN FAILURE	9.0% 13/144 • Number of events 13 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	5.3% 8/152 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	4.9% 7/144 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	7.2% 11/152 • Number of events 12 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISEASE PROGRESSION	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DEATH	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ASTHENIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BRAIN DEATH	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GENERAL PHYSICAL HEALTH DETERIORATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	3.5% 5/144 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	5.9% 9/152 • Number of events 9 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	4.9% 7/144 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.6% 4/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BACTERAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EMPYEMA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISSEMINATED TUBERCULOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HERPES ZOSTER MENINGOENCEPHALITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ABSCESS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MENINGITIS ASPERGILLUS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 NEUTROPENIC SEPSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PERITONITIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INFLUENZAL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PSEUDOMONAL	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 RESPIRATORY TRACT INFECTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SYSTEMIC CANDIDA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 UROSEPSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SHOCK HAEMORRHAGIC	4.2% 6/144 • Number of events 6 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SHOCK	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.6% 4/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	2.8% 4/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 THROMBOSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ARREST	2.8% 4/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MYOCARDIAL INFARCTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BRADYCARDIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISORDER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CARDIO-RESPIRATORY ARREST	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CARDIOGENIC SHOCK	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PULSELESS ELECTRICAL ACTIVITY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TORSADE DE POINTES	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VENTRICULAR FIBRILLATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CRITICAL ILLNESS POLYNEUROPATHY	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BASAL GANGLIA HAEMORRHAGE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BRAIN HYPOXIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BRAIN INJURY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CEREBRAL INFARCTION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CEREBRAL VENOUS THROMBOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DEPRESSED LEVEL OF CONSCIOUSNESS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EPILEPSY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOXIC-ISCHAEMIC ENCEPHALOPATHY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INTRAVENTRICULAR HAEMORRHAGE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 STROKE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 QUADRIPLEGIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SEIZURE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMORRHAGE	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ABDOMINAL PAIN	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DUODENAL ULCER HAEMORRHAGE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GASTRITIS HAEMORRHAGIC	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OBSTRUCTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INTRA-ABDOMINAL HAEMATOMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MELAENA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SMALL INTESTINAL HAEMORRHAGE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 UPPER GASTROINTESTINAL HAEMORRHAGE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ACUTE MYELOID LEUKAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ADENOCARCINOMA OF THE CERVIX	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CHOLANGIOCARCINOMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLORECTAL CANCER METASTATIC	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) DIFFUSE LARGE B-CELL LYMPHOMA RECURRENT	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG ADENOCARCINOMA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM MALIGNANT	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO KIDNEY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO LIVER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO LUNG	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEUROENDOCRINE CARCINOMA OF THE SKIN	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NON-HODGKIN'S LYMPHOMA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SMALL CELL LUNG CANCER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 POST INFECTION GLOMERULONEPHRITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 IMPAIRMENT	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ANASTOMOTIC LEAK	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BAROTRAUMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DELAYED RECOVERY FROM ANAESTHESIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GASTROINTESTINAL ANASTOMOTIC COMPLICATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GASTROINTESTINAL ANASTOMOTIC LEAK	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HUMERUS FRACTURE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VASCULAR ACCESS COMPLICATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures RENAL REPLACEMENT THERAPY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures WITHDRAWAL OF LIFE SUPPORT	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures EXTRACORPOREAL MEMBRANE OXYGENATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures GASTRIC OPERATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures LAPAROTOMY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TRANSAMINASES INCREASED	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BIOPSY BONE MARROW ABNORMAL	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISSEMINATED INTRAVASCULAR COAGULATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE HEPATIC FAILURE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERBILIRUBINAEMIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ISCHAEMIC HEPATITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders RASH	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders SUBCUTANEOUS EMPHYSEMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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=144 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	Placebo n=152 participants at risk Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
Infections and infestations PNEUMONIA	5.6% 8/144 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.6% 4/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	5.6% 8/144 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BACTERAEMIA	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SEPSIS	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CYTOMEGALOVIRUS INFECTION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INFECTION	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ABSCESS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PSEUDOMONAL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BRONCHITIS	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ENDOCARDITIS	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ENTEROBACTER PNEUMONIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 IMPETIGO	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LOWER RESPIRATORY TRACT INFECTION	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INFLUENZAL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SUPERINFECTION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SYSTEMIC CANDIDA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ASPERGILLUS INFECTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BACTERIAL DISEASE CARRIER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BRONCHOPULMONARY ASPERGILLOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMONIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CANDIDURIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CELLULITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ENTEROCOCCAL INFECTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EPIGLOTTITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ESCHERICHIA BACTERAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FUNGAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GENITAL HERPES SIMPLEX	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HERPES SIMPLEX PNEUMONIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INFECTIOUS PLEURAL EFFUSION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LYMPHANGITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OESOPHAGEAL CANDIDIASIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ORAL CANDIDIASIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OTITIS EXTERNA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OTITIS MEDIA ACUTE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PANCREATIC ABSCESS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMOCYSTIS JIROVECII PNEUMONIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ESCHERICHIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 STAPHYLOCOCCAL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VIRAL	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PULMONARY SEPSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 RENAL ABSCESS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SINUSITIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SPUTUM PURULENT	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 STAPHYLOCOCCAL BACTERAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 STAPHYLOCOCCAL INFECTION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 THROMBOPHLEBITIS SEPTIC	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TINEA CRURIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VULVOVAGINAL CANDIDIASIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VULVOVAGINITIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOXIA	2.8% 4/144 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMOTHORAX	2.1% 3/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	5.3% 8/152 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	5.6% 8/144 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.6% 4/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE RESPIRATORY DISTRESS SYNDROME	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMOMEDIASTINUM	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE PULMONARY OEDEMA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EPISTAXIS	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMONIA ASPIRATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE RESPIRATORY FAILURE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMOPTYSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERCAPNIA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INCREASED BRONCHIAL SECRETION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FIBROSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISTRESS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMOTHORAX	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INTERSTITIAL LUNG DISEASE	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 COUGH	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DYSPNOEA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HICCUPS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LARYNGEAL DYSPNOEA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CONSOLIDATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISORDER	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OROPHARYNGEAL PAIN	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PNEUMOTHORAX SPONTANEOUS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACIDOSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ALKALOSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 STRIDOR	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	11.8% 17/144 • Number of events 21 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	7.9% 12/152 • Number of events 12 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GENERALISED OEDEMA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERTHERMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOTHERMIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MEDICAL DEVICE COMPLICATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ADVERSE DRUG REACTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CATHETER SITE NECROSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISEASE RECURRENCE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DRUG WITHDRAWAL SYNDROME	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERTHERMIA MALIGNANT	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OEDEMA PERIPHERAL	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	7.6% 11/144 • Number of events 12 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	9.2% 14/152 • Number of events 14 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	3.5% 5/144 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	4.6% 7/152 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VOMITING	2.8% 4/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 IMPAIRED GASTRIC EMPTYING	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.6% 4/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MELAENA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DYSPHAGIA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMORRHAGE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMORRHAGE	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PARALYTIC	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 RECTAL HAEMORRHAGE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ABDOMINAL COMPARTMENT SYNDROME	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ABDOMINAL PAIN	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PANCREATITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 UPPER GASTROINTESTINAL HAEMORRHAGE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 COLITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DUODENAL ULCER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GASTRITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMATEMESIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MOUTH HAEMORRHAGE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OESOPHAGITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PANCREATITIS ACUTE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 REGURGITATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	6.2% 9/144 • Number of events 11 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	9.9% 15/152 • Number of events 16 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.9% 6/152 • Number of events 6 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SUPRAVENTRICULAR TACHYCARDIA	2.1% 3/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BRADYCARDIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISORDER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ARRHYTHMIA SUPRAVENTRICULAR	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FLUTTER	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MYOCARDIAL ISCHAEMIA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VENTRICULAR TACHYCARDIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ARRHYTHMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TACHYCARDIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ATRIOVENTRICULAR BLOCK	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BUNDLE BRANCH BLOCK RIGHT	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CARDIOPULMONARY FAILURE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CYANOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PERICARDITIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SINUS BRADYCARDIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SINUS TACHYCARDIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERNATRAEMIA	6.2% 9/144 • Number of events 10 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	4.6% 7/152 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FLUID OVERLOAD	5.6% 8/144 • Number of events 9 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.6% 4/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	3.5% 5/144 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.9% 6/152 • Number of events 9 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOPHOSPHATAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOALBUMINAEMIA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPONATRAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 METABOLIC ALKALOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ALKALOSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FLUID RETENTION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERKALAEMIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MALNUTRITION	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DEHYDRATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DIABETES MELLITUS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FOOD INTOLERANCE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GOUT	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERAMMONAEMIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERPHOSPHATAEMIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERTRIGLYCERIDAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOCALCAEMIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPOVOLAEMIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OVERWEIGHT	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	7.6% 11/144 • Number of events 13 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	6.6% 10/152 • Number of events 10 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SHOCK HAEMORRHAGIC	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.9% 6/152 • Number of events 6 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VENOUS THROMBOSIS	2.8% 4/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DEEP VEIN THROMBOSIS	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 THROMBOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CIRCULATORY COLLAPSE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMODYNAMIC INSTABILITY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMORRHAGE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ORTHOSTATIC HYPOTENSION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PHLEBITIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SUBCLAVIAN VEIN THROMBOSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 THROMBOPHLEBITIS SUPERFICIAL	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VASCULAR OCCLUSION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VENOUS THROMBOSIS LIMB	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TRANSAMINASES INCREASED	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	4.6% 7/152 • Number of events 9 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PHOSPHOKINASE INCREASED	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.6% 4/152 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CHLORIDE INCREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LACTIC ACID INCREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INCREASED	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GAMMA-GLUTAMYLTRANSFERASE INCREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 OXYGEN SATURATION DECREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ANTICOAGULATION DRUG LEVEL INCREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GLUCOSE DECREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 GLUCOSE INCREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 IRON DECREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LACTATE DEHYDROGENASE INCREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PHOSPHORUS DECREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TRIGLYCERIDES INCREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 UREA INCREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CLOSTRIDIUM TEST POSITIVE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EJECTION FRACTION DECREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ELECTROCARDIOGRAM ABNORMAL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ELECTROENCEPHALOGRAM ABNORMAL	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EOSINOPHIL COUNT INCREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MYOGLOBIN BLOOD INCREASED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PO2 DECREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 RED BLOOD CELL COUNT DECREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SPLEEN SCAN ABNORMAL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TROPONIN INCREASED	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	11.1% 16/144 • Number of events 18 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	7.2% 11/152 • Number of events 11 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	4.9% 7/144 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.9% 6/152 • Number of events 6 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 THROMBOCYTOSIS	3.5% 5/144 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 COAGULOPATHY	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISSEMINATED INTRAVASCULAR COAGULATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMOLYSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HISTIOCYTOSIS HAEMATOPHAGIC	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LEUKOPENIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MICROCYTIC ANAEMIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HEPATOCELLULAR INJURY	6.2% 9/144 • Number of events 9 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	5.3% 8/152 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CHOLESTASIS	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYPERBILIRUBINAEMIA	2.8% 4/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FUNCTION ABNORMAL	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ACUTE HEPATIC FAILURE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CHOLECYSTITIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CIRRHOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HEPATORENAL SYNDROME	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HEPATOTOXICITY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 JAUNDICE CHOLESTATIC	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LIVER DISORDER	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 LIVER INJURY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	4.2% 6/144 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	4.6% 7/152 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	5.6% 8/144 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	2.8% 4/144 • Number of events 4 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INSOMNIA	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DEPRESSION	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 WITHDRAWAL SYNDROME	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HALLUCINATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 NIGHTMARE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	4.9% 7/144 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	5.3% 8/152 • Number of events 8 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	4.2% 6/144 • Number of events 6 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	3.3% 5/152 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMATURIA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CHRONIC KIDNEY DISEASE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 INJURY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 URINARY RETENTION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 URINARY INCONTINENCE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CRITICAL ILLNESS POLYNEUROPATHY	2.1% 3/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	4.6% 7/152 • Number of events 7 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CONFUSIONAL STATE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EPILEPSY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 NERVOUS SYSTEM DISORDER	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SEIZURE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CEREBROVASCULAR DISORDER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 COMA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HEADACHE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HYDROCEPHALUS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 POLYNEUROPATHY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SEDATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TREMOR	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 VOCAL CORD PARALYSIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ENDOTRACHEAL INTUBATION COMPLICATION	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ANASTOMOTIC LEAK	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 BAROTRAUMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TRACHEAL INJURY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ANIMAL BITE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 EAR INJURY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FACE INJURY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FALL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 FOREIGN BODY ASPIRATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 JOINT DISLOCATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 JOINT INJURY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MECHANICAL VENTILATION COMPLICATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 COMPLICATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TENDON RUPTURE	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 TRANSFUSION REACTION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 HAEMATOMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders RASH	1.4% 2/144 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	2.0% 3/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders DECUBITUS ULCER	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 3 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders RASH GENERALISED	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders DERMATITIS ALLERGIC	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders URTICARIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders DERMATITIS CONTACT	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders ECCHYMOSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders PRURITUS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders PSORIASIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders RASH MACULO-PAPULAR	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders SKIN DISCOLOURATION	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders SKIN NECROSIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Skin and subcutaneous tissue disorders SKIN ULCER	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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	3.5% 5/144 • Number of events 5 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MUSCULOSKELETAL PAIN	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PAIN IN EXTREMITY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MIXED CONNECTIVE TISSUE DISEASE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MYALGIA	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 MYOPATHY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 RHEUMATOID ARTHRITIS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 SYSTEMIC LUPUS ERYTHEMATOSUS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures RENAL REPLACEMENT THERAPY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures ENDOTRACHEAL INTUBATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	1.3% 2/152 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures EXTRACORPOREAL MEMBRANE OXYGENATION	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures GASTRECTOMY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures GASTROSTOMY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Surgical and medical procedures TRACHEOSTOMY	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Neoplasms benign, malignant and unspecified (incl cysts and polyps) KAPOSI'S SARCOMA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CONJUNCTIVAL OEDEMA	1.4% 2/144 • Number of events 2 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 CONJUNCTIVAL HAEMORRHAGE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DIPLOPIA	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DRY EYE	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 DISORDER	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 PUPILS UNEQUAL	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 ULCERATIVE KERATITIS	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Congenital, familial and genetic disorders HYPERTROPHIC CARDIOMYOPATHY	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Ear and labyrinth disorders TINNITUS	0.69% 1/144 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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% 0/152 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )
Endocrine disorders HYPERTHYROIDISM	0.00% 0/144 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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 )	0.66% 1/152 • Number of events 1 • The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360. 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

Phone: +3584005529411

Email: medical@faron.com

Results disclosure agreements

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