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Clinical Trial Results:
A Phase 2 Randomised, Double-blind, Placebo-controlled, Single-dose, Dose-ranging Study of the Efficacy and Safety of MEDI4893, a Human Monoclonal Antibody Against Staphylococcus aureus Alpha Toxin in Mechanically Ventilated Adult Subjects

Summary
EudraCT number	2014-001097-34
Trial protocol	BE GR DE ES CZ PT HU GB IE
Global end of trial date	02 Oct 2018

Results information
Results version number	v2(current)
This version publication date	27 Dec 2019
First version publication date	16 Oct 2019
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CD-ID-MEDI4893-1139

ISRCTN number

US NCT number

NCT02296320

WHO universal trial number (UTN)

Sponsor organisation name

MedImmune, LLC

Sponsor organisation address

One MedImmune Way, Gaithersburg, United States, 20878

Public contact

Hasan S. Jafri, MedImmune, LLC, MD +1 3013984431, information.center@astrazeneca.com

Scientific contact

Hasan S. Jafri, MedImmune, LLC, MD +1 3013984431, information.center@astrazeneca.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

14 Dec 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

02 Oct 2018

Global end of trial reached?

Yes

Global end of trial date

02 Oct 2018

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study is to evaluate the safety and efficacy of a single intravenous (IV) dose of MEDI4893 in reducing the incidence of Staphylococcus aureus pneumonia.

Protection of trial subjects

The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Oct 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 26

Country: Number of subjects enrolled

Czech Republic: 5

Country: Number of subjects enrolled

France: 119

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Greece: 4

Country: Number of subjects enrolled

Hungary: 3

Country: Number of subjects enrolled

Portugal: 2

Country: Number of subjects enrolled

Spain: 35

Country: Number of subjects enrolled

Switzerland: 16

Worldwide total number of subjects

213

EEA total number of subjects

197

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

139

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted between 10Oct2014 and 02Oct2018.

Screening details

A total of 767 participants consented to participate in the study, of which 554 were screen failures. A total of 213 participants were randomised in the study. Out of 213 randomised participates, 2 participants were not treated with the study drug and therefore the data for "Baseline Characteristics" were not collected.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received a single intravenous (IV) dose of placebo matched to MEDI4893 on Day 1 of the study.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous drip use

Dosage and administration details

A single IV dose matched to MEDI4893 on Day 1 of the study.

MEDI4893 2000 mg

Arm description

Participants received a single IV dose of MEDI4893 2000 milligrams (mg) on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

MEDI4893

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous drip use

Dosage and administration details

A single IV dose of 2000 mg on Day 1 of the study.

MEDI4893 5000 mg

Arm description

Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

MEDI4893

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous drip use

Dosage and administration details

A single IV dose of 5000 mg on Day 1 of the study.

Number of subjects in period 1 ^[1]	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Started	100	15	96
Completed	67	10	59
Not completed	33	5	37
Adverse event, serious fatal	24	3	27
Consent withdrawn by subject	4	-	2
Not - specified	-	-	1
Lost to follow-up	5	2	7

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Total subjects enrolled worldwide were 213; of which 2 subjects were randomized but not treated. These 2 subjects were not included in As-treated population and data for these subjects were not captured for baseline characteristics

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received a single intravenous (IV) dose of placebo matched to MEDI4893 on Day 1 of the study.

Reporting group title

MEDI4893 2000 mg

Reporting group description

Participants received a single IV dose of MEDI4893 2000 milligrams (mg) on Day 1 of the study.

Reporting group title

MEDI4893 5000 mg

Reporting group description

Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.

Reporting group values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg	Total
Number of subjects	100	15	96	211
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	67	13	58	138
From 65-84 years	30	2	37	69
85 years and over	3	0	1	4
Age Continuous
Units: Years
arithmetic mean (standard deviation)	55.7 ( 16.6 )	52.5 ( 14.6 )	57.7 ( 15.7 )	-
Sex: Female, Male
Units: Subjects
Female	45	5	37	87
Male	55	10	59	124
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0
Asian	0	1	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	3	1	2	6
White	97	13	94	204
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	4	0	4	8
Not Hispanic or Latino	96	15	92	203
Unknown or Not Reported	0	0	0	0

End points

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Reporting group title

Placebo

Reporting group description

Participants received a single intravenous (IV) dose of placebo matched to MEDI4893 on Day 1 of the study.

Reporting group title

MEDI4893 2000 mg

Reporting group description

Participants received a single IV dose of MEDI4893 2000 milligrams (mg) on Day 1 of the study.

Reporting group title

MEDI4893 5000 mg

Reporting group description

Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.

Primary: Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus aureus (S aureus) Pneumonia

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End point title

Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus aureus (S aureus) Pneumonia

End point description

EAC S aureus pneumonia was based on (a) clinical criteria: 1 major criteria (PaO2/FiO2 ratio <240 mmHg or decrease in PaO2/FiO2 by >=50 mmHg maintained for at least 4 hrs or a need to initiate non-invasive mechanical ventilation/re-initiate invasive mechanical ventilation because of respiratory failure/worsening of respiratory status); and at least 2 of minor criteria: systemic signs of infection, production of purulent sputum/endotracheal secretions, new onset of cough, physical examination findings consistent with pneumonia/pulmonary consolidation, dyspnea, and/or tachypnea; (b) radiographic criteria: new/worsening infiltrate consistent with pneumonia on chest X-ray obtained within 24hrs of event; (c) microbiologic criteria: at least 1 culture positive for S aureus (respiratory specimen/blood/pleural fluid aspirate/lung tissue culture). Modified Intent-to-treat (mITT) population: all participants who received any dose of study drug; analysed according to randomised treatment group

End point type

Primary

End point timeframe

Day 1 through Day 31

End point values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	100	15	96
Units: Percentage of Participants
number (not applicable)	26.0	20	17.7

Comparison of EAC-Determined S aureus pneumonia

Statistical analysis description

The key efficacy analyses were based on 5000 mg MEDI4893 and placebo. Participants who received 2000 mg MEDI4893 were summarised descriptively.

Comparison groups

Placebo v MEDI4893 5000 mg

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

P-value

= 0.166

Method

Poisson regression with robust variance

Parameter type

Relative risk reduction

Point estimate

31.9

Confidence interval

level

90%

sides

2-sided

lower limit

-7.5

upper limit

56.8

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days

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End point title

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days ^[1]

End point description

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population was analysed for this end point, which included all participants, who received any dose of study drug and analysed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 through Day 31

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

End point values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	100	15	96
Units: Participants	90	15	87

No statistical analyses for this end point

Primary: Number of Participants With TEAEs Through 91 Days

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End point title

Number of Participants With TEAEs Through 91 Days ^[2]

End point description

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population was analysed for this end point, which included all participants, who received any dose of study drug and analysed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 through Day 91

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

End point values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	100	15	96
Units: Participants	92	15	89

No statistical analyses for this end point

Primary: Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)

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End point title

Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) ^[3]

End point description

A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population was analysed for this end point, which included all participants, who received any dose of study drug and analysed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 through Day 191

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

End point values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	100	15	96
Units: Participants	40	7	50

No statistical analyses for this end point

Primary: Number of Participants With Adverse Events of Special Interest (AESIs)

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End point title

Number of Participants With Adverse Events of Special Interest (AESIs) ^[4]

End point description

An AESI is one of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. An AESI may have been serious or non-serious. As-treated population was analysed for this end point, which included all participants, who received any dose of study drug and analysed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 through Day 191

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point

End point values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	100	15	96
Units: Participants	0	4	3

No statistical analyses for this end point

Primary: Number of Participants With New Onset Chronic Diseases (NOCDs)

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End point title

Number of Participants With New Onset Chronic Diseases (NOCDs) ^[5]

End point description

An NOCD defined as a newly diagnosed medical condition that is of a chronic, ongoing nature. It is observed after receiving the study drug and is assessed by the investigator as medically significant. As-treated population was analysed for this end point, which included all participants, who received any dose of study drug and analysed according to the treatment they actually received.

End point type

Primary

End point timeframe

Day 1 through Day 191

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.

End point values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	100	15	96
Units: Participants	2	0	3

No statistical analyses for this end point

Secondary: Maximum Observed Serum Concentration (Cmax) of MEDI4893

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End point title

Maximum Observed Serum Concentration (Cmax) of MEDI4893 ^[6]

End point description

Maximum observed serum concentration (Cmax) of MEDI4893 is reported. An Intent-to-treat (ITT) population was analysed for this endpoint, which included all randomised participants who were analysed according to their randomised treatment group and had quantifiable pharmacokinetic (PK) samples.

End point type

Secondary

End point timeframe

Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point

End point values	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	14	94
Units: μg/mL
arithmetic mean (standard deviation)	471.9 ( 123.0 )	1143.7 ( 375.6 )

No statistical analyses for this end point

Secondary: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893

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End point title

Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893 ^[7]

End point description

Area under the serum concentration time curve from time zero to last measurable concentration ([AUC 0-last]) of MEDI4893 is reported. An ITT population was analysed for this endpoint, which included all randomised participants who were analysed according to their randomised treatment group and had quantifiable PK samples.

End point type

Secondary

End point timeframe

Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	14	94
Units: day*μg/mL
arithmetic mean (standard deviation)	9045.5 ( 5383.1 )	20127.5 ( 12852.2 )

No statistical analyses for this end point

Secondary: Observed Serum Concentration of MEDI4893 through 30 Days Post Dose (C30)

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End point title

Observed Serum Concentration of MEDI4893 through 30 Days Post Dose (C30) ^[8]

End point description

Observed serum concentration of MEDI4893 through 30 days post dose (C30) is reported. Serum concentration of MEDI4893 through 30 days post dose accounted the overall concentration of MEDI4893 measured on specified time points (Days 1, 4, 8, 15, 22, and 30). An ITT population was analysed for this endpoint, which included all randomised participants who were analysed according to their randomised treatment group and had quantifiable PK samples.

End point type

Secondary

End point timeframe

Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, and 30

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	13	68
Units: μg/mL
arithmetic mean (standard deviation)	122.0 ( 65.0 )	295.9 ( 130.6 )

No statistical analyses for this end point

Secondary: Observed Serum Concentration of MEDI4893 through 90 Days Post Dose (C90)

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End point title

Observed Serum Concentration of MEDI4893 through 90 Days Post Dose (C90) ^[9]

End point description

Observed serum concentration of MEDI4893 through 90 days post dose (C90) is reported. Serum concentration of MEDI4893 through 90 days post dose accounted the overall concentration of MEDI4893 measured on specified time points (Days 1, 4, 8, 15, 22, 31, 61, and 91). An ITT population was analysed for this endpoint, which included all randomised participants who were analysed according to their randomised treatment group and had quantifiable PK samples.

End point type

Secondary

End point timeframe

Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 90

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	11	54
Units: μg/mL
arithmetic mean (standard deviation)	71.5 ( 35.5 )	192.0 ( 84.0 )

No statistical analyses for this end point

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titre to MEDI4893

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End point title

Number of Participants With Positive Anti-Drug Antibodies (ADA) Titre to MEDI4893

End point description

Participants with ADA-positive at any of Day 31, Day 61, or Day 91 post-baseline assessments were always counted as "positive" at post-baseline. As-treated population was analysed for this end point, which included all participants, who received any dose of study drug and analysed according to the treatment they actually received.

End point type

Secondary

End point timeframe

Days 1 (Pre dose), 31, 61, and, 91

End point values	Placebo	MEDI4893 2000 mg	MEDI4893 5000 mg
Number of subjects analysed	100	15	96
Units: Participants
Positive at baseline	3	0	2
Positive post-baseline	5	0	0
Positive at baseline and post-baseline	2	0	0
Not detected at baseline; positive post-baseline	3	0	0
Positive at baseline; not detected post-baseline	0	0	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs: Day 1 through Day 191 AEs: Day 1 through Day 91

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Placebo

Reporting group description

Participants received a single IV dose of placebo matched to MEDI4893 on Day 1 of the study

Reporting group title

MEDI4893 5000 mg

Reporting group description

Participants received a single IV dose of MEDI4893 5000 mg on Day 1 of the study.

Reporting group title

MEDI4893 2000 mg

Reporting group description

Participants received a single IV dose of MEDI4893 2000 mg on Day 1 of the study.

Serious adverse events	Placebo	MEDI4893 5000 mg	MEDI4893 2000 mg
Total subjects affected by serious adverse events
subjects affected / exposed	40 / 100 (40.00%)	50 / 96 (52.08%)	7 / 15 (46.67%)
number of deaths (all causes)	24	27	3
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Glioblastoma
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Glioma
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Hepatocellular carcinoma
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Laryngeal cancer
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Shock haemorrhagic
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Brain death
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 1	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0
Aspiration
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Bronchospasm
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	3 / 100 (3.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Laryngeal oedema
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Obstructive airways disorder
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Pleural effusion
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory arrest
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Respiratory failure
subjects affected / exposed	0 / 100 (0.00%)	5 / 96 (5.21%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 4	0 / 0
Stridor
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Coma scale abnormal
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Extradural haematoma
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tracheostomy malfunction
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular pseudoaneurysm
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Weaning failure
subjects affected / exposed	3 / 100 (3.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 2	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Congestive cardiomyopathy
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Nervous system disorders
Brain hypoxia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Brain oedema
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Brain stem stroke
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Coma
subjects affected / exposed	1 / 100 (1.00%)	5 / 96 (5.21%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 4	0 / 1
Depressed level of consciousness
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydrocephalus
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypercapnic coma
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxic-ischaemic encephalopathy
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Intracranial pressure increased
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Intraventricular haemorrhage
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 100 (0.00%)	3 / 96 (3.13%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 3	0 / 0
Multiple system atrophy
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Myasthenia gravis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0
Neuralgia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neurological decompensation
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Partial seizures
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ruptured cerebral aneurysm
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Status epilepticus
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vocal cord paralysis
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Intestinal ischaemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Strangulated umbilical hernia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatocellular injury
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscular weakness
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Infections and infestations
Acinetobacter infection
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Brain abscess
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Klebsiella infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Klebsiella sepsis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningitis enterococcal
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningitis staphylococcal
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia klebsiella
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pneumonia serratia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pneumonia staphylococcal
subjects affected / exposed	3 / 100 (3.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Septic shock
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Serratia infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Serratia sepsis
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection pseudomonal
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Creutzfeldt-jakob disease
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo	MEDI4893 5000 mg	MEDI4893 2000 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	90 / 100 (90.00%)	85 / 96 (88.54%)	15 / 15 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Leiomyoma
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Osteoma
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Haemodynamic instability
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	3	0	1
Hot flush
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Hypertension
subjects affected / exposed	8 / 100 (8.00%)	7 / 96 (7.29%)	1 / 15 (6.67%)
occurrences all number	8	7	1
Hypotension
subjects affected / exposed	2 / 100 (2.00%)	7 / 96 (7.29%)	1 / 15 (6.67%)
occurrences all number	3	10	2
Jugular vein thrombosis
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Peripheral venous disease
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Phlebitis
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Shock
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Thrombophlebitis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Venous thrombosis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
General disorders and administration site conditions
Catheter site haematoma
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Chills
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Generalised oedema
subjects affected / exposed	3 / 100 (3.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	3	1	0
Hyperthermia
subjects affected / exposed	3 / 100 (3.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	4	1	0
Hypothermia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Implant site haematoma
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Infusion site extravasation
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Localised oedema
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Medical device site pain
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Non-cardiac chest pain
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Oedema peripheral
subjects affected / exposed	3 / 100 (3.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	3	0	1
Pain
subjects affected / exposed	3 / 100 (3.00%)	3 / 96 (3.13%)	0 / 15 (0.00%)
occurrences all number	3	3	0
Pyrexia
subjects affected / exposed	15 / 100 (15.00%)	8 / 96 (8.33%)	2 / 15 (13.33%)
occurrences all number	26	9	5
Vascular complication associated with device
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Reproductive system and breast disorders
Male genital tract fistula
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Prostatitis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	1
Vaginal discharge
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Acute respiratory distress syndrome
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Acute respiratory failure
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Asthma
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Atelectasis
subjects affected / exposed	3 / 100 (3.00%)	7 / 96 (7.29%)	1 / 15 (6.67%)
occurrences all number	5	7	1
Bronchial disorder
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Bronchial hyperreactivity
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Bronchial obstruction
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Bronchial secretion retention
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Bronchospasm
subjects affected / exposed	4 / 100 (4.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	4	2	0
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Cough
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Dysphonia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Dyspnoea
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Epistaxis
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Haemoptysis
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Hiccups
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Hypercapnia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Hypoxia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	6	0	1
Increased bronchial secretion
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	2	1	0
Increased viscosity of bronchial secretion
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	2	1	0
Laryngeal dyspnoea
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Laryngeal granuloma
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Laryngeal oedema
subjects affected / exposed	6 / 100 (6.00%)	1 / 96 (1.04%)	2 / 15 (13.33%)
occurrences all number	6	1	2
Laryngeal pain
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Laryngeal ulceration
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Lung disorder
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pleural effusion
subjects affected / exposed	4 / 100 (4.00%)	6 / 96 (6.25%)	0 / 15 (0.00%)
occurrences all number	5	6	0
Pneumomediastinum
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pneumonia aspiration
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	2	1	0
Pneumothorax
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pneumothorax spontaneous
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Pulmonary embolism
subjects affected / exposed	3 / 100 (3.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	0	0
Pulmonary oedema
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Rales
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Respiratory acidosis
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Respiratory disorder
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Respiratory failure
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Respiratory tract congestion
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Tachypnoea
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Psychiatric disorders
Aggression
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Agitation
subjects affected / exposed	3 / 100 (3.00%)	6 / 96 (6.25%)	0 / 15 (0.00%)
occurrences all number	4	6	0
Anxiety
subjects affected / exposed	5 / 100 (5.00%)	8 / 96 (8.33%)	1 / 15 (6.67%)
occurrences all number	5	8	1
Confusional state
subjects affected / exposed	2 / 100 (2.00%)	5 / 96 (5.21%)	1 / 15 (6.67%)
occurrences all number	2	7	1
Delirium
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Depression
subjects affected / exposed	2 / 100 (2.00%)	4 / 96 (4.17%)	1 / 15 (6.67%)
occurrences all number	2	4	1
Flat affect
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Hallucination, visual
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Initial insomnia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Insomnia
subjects affected / exposed	4 / 100 (4.00%)	5 / 96 (5.21%)	1 / 15 (6.67%)
occurrences all number	4	5	1
Organic brain syndrome
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Stress
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	0	2	1
Aspartate aminotransferase increased
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Blood potassium decreased
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Body temperature increased
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	3
Hepatic enzyme increased
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
International normalised ratio increased
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Liver function test abnormal
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Mononucleosis heterophile test positive
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Pancreatic enzymes increased
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Transaminases increased
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Weight decreased
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Injury, poisoning and procedural complications
Endotracheal intubation complication
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Eschar
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Facial bones fracture
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Fall
subjects affected / exposed	2 / 100 (2.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	2	2	0
Infusion related reaction
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	0	2	1
Mechanical ventilation complication
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Post procedural haematoma
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Postoperative wound complication
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Procedural haemorrhage
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Procedural hypotension
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Procedural pain
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Spinal compression fracture
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Tracheostomy malfunction
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Traumatic shock
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Unintentional medical device removal
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Vasoplegia syndrome
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Weaning failure
subjects affected / exposed	2 / 100 (2.00%)	3 / 96 (3.13%)	1 / 15 (6.67%)
occurrences all number	2	3	1
Congenital, familial and genetic disorders
Muscular dystrophy
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Right-to-left cardiac shunt
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Arrhythmia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Arrhythmia supraventricular
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Atrial fibrillation
subjects affected / exposed	3 / 100 (3.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	3	2	1
Atrial flutter
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Atrial thrombosis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Atrioventricular block complete
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Atrioventricular block second degree
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Bradycardia
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Cardiac arrest
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Cardiac failure
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Left ventricular dysfunction
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Mitral valve incompetence
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Pericardial effusion
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Sinus tachycardia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Supraventricular tachycardia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	1
Tachycardia
subjects affected / exposed	3 / 100 (3.00%)	3 / 96 (3.13%)	0 / 15 (0.00%)
occurrences all number	3	3	0
Ventricular extrasystoles
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Ventricular tachycardia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Nervous system disorders
Altered state of consciousness
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Aphasia
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Aphonia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Cerebral ischaemia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Cerebrovascular accident
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Cognitive disorder
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Diabetic hyperosmolar coma
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Disturbance in attention
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Dysaesthesia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Dysarthria
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Encephalitis autoimmune
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Epilepsy
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Generalised tonic-clonic seizure
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Headache
subjects affected / exposed	3 / 100 (3.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	3	3	1
Hemiplegia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Hypoglossal nerve paralysis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Intracranial pressure increased
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	0	2	1
Multiple system atrophy
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Muscle tone disorder
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Myasthenia gravis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Myelopathy
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Myoclonic epilepsy
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Neuralgia
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Neurological decompensation
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Paraplegia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Quadriplegia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Sciatica
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Seizure
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Subdural hygroma
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Vasculitis cerebral
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Vocal cord paresis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	12 / 100 (12.00%)	11 / 96 (11.46%)	2 / 15 (13.33%)
occurrences all number	24	11	2
Coagulopathy
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Iron deficiency anaemia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Leukopenia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	1
Normochromic anaemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Thrombocytopenia
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Thrombocytosis
subjects affected / exposed	3 / 100 (3.00%)	6 / 96 (6.25%)	1 / 15 (6.67%)
occurrences all number	3	6	1
Ear and labyrinth disorders
Excessive cerumen production
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Vertigo
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Eyelid ptosis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Keratitis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Abdominal pain
subjects affected / exposed	4 / 100 (4.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	5	1	1
Abdominal pain upper
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Barrett's oesophagus
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Constipation
subjects affected / exposed	15 / 100 (15.00%)	7 / 96 (7.29%)	1 / 15 (6.67%)
occurrences all number	16	7	1
Diarrhoea
subjects affected / exposed	8 / 100 (8.00%)	8 / 96 (8.33%)	3 / 15 (20.00%)
occurrences all number	11	13	4
Dysphagia
subjects affected / exposed	3 / 100 (3.00%)	4 / 96 (4.17%)	0 / 15 (0.00%)
occurrences all number	3	4	0
Faecaloma
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Gastritis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Gastrointestinal haemorrhage
subjects affected / exposed	5 / 100 (5.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	5	1	0
Gastrointestinal hypomotility
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Gastrointestinal obstruction
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Haematemesis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Ileus paralytic
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Impaired gastric emptying
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Nausea
subjects affected / exposed	3 / 100 (3.00%)	4 / 96 (4.17%)	0 / 15 (0.00%)
occurrences all number	3	5	0
Oesophagitis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Oral pain
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pancreatic disorder
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Salivary hypersecretion
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Vomiting
subjects affected / exposed	6 / 100 (6.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	6	0	0
Hepatobiliary disorders
Biliary cirrhosis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Cholestasis
subjects affected / exposed	4 / 100 (4.00%)	7 / 96 (7.29%)	4 / 15 (26.67%)
occurrences all number	4	7	4
Hepatic function abnormal
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	2 / 15 (13.33%)
occurrences all number	0	0	3
Hepatocellular injury
subjects affected / exposed	5 / 100 (5.00%)	6 / 96 (6.25%)	4 / 15 (26.67%)
occurrences all number	5	6	4
Hyperbilirubinaemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Hypertransaminasaemia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Jaundice cholestatic
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Liver disorder
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Blister
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Decubitus ulcer
subjects affected / exposed	4 / 100 (4.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	5	1	1
Dermatitis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Dermatitis diaper
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Dry skin
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Eczema
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Erythema
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Generalised erythema
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pruritus
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Pruritus generalised
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Purpura
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Rash
subjects affected / exposed	3 / 100 (3.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	3	1	0
Rash maculo-papular
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Rash papular
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Rosacea
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Seborrhoeic dermatitis
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Skin lesion
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Skin ulcer
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	1	2	1
Bladder spasm
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Chronic kidney disease
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Haematuria
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	2 / 15 (13.33%)
occurrences all number	0	2	2
Hypertonic bladder
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Oliguria
subjects affected / exposed	1 / 100 (1.00%)	3 / 96 (3.13%)	0 / 15 (0.00%)
occurrences all number	1	3	0
Polyuria
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Renal failure
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Renal impairment
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Urinary retention
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Endocrine disorders
Diabetes insipidus
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Goitre
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Hyperthyroidism
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Hypothyroidism
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
Amyotrophy
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Arthralgia
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Back pain
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Bone pain
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Joint stiffness
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Muscle haemorrhage
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Muscular weakness
subjects affected / exposed	1 / 100 (1.00%)	3 / 96 (3.13%)	0 / 15 (0.00%)
occurrences all number	1	3	0
Musculoskeletal pain
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Myalgia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Myopathy
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Neck pain
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Pain in extremity
subjects affected / exposed	3 / 100 (3.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	3	3	0
Torticollis
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Infections and infestations
Abscess bacterial
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Acinetobacter bacteraemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Bacteraemia
subjects affected / exposed	2 / 100 (2.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	2	2	0
Bacterial disease carrier
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Bacterial pyelonephritis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	1
Bacterial sepsis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Bacteroides bacteraemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Bronchitis bacterial
subjects affected / exposed	5 / 100 (5.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	6	2	0
Bronchitis pneumococcal
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Citrobacter infection
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Citrobacter sepsis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Clostridium difficile colitis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Conjunctivitis
subjects affected / exposed	2 / 100 (2.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	4	2	0
Cystitis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Cytomegalovirus infection
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Device related infection
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Enterobacter bacteraemia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Enterobacter infection
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	2
Enterobacter pneumonia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Enterococcal bacteraemia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Enterococcal infection
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Enterococcal sepsis
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Epididymitis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Escherichia bacteraemia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	2	0	1
Escherichia infection
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Escherichia sepsis
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Escherichia urinary tract infection
subjects affected / exposed	14 / 100 (14.00%)	18 / 96 (18.75%)	4 / 15 (26.67%)
occurrences all number	18	23	4
Fungal infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Fungal skin infection
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Genital herpes
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Haemophilus infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Helicobacter gastritis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Herpes zoster
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	1
Infection
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Infectious pleural effusion
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Klebsiella bacteraemia
subjects affected / exposed	3 / 100 (3.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	0	0
Klebsiella infection
subjects affected / exposed	2 / 100 (2.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	2	2	1
Laryngitis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Localised infection
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Meningitis bacterial
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Moraxella infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Morganella infection
subjects affected / exposed	3 / 100 (3.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	5	2	0
Nasopharyngitis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Oral candidiasis
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	2	1	0
Oropharyngeal candidiasis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Otitis externa
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Otitis media
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pneumonia
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Pneumonia bacterial
subjects affected / exposed	17 / 100 (17.00%)	7 / 96 (7.29%)	1 / 15 (6.67%)
occurrences all number	17	7	1
Pneumonia escherichia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Pneumonia haemophilus
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	1
Pneumonia klebsiella
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pneumonia moraxella
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Pneumonia pseudomonal
subjects affected / exposed	4 / 100 (4.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	4	0	0
Pneumonia serratia
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Pneumonia staphylococcal
subjects affected / exposed	13 / 100 (13.00%)	13 / 96 (13.54%)	2 / 15 (13.33%)
occurrences all number	13	13	2
Postoperative wound infection
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Proteus infection
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	0	2	1
Pseudomembranous colitis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Pseudomonal bacteraemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	1
Pseudomonas bronchitis
subjects affected / exposed	1 / 100 (1.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	1	1	0
Pseudomonas infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Puncture site abscess
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Serratia bacteraemia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	2	0	0
Serratia infection
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	2	1	0
Sinusitis
subjects affected / exposed	3 / 100 (3.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	3	2	0
Staphylococcal bacteraemia
subjects affected / exposed	6 / 100 (6.00%)	3 / 96 (3.13%)	1 / 15 (6.67%)
occurrences all number	7	3	1
Staphylococcal infection
subjects affected / exposed	4 / 100 (4.00%)	4 / 96 (4.17%)	0 / 15 (0.00%)
occurrences all number	5	4	0
Staphylococcal sepsis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Staphylococcal skin infection
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Streptococcal bacteraemia
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	1	2	1
Streptococcal infection
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Systemic infection
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Tracheobronchitis
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Urinary tract infection
subjects affected / exposed	2 / 100 (2.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	2	4	0
Urinary tract infection bacterial
subjects affected / exposed	2 / 100 (2.00%)	3 / 96 (3.13%)	1 / 15 (6.67%)
occurrences all number	2	3	1
Urinary tract infection fungal
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Urinary tract infection pseudomonal
subjects affected / exposed	3 / 100 (3.00%)	4 / 96 (4.17%)	1 / 15 (6.67%)
occurrences all number	3	4	1
Urinary tract infection staphylococcal
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	2	0	1
Viral upper respiratory tract infection
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Vulvovaginal candidiasis
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0
Wound infection bacterial
subjects affected / exposed	2 / 100 (2.00%)	3 / 96 (3.13%)	0 / 15 (0.00%)
occurrences all number	2	3	0
Wound infection staphylococcal
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Metabolism and nutrition disorders
Cerebral salt-wasting syndrome
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	1	0	1
Fluid overload
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	2
Folate deficiency
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Gout
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	2	2	0
Hyperglycaemia
subjects affected / exposed	4 / 100 (4.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	4	1	1
Hyperkalaemia
subjects affected / exposed	2 / 100 (2.00%)	2 / 96 (2.08%)	1 / 15 (6.67%)
occurrences all number	2	2	2
Hyperlactacidaemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Hypernatraemia
subjects affected / exposed	1 / 100 (1.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	1	2	0
Hypoalbuminaemia
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Hypocalcaemia
subjects affected / exposed	2 / 100 (2.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	3	2	0
Hypoglycaemia
subjects affected / exposed	2 / 100 (2.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	0	0
Hypokalaemia
subjects affected / exposed	7 / 100 (7.00%)	11 / 96 (11.46%)	1 / 15 (6.67%)
occurrences all number	9	13	2
Hypomagnesaemia
subjects affected / exposed	0 / 100 (0.00%)	2 / 96 (2.08%)	0 / 15 (0.00%)
occurrences all number	0	2	0
Hyponatraemia
subjects affected / exposed	4 / 100 (4.00%)	4 / 96 (4.17%)	1 / 15 (6.67%)
occurrences all number	5	5	1
Hypophosphataemia
subjects affected / exposed	1 / 100 (1.00%)	4 / 96 (4.17%)	0 / 15 (0.00%)
occurrences all number	1	4	0
Hypoproteinaemia
subjects affected / exposed	2 / 100 (2.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	2	1	0
Hypovolaemia
subjects affected / exposed	0 / 100 (0.00%)	0 / 96 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	3
Iron deficiency
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	1 / 15 (6.67%)
occurrences all number	0	1	1
Metabolic alkalosis
subjects affected / exposed	3 / 100 (3.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	3	0	0
Vitamin b12 deficiency
subjects affected / exposed	1 / 100 (1.00%)	0 / 96 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0
Vitamin k deficiency
subjects affected / exposed	0 / 100 (0.00%)	1 / 96 (1.04%)	0 / 15 (0.00%)
occurrences all number	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

07 Aug 2014

Text was added to indicate that enrolment would continue in only the 5000 mg MEDI4893 and placebo arms during interim analyses. A second interim analysis for futility assessment was added to be conducted when approximately 33% to 40% of the enrolled participants were followed through 30 days post dose. Under Microbiologic confirmation, it was clarified that at least one of the bulleted confirmations (ie, not just the first bullet) should be obtained within 24 hours of onset of the event for mechanically ventilated participants and within 72 hours of onset of the event for non-mechanically ventilated participants. Added a section for unblinding for futility analysis purposes. The point at which the sample size may be modified was changed from after 40% to 50% of participants enrolled to after 33% to 40% of participants enrolled, and the sample size reassessment was to be performed prior to the futility assessment. Added the interim analysis for futility.

04 Jun 2015

Modified text to indicate that the data monitoring committee (DMC) would review pharmacokinetics (PK) data and recommend dose adjustment or study termination during the interim analysis. Modified exclusion criterion for Sequential Organ Failure Assessment (SOFA) score based on the Glasgow Coma Scale score. Modified text to clarify that the criterion of dullness to percussion was not elicited by auscultation and it was a separate criterion. It was clarified that the acute changes in PaO2/FiO2 have to be maintained for at least 4 hours. Added details regarding the PK analysis and presentation to the DMC to further describe how the DMC would recommend dose adjustments or potential study termination. Modified text to note that assessment of time to first S aureus pneumonia might have been analysed by survival methods, which could have been potentially broader than the specific Kaplan-Meier approach originally indicated. In addition, language for subgroup analysis was modified to match the Statistical Analysis Plan. It was added that the DMC would be responsible for recommending dose adjustment or potential study termination.

14 Aug 2015

Tracheal/bronchial aspirates for both Gram stain and culture were added to the screening procedures and removed from the post-dose procedures. Clarified that the adjudication committee could have requested to review all data relevant to a potential case, including radiographic and imaging studies, as well as other clinical and/or microbiologic data.

20 Oct 2016

Recommended 2000 mg MEDI4893 group to be discontinued and no dose adjustment to be made to 3000 mg. New participants will be enrolled and randomised to 1 of 2 treatment groups: 5000 mg MEDI4893 or placebo. Change in stratification by receipt of anti-S aureus systemic antibiotic within 72 hours prior to randomisation. Restriction that no more than ~75% of study population would consist of participants in either stratification level of prior anti-S aureus systemic antibiotic was removed. Modified inclusion criteria as: new follow-up duration of 190 days post dose instead of 360 days. Modified exclusion criteria as: to exclude enrolment of participants who received anti-S aureus antibiotics antibiotics for > 48 hours within 72 hours prior to randomisation; exclude enrolment of participants with SOFA score of >= 9 at time of randomisation and to clarify that vasopressors used only to improve cerebral perfusion pressure will not entered in the calculation of cardiovascular component of SOFA score; allow enrolment of participants with asymptomatic human immunodeficiency virus infection; and change time frame for exclusion of patients receiving chemotherapy from 6 months to 2 months. Specimen of expectorated sputum is acceptable for microbiologic confirmation in non- intubated participants but met protocol definition of mechanical ventilation. Participant was not considered mechanically ventilated when endotracheal/nasotracheal tube was not in place and did not require positive ventilation support for at least 8 hours. No adjustments were made for 2000 mg dose when discontinued; 3000 mg dose was removed from key efficacy analyses. Sample size methodology was modified to use Poisson regression with robust variance

15 Mar 2018

Objective “To evaluate the effect of MEDI4893 in reducing the incidence of S aureus pneumonia by mechanical ventilation status” and corresponding endpoint was removed. Revised timelines for analysis of exploratory endpoints 1 to 8, 12, and 15 to 30 days post dose only; 90 days post dose removed. Number of participants to be enrolled reduced from 285 to ~221. Modified power calculation from 80% to 70%; removed text describing sample size reassessment and futility analysis. Stage 1 analysis to be conducted after last participant completed follow-up through 30 days post dose (instead of 90 days). Safety, serum PK and antidrug antibody to be summarized through 30 days post dose and stage 2 analysis safety summarised through 90 days post dose and through end of the study. Primary analysis population changed from Intent-to-treat to modified Intent-to-treat population. Stratification factors for country and prior systemic antibiotics not to be included in the analysis model. Further clarification regarding the analysis was also added Secondary efficacy analysis section was removed.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Phase 2 Randomised, Double-blind, Placebo-controlled, Single-dose, Dose-ranging Study of the Efficacy and Safety of MEDI4893, a Human Monoclonal Antibody Against Staphylococcus aureus Alpha Toxin in Mechanically Ventilated Adult Subjects

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus aureus (S aureus) Pneumonia

Primary: Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus aureus (S aureus) Pneumonia

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days

Primary: Number of Participants With TEAEs Through 91 Days

Primary: Number of Participants With TEAEs Through 91 Days

Primary: Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Adverse Events of Special Interest (AESIs)

Primary: Number of Participants With Adverse Events of Special Interest (AESIs)

Primary: Number of Participants With New Onset Chronic Diseases (NOCDs)

Primary: Number of Participants With New Onset Chronic Diseases (NOCDs)

Secondary: Maximum Observed Serum Concentration (Cmax) of MEDI4893

Secondary: Maximum Observed Serum Concentration (Cmax) of MEDI4893

Secondary: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893

Secondary: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893

Secondary: Observed Serum Concentration of MEDI4893 through 30 Days Post Dose (C30)

Secondary: Observed Serum Concentration of MEDI4893 through 30 Days Post Dose (C30)

Secondary: Observed Serum Concentration of MEDI4893 through 90 Days Post Dose (C90)

Secondary: Observed Serum Concentration of MEDI4893 through 90 Days Post Dose (C90)

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titre to MEDI4893

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titre to MEDI4893

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 2 Randomised, Double-blind, Placebo-controlled, Single-dose, Dose-ranging Study of the Efficacy and Safety of MEDI4893, a Human Monoclonal Antibody Against Staphylococcus aureus Alpha Toxin in Mechanically Ventilated Adult Subjects

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus aureus (S aureus) Pneumonia

Primary: Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus aureus (S aureus) Pneumonia

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days

Primary: Number of Participants With TEAEs Through 91 Days

Primary: Number of Participants With TEAEs Through 91 Days

Primary: Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Adverse Events of Special Interest (AESIs)

Primary: Number of Participants With Adverse Events of Special Interest (AESIs)

Primary: Number of Participants With New Onset Chronic Diseases (NOCDs)

Primary: Number of Participants With New Onset Chronic Diseases (NOCDs)

Secondary: Maximum Observed Serum Concentration (Cmax) of MEDI4893

Secondary: Maximum Observed Serum Concentration (Cmax) of MEDI4893

Secondary: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893

Secondary: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893

Secondary: Observed Serum Concentration of MEDI4893 through 30 Days Post Dose (C30)

Secondary: Observed Serum Concentration of MEDI4893 through 30 Days Post Dose (C30)

Secondary: Observed Serum Concentration of MEDI4893 through 90 Days Post Dose (C90)

Secondary: Observed Serum Concentration of MEDI4893 through 90 Days Post Dose (C90)

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titre to MEDI4893

Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titre to MEDI4893

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2 Randomised, Double-blind, Placebo-controlled, Single-dose, Dose-ranging Study of the Efficacy and Safety of MEDI4893, a Human Monoclonal Antibody Against Staphylococcus aureus Alpha Toxin in Mechanically Ventilated Adult Subjects