Lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony... | NCT03306589

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Subjects receiving LPS: Part I and Part II	Experimental	Eligible subjects will be randomized to receive LPS in a dose-escalation manner ranging from 0.5 nanogram (ng)/kg to 4 ng/kg. Subjects will be hydrated prior to administration of LPS with normal saline at a rate of 250 mL/hour for 4 hours prior to dosing and 8 hours after dosing.	Biological: Cantharidin Biological: Lipopolysaccharide Drug: Saline Solution
Subjects receiving GM-CSF: Part I and Part II	Experimental	Eligible subjects will be randomized to receive GM-CSF in a dose-escalation manner ranging from 5 to 15 microgram (µg)/kg.	Biological: Cantharidin Biological: Granulocyte-Macrophage Colony-Stimulating Factor

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cantharidin	Biological	5 microliter (µL) of 0.2 percent Cantharidin solution (diluted in acetone) will be applied to all subjects on forearm by topical route.	Subjects receiving GM-CSF: Part I and Part II

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: Tumor Necrosis Factor (TNF) Alpha and Interleukin (IL) 6 for LPS Arm	Blood samples were collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Each session was for three days. NA indicates that data was not available as standard deviation could not be calculated for a single participant. All participants who were randomized to receive the treatment (LPS or GM-CSF challenge) and received one dose of challenge agent were included in Safety Population.	Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes,5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3
Part 1: Change From Baseline in Primary Soluble Inflammatory Mediators : Urinary Tetranor Prostaglandin D Metabolite (PGDM) LPS Arm	The post-challenge urine samples were collected during session 2 after LPS challenge. In session 2, participants were encouraged to pass urine immediately before LPS challenge dose and urine voids were collected from after LPS until 12 hours post-LPS and the time of the urine collection were recorded as post-challenge 1 to 11. These samples were collected for measurement of tetranor-PGDM. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. The data for normalized Tetranor PGDM was normalized by (Tetranor PGDM [pg/mL] divided by Creatinine [milligram per deciliter]) multiplied by 100. NA indicates that data was not available as standard deviation could not be calculated for a single participant.	Baseline, Session 2 Day 1
Part 2: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: TNF Alpha and IL 6: LPS Arm	Blood samples were planned to be collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Secondary Outcomes

Measure	Description	Time Frame
Part 1: Change From Baseline Soluble Inflammatory Biomarkers in Skin Blister	Blister samples were collected at indicated time-points for the analysis of soluble inflammatory mediators like IL-1 beta (b), Interferon-gamma (INFg), IL-6, IL-2, IL-8, Monocyte chemotactic protein-1 (MCP-1) and TNF-alpha. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must be 18 to 45 years of age inclusive, at the time of signing the informed consent.
Subjects who are overtly healthy as determined by medical evaluation including: medical history, physical examination, laboratory tests, and electrocardiogram (ECG).
Body mass index (BMI) within the range 19.0-30.0 kilogram per meter square (kg/m^2) (inclusive).
All male subjects. All subjects must agree to use contraception during session 2 and refrain from donating sperm from session 2 to end of study (follow up 2 visits).
Capable of giving signed informed consent.

Exclusion criteria:

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
A positive test for human immuno deficiency virus (HIV) antibody.
Persistent abnormal C-reactive protein/ white cell count (CRP/ WCC) levels at screening.
Abnormal liver function tests at screening. For healthy subjects: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin more than or equal to 1.5xupper limit of normal (ULN) (isolated bilirubin more than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent) at screening.
A positive pre-study drug/alcohol screen.
Current, or chronic history of (h/o): liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), anaphylaxis, and /or anaphylactoid (resembling anaphylaxis) reactions; Cardiac, respiratory or renal disease (childhood asthma can be included); Sensitivity or severe allergic responses to any of the challenge agents or cantharidin, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation; Vasovagal syncope; Surgery or significant trauma in 3 months leading to study enrolment; Relevant skin conditions (for example recent h/o eczema or recurrent eczema, keloid, skin allergies, psoriasis, atopic dermatitis, and vitiligo) which in the opinion of the investigator could pose safety issues or cause interference with study procedures; Sepsis or known coagulation disorders; Peripheral edema, lymphangitis, lymph edema, pleural or pericardial effusion; Respiratory conditions including but not limited to asthma, Chronic obstructive pulmonary disease (COPD), and bronchiectasis and any current respiratory infection.
Presence on either forearm of tattoos, naevi, hypertrophic scars, keloids, hyper or hypo-pigmentation. Subjects with very fair skin, very dark skin, excessive hair or any skin abnormalities that may, in the opinion of the Investigator, interfere with study assessments.
Unable to refrain from the use of prescription drugs taken on an intermittent (as needed) basis or non-prescription drugs; these include non-steroidal anti-inflammatory drugs (NSAIDs), vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to Day 1 of session 1 and continuing until the final follow up visit).
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) or currently in a study of an investigational device.
Previous exposure to LPS in a clinical research setting. Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 56-day period; Current smoker or former regular smoker within 6 months before the screening visit; Unwillingness or inability to follow the procedures outlined in the protocol.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Cambridge		CB2 2GG	United Kingdom

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 nanogram/kilogram (ng/kg) LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
FG001	Part 1: LPS 0.75 ng/kg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 7, 2017	Dec 12, 2018

Arm/Group Information

ID	Title	Description
BG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 nanogram/kilogram (ng/kg) LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
BG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
BG002	Part 1: LPS 1 ng/kg	Participants were randomized to receive 1 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
BG003	Part 1: GM-CSF 60 µg/m^2	Participants were randomized to receive 60 microgram per meter square (µg/m^2) GM-CSF IV infusion. After administration of GM-CSF participant had two blisters induced on each arm followed by blood sample collection
BG004	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
BG005	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum of 480 µg/m^2) during Part 2 of the study.
BG006	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part 1: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: Tumor Necrosis Factor (TNF) Alpha and Interleukin (IL) 6 for LPS Arm

Blood samples were collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Each session was for three days. NA indicates that data was not available as standard deviation could not be calculated for a single participant. All participants who were randomized to receive the treatment (LPS or GM-CSF challenge) and received one dose of challenge agent were included in Safety Population.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Picograms per milliliter

Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes,5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002	Part 1: LPS 1 ng/kg	Participants were randomized to receive 1 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Units	Counts
Participants	OG0002 OG0014 OG0022

Title

Denominators

Categories

IL-6, Session2,Day1, -5 minutes, n=2, 4, 2

- ParticipantsOG0002
- ParticipantsOG0014
- ParticipantsOG0022

Title	Measurements

Primary

Part 1: Change From Baseline in Primary Soluble Inflammatory Mediators : Urinary Tetranor Prostaglandin D Metabolite (PGDM) LPS Arm

The post-challenge urine samples were collected during session 2 after LPS challenge. In session 2, participants were encouraged to pass urine immediately before LPS challenge dose and urine voids were collected from after LPS until 12 hours post-LPS and the time of the urine collection were recorded as post-challenge 1 to 11. These samples were collected for measurement of tetranor-PGDM. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. The data for normalized Tetranor PGDM was normalized by (Tetranor PGDM [pg/mL] divided by Creatinine [milligram per deciliter]) multiplied by 100. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Picograms per milligram

Baseline, Session 2 Day 1

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg

Primary

Part 2: Change From Baseline Primary Soluble Inflammatory Mediators in Blood: TNF Alpha and IL 6: LPS Arm

Blood samples were planned to be collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like TNF-alpha and IL-6 in blood. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.

Units	Counts
Participants	OG000

Primary

Part 2: Change From Baseline Primary Soluble Inflammatory Mediators : Urinary Tetranor PGDM: LPS Arm

Urine samples were planned to be collected for analysis. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 2 Day 1

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.

Units	Counts
Participants	OG000

Primary

Part 1: Change From Baseline in White Blood Cell Numbers in Blood: GM-CSF

Blood samples were collected at indicated time-points for analysis of white blood cells. Latest pre-challenge GM-CSF assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.

Safety Population.

Posted

Mean

Standard Deviation

Giga cells per liter

Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: GM-CSF 60 µg/m^2	Participants were randomized to receive 60 µg/m^2 GM-CSF IV infusion. After administration of GM-CSF participant had two blisters induced on each arm followed by blood sample collection

Units	Counts
Participants	OG000

Secondary

Part 1: Change From Baseline Soluble Inflammatory Biomarkers in Skin Blister

Blister samples were collected at indicated time-points for the analysis of soluble inflammatory mediators like IL-1 beta (b), Interferon-gamma (INFg), IL-6, IL-2, IL-8, Monocyte chemotactic protein-1 (MCP-1) and TNF-alpha. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Picograms per milliliter

Baseline; Session1: 48 hours on Day3; Session 2: 24 hours on Day 2 and 48 hours on Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2: Change From Baseline Soluble Inflammatory Biomarkers in Skin Blister

Blister samples were planned to be collected at indicated time-points for the analysis of soluble inflammatory mediators like IL-1 beta, INFg, IL-6, IL-2, IL-8, MCP-1 and TNF-alpha. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline; Session1: 48 hours Day3; Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1: Absolute Values of Blister Volume

Blister samples were collected at indicated time-points for analysis of blister volumes. . Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline.

Safety Population.

Posted

Mean

Standard Deviation

Microliter

Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002	Part 1: LPS 1 ng/kg	Participants were randomized to receive 1 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2: Absolute Values of Blister Volume

Blister samples were planned to be collected at indicated time-points for analysis of blister volumes. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants	OG000

Secondary

Part 1: Change From Baseline in Cell Numbers in Blister

Blister samples were collected at indicated time-points for analysis of white blood cell in blister. Latest pre-challenge LPS assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Cells per milliliter

Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002	Part 1: LPS 1 ng/kg	Participants were randomized to receive 1 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2: Change From Baseline in Cell Numbers in Blister

Blood samples were planned to be collected at indicated time-points for analysis of white blood cell in blister. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 1: 48 hours Day 3. Session 2: 24 hours Day 2, 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blister

Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for monocytes in blister. Activation markers included Cluster of Differentiation (CD) 16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and Human Leukocyte Antigen - antigen D Related (HLA-DR). Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Mean fluorescence intensity

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blister

Blister samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Monocytes in Blister

Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for monocytes in blister like CD40+/CD80+. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Ratio

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002

Secondary

Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Monocytes in Blister

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blister

Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for dendritic cells in blister. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Mean fluorescence intensity

Baseline; Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blister

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Dendritic Cells in Blister

Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for dendritic cells in blister like CD40+/CD80+. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Ratio

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002

Secondary

Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Dendritic Cells in Blister

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1:Change From Baseline in Cell Activation Markers by Flow Cytometry on Macrophages in Blister

Blister samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for macrophages in blister. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Mean fluorescence intensity

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2:Change From Baseline in Cell Activation Markers by Flow Cytometry on Macrophages in Blister

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Macrophages in Blister

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Ratio

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002

Secondary

Part 2:Change From Baseline of CD40+/CD80+ by Flow Cytometry on Macrophages in Blister

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session1: 48 hours Day 3, Session 2: 24 hours Day 2 and 48 hours Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1:Change From Baseline in Soluble Inflammatory Mediators in Blood

Blood samples were collected at indicated timepoints for the analysis of primary soluble inflammatory mediators like IL-1 beta, INFg, IL-2, IL-8, and MCP-1 in blood. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates that data was not available as standard deviation could not be calculated for a single participant.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Picograms per milliliter

Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2:Change From Baseline in Soluble Inflammatory Mediators in Blood

Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Soluble Inflammatory Mediators in Blood: TNF-alpha, IL-6 and GM-CSF: GM-CSF Arm

Blood samples were collected at indicated time-points for the analysis of soluble inflammatory mediators like TNF-alpha, IL-6 and GM-CSF in blood. Latest pre-challenge GM-CSF assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.

Safety Population.

Posted

Mean

Standard Deviation

Picograms per milliliter

Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: GM-CSF 60 µg/m^2	Participants were randomized to receive 60 µg/m^2 GM-CSF IV infusion. After administration of GM-CSF participant had two blisters induced on each arm followed by blood sample collection

Units	Counts
Participants	OG000

Secondary

Part 2: Change From Baseline in Soluble Inflammatory Mediators in Blood: TNF-alpha, IL-6 and GM-CSF for GM-CSF Arm

Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge GM-CSF assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 2: -5, 10, 25, 40 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants	OG000

Secondary

Part 1: Change From Baseline in Soluble Inflammatory Mediators in Blood: C-reactive Protein (CRP)

Blood samples were collected at indicated time-points for the analysis of soluble inflammatory mediators like CRP in blood. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.

Safety Population.

Posted

Mean

Standard Deviation

Milligrams per liter

Baseline; Session 2: Post challenge Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002	Part 1: LPS 1 ng/kg	Participants were randomized to receive 1 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2: Change From Baseline in Soluble Inflammatory Mediators in Blood: CRP

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline; Session 2: Post challenge Day 1; Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blood

Blood samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for monocytes in blood. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Mean fluorescence intensity

Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2: Change From Baseline in Cell Activation Markers by Flow Cytometry on Monocytes in Blood

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 2: 40 minutes, 2 hour 40 minutes, 5 hour 40 minutes,9hours 40 minutes on Day 1; Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blood

Blood samples were collected at indicated time-points for the measurement of activation markers by flow cytometry for dendritic cells in blood. Activation markers included CD16, CD163, CD206, CD209, CD40, CD80, CD83, CD86 and HLA-DR. Latest pre-challenge (LPS or GM-CSF) assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Posted

Mean

Standard Deviation

Mean fluorescence intensity

Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2: Change From Baseline in Cell Activation Markers by Flow Cytometry on Dendritic Cells in Blood

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.
OG001	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants

Secondary

Part 1: Change From Baseline in Circulating Leukocyte Numbers in Blood: LPS Arm

Blood samples were collected at indicated time-points for analysis of leukocyte. Latest pre-challenge assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value.

Safety Population.

Posted

Mean

Standard Deviation

Cells per milliliter

Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.
OG002	Part 1: LPS 1 ng/kg	Participants were randomized to receive 1 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.

Secondary

Part 2: Change From Baseline in Circulating Leukocyte Numbers in Blood: LPS Arm

Blood samples were planned to be collected at indicated time-points for the measurement of activation. Latest pre-challenge assessment with a non-missing value, including those from unscheduled visits was considered as Baseline. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline; Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study.

Units	Counts
Participants	OG000

Primary

Part 2: Change From Baseline in White Blood Cell Numbers in Blood: GM-CSF

Blood samples were planned to be collected at indicated time-points for analysis of white blood cells. Baseline value is Session 2 Day 1. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Part 2 of the study was not conducted as agreed criteria for Interim analysis was achieved.

Safety Population. Data was not collected for Part 2 as participants were not enrolled for Part 2.

Posted

Baseline, Session 2: 40 minutes, 2 hours 40 minutes, 5 hours 40 minutes, 9 hours 40 minutes on Day 1. Pre-fluid sample on Day 2 and Day 3

ID	Title	Description
OG000	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: LPS 0.5 ng/kg	Participants were randomized to receive 0.5 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.	2	2	2	2
EG001	Part 1: LPS 0.75 ng/kg	Participants were randomized to receive 0.75 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.	4	4	4	4
EG002	Part 1: LPS 1 ng/kg	Participants were randomized to receive 1 ng/kg LPS as intravenous injection. After administration of LPS participant had two blisters induced on each arm followed by blood sample collection.	2	2	2	2
EG003	Part 1: GM-CSF 60 µg/m^2	Participants were randomized to receive 60 µg/m^2 GM-CSF IV infusion. After administration of GM-CSF participant had two blisters induced on each arm followed by blood sample collection.	4	4	3	4
EG004	Part 2: Participants With LPS	Participants were planned to be dosed with LPS (0.5 with possible escalation up to 4 ng/kg) during Part 2 of the study	0	0	0	0
EG005	Part 2: Participants With GM-CSF	Participants were planned to be dosed with GM-CSF (60 to a maximum dose of 480 µg/m^2) during Part 2 of the study.	0	0	0	0

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chills	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0014 events4 affected4 at risk EG0022 events2 affected2 at risk EG0030 events0 affected4 at risk EG0040 events0 affected0 at risk EG0050 events0 affected0 at risk
Chest discomfort	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected4 at risk EG0020 events0 affected2 at risk EG003
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Feeling cold	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected4 at risk EG0020 events0 affected2 at risk EG003
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected4 at risk EG0022 events2 affected2 at risk EG003
Presyncope	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected4 at risk EG0020 events0 affected2 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0012 events2 affected4 at risk EG0021 events1 affected2 at risk EG003
Folliculitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0021 events1 affected2 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected4 at risk EG0021 events1 affected2 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected4 at risk EG0020 events0 affected2 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected4 at risk EG0020 events0 affected2 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected4 at risk EG0020 events0 affected2 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0021 events1 affected2 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0021 events1 affected2 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0021 events1 affected2 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Blood creatinine increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0021 events1 affected2 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0020 events0 affected2 at risk EG003
Hot flush	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected4 at risk EG0021 events1 affected2 at risk EG003

ID	Term
D001172	Arthritis, Rheumatoid
D007249	Inflammation
D001768	Blister

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D012872	Skin Diseases, Vesiculobullous
D012871	Skin Diseases
D020763	Pathological Conditions, Anatomical

ID	Term
D001572	Benzofurans
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D006001	Glycoconjugates
D002241	Carbohydrates
D011135	Polysaccharides, Bacterial
D011134	Polysaccharides
D008055	Lipids
D000942	Antigens, Bacterial
D000941	Antigens
D001685	Biological Factors
D004731	Endotoxins
D001427	Bacterial Toxins
D014118	Toxins, Biological
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D000077324	Crystalloid Solutions
D007552	Isotonic Solutions
D012996	Solutions
D004364	Pharmaceutical Preparations

ID	Term
D002193	Cantharidin
D008070	Lipopolysaccharides
D016178	Granulocyte-Macrophage Colony-Stimulating Factor
D000077330	Saline Solution