Safety, Tolerability, Pharmacokinetics (PK) and Pharmacod... | NCT03965533

Label	Type	Description	Intervention Names
Part A: Placebo IV- Caucasian Participants	Placebo Comparator	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Drug: Placebo
Part A: GSK2831781 450 mg IV- Caucasian Participants	Experimental	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.	Drug: GSK2831781
Part A: Placebo IV- Japanese Participants	Placebo Comparator	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Drug: Placebo
Part A: GSK2831781 450 mg IV- Japanese Participants	Experimental	Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.	Drug: GSK2831781
Part B: Placebo SC	Placebo Comparator	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.

Name	Type	Description	Arm Group Labels	Other Names
GSK2831781	Drug	GSK2831781 will be available as Dose-1 and Dose-2 as IV infusion or SC injection. Subjects will receive GSK2831781 Dose-1 IV diluted in 0.9% saline or GSK2831781 SC as multiples of Dose-2 SC.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants who had SAEs and non-SAEs are presented.	Up to Day 112
Part B: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants who had SAEs and non-SAEs are presented.	Up to Day 112
Part A: Number of Participants With Vital Signs of Potential Clinical Importance	Vital signs were measured in a semi-supine position after five minutes of rest and included temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate. The clinical concern range for the parameters were: SBP (low: <85 millimeters of mercury [mmHg] and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg), heart rate (low: <40 beats per minute [bpm] and high: >110 bpm) and temperature (low: <35 degrees celsius [°C] and high: >=37.5 °C). Number of participants with any vital sign value of potential clinical importance is reported.	Up to Day 112
Part B: Number of Participants With Vital Signs of Potential Clinical Importance

Secondary Outcomes

Measure	Description	Time Frame
Part A: Area Under the Plasma Drug Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0 to t]) of GSK2831781 Following IV Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.	Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and 12-lead ECGs. A subject with a clinical abnormality or laboratory parameter(s) outside the reference range for the population being studied that is not specifically listed in the inclusion or exclusion criteria may be included if the Investigator (in consultation with the Medical Monitor if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or interpretation.
Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Body weight >=40 kilogram (kg) and body mass index (BMI) <=30 kilogram per meter square (kg/m^2).
Male.
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Japanese ancestry, defined as having been born in Japan, being descendants of four ethnic Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport or identity papers, and being able to speak Japanese. Subjects should have lived outside Japan for less than 10 years at the time of screening.
Caucasian ancestry, defined as Caucasian descent as evidenced by appearance and verbal confirmation of familial heritage (a subject has 2 Caucasian parents and 4 Caucasian grandparents).

Exclusion Criteria:

History or presence of a disease that in the opinion of the investigator constitutes a risk when taking the study intervention or interfering with study assessment or interpretation of the data.
A medical history of severe allergic reaction, angioedema, anaphylaxis, clinically significant drug hypersensitivity reaction, or autoimmune or immunodeficiency disorder.
An active infection or a history of serious infections as follows:
1. Use of antimicrobials (antibacterials, antivirals, antifungals or antiparasitic agents) for an infection within 30 days before first dose. Topical treatments may be allowed at the Medical Monitor's discretion.
2. A history of opportunistic infections.
3. Recurrent or chronic infection, or other active infection, that in the opinion of the Investigator might cause this study to be detrimental to the subject.
4. Symptomatic herpes zoster within 3 months prior to screening.
5. History of tuberculosis (TB) (active or latent) irrespective of treatment status.
6. A positive diagnostic TB test at screening (defined as a positive QuantiFERON test). In cases where the QuantiFERON test is indeterminate, the subject may have the test repeated once and if their second test is negative they will be eligible. In the event a second test is also indeterminate, the investigator has the option to undertake purified protein derivative (PPD) testing. If the PPD reaction is <5 millimeter (mm) at 48 to 72 hours, then the subject is eligible. If the reaction is >=5 mm, or PPD testing is not undertaken, the subject is not eligible.
Any planned major surgical procedure during the study.
A history of malignant neoplasm within the last 10 years, except for fully treated nonmetastatic basal or squamous cell cancers of the skin (within 3 years) that shows no evidence of recurrence.
Use of prescription or non-prescription drugs (including recreational drugs and herbal medications) within 7 days or 5 half-lives (whichever is longer) prior to dosing, unless in the opinion of the investigator, the medication will not interfere with the study or compromise subject safety. Paracetamol (acetaminophen) at doses of <=4 grams per day, and occasional use of non-steroidal anti-inflammatory drugs (NSAIDs) at licensed doses, are permitted.
Received live vaccination within 4 weeks of Day 1, or plan to receive a live vaccination during the study until follow-up.
Previous exposure to GSK2831781, or hypersensitivity to any excipients in the clinical formulation of GSK2831781.
Treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
Participation in a clinical trial and has received an investigational medicinal product (IMP) within the following time period prior to screening in the current study: 3 months, 5 half-lives, or twice the duration of the biological effect of the IMP (whichever is longer).
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
Neutrophil or lymphocyte counts below the normal range.
eGFR by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) calculation <=90 milliliter per minute per 1.73 meter square (mL/min/1.73m^2) at screening.
ALT >2x upper limit of normal (ULN) and bilirubin >1.5x ULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
Other clinically significant abnormalities of laboratory assessments, as judged by the Investigator and/or GSK Medical Monitor, that could affect the safety of the subject, or the interpretation of the data from the study.
Presence of hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), or positive hepatitis C antibody result at screening (Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C ribonucleic acid [RNA] test is obtained).
Positive serology for human immunodeficiency virus (HIV) at screening.
Positive pre-study drug/alcohol screen.
QTc >450 millisecond (msec), based on the mean of triplicate ECGs. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF; preferred method), or another method, machine or overread.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units. One unit is equivalent to 8 grams (g) of alcohol: a halfpint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Unstable lifestyle factors, to the extent that in the opinion of the investigator they would interfere with the ability of a subject to complete the study.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		London		NW10 7EW	United Kingdom

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
FG001	Part A: GSK2831781 450 mg IV- Caucasian Participants

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	May 6, 2019	Oct 23, 2020

Arm/Group Information

ID	Title	Description
BG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
BG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
BG002	Part A: Placebo IV- Japanese Participants	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
BG003	Part A: GSK2831781 450 mg IV- Japanese Participants	Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
BG004	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
BG005	Part B: GSK2831781 150 mg SC	Arm Description: Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
BG006	Part B: GSK2831781 450 mg SC	Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
BG007	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 A: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants who had SAEs and non-SAEs are presented.

Safety Population comprised of all randomized (all participants who were randomized into the study and received a randomization number) participants who received study intervention.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG002	Part A: Placebo IV- Japanese Participants	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
OG003	Part A: GSK2831781 450 mg IV- Japanese Participants	Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.

Units	Counts
Participants	OG0002 OG0016 OG0022 OG003

Title

Denominators

Categories

Non-SAEs

Title	Measurements
	OG0002 OG0015 OG0020 OG003

Primary

Part B: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants who had SAEs and non-SAEs are presented.

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG002	Part B: GSK2831781 450 mg SC

Primary

Part A: Number of Participants With Vital Signs of Potential Clinical Importance

Vital signs were measured in a semi-supine position after five minutes of rest and included temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate. The clinical concern range for the parameters were: SBP (low: <85 millimeters of mercury [mmHg] and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg), heart rate (low: <40 beats per minute [bpm] and high: >110 bpm) and temperature (low: <35 degrees celsius [°C] and high: >=37.5 °C). Number of participants with any vital sign value of potential clinical importance is reported.

Safety Population

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG002	Part A: Placebo IV- Japanese Participants	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.

Primary

Part B: Number of Participants With Vital Signs of Potential Clinical Importance

Vital signs were measured in a semi-supine position after five minutes of rest and included temperature, SBP, DBP and heart rate. The clinical concern range for the parameters were: SBP (low: <85 mmHg and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg), heart rate (low: <40 bpm and high: >110 bpm) and temperature (low: <35 °C and high: >=37.5 °C). Number of participants with any vital sign value of potential clinical importance is reported.

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG002	Part B: GSK2831781 450 mg SC	Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.

Primary

Part A: Number of Participants With Any Hematology Parameter of Potential Clinical Importance

Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from Baseline <0.075 proportion of red cells in blood); hemoglobin (high: >180 grams per liter [g/L] and low: change from Baseline <25 g/L), lymphocytes (low: <0.8 Giga cells per liter [Giga cells/L]); neutrophil count (low: <1.5 Giga cells/L); eosinophil count (high: >1 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L) and white blood cells count (low: <3 Giga cells/L and high: >20 Giga cells/L). Number of participants with any hematology parameter value of potential clinical importance is reported.

Safety Population

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG002

Primary

Part B: Number of Participants With Any Hematology Parameter of Potential Clinical Importance

Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from Baseline <0.075 proportion of red cells in blood); hemoglobin (high: >180 g/L and low: change from Baseline <25 g/L), lymphocytes (low: <0.8 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); eosinophil count (high: >1 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L) and white blood cells count (low: <3 Giga cells/L and high: >20 Giga cells/L). Number of participants with any hematology parameter value of potential clinical importance is reported.

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.

Primary

Part A: Number of Participants With Any Clinical Chemistry Parameter of Potential Clinical Importance

Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: alanine aminotransferase (high: >=2 times upper limit of normal [ULN]); aspartate aminotransferase (high: >=2 times ULN); alkaline phosphatase (high: >=2 times ULN); total bilirubin (high: >=1.5 times ULN); blood urea nitrogen (high: >10.5 millimoles per liter [mmol/L]); calcium (low: <2 mmol/L and high: >2.75 mmol/L); creatinine (high: change from Baseline >26 micromoles per liter); estimated glomerular filtration rate (low: <60 milliliter per minute per 1.73 squared meter); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L); sodium (low: <130 mmol/L and high: >150 mmol/L) and total protein (low: <50 g/L and high: >85 g/L). Number of participants with any clinical chemistry parameter value of potential clinical importance is reported.

Safety Population

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.

Primary

Part B: Number of Participants With Any Clinical Chemistry Parameter of Potential Clinical Importance

Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: alanine aminotransferase (high: >=2 times ULN); aspartate aminotransferase (high: >=2 times ULN); alkaline phosphatase (high: >=2 times ULN); total bilirubin (high: >=1.5 times ULN); blood urea nitrogen (high: >10.5 mmol/L]); calcium (low: <2 mmol/L and high: >2.75 mmol/L); creatinine (high: change from Baseline >26 micromoles per liter); estimated glomerular filtration rate (low: <60 milliliter per minute per 1.73 squared meter); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L); sodium (low: <130 mmol/L and high: >150 mmol/L) and total protein (low: <50 g/L and high: >85 g/L). Number of participants with any clinical chemistry parameter value of potential clinical importance is reported.

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.

Primary

Part A: Number of Participants With Any Urinalysis Parameter of Potential Clinical Importance (PCI)

Urine samples were analyzed for bilirubin (Bil.),glucose (Gl.),ketones (Keto),leukocytes (leuko),nitrite (Nit.),occult blood (OB) and protein (Pro.) by dipstick method. Urine red blood cells (RBC) and white blood cells (WBC) were assessed by microscopy. Urine potential of hydrogen (pH) and specific gravity (Sp.Gr.) were also analyzed. The dipstick results are read as Trace,1+,2+ indicating proportional concentrations. pH is measured on a numeric scale of 0 to 14 (pH 7: neutral, pH <7: acidic and pH >7: basic). Urine Sp. Gr. is a measure of the concentration of solutes in the urine and indicated as ratio of urine density to water density. The clinical concern range for these parameters were: Bil., Gl., Leuko, OB and Pro. (high: >1+),Keto (high: >2+),Nit. (high: positive),pH (low: <4.6 and high: >8),Sp.Gr. (low: <1.001 and high: >1.035),RBC (high: >3 cells/high power field [hpf]) and WBC (high: >5 cells/hpf). Number of participants with any urinalysis parameter value of PCI is reported.

Safety Population

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.

Primary

Part B: Number of Participants With Any Urinalysis Parameter of Potential Clinical Importance

Urine samples were analyzed for Bil., Gl., Keto, leuko, Nit., OB and Pro. by dipstick method. Urine RBC and WBC were assessed by microscopy. Urine pH and Sp.Gr. were also analyzed. The dipstick results are read as Trace, 1+, 2+ indicating proportional concentrations. pH is measured on a numeric scale of 0 to 14 (pH 7: neutral, pH <7: acidic and pH >7: basic). Urine Sp. Gr. is a measure of the concentration of solutes in the urine and indicated as ratio of urine density to water density. The clinical concern range for these parameters were: Bil., Gl., Leuko, OB and Pro. (high: >1+), Keto (high: >2+), Nit. (high: positive), pH (low: <4.6 and high: >8), Sp.Gr. (low: <1.001 and high: >1.035), RBC (high: >3 cells/hpf) and WBC (high: >5 cells/hpf). Number of participants with any urinalysis parameter value of PCI is reported.

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.

Primary

Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Twelve-lead ECGs were recorded with the participants in a semi-supine position, after 5 minutes of rest using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Safety Population

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG002	Part A: Placebo IV- Japanese Participants	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.

Primary

Part B: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Twelve-lead ECGs were recorded with the participants in a semi-supine position, after 5 minutes of rest using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG002	Part B: GSK2831781 450 mg SC

Primary

Part A: Number of Participants With Injection Site Reaction

Local tolerability as measured by injection site reaction example; bruise at the site of injection and/or itching, pain, blistering or skin damage. Number of participants with any injection site reaction are presented.

Safety Population

Posted

Count of Participants

Participants

Up to 24 hours (Day 1)

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG002	Part A: Placebo IV- Japanese Participants	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
OG003	Part A: GSK2831781 450 mg IV- Japanese Participants

Primary

Part B: Number of Participants With Injection Site Reaction

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 8

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG002	Part B: GSK2831781 450 mg SC	Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.

Secondary

Part A: Area Under the Plasma Drug Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0 to t]) of GSK2831781 Following IV Dose

Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Pharmacokinetic Population comprised of all safety participants for whom a pharmacokinetic sample was obtained and analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*micrograms per milliliter

Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112

ID	Title	Description
OG000	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG001	Part A: GSK2831781 450 mg IV- Japanese Participants	Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.

Units	Counts
Participants

Secondary

Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2831781 Following IV Dose

Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Pharmacokinetic Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112

ID	Title	Description
OG000	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG001	Part A: GSK2831781 450 mg IV- Japanese Participants	Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.

Units	Counts
Participants	OG000

Secondary

Part A: Time to Maximum Observed Plasma Concentration (Tmax) of GSK2831781 Following IV Dose

Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Pharmacokinetic Population

Posted

Median

Full Range

Hours

Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112

ID	Title	Description
OG000	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG001	Part A: GSK2831781 450 mg IV- Japanese Participants	Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.

Units	Counts
Participants	OG000

Secondary

Part B: AUC(0 to t) of GSK2831781 Following SC Dose

Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Pharmacokinetic Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*micrograms per milliliter

Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112

ID	Title	Description
OG000	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG001	Part B: GSK2831781 450 mg SC	Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.

Units	Counts
Participants

Secondary

Part B: Cmax of GSK2831781 Following SC Dose

Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Pharmacokinetic Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112

ID	Title	Description
OG000	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG001	Part B: GSK2831781 450 mg SC	Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.

Units	Counts
Participants

Secondary

Part B: Tmax of GSK2831781 Following SC Dose

Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Pharmacokinetic Population

Posted

Median

Full Range

Hours

Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112

ID	Title	Description
OG000	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG001	Part B: GSK2831781 450 mg SC	Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.

Units	Counts
Participants	OG000

Secondary

Part A and Part B: Bioavailability (F) of GSK2831781 Following IV Dosing at 450 mg (Caucasian and Japanese Participants) or SC Dosing at 150 mg and 450 mg (Caucasian Participants)

Blood samples were collected at indicated time points for pharmacokinetic analysis in Part A (IV dose) and Part B (SC doses). Bioavailability of GSK2831781 was estimated by fitting a population pharmacokinetic model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and total soluble lymphocyte activation gene-3 (LAG3) concentrations in serum and was expressed as a percentage.

Pharmacokinetic Population. Given the non-linearity in pharmacokinetics, a population pharmacokinetic analysis of pooled data from Part A and Part B was more appropriate. Hence, this outcome measure was estimated on pooled data from Part A and Part B.

Posted

Number

95% Confidence Interval

Percentage Bioavailability

Part A (IV): Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112; Part B (SC): Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112

ID	Title	Description
OG000	Part A and Part B: All Participants	In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.

Secondary

Degradation Rate of LAG3 Positive T Cells (Kout) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and Part B)

Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) pharmacokinetic/pharmacodynamic (PK/PD) model. Kout was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; Kout is presented.

Pharmacokinetic Population. Given the limited dose range (150 mg-450 mg) in each part, a population PK/PD analysis of combined data from Part A and Part B was more appropriate. Hence, this outcome measure was estimated on combined data from Part A and Part B.

Posted

Mean

95% Confidence Interval

Per hour

Up to Day 112

ID	Title	Description
OG000	Part A and Part B: All Participants	In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.

Secondary

Baseline of LAG3 Positive T Cell Count (CELL0) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)

Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. CELL0 was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; CELL0 is presented.

Posted

Mean

95% Confidence Interval

Cells per microliter

Up to Day 112

ID	Title	Description
OG000	Part A and Part B: All Participants	In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.

Secondary

Concentration of Free GSK2831781 at Which Half Maximum Effect on Kout is Achieved (EC50) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)

Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. EC50 was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. As there was a limited dose range, to allow for a successful model conversion, EC50 was fixed to the EC50 value estimated from a previous study. The model parameter; EC50 is presented.

Pharmacokinetic Population. Given the limited dose range (150 mg-450 mg) in each part, a population PK/PD analysis of combined data from Part A and Part B was more appropriate. This outcome measure was fixed to the EC50 value estimated from a previous study.

Posted

Mean

95% Confidence Interval

Nanograms per milliliter

Up to Day 112

ID	Title	Description
OG000	Part A and Part B: All Participants	In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.

Secondary

Maximum Effect of Change in Kout (Emax) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)

Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. Emax, a unitless parameter that describes the maximum change in Kout at infinite GSK2831781 concentration, was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; Emax is presented.

Posted

Mean

95% Confidence Interval

Unitless

Up to Day 112

ID	Title	Description
OG000	Part A and Part B: All Participants	In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.

Secondary

Hill Coefficient (GAM) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)

Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. The Hill coefficient GAM, a unitless parameter defining the steepness of the concentration-effect curve, was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; GAM is presented.

Posted

Mean

95% Confidence Interval

Unitless

Up to Day 112

ID	Title	Description
OG000	Part A and Part B: All Participants	In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.

Secondary

Part A: Number of Participants With Confirmed Positive Post-Baseline Anti-drug Antibody Result

Serum samples were analyzed for the presence of anti-GSK2831781 antibodies using a validated immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'confirmed positive'. Number of participants with confirmed positive post-Baseline ADA result are presented.

Safety Population

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
OG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
OG002	Part A: Placebo IV- Japanese Participants	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.

Secondary

Part B: Number of Participants With Confirmed Positive Post-Baseline Anti-drug Antibody Result

Safety Population. Placebo arms across similar dosing strategies were combined in Part B.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
OG001	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
OG002	Part B: GSK2831781 450 mg SC

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A: Placebo IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	2	0	2	2	2
EG001	Part A: GSK2831781 450 mg IV- Caucasian Participants	Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.	6	0	6	5	6
EG002	Part A: Placebo IV- Japanese Participants	Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	2	0	2	0	2
EG003	Part A: GSK2831781 450 mg IV- Japanese Participants	Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.	6	0	6	4	6
EG004	Part B: Placebo SC	Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.	4	0	4	4	4
EG005	Part B: GSK2831781 150 mg SC	Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.	8	1	8	6	8
EG006	Part B: GSK2831781 450 mg SC	Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.	8	0	8	4	8

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site bruising	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG0032 affected6 at risk EG0040 affected4 at risk EG0050 affected8 at risk EG0060 affected8 at risk
Catheter site bruise	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Fatigue	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Injection site erythema	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Vessel puncture site bruise	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected2 at risk EG0012 affected6 at risk EG0020 affected2 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0012 affected6 at risk EG0020 affected2 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0012 affected6 at risk EG0020 affected2 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected6 at risk EG0020 affected2 at risk EG003
Cellulitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Tooth infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected6 at risk EG0020 affected2 at risk EG003