Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK2831781 After an Intravenous (IV) Dose in Healthy Japanese and Caucasian Subjects, and a Subcutaneous (SC) Dose in Healthy Caucasian Subjects (NCT NCT03965533)

NCT ID: NCT03965533

Last Updated: 2020-11-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 36 participants
• Primary outcome timeframe: Up to Day 112
• Results posted on: 2020-11-18

Participant Flow

This was a double-blind, placebo-controlled, randomized, parallel group, two-part study to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous (IV) dose of GSK2831781 in healthy Japanese and Caucasian participants (Part A) and subcutaneous (SC) dose of GSK2831781 in healthy Caucasian participants (Part B).

A total of 30 participants were screened and 16 participants were enrolled in Part A (14 were screen failures). A total of 41 participants were screened and 20 participants were enrolled in Part B (21 were screen failures). Placebo arms across similar dosing strategies were combined in Part B.

Participant milestones

Measure	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.	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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.	Part B: Placebo SC Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.	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.	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.
Part A (112 Days) STARTED	2	6	2	6	0	0	0
Part A (112 Days) COMPLETED	2	6	2	6	0	0	0
Part A (112 Days) NOT COMPLETED	0	0	0	0	0	0	0
Part B (112 Days) STARTED	0	0	0	0	4	8	8
Part B (112 Days) COMPLETED	0	0	0	0	4	8	8
Part B (112 Days) NOT COMPLETED	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK2831781 After an Intravenous (IV) Dose in Healthy Japanese and Caucasian Subjects, and a Subcutaneous (SC) Dose in Healthy Caucasian Subjects

Baseline characteristics by cohort

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.	Part B: Placebo SC n=4 Participants Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.	Part B: GSK2831781 150 mg SC n=8 Participants 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.	Part B: GSK2831781 450 mg SC n=8 Participants 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.	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	8 Participants n=8 Participants	8 Participants n=8 Participants	36 Participants n=24 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	8 Participants n=8 Participants	8 Participants n=8 Participants	36 Participants n=24 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage (H)	2 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants	8 Participants n=8 Participants	8 Participants n=8 Participants	28 Participants n=24 Participants
Race/Ethnicity, Customized Asian-Japanese H/East Asian H/South East Asian H	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	8 Participants n=24 Participants

PRIMARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) Non-SAEs	2 Participants	5 Participants	0 Participants	4 Participants
Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) SAEs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) Non-SAEs	4 Participants	6 Participants	4 Participants	—
Part B: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) SAEs	0 Participants	1 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Day 112

Population: Safety Population

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Vital Signs of Potential Clinical Importance	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Vital Signs of Potential Clinical Importance	1 Participants	0 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to Day 112

Population: Safety Population

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Any Hematology Parameter of Potential Clinical Importance	0 Participants	1 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Any Hematology Parameter of Potential Clinical Importance	0 Participants	0 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to Day 112

Population: Safety Population

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Any Clinical Chemistry Parameter of Potential Clinical Importance	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Any Clinical Chemistry Parameter of Potential Clinical Importance	0 Participants	0 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to Day 112

Population: Safety Population

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Any Urinalysis Parameter of Potential Clinical Importance (PCI)	2 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Any Urinalysis Parameter of Potential Clinical Importance	1 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Day 112

Population: Safety Population

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal-Clinically significant	0 Participants	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal-not Clinically significant	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal-not Clinically significant	0 Participants	1 Participants	0 Participants	—
Part B: Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal-Clinically significant	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to 24 hours (Day 1)

Population: Safety Population

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Injection Site Reaction	0 Participants	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to Day 8

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Injection Site Reaction	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: 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

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

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

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=6 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
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	44261.755 Hours*micrograms per milliliter Geometric Coefficient of Variation 23.8009	49650.933 Hours*micrograms per milliliter Geometric Coefficient of Variation 19.6053	—	—

SECONDARY outcome

Timeframe: 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

Population: Pharmacokinetic Population

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

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=6 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2831781 Following IV Dose	137.61 Micrograms per milliliter Geometric Coefficient of Variation 22.449	166.20 Micrograms per milliliter Geometric Coefficient of Variation 20.428	—	—

SECONDARY outcome

Timeframe: 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

Population: Pharmacokinetic Population

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

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=6 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part A: Time to Maximum Observed Plasma Concentration (Tmax) of GSK2831781 Following IV Dose	1.980 Hours Interval 1.98 to 2.17	1.990 Hours Interval 1.95 to 6.02	—	—

SECONDARY outcome

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

Population: Pharmacokinetic Population

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

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=8 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: AUC(0 to t) of GSK2831781 Following SC Dose	6633.227 Hours*micrograms per milliliter Geometric Coefficient of Variation 26.6369	24269.036 Hours*micrograms per milliliter Geometric Coefficient of Variation 40.4247	—	—

SECONDARY outcome

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

Population: Pharmacokinetic Population

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

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=8 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Cmax of GSK2831781 Following SC Dose	14.61 Micrograms per milliliter Geometric Coefficient of Variation 30.229	41.13 Micrograms per milliliter Geometric Coefficient of Variation 34.252	—	—

SECONDARY outcome

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

Population: Pharmacokinetic Population

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

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=8 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Tmax of GSK2831781 Following SC Dose	95.750 Hours Interval 46.92 to 167.75	120.270 Hours Interval 69.72 to 169.73	—	—

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=28 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
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)	76.5 Percentage Bioavailability Interval 76.5 to 76.5	—	—	—

SECONDARY outcome

Timeframe: Up to Day 112

Population: 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.

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=28 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
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)	0.0256 Per hour Interval 0.0161 to 0.0405	—	—	—

SECONDARY outcome

Timeframe: Up to Day 112

Population: 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.

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=28 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
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)	1.15 Cells per microliter Interval 1.11 to 1.19	—	—	—

SECONDARY outcome

Timeframe: Up to Day 112

Population: 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.

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=28 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
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)	9509 Nanograms per milliliter Interval 174.0 to 540000.0	—	—	—

SECONDARY outcome

Timeframe: Up to Day 112

Population: 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.

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=28 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
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)	2.35 Unitless Interval 1.9 to 2.9	—	—	—

SECONDARY outcome

Timeframe: Up to Day 112

Population: 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.

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=28 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	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.	Part A: Placebo IV- Japanese Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
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)	0.0942 Unitless Interval 0.0453 to 0.196	—	—	—

SECONDARY outcome

Timeframe: Up to Day 112

Population: Safety Population

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=2 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 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.	Part A: Placebo IV- Japanese Participants n=2 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 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.
Part A: Number of Participants With Confirmed Positive Post-Baseline Anti-drug Antibody Result	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 112

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

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.

Outcome measures

Measure	Part A: Placebo IV- Caucasian Participants n=4 Participants Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=8 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.	Part A: Placebo IV- Japanese Participants n=8 Participants Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	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.
Part B: Number of Participants With Confirmed Positive Post-Baseline Anti-drug Antibody Result	0 Participants	0 Participants	0 Participants	—

Adverse Events

Part A: Placebo IV- Caucasian Participants

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: GSK2831781 450 mg IV- Caucasian Participants

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part A: Placebo IV- Japanese Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part A: GSK2831781 450 mg IV- Japanese Participants

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part B: Placebo SC

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part B: GSK2831781 150 mg SC

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B: GSK2831781 450 mg SC

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A: Placebo IV- Caucasian Participants n=2 participants at risk Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 participants at risk 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.	Part A: Placebo IV- Japanese Participants n=2 participants at risk Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 participants at risk Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.	Part B: Placebo SC n=4 participants at risk Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.	Part B: GSK2831781 150 mg SC n=8 participants at risk 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.	Part B: GSK2831781 450 mg SC n=8 participants at risk 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.
Infections and infestations Tonsillitis	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.

Other adverse events

Measure	Part A: Placebo IV- Caucasian Participants n=2 participants at risk Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.	Part A: GSK2831781 450 mg IV- Caucasian Participants n=6 participants at risk 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.	Part A: Placebo IV- Japanese Participants n=2 participants at risk Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.	Part A: GSK2831781 450 mg IV- Japanese Participants n=6 participants at risk Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.	Part B: Placebo SC n=4 participants at risk Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.	Part B: GSK2831781 150 mg SC n=8 participants at risk 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.	Part B: GSK2831781 450 mg SC n=8 participants at risk 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.
General disorders Injection site bruising	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
General disorders Catheter site bruise	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
General disorders Fatigue	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
General disorders Injection site erythema	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
General disorders Vessel puncture site bruise	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	25.0% 1/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Nervous system disorders Headache	50.0% 1/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Nervous system disorders Paraesthesia	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Infections and infestations Nasopharyngitis	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	25.0% 2/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Musculoskeletal and connective tissue disorders Back pain	50.0% 1/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	50.0% 1/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	33.3% 2/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Gastrointestinal disorders Toothache	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Psychiatric disorders Anxiety	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Renal and urinary disorders Nocturia	50.0% 1/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Skin and subcutaneous tissue disorders Rash	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	16.7% 1/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Infections and infestations Cellulitis	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	25.0% 1/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Infections and infestations Tooth infection	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	25.0% 1/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	25.0% 1/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
General disorders Pain	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	25.0% 1/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	25.0% 1/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/2 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/6 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/4 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	12.5% 1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.	0.00% 0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.

Additional Information

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• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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