Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Investigation of GSK3335065 Intravenous (IV) Infusion in Healthy Adults

Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.

Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.

Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF) and Bazett's QT interval corrected for heart rate (QTcB). ECG measurements were preceded by at least 5 minutes rest for the participant in a semi-recumbent position. Number of participants with abnormal-clinically significant and abnormal-not clinically significant ECG findings at worst case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Time frame: Up to Day 22

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Urine samples were taken for the assessment of following urine parameters: specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed and collected for any abnormal dipstick results. Number of participants with abnormal urine parameters any time post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Time frame: Up to Day 22

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Urine samples were planned to be collected for the assessment of urine parameters.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.

Urine samples were planned to be collected for the assessment of urine parameters.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.

Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, respiration rate and temperature were measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Participants are counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the To Normal or No Change category. Data for worst case post-Baseline relative to Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Time frame: Up to Day 22

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.

Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Time frame: Up to Day 22

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 millimoles per liter \[mmol/L\]); alanine aminotransferase (ALT) (high: \>=2xupper limit of normal \[ULN\]); aspartate aminotransferase (AST) (high: \>=2xULN); alkaline phosphatase (ALP) (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Time frame: Up to Day 22

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples were planned to be collected for the assessment of clinical chemistry parameters.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples were planned to be collected for the assessment of clinical chemistry parameters.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.

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); hemoglobin (high: \>180 grams per liter \[g/L\]), lymphocytes (low: \<0.8x10\^9 cells per liter \[cells/L\]); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells count (low: \<3x10\^9 cells/L and high: \>20x10\^9 cells/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Time frame: Up to Day 22

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples were planned to be collected for the assessment of hematology parameters.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples were planned to be collected for the assessment of hematology parameters.

Time frame: Up to Day 34

Population: All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population. Only participants with PK parameters that could be derived are summarized.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population. Only participants with PK parameters that could be derived are summarized.

Blood samples for pharmacokinetic (PK) analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. PK Parameter Population comprised of all active participants whose PK sample was obtained and analyzed and who provided PK parameters.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples were collected to measure the kynurenine-3-monooxygenase (KMO) enzyme inhibition by determining the levels of the biomarkers Kynurenine (Kyn) and 3-hydroxykynurenine (3-HK). Baseline was the average of all pre-dose measurements (Day 1 \[pre-dose at 1 hour and 30 minutes\]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.

Time frame: Baseline, 6, 15 and 30 minutes, 1, 1.5, 2, 3, 4.5, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: All Subject Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). Data was not collected for placebo arms of Cohorts 1 and 2.

Blood samples were collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK. Baseline was the average of all pre-dose measurements (Day -1 \[pre-dose at 16 hours, 14 hours, 12 hours and 10 hours\] and Day 1 \[pre-dose at 30 minutes and 2 hours\]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.

Time frame: Baseline, 6, 15 and 30 minutes, 1, 1.5, 2, 3, 4.5, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled. Only those participants with data available at the specified time points were analyzed.

Blood samples were planned to be collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18 hours post-infusion), Days2 to 7 (pre-dose), Day8 (6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours post-infusion)

Population: All Subject Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples were planned to be collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18 hours post-infusion), Days2 to 7 (pre-dose), Day8 (6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours post-infusion)

Population: All Subject Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population. Only participants with PK parameters that could be derived are summarized.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population

Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population. Only participants with PK parameters that could be derived are summarized.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part B of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.

Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.

Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Population: PK Parameter Population. Data was not collected as no participants were enrolled in Part C of the study.