GSK3640254 First Time in Human (FTIH) Study in Healthy Volunteers

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03231943
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 78
• Location: 1
• Arms: 3
• Actual Duration (Months): 11.7
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

Human immuno deficiency virus 1 (HIV-1) infections continues to be a serious health threat throughout the world and development of medicines with new mechanism of action have an important role to play. GSK3640254 is a maturation inhibitor (MI) and can be effective in HIV-1 treatment. This randomized, 2-part, single and repeat increasing dose study will collect information on safety, tolerability and drug levels in the body of in healthy subjects for GSK3640254. The information collected in this study will help in further clinical development of GSK3640254, including a Phase IIA Proof of Concept (PoC) study in HIV-infected subjects. Approximately 16 healthy subjects will be randomized to receive single oral dose of GSK3640254 and placebo in Part 1 and approximately 56 healthy subjects will be randomized to receive repeat oral dose of GSK3640254 or placebo in Part 2. All doses will be given immediately after a moderate fat meal. Maximum duration of study participation will be approximately 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus; HIV Infections	Drug: GSK3640254; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: This is a dose-escalation study and dose will be escalated based on the safety data of the initial dose.This is a dose-escalation study and dose will be escalated based on the safety data of the initial dose.
• Masking: Double (Participant, Investigator)
• Masking Description: This will be a double-blind study with subjects and the site-staff blinded and sponsor unblinded.
• Primary Purpose: Treatment
• Official Title: A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3640254 in Healthy Participants
• Actual Study Start Date: Sep 19, 2017
• Actual Primary Completion Date: Sep 9, 2018
• Actual Study Completion Date: Sep 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects in cohort 1-2: Part 1 Eligible subjects will participate in cohort 1 or 2 and each of these two cohorts will contain up to four escalating doses of GSK3640254. In each cohort, 6 subjects will be randomized to receive single oral dose of GSK3640254 and 2 subjects will be randomized to receive placebo. Hence, each subject in cohort 1 and 2 will receive up to 3 escalating doses of GSK3640254 and one placebo in crossover manner.	Drug: GSK3640254; GSK3640254 is a capsule available in 1 milligram (mg), 10 mg and 100 mg dosing strength. GSK3640254 capsule will be given via oral route during each dosing day with approximately 240 mL of water.; Drug: Placebo; Placebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.
Experimental: GSK3640254 receivers (cohort 3-6 and expansion): Part 2 Eligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 6 subjects will be randomized to receive a once-daily oral dose of GSK3640254 for 14 days. After the safety data of cohort 3-6 is available, 18 eligible subjects will be randomized to receive once daily oral dose of GSK3640254 for 14 days in expansion cohort.	Drug: GSK3640254; GSK3640254 is a capsule available in 1 milligram (mg), 10 mg and 100 mg dosing strength. GSK3640254 capsule will be given via oral route during each dosing day with approximately 240 mL of water.
Placebo Comparator: Subjects receiving placebo (cohort 3-6): Part 2 Eligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 2 subjects will be randomized to receive a once-daily oral dose of placebo for 14 days. After the safety data of cohort 3-6 is available, 6 eligible subjects will be randomized to receive once daily oral dose of placebo for 14 days in expansion cohort.	Drug: Placebo; Placebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.

Outcome Measures

Primary Outcome Measures

1. Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [Up to Day 15]

   An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Results are presented treatment wise.

2. Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

3. Part 1: Change From Baseline in Hematology Parameters: Erythrocytes. [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the hematology parameters: erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.

4. Part 1: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume (Erythrocyte MCV). [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the hematology parameters: erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

5. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH) [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the hematology parameter: Erythrocyte MCH. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.

6. Part 1: Change From Baseline in Hematology Parameter: Hematocrit [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

7. Part 1: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

8. Part 1: Change From Baseline in Hematology Parameter: Hemoglobin (Hb) [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

9. Part 1: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

   Blood samples were collected to analyze the chemistry parameter: ALT, AST, and ALP. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

10. Part 1: Change From Baseline in Clinical Chemistry Parameters : Bicarbonate, Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

    Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

11. Part 1: Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Cholesterol (LDL) Cholesterol, Triglycerides [Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)]

    Blood samples were collected to analyze the chemistry parameter: cholesterol, glucose, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

12. Part 1: Change From Baseline in Chemistry Parameter: Glucose [Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)]

    Blood samples were collected to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

13. Part 1: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

    Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

14. Part 1: Change From Baseline in Clinical Chemistry Parameter: Protein [Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)]

    Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

15. Part 1: Number of Participants With Abnormal Urinalysis [Up to Day 15]

    Urine samples were collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.

16. Part 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)]

    SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

17. Part 1: Change From Baseline in Vital Signs: Pulse Rate [Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)]

    Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

18. Part 1: Change From Baseline in Vital Signs: Temperature [Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)]

    Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

19. Part 1: Change From Baseline in Vital Sign: Respiratory Rate [Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)]

    Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

20. Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Baseline (Day 1 predose), 1,2,4,6,12,24,48,72,96 hours post dose and Follow up (Day 15)]

    12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).

21. Part 2: Number of Participants AEs and SAEs [Up to Day 28]

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Results are presented treatment wise.

22. Part 2: Change From Baseline in Abnormal Hematology Findings: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. [Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14 : 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

23. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes [Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

24. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes MCV [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

25. Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH) [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocyte MCH. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

26. Part 2: Change From Baseline in Hematology Parameter: Hematocrit [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

27. Part 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

28. Part 2: Change From Baseline in Hematology Parameter: Hb [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

29. Part 2: Change From Baseline in Chemistry Parameter: ALT, AST,ALP [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected to analyze the chemistry parameter: ALT, AST,ALP. Day -2was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

30. Part 1: Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Magnesium, Phosphate, Potassium, Sodium, Urea [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

31. Part 2: Change From Baseline in Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides [Baseline (Day -2), Day 8 (pre dose), Day 14 (48 hours) post dose and Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the chemistry parameter: cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

32. Part 2: Change From Baseline in Chemistry Parameter: Glucose [Baseline (Day -2), Day 8 (predose), Day 14 (48 hours) post dose and Follow up (Day 28)]

    Blood samples were collected at indicated time points to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

33. Part 2: Change From Baseline in Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

34. Part 2: Change From Baseline in Chemistry Parameter: Protein [Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)]

    Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

35. Part 2: Number of Participants With Abnormal Urinalysis [Up to Day 28]

    Urine samples were collected analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.

36. Part 2: Change From Baseline in Vital Signs: SBP and DBP [Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12,and 14 (pre dose and 72 hours) and Follow up (Day 28)]

    SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

37. Part 2: Change From Baseline in Vital Sign: Pulse Rate [Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)]

    Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

38. Part 2: Change From Baseline in Vital Sign: Temperature [Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)]

    Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

39. Part 2: Change From Baseline in Vital Sign: Respiratory Rate [Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12 and 14 (pre dose and 72 hours) and Follow up (Day 28)]

    Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.

40. Part 2: Number of Participants With Abnormal ECG Findings [Day 1 (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5, 5.5, 6, 8, 12, 24 hours); Pre-dose on Days 3, 4, 6, 8, 10, 12; Day 14: Pre-dose, 1, 2, 4.5, 5, 6, 12, 24, 48, 72 and 96 hours post-dose and follow up (Day 28)]

    12-lead ECG were obtained at given time points. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).Results are presented treatment wise.

Secondary Outcome Measures

1. Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hour (AUC[0-24]) of GSK3640254 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,24 hours post-dose]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

2. Part 1: AUC From Zero to Time of Last Sample Taken (AUC[0-Tlast]) of GSK3640254 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

3. Part 1: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3640254 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

4. Part 1: Apparent Terminal Phase Half-life (T1/2) of GSK3640254 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Most of the concentrations were below limit of quantification (BLQ) at this dose group this value and/ or %AUC extrapolated was >20% for all participants so this value should be used with caution. Results are presented treatment wise.

5. Part 1: Apparent Oral Clearance (CL/F) of GSK3640254 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

6. Part 1: Maximum Observed Concentration (Cmax), Concentration of GSK3640254 at 24 Hours (C24) and Last Quantifiable Concentration (Clast) of GSK3640254 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.

7. Part 1: Time of Occurrence of Cmax (Tmax), Lag Time (Tlag), and Time to Reach Clast (Tlast) of GSK3640254 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

8. Part 2: AUC(0-24) of GSK3640254: Day 1 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 and 24 hours post-dose on Day 1]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

9. Part 2: Cmax, C24 of GSK3640254 on Day 1 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1]

   Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

10. Part 2: Tmax, Tlag of GSK3640254 on Day 1 [Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1]

    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.

11. Part 2: Tmax GSK3640254 on Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

12. Part 2: Cmax of GSK3640254 on Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

13. Part 2: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

14. Part 2: Plasma Trough Concentration (Ctau) of GSK3640254: Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The PK parameter name for Part 2 (Day 14) trough concentration was changed using Phoenix WinNonlin 8 from Ct to Ctrough. Day 15 Ctrough values were used for dose proportionality and time to steady-state assessments.

15. Part 2: T1/2 of GSK3640254: Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.

16. Part 2: CL/F of GSK3640254: Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.

17. Part 1: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3640254 on Day 1 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

18. Part 1: Dose Proportionality (AUC0-24) Following Single Dose of GSK3640254 on Day 1 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

19. Part 1: Dose Proportionality for Cmax Following Single Dose of GSK3640254 on Day 1 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

20. Part 2: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3640254 on Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

21. Part 2: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3640254 on Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

22. Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 on Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

23. Part 2: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) From Day 1 to Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.

24. Part 2: Accumulation Ratio of Cmax (R [CMAX]) From Day 1 to Day 14 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.

25. Part 2: Accumulation Ratio of C(Tau) (R[CTAU]) From Day 2 to Day 15 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 15 dose]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 15 and Day 2, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.

26. Part 2: Pre-dose Concentration of GSK3640254 on Day 2 to Day 14 [Pre-dose on Days 2,3,4,6,8,10,12 and 14]

    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. results are presented treatment wise.

27. Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 at Day 1 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

28. Part 2: Dose Proportionality (AUC0-24) Following Repeated Dose of GSK3640254 at Day 1 [Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose]

    Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects must be 18 to 55 years of age inclusive, at the time of signing the informed consent.

• Subjects who are overtly healthy as determined by medical evaluation including medical history and psychiatric history, physical examination, laboratory tests, and 24 hour Holter monitoring.

• Body weight >=50.0 kilogram (kg) (110 pounds) for men and 45.0kg (99 pounds) for women and body mass index (BMI) within the range 18.5-32.0 kg per meter square (kg/m^2) (inclusive).

• Male or female subjects. A male subject must agree to use contraception during the treatment period and for at least 14 weeks following the last dose, corresponding to the time needed to eliminate study treatment for potential genotoxic and teratogenic study treatments plus an additional 90 days (spermatogenesis cycle). In addition, male subjects must refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WOCBP).

• Capable of giving signed informed consent.

Exclusion Criteria:

• Alanine transaminase (ALT) >1.5 into upper limit of normal (ULN).

• Bilirubin >1.5 into ULN (isolated bilirubin >1.5 into ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities.

• Pre-existing clinically relevant, in the opinion of the primary investigator (PI), gastro-intestinal pathology or diagnosis - example irritable bowel syndrome, inflammatory bowel disease, and/or significant Baseline signs and symptoms.

• Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.

• Any known or suspected pre-existing psychiatric condition.

• Any other clinical condition (including but not limited to active substance use) or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits; or a condition that could affect the absorption, distribution, metabolism or excretion of the drug.

• Unable to refrain from the use of prescription or non-prescription drugs (with the exception of paracetamol), including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and for the duration of the study, unless in the opinion of the Investigator and ViiV Healthcare Sponsor and medical monitor, the medication will not interfere with the study medications, procedures, or compromise subject safety.

• Unwillingness to abstain from ingestion of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos within 7 days prior to the first dose of study treatment(s) or until the end of the study.

• Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 56 days.

• Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.

• A positive pre-study drug/alcohol screen.

• A positive test for a diagnostic HIV-1 polymerase chain reaction (PCR).

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Exclusion criteria for screening ECG: Heart rate <45 or >100 beats per minute (bpm) for males and <50 or >100 bpm for females; PR interval <120 or >220 millisecond (msec); QRS duration <70 or >120 msec; the Fridericia's QT correction formula (QTcF) interval >450 msec.

• Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).

• Any conduction abnormality (including but not specific to left or right complete bundle branch block, Atrioventricular block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome).

• Sinus Pauses >3 seconds.

• Any significant arrhythmia which, in the opinion of the Investigator or GlaxoSmithKline/ViiV medical monitor, will interfere with the safety for the individual subject.

• Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).

• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 gram of alcohol: a half-pint approximately 240 mL of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

• Regular use of tobacco- or nicotine-containing products within 3 months prior to screening.

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or medical monitor, contraindicates their participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Cambridge		United Kingdom	CB2 2GG

Sponsors and Collaborators

• ViiV Healthcare
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

• Study Protocol - May 17, 2018
• Statistical Analysis Plan - Sep 8, 2018

More Information

Publications

• Joshi SR, Fernando D, Igwe S, McKenzie L, Krishnatry AS, Halliday F, Zhan J, Greene TJ, Xu J, Ferron-Brady G, Lataillade M, Min S. Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor. Pharmacol Res Perspect. 2020 Dec;8(6):e00671. doi: 10.1002/prp2.671.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT03231943
• Other Study ID Numbers: 207187; 2017-001367-21
• First Posted: Jul 27, 2017
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ViiV Healthcare: FTIH; Healthy; Tolerability; Dose-escalation; HIV-1; Safety; PK; GSK3640254; Maturation inhibitor
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome

Study Results

Participant Flow

Recruitment Details	This study was conducted to evaluate safety, tolerability and pharmacokinetic (PK) of GSK3640254 in healthy participants at one center in United Kingdom from 19-September-2017 to 09-September-2018
Pre-assignment Detail	Total 78 participants were enrolled in the study. This was a two part study, Part 1 was single ascending dose (SAD) and Part 2 was multiple ascending dose (MAD).

Arm/Group Title	Part 1: Placebo Followed by GSK3640254 10mg/100mg/400mg	Part 1: GSK3640254 1mg/ Placebo /100 mg/400 mg	Part 1: GSK3640254 1mg/10mg/Placebo /400mg	Part 1: GSK3640254 1mg/10mg/100mg/Placebo	Part 1: Placebo/ GSK3640254 30mg/200 mg/700 mg	Part1:GSK3640254 3mg/Placebo/200mg/700mg	Part 1:GSK3640254 3mg/30mg/Placebo/GSK3640254 700mg	Part 1:GSK3640254 3mg/30mg/GSK3640254 200mg/Placebo	Part 2: Repeated Dose GSK3640254 50 mg	Part 2: Repeated Dose GSK3640254 100mg	Part 2: GSK3640254 200mg + Expansion	Part 2: Repeated Dose GSK3640254 320mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received single dose placebo followed by GSK3640254 10 milligram (mg) followed by GSK3640254 100 mg followed by GSK3640254 400 mg oral dose on Day 1	Participants received single dose GSK3640254 1mg followed by placebo followed by GSK3640254 100 mg followed by GSK3640254 400 mg oral dose on Day 1	Participants received single dose GSK3640254 1mg followed by GSK3640254 10 mg followed by placebo followed by GSK3640254 400 mg oral dose on Day 1	Participants received single dose GSK3640254 1mg followed by GSK3640254 10 mg followed by GSK3640254 100 mg followed by placebo as oral dose on Day 1	Participants received single dose placebo followed by GSK3640254 30mg followed by GSK3640254 200 mg followed by GSK3640254 700 mg as oral dose on Day 1	Participants received single dose GSK3640254 3mg followed by placebo followed by GSK3640254 200 mg followed by GSK3640254 700 mg as oral dose on Day 1	Participants received single dose GSK3640254 3 mg followed by GSK3640254 30 mg followed by placebo followed by GSK3640254 700 mg as oral dose on Day 1	Participants received single dose GSK3640254 3mg followed by GSK3640254 30mg followed by GSK3640254 200mg followed by placebo as oral dose on Day 1	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Period Title: Part 1, Period 1 (up to Day 15)
STARTED	2	2	2	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	2	2	2	2	2	2	2	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to Day 15)
STARTED	2	2	2	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	0	1	2	2	2	2	2	0	0	0	0	0
NOT COMPLETED	0	2	1	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to Day 15)
STARTED	2	2	2	2	2	2	2	2	0	0	0	0	0
COMPLETED	1	2	2	2	2	2	2	2	0	0	0	0	0
NOT COMPLETED	1	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to Day 15)
STARTED	2	2	2	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	2	2	2	2	2	2	2	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to Day 15)
STARTED	0	0	0	0	0	0	0	0	6	6	25	7	14
COMPLETED	0	0	0	0	0	0	0	0	6	6	24	6	14
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	1	1	0

Baseline Characteristics

Arm/Group Title	Part 1: Cohort 1	Part 1: Cohort 2	Part 2: Repeated Dose GSK3640254 50 mg	Part 2: Repeated Dose GSK3640254 100 mg	Part 2: Repeated Dose GSK3640254 200 mg + Expansion	Part 2: Repeated Dose GSK3640254 320 mg	Part 2: Repeated Dose Placebo	Total
Arm/Group Description	Participants received GSK3640254 1mg, GSK3640254 10 mg, GSK3640254 100mg, GSK3640254 400mg as ascending single dose on Day 1 of each period, each participant received placebo in one of the four periods	Participants received GSK3640254 3mg, GSK3640254 30 mg, GSK3640254 200mg, GSK3640254 700mg as ascending single dose on Day 1 of each period, each participant received placebo in one of the four periods	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days	Total of all reporting groups
Overall Participants	12	8	6	6	25	7	14	78
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	8 100%	6 100%	6 100%	25 100%	7 100%	14 100%	78 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	12 100%	8 100%	6 100%	6 100%	25 100%	7 100%	14 100%	78 100%
Race/Ethnicity, Customized (Count of Participants)
ASIAN - CENTRAL/SOUTH ASIAN HERITAGE	2 16.7%	0 0%	0 0%	0 0%	0 0%	1 14.3%	0 0%	3 3.8%
BLACK OR AFRICAN AMERICAN	1 8.3%	1 12.5%	1 16.7%	1 16.7%	4 16%	0 0%	2 14.3%	10 12.8%
WHITE-WHITE/CAUCASIAN/EUROPEAN HERITAGE	9 75%	6 75%	5 83.3%	5 83.3%	20 80%	5 71.4%	11 78.6%	61 78.2%
MULTIPLE	0 0%	1 12.5%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.3%
ASIAN - EAST ASIAN HERITAGE	0 0%	0 0%	0 0%	0 0%	1 4%	0 0%	0 0%	1 1.3%
ASIAN - SOUTH EAST ASIAN HERITAGE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 7.1%	1 1.3%
WHITE - ARABIC/NORTH AFRICAN HERITAGE	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	0 0%	1 1.3%

Outcome Measures

1. Primary Outcome

Title	Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Description	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Results are presented treatment wise.
Time Frame	Up to Day 15

Outcome Measure Data

Analysis Population Description

Safety Population. It is comprised of all participants who received at least one dose of a study treatment.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
AE	3 25%	2 25%	4 66.7%	3 50%	3 12%	4 57.1%	4 28.6%	1 1.3%	7 NaN
SAE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN

2. Primary Outcome

Title	Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Description	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
Basophils, 24 hours, n=6,6,6,6,6,6,5,6,16	-0.002 (0.0075)	-0.002 (0.0147)	0.005 (0.0084)	-0.002 (0.0075)	-0.007 (0.0103)	0.002 (0.0098)	-0.002 (0.0148)	-0.007 (0.0121)	0.001 (0.0106)
Basophils, 48 hours, n=6,6,5,6,6,6,6,6,16	-0.002 (0.0098)	0.012 (0.0117)	0.010 (0.0187)	-0.007 (0.0103)	-0.005 (0.00550)	0.007 (0.0082)	0.000 (0.0167)	0.000 (0.0110)	0.005 (0.0115)
Basophils, 96 hours, n=6,6,6,6,6,6,6,6,15	0.003 (0.0103)	0.000 (0.0155)	-0.003 (0.0103)	-0.002 (0.0147)	-0.005 (0.0152)	0.002 (0.0098)	-0.007 (0.0052)	-0.002 (0.0147)	0.004 (0.0118)
Basophils, Day 15,n=6,6,6,6,6,6,6,6,16	0.002 (0.0133)	0.012 (0.0117)	0.000 (0.0110)	0.002 (0.0098)	-0.007 (0.0082)	0.010 (0.0063)	-0.005 (0.0207)	-0.005 (0.0084)	0.007 (0.0178)
Eosinophils, 24 hours, n=6,6,6,6,6,6,5,6,16	-0.022 (0.1876)	0.012 (0.0376)	0.005 (0.0650)	0.015 (0.0489)	0.008 (0.0508)	-0.017 (0.0186)	-0.032 (0.0642)	0.023 (0.0266)	0.005 (0.0648)
Eosinophils, 48 hour, 6,6,5,6,6,6,6,6,16	-0.032 (0.1982)	0.018 (0.0731)	0.008 (0.0497)	0.010 (0.0544)	0.010 (0.0544)	0.020 (0.0346)	-0.030 (0.0443)	0.012 (0.0796)	0.037 (0.0266)
Eosinophils, 96 hours, n=6,6,6,6,6,6,6,6,15	-0.052 (0.1970)	0.035 (0.0575)	-0.012 (0.0591)	0.003 (0.0602)	0.013 (0.0207)	-0.018 (0.0382)	0.028 (0.0861)	0.022 (0.0256)	0.013 (0.0656)
Eosinophils, FU (Day 15), n=6,6,6,6,6,6,6,6,16	-0.023 (0.1328)	0.012 (0.0534)	0.000 (0.0335)	0.020 (0.0921)	0.018 (0.0542)	0.012 (0.0471)	-0.032 (0.0960)	-0.012 (0.0354)	-0.015 (0.0791)
Leukocytes, 24 hours, n=6,6,6,6,6,6,5,6,16	0.592 (0.9839)	0.877 (0.7228)	-0.910 (1.1691)	0.058 (0.8437)	0.132 (0.8528)	-0.742 (2.2552)	-0.088 (0.4219)	0.078 (0.6916)	0.079 (0.8700)
Leukocytes, 48 hours, n=6,6,5,6,6,6,6,6,16	0.603 (1.3012)	0.388 (0.8506)	-0.878 (1.2611)	-0.292 (0.9476)	0.307 (1.1555)	-0.673 (1.8656)	1.220 (2.6559)	0.312 (0.6725)	0.104 (0.8442)
Leukocytes 96 hours, n=6,6,6,6,6,6,6,6,15	0.693 (1.1514)	0.953 (0.8659)	-0.897 (0.9192)	-0.107 (0.9821)	0.503 (1.1885)	-0.458 (2.3501)	0.390 (1.3833)	0.557 (0.5838)	0.272 (0.8542)
Leukocytes, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.348 (1.0652)	0.502 (1.2216)	-0.113 (1.8444)	-0.007 (1.0958)	0.292 (0.6240)	-0.835 (1.6488)	-0.142 (1.5163)	0.327 (0.9991)	-0.111 (0.7964)
Lymphocytes, 24 hours, n=6,6,6,6,6,6,5,6,16	0.073 (0.3189)	0.243 (0.1888)	-0.248 (0.3124)	-0.140 (0.2305)	-0.188 (0.3172)	-0.158 (0.1659)	-0.124 (0.0727)	-0.005 (0.2375)	0.027 (0.2972)
Lymphocytes, 48 hours, n=6,6,5,6,6,6,6,6,16	0.082 (0.3344)	0.320 (0.2909)	-0.244 (0.4865)	-0.238 (0.2739)	-0.050 (0.2748)	-0.110 (0.2873)	-0.303 (0.4113)	0.082 (0.2490)	0.164 (0.3759)
Lymphocytes, 96 hours, n=6,6,6,6,6,6,6,6,15	0.142 (0.2643)	0.207 (0.2388)	-0.215 (0.3661)	-0.035 (0.1747)	0.000 (0.3509)	-0.143 (0.1766)	-0.093 (0.3449)	0.285 (0.2741)	0.181 (0.4474)
Lymphocytes, FU (Day 15), n=6,6,6,6,6,6,6,6,16	-0.027 (0.4607)	0.082 (0.2491)	-0.165 (0.6984)	-0.012 (0.4303)	-0.067 (0.4020)	-0.097 (0.4866)	-0.232 (0.3513)	-0.130 (0.3107)	0.005 (0.3483)
Monocytes, 24 hours, n=6,6,6,6,6,6,5,6,16	0.017 (0.0755)	0.040 (0.0846)	-0.107 (0.1405)	-0.045 (0.0505)	-0.022 (0.1342)	0.068 (0.2099)	-0.042 (0.1252)	0.028 (0.0643)	-0.014 (0.0870)
Monocytes, 48 hours, 6,6,5,6,6,6,6,6,16	0.048 (0.1052)	0.043 (0.1198)	-0.104 (0.1146)	-0.050 (0.0885)	-0.002 (0.0854)	0.083 (0.1533)	0.083 (0.2224)	0.037 (0.0441)	0.002 (0.0795)
Monocytes, 96 hours, n=6,6,6,6,6,6,6,6,15	0.015 (0.1266)	0.082 (0.1219)	-0.090 (0.1307)	-0.047 (0.0579)	-0.018 (0.1184)	0.078 (0.1242)	0.020 (0.1655)	0.033 (0.0572)	0.020 (0.0890)
Monocytes,FU (Day 15), n= 6,6,6,6,6,6,6,6,16	-0.003 (0.0771)	0.048 (0.0826)	-0.022 (0.1309)	0.020 (0.1619)	0.045 (0.0896)	0.115 (0.0789)	0.008 (0.1439)	-0.003 (0.0855)	-0.002 (0.0878)
Neutrophils, 24 hours, n=6,6,6,6,6,6,5,6,16	0.528 (0.5383)	0.583 (0.6552)	-0.562 (0.7714)	0.230 (0.8517)	0.342 (0.4796)	-0.500 (2.0326)	0.110 (0.2985)	0.035 (0.6405)	0.059 (0.7913)
Neutrophils, 48 hours, n=6,6,5,6,6,6,6,6,16	0.507 (0.8878)	-0.003 (0.5852)	-0.546 (0.6919)	-0.007 (0.9485)	0.342 (0.9186)	-0.455 (1.6850)	1.425 (2.7042)	0.153 (0.5704)	-0.085 (0.7056)
Neutrophils, 96 hours, n=6,6,6,6,6,6,6,6,15	0.587 (0.7991)	0.628 (0.6082)	-0.575 (0.6277)	-0.027 (0.9432)	0.513 (0.9082)	-0.218 (2.3225)	0.440 (1.1395)	0.218 (0.4922)	0.055 (0.6401)
Neutrophils, FU (Day 15), n= 6,6,6,6,6,6,6,6,16	0.398 (0.6349)	0.345 (0.9399)	0.077 (1.0609)	-0.037 (0.9710)	0.302 (0.6797)	-0.643 (1.4316)	0.120 (1.1397)	0.475 (0.7676)	-0.107 (0.7009)
Platelets, 24 hours, n=6,6,6,6,6,6,5,6,16	-0.3 (11.40)	9.7 (30.29)	-8.5 (16.11)	-17.5 (27.90)	-2.8 (14.48)	7.2 (9.54)	-9.0 (37.33)	-1.7 (31.17)	-3.3 (34.99)
Platelets, 48 hours, n=6,6,5,6,6,6,6,6,16	-1.5 (15.95)	-3.2 (17.33)	-11.0 (21.13)	-1.7 (13.08)	0.7 (14.98)	9.5 (11.64)	-14.7 (36.62)	-2.8 (18.97)	0.8 (22.54)
Platelets, 96 hours, n=6,6,6,6,6,6,6,6,15	-8.2 (15.75)	7.3 (14.65)	-6.8 (14.99)	1.3 (17.29)	2.3 (24.57)	6.7 (15.02)	-13.2 (44.37)	0.3 (24.34)	-1.7 (22.98)
Platelets, FU (Day 15), n=6,6,6,6,6,6,6,6,16	-10.4 (21.59)	19.2 (14.66)	-16.7 (36.59)	13.0 (15.85)	6.5 (22.64)	13.0 (29.48)	-13.0 (48.17)	-4.0 (18.64)	-1.6 (32.94)

3. Primary Outcome

Title	Part 1: Change From Baseline in Hematology Parameters: Erythrocytes.
Description	Blood samples were collected to analyze the hematology parameters: erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
24 hours, n=6,6,6,6,6,6,5,6,16	0.118 (0.2576)	0.338 (0.1150)	-0.005 (0.1747)	0.147 (0.2925)	0.212 (0.2335)	0.198 (0.0933)	0.084 (0.1928)	0.302 (0.1447)	0.197 (0.2148)
48 hours, n=6,6,5,6,6,6,6,6,16	0.162 (0.2899)	0.142 (0.1607)	-0.024 (0.2501)	0.108 (0.3252)	0.152 (0.1528)	0.288 (0.1082)	0.087 (0.2295)	0.180 (0.2440)	0.171 (0.2112)
96 hours, n=6,6,6,6,6,6,6,6,15	0.155 (0.2290)	0.202 (0.1683)	0.083 (0.2499)	0.178 (0.2320)	-0.035 (0.2672)	0.112 (0.0674)	0.062 (0.2528)	0.237 (0.2530)	0.189 (0.1834)
Follow Up (Day 15), n=6,6,6,6,6,6,6,6,16	0.027 (0.1876)	0.145 (0.2041)	-0.060 (0.3138)	0.023 (0.3370)	-0.205 (0.1639)	0.053 (0.1549)	-0.295 (0.2001)	0.007 (0.2067)	0.032 (0.2691)

4. Primary Outcome

Title	Part 1: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume (Erythrocyte MCV).
Description	Blood samples were collected to analyze the hematology parameters: erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
24 hour, n=6,6,6,6,6,6,5,6,16	-0.50 (1.390)	-0.03 (0.497)	0.17 (0.689)	0.70 (0.494)	-1.07 (0.575)	-0.28 (1.192)	-0.64 (0.754)	-0.25 (0.853)	0.05 (0.797)
48 hour, n=6,6,5,6,6,6,6,6,16	-0.42 (0.966)	0.35 (1.231)	0.06 (0.673)	0.13 (0.659)	-0.57 (0.843)	0.10 (1.135)	-1.18 (0.703)	-0.18 (0.725)	0.24 (0.932)
96 hour,n=6,6,6,6,6,6,6,6,15	1.75 (0.619)	0.43 (0.950)	0.02 (0.979)	-0.22 (1.030)	-0.85 (1.214)	0.28 (1.177)	-0.15 (0.616)	-0.13 (0.388)	0.20 (1.196)
Follow up (Day 15), n=6,6,6,6,6,6,6,6,16	0.15 (1.263)	1.83 (0.505)	0.53 (0.850)	-0.20 (1.241)	-0.15 (1.253)	0.42 (1.339)	-0.10 (1.567)	-0.28 (0.840)	0.14 (1.153)

5. Primary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Description	Blood samples were collected to analyze the hematology parameter: Erythrocyte MCH. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
24 hours, n=6,6,6,6,6,6,5,6,16	0.12 (0.337)	0.18 (0.147)	0.00 (0.438)	-0.15 (0.596)	0.25 (0.485)	0.15 (0.339)	0.08 (0.963)	-0.07 (0.700)	0.01 (0.635)
48 hours, n=6,6,5,6,6,6,6,6,16	0.15 (0.464)	0.08 (0.271)	0.14 (0.321)	0.37 (0.779)	0.73 (0.450)	-0.18 (0.397)	-0.03 (0.821)	0.13 (0.446)	0.18 (0.583)
96 hours,n=6,6,6,6,6,6,6,6,15	0.47 (0.339)	0.02 (0.194)	-0.33 (0.301)	0.17 (1.111)	0.63 (0.589)	-0.02 (0.319)	-0.13 (0.459)	-0.13 (0.497)	0.17 (0.442)
Follow up, Day 15,n=6,6,6,6,6,6,6,6,16	-0.07 (0.266)	-0.27 (0.459)	0.35 (0.660)	0.03 (0.665)	0.92 (0.741)	-0.40 (0.514)	-0.03 (0.207)	0.02 (0.319)	0.03 (0.639)

6. Primary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Hematocrit
Description	Blood samples were collected to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
24 hours, n=6,6,6,6,6,6,5,6,16	0.0080 (0.02666)	0.0288 (0.01150)	0.0003 (0.01791)	0.0163 (0.02526)	0.0128 (0.02031)	0.0155 (0.01058)	0.0038 (0.01333)	0.0250 (0.01416)	0.0174 (0.0174)
48 hours, n=6,6,5,6,6,6,6,6,16	0.0123 (0.02767)	0.0143 (0.01521)	-0.0018 (0.02255)	0.0102 (0.02851)	0.0103 (0.01256)	0.0252 (0.00970)	0.0013 (0.01739)	0.0148 (0.02179)	0.0163 (0.0163)
96 hours,n=6,6,6,6,6,6,6,6,15	0.0223 (0.01896)	0.0198 (0.01771)	0.0078 (0.02337)	0.0145 (0.02346)	-0.0072 (0.02753)	0.0108 (0.00947)	0.0045 (0.02345)	0.0200 (0.02265)	0.0177 (0.0177)
Follow up (Day 15), n=6,6,6,6,6,6,6,6,16	0.0032 (0.02247)	0.0222 (0.01879)	-0.0025 (0.02848)	0.0012 (0.03201)	-0.0185 (0.01816)	0.0070 (0.01534)	-0.0265 (0.01852)	-0.0007 (0.01945)	0.0035 (0.02603)

7. Primary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Description	Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
24 hours, n=6,6,6,6,6,6,5,6,16	0.00050 (0.001390)	0.00055 (0.001608)	0.00118 (0.001955)	-0.00023 (0.002223)	0.00022 (0.001694)	-0.00015 (0.001276)	0.00156 (0.002490)	0.00057 (0.000579)	0.00071 (0.001808)
48 hours, n=6,6,5,6,6,6,6,6,16	0.00082 (0.001496)	0.00123 (0.001334)	0.00154 (0.001790)	-0.00017 (0.002028)	0.00070 (0.001451)	0.00075 (0.001838)	0.00260 (0.002924)	0.00117 (0.001859)	0.00118 (0.002221)
96 hours,n=6,6,6,6,6,6,6,6,15	-0.00005 (0.002040)	0.00160 (0.001615)	0.00095 (0.002517)	0.00023 (0.001965)	0.00138 (0.001841)	0.00060 (0.001663)	0.00265 (0.002867)	0.00175 (0.002019)	0.00162 (0.002889)
Follow up (Day 15), n=6,6,6,6,6,6,6,6,16	-0.00018 (0.001273)	0.00435 (0.001628)	-0.00077 (0.002293)	-0.00042 (0.002832)	0.00092 (0.002495)	-0.00015 (0.001640)	-0.00002 (0.001841)	0.00055 (0.002230)	0.00061 (0.003329)

8. Primary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Hemoglobin (Hb)
Description	Blood samples were collected to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
24 hours, n=6,6,6,6,6,6,5,6,16	4.2 (8.93)	10.8 (3.43)	0.0 (5.51)	3.5 (7.34)	7.7 (5.82)	6.8 (1.72)	3.0 (6.04)	8.8 (7.91)	5.9 (7.29)
48 hours, n=6,6,5,6,6,6,6,6,16	5.7 (10.65)	4.7 (5.89)	0.0 (6.60)	5.2 (6.88)	8.3 (3.20)	7.7 (3.72)	2.5 (6.35)	6.2 (7.88)	6.0 (7.85)
96 hours, n=6,6,6,6,6,6,6,6,15	6.8 (6.27)	6.0 (5.33)	0.8 (6.49)	6.3 (7.00)	2.3 (7.97)	3.2 (2.71)	1.2 (9.13)	6.5 (9.67)	6.6 (5.51)
Follow up (Day 15), n=6,6,6,6,6,6,6,6,16	0.5 (5.75)	3.0 (7.24)	0.0 (11.05)	1.0 (7.97)	-1.5 (7.06)	-0.5 (3.39)	-9.2 (6.82)	0.2 (6.37)	1.0 (8.25)

9. Primary Outcome

Title	Part 1: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP)
Description	Blood samples were collected to analyze the chemistry parameter: ALT, AST, and ALP. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
ALT, 24 hours, n=6,6,6,6,6,6,6,6,16	-1.7 (4.55)	0.3 (3.39)	0.8 (3.60)	-3.8 (2.04)	-0.5 (4.93)	-3.8 (3.49)	0.0 (5.44)	-0.3 (5.05)	-0.8 (4.68)
ALT, 48 hours, n=6,6,6,6,6,6,6,5,16	-1.5 (5.75)	-0.2 (4.49)	0.3 (4.37)	1.2 (2.23)	0.5 (4.04)	-2.7 (6.25)	-2.7 (4.89)	5.0 (10.17)	-0.1 (4.94)
ALT, 96 hours, n=6,6,6,6,6,6,6,6,15	-0.5 (5.01)	4.0 (3.90)	1.3 (4.68)	2.2 (3.19)	2.5 (5.47)	-3.5 (8.26)	0.5 (4.85)	3.8 (10.76)	2.5 (8.08)
ALT, FU (Day 15), n=6,6,6,6,6,6,6,6,16	-0.3 (10.01)	2.3 (4.32)	2.3 (3.56)	9.5 (14.46)	5.2 (9.95)	0.3 (14.35)	1.0 (4.34)	5.3 (6.06)	5.1 (15.95)
AST, 24 hours, n=6,6,6,6,6,6,6,6,16	-5.7 (7.63)	-0.4 (3.13)	-2.5 (2.88)	-4.2 (1.94)	-3.5 (4.72)	-4.7 (6.74)	-0.7 (3.72)	-1.3 (2.94)	-3.0 (3.60)
AST, 48 hours, n=6,6,6,6,6,6,6,5,16	-4.3 (7.50)	-2.3 (3.83)	-3.0 (2.10)	-2.2 (1.72)	-0.7 (4.80)	-2.5 (3.33)	-2.0 (3.85)	1.4 (5.86)	-2.6 (4.11)
AST, 96 hours, n=6,6,6,6,6,6,6,6,15	-4.2 (8.57)	-1.7 (3.20)	-4.2 (3.97)	-1.3 (2.73)	-3.3 (4.89)	-4.5 (4.85)	-1.8 (4.31)	-1.5 (4.89)	-1.4 (3.48)
AST, FU (Day 15), n=6,6,6,6,6,6,6,6,16	-1.5 (8.53)	4.5 (9.57)	1.0 (5.18)	-0.5 (2.88)	4.5 (5.36)	-1.7 (2.80)	2.2 (8.26)	0.9 (5.87)	0.9 (5.87)
ALP, 24 hours, n=6,6,6,6,6,6,6,6,16	2.8 (4.54)	6.0 (3.74)	1.2 (8.28)	-1.0 (6.66)	-2.8 (6.15)	-1.2 (8.42)	-0.2 (4.67)	0.7 (3.78)	-2.9 (4.10)
ALP, 48 hours, n=6,6,6,6,6,6,6,5,16	3.3 (4.93)	1.7 (5.13)	2.2 (6.24)	-0.8 (5.31)	-1.7 (6.65)	-1.5 (8.29)	-0.8 (5.31)	0.6 (2.97)	-2.4 (4.84)
ALP, 96 hours, n=6,6,6,6,6,6,6,6,15	3.3 (4.18)	5.2 (2.93)	3.5 (10.09)	0.0 (5.18)	0.5 (4.85)	-4.8 (9.11)	1.5 (6.19)	1.2 (3.49)	-1.1 (4.16)
ALP, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.3 (1.37)	1.5 (3.27)	-0.5 (4.81)	2.2 (6.62)	-1.2 (6.97)	-1.8 (6.01)	-0.8 (5.98)	-0.3 (1.97)	-0.4 (6.37)

10. Primary Outcome

Title	Part 1: Change From Baseline in Clinical Chemistry Parameters : Bicarbonate, Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea
Description	Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
Bicarbonate, 24 hours, n=6,6,6,6,6,6,6,6,16	0.7 (1.86)	3.0 (3.03)	-3.2 (3.06)	2.2 (2.04)	-0.2 (2.14)	0.5 (1.76)	-2.2 (1.47)	0.0 (1.67)	0.8 (2.59)
Bicarbonate, 48 hours, n=6,6,6,6,6,6,6,5,16	0.3 (1.86)	3.5 (2.66)	-1.3 (2.42)	2.7 (1.86)	2.2 (1.94)	5.8 (3.71)	-0.5 (1.38)	-1.8 (1.64)	2.1 (3.57)
Bicarbonate, 96 hours, n=6,6,6,6,6,6,6,6,15	-1.2 (1.72)	2.0 (3.41)	-2.0 (2.76)	1.3 (2.50)	-1.2 (4.31)	0.8 (1.94)	-2.2 (2.04)	-2.2 (2.32)	1.1 (2.47)
Bicarbonate,FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.2 (1.47)	1.5 (1.05)	-1.8 (2.64)	1.7 (1.75)	1.2 (1.94)	1.2 (2.93)	-0.3 (2.88)	-0.8 (1.47)	1.1 (1.65)
Calcium, 24 hours, n=6,6,6,6,6,6,6,6,16	-0.045 (0.0931)	0.038 (0.0627)	-0.037 (0.0866)	-0.033 (0.0987)	-0.012 (0.0492)	0.060 (0.0562)	0.035 (0.0731)	0.002 (0.0454)	0.005 (0.0647)
Calcium, 48 hours, n=6,6,6,6,6,6,6,5,16	0.047 (0.0997)	0.042 (0.0581)	-0.032 (0.0731)	-0.008 (0.0808)	0.008 (0.0736)	0.145 (0.0568)	-0.017 (0.0476)	-0.018 (0.0349)	0.031 (0.0762)
Calcium, 96 hours, n=6,6,6,6,6,6,6,6,15	-0.005 (0.0909)	0.070 (0.0687)	-0.012 (0.0838)	0.027 (0.0747)	-0.015 (0.0680)	0.097 (0.0625)	0.025 (0.0497)	-0.045 (0.0836)	0.034 (0.0687)
Calcium, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.003 (0.0686)	0.060 (0.0620)	0.008 (0.1194)	0.003 (0.0709)	-0.047 (0.0528)	0.043 (0.0753)	-0.017 (0.1134)	-0.027 (0.0455)	0.033 (0.0694)
Chloride, 24 hours, n=6,6,6,6,6,6,6,6,16	1.8 (1.47)	-2.2 (2.04)	2.7 (2.07)	-0.5 (1.87)	0.2 (3.06)	0.5 (2.66)	-0.7 (2.16)	0.3 (2.73)	0.6 (2.00)
Chloride, 48 hours, n=6,6,6,6,6,6,6,5,16	1.8 (1.47)	-0.8 (1.47)	2.3 (1.63)	-2.0 (1.90)	-0.2 (2.32)	0.7 (3.08)	-0.7 (2.73)	0.6 (1.95)	0.5 (1.75)
Chloride, 96 hours, n=6,6,6,6,6,6,6,6,15	1.7 (1.21)	-1.2 (2.99)	1.0 (2.00)	0.0 (1.79)	-0.5 (2.88)	0.3 (2.94)	0.7 (2.16)	-1.3 (1.97)	0.1 (2.76)
Chloride, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.7 (1.37)	-0.3 (2.25)	0.5 (1.64)	-0.3 (2.07)	1.3 (3.39)	0.8 (2.48)	0.8 (2.48)	-0.7 (3.27)	-0.6 (1.75)
Magnesium, 24 hours, n=6,6,6,6,6,6,6,6,16	-0.018 (0.0483)	-0.017 (0.0350)	0.023 (0.0393)	0.023 (0.0398)	0.003 (0.0393)	0.033 (0.0398)	0.003 (0.0339)	0.012 (0.0560)	0.014 (0.0495)
Magnesium, 48 hours, n=6,6,6,6,6,6,6,5,16	0.043 (0.0983)	0.005 (0.0513)	0.035 (0.0468)	0.012 (0.0349)	0.017 (0.0476)	0.060 (0.0369)	0.025 (0.0459)	0.034 (0.0513)	0.034 (0.0626)
Magnesium, 96 hours, n=6,6,6,6,6,6,6,6,15	0.010 (0.0525)	0.022 (0.0488)	0.037 (0.0535)	0.015 (0.0568)	0.002 (0.0264)	0.048 (0.0204)	0.033 (0.0308)	0.007 (0.0476)	0.042 (0.0507)
Magnesium, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.008 (0.0643)	-0.035 (0.0367)	-0.020 (0.0583)	0.010 (0.0502)	-0.017 (0.0361)	0.017 (0.0367)	0.013 (0.0550)	-0.015 (0.0468)	0.002 (0.0489)
Phosphate, 24 hours, n=6,6,6,6,6,6,6,6,16	0.088 (0.1074)	0.117 (0.1777)	0.098 (0.1843)	-0.080 (0.1370)	-0.003 (0.1279)	-0.010 (0.1803)	0.032 (0.1647)	-0.018 (0.0968)	0.020 (0.1363)
Phosphate, 48 hours, n=6,6,6,6,6,6,6,5,16	0.148 (0.0679)	-0.022 (0.1713)	0.107 (0.1540)	-0.063 (0.1528)	-0.043 (0.1499)	-0.058 (0.1816)	0.025 (0.1801)	-0.076 (0.0963)	0.022 (0.1561)
Phosphate, 96 hours, n=6,6,6,6,6,6,6,6,15	0.077 (0.1084)	0.122 (0.1854)	0.098 (0.1485)	-0.055 (0.1934)	-0.028 (0.0995)	-0.027 (0.1645)	0.092 (0.1240)	0.042 (0.1144)	0.029 (0.1391)
Phosphate, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.107 (0.1224)	-0.018 (0.1230)	0.1230 (0.1378)	-0.090 (0.1485)	0.042 (0.1865)	-0.055 (0.1407)	0.063 (0.1138)	0.002 (0.1341)	-0.022 (0.1285)
Potassium, 24 hours, n=6,6,6,6,6,6,6,6,16	0.03 (0.647)	0.42 (0.313)	0.33 (0.327)	0.20 (0.290)	0.20 (0.276)	0.22 (0.313)	0.10 (0.245)	-0.05 (0.423)	0.25 (0.316)
Potassium, 48 hours, n=6,6,6,6,6,6,6,5,16	0.28 (0.417)	0.30 (0.310)	0.25 (0.217)	0.07 (0.258)	0.20 (0.253)	0.30 (0.228)	0.07 (0.163)	0.06 (0.251)	0.16 (0.278)
Potassium, 96 hours, n=6,6,6,6,6,6,6,6,15	0.00 (0.525)	0.30 (0.335)	0.38 (0.306)	0.12 (0.232)	0.20 (0.352)	0.20 (0.316)	0.08 (0.232)	-0.12 (0.204)	0.30 (0.314)
Potassium, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.12 (0.436)	0.43 (0.413)	-0.05 (0.207)	-0.03 (0.356)	0.07 (0.250)	0.18 (0.183)	0.05 (0.339)	-0.27 (0.314)	0.10 (0.379)
Sodium, 24 hours, n=6,6,6,6,6,6,6,6,16	0.0 (1.26)	0.0 (1.90)	0.3 (2.16)	-0.7 (1.63)	-1.5 (0.55)	-0.3 (2.42)	-1.3 (1.21)	0.5 (2.26)	0.3 (1.95)
Sodium, 48 hours, n=6,6,6,6,6,6,6,5,16	1.0 (1.10)	-0.2 (2.14)	1.0 (1.67)	-0.7 (1.37)	-1.8 (1.60)	1.2 (2.23)	-1.3 (2.25)	0.8 (1.92)	0.8 (1.80)
Sodium, 96 hours, n=6,6,6,6,6,6,6,6,15	0.8 (1.47)	0.5 (1.64)	0.7 (1.21)	1.3 (3.01)	-1.7 (1.86)	0.0 (0.20)	0.8 (1.83)	1.3 (1.03)	0.5 (2.42)
Sodium, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.8 (2.14)	0.3 (2.07)	-0.2 (1.47)	-0.2 (1.47)	0.8 (1.72)	0.7 (2.07)	0.5 (2.17)	0.0 (2.19)	0.4 (1.82)
Urea, 24 hours, n=6,6,6,6,6,6,6,6,16	0.033320 (0.3443425)	0.283220 (1.0396160)	0.299880 (0.6630596)	-0.649740 (1.0517198)	-0.166600 (0.8450414)	-0.599760 (0.7717016)	0.133280 (0.3880028)	-0.849660 (1.3570283)	-0.187425 (0.9102217)
Urea, 48 hours, n=6,6,6,6,6,6,6,5,16	-0.316540 (0.8081731)	0.416500 (0.8769556)	0.116620 (0.7701895)	-0.683060 (1.0103710)	-0.233240 (0.9601712)	-0.316540 (0.6366649)	0.083300 (0.7108180)	-1.099560 (0.8242913)	-0.187425 (1.0590572)
Urea, 96 hours, n=6,6,6,6,6,6,6,6,15	-0.116620 (0.7274909)	0.233240 (0.9476011)	0.316540 (1.0510863)	-0.733040 (1.1736967)	-0.433160 (0.5986483)	0.049980 (0.5955804)	0.166600 (0.9241120)	-0.916300 (1.5178348)	0.046648 (1.2598057)
Urea,FU (Day 15), n=6,6,6,6,6,6,6,6,16	-0.483140 (0.9491815)	0.466480 (0.9929136)	0.466480 (0.3828177)	-0.499800 (0.5930586)	-0.233240 (2.0187631)	-0.649740 (0.7173480)	-0.033320 (1.0907403)	-1.332800 (1.4230410)	-0.099960 (0.6590288)

11. Primary Outcome

Title	Part 1: Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Cholesterol (LDL) Cholesterol, Triglycerides
Description	Blood samples were collected to analyze the chemistry parameter: cholesterol, glucose, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
Cholesterol,Day1,96 hours,n=5,6,6,6,5,6,6,6,14	0.40 (0.324)	0.32 (0.271)	-0.05 (0.628)	0.02 (0.422)	-0.06 (0.699)	0.13 (0.516)	0.45 (0.373)	0.43 (0.641)	0.30 (0.445)
Cholesterol, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.25 (0.404)	0.23 (0.327)	0.07 (0.579)	0.23 (0.493)	-0.16 (0.590)	-0.40 (0.562)	0.08 (0.445)	0.22 (0.496)	0.16 (0.566)
HDL cholesterol,Day1,96 hours,n=6,6,6,6,5,6,6,6,15	-0.02 (0.041)	-0.05 (0.105)	-0.15 (0.152)	-0.12 (0.147)	-0.22 (0.084)	-0.12 (0.098)	-0.02 (0.133)	-0.13 (0.103)	-0.08 (0.174)
HDL cholesterol, FU (Day 15), n=6,6,6,6,5,6,6,6,16	0.07 (0.137)	-0.05 (0.122)	-0.02 (0.160)	0.00 (0.179)	-0.18 (0.148)	-0.05 (0.105)	-0.02 (0.264)	-0.03 (0.103)	0.00 (0.219)
LDL cholesterol,Day1, 96hours,n=5,6,6,6,5,6,6,6,14	0.30 (0.122)	0.10 (0.562)	-0.12 (0.519)	-0.13 (0.408)	-0.04 (0.428)	-0.03 (0.361)	0.43 (0.441)	0.25 (0.281)	0.16 (0.386)
LDL cholesterol, FU(Day 15), n=6,6,6,6,5,6,6,6,16	0.30 (0.210)	0.15 (0.295)	0.22 (0.564)	0.07 (0.314)	-0.14 (0.472)	-0.35 (0.451)	0.37 (0.308)	0.07 (0.327)	0.13 (0.491)
Triglycerides,Day1,96 hours,n=5,6,6,6,5,6,6,6,14	0.28 (0.531)	0.60 (1.079)	0.45 (0.468)	0.62 (1.026)	0.52 (0.931)	0.60 (0.883)	0.03 (0.468)	0.70 (0.834)	0.49 (0.360)
Triglycerides, FU (Day 15),n=6,6,6,6,5,6,6,6,16	-0.20 (0.297)	0.32 (0.838)	-0.30 (0.303)	0.40 (0.940)	0.40 (0.831)	0.02 (0.279)	-0.55 (0.501)	0.40 (0.410)	0.05 (0.588)

12. Primary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameter: Glucose
Description	Blood samples were collected to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
Day 1 (96 hours), n=5,6,6,6,6,6,6,6,14	-0.16 (0.288)	-0.30 (0.110)	-0.25 (0.414)	-0.28 (0.527)	-0.17 (0.446)	-0.08 (0.349)	-0.07 (0.432)	-0.33 (0.175)	-0.21 (0.279)
FU (Day 15), n=6,6,6,6,6,6,6,6,16	-0.03 (0.513)	-0.05 (0.345)	-0.12 (0.605)	-0.22 (0.471)	0.07 (0.582)	-0.27 (0.367)	-0.27 (0.745)	0.00 (0.374)	-0.04 (0.379)

13. Primary Outcome

Title	Part 1: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Description	Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
Bilirubin, 24 hours, n=6,6,6,6,6,6,6,6,16	-2.5 (2.88)	-0.2 (3.37)	-5.3 (3.33)	-1.5 (5.32)	0.2 (3.19)	-1.7 (2.94)	-2.5 (1.97)	-0.3 (1.37)	-1.2 (3.19)
Bilirubin, 48 hours, n=6,6,6,6,6,6,6,5,16	-2.2 (3.19)	-0.8 (4.26)	-4.7 (3.20)	-0.7 (4.13)	0.3 (2.50)	0.3 (1.51)	-0.5 (2.35)	-1.6 (2.07)	-0.6 (2.97)
Bilirubin, 96 hours, n=6,6,6,6,6,6,6,6,15	-3.2 (2.32)	-2.5 (4.04)	-3.8 (3.60)	-1.3 (4.80)	-1.7 (3.14)	-0.2 (2.23)	-2.2 (2.79)	-1.05 (1.05)	-0.6 (2.61)
Bilirubin, FU (Day 15),n=6,6,6,6,6,6,6,6,16	-0.8 (3.43)	3.3 (4.13)	-0.8 (2.56)	2.5 (2.88)	1.0 (5.10)	-1.0 (3.10)	2.2 (4.92)	2.0 (2.97)	1.2 (4.20)
Creatinine, 24 hours, n=6,6,6,6,6,6,6,6,16	-7.0 (7.13)	3.2 (5.85)	-0.5 (3.62)	0.2 (5.49)	-1.2 (1.83)	6.8 (4.62)	-0.7 (6.12)	-1.5 (9.03)	0.6 (6.83)
Creatinine, 48 hours, n=6,6,6,6,6,6,6,5,16	-6.7 (7.15)	7.2 (4.96)	-1.2 (2.14)	-3.8 (5.34)	0.8 (4.92)	6.5 (6.25)	-1.7 (7.39)	-2.8 (8.76)	0.8 (6.69)
Creatinine, 96 hours, n=6,6,6,6,6,6,6,6,15	-2.5 (7.34)	8.7 (4.89)	3.2 (4.71)	0.0 (5.33)	0.0 (8.72)	7.2 (4.36)	-5.3 (6.44)	-0.7 (5.47)	4.6 (7.56)
Creatinine, FU (Day 15), n=6,6,6,6,6,6,6,6,16	-2.5 (6.38)	9.3 (7.76)	-1.3 (5.09)	-1.7 (7.20)	2.5 (4.97)	3.0 (3.95)	-0.8 (7.05)	-11.2 (9.02)	1.9 (6.69)
Direct bilirubin, 24 hours, n=6,6,6,6,6,6,6,6,16	-1.0 (1.26)	-0.5 (1.29)	-1.2 (1.30)	0.2 (1.48)	-0.2 (1.10)	-1.0 (0.71)	-1.0 (0.63)	-0.3 (0.82)	-0.3 (1.23)
Direct bilirubin, 48 hours, n=6,6,6,6,6,6,6,5,16	-1.0 (1.55)	-0.8 (1.26)	-1.2 (0.75)	-0.3 (1.03)	0.0 (0.71)	-0.2 (0.45)	-0.5 (0.55)	-0.8 (0.96)	-0.5 (1.10)
Direct bilirubin, 96 hours, n=6,6,6,6,6,6,6,6,15	-0.8 (1.48)	-1.0 (1.15)	-0.6 (1.14)	-0.3 (1.37)	-0.3 (0.50)	-0.2 (0.84)	-0.8 (0.45)	-0.8 (0.50)	-0.3 (0.90)
Direct bilirubin, FU (Day 15),n=6,6,6,6,6,6,6,6,16	-0.7 (1.21)	1.0 (1.22)	0.2 (0.75)	1.0 (0.89)	0.8 (0.96)	0.0 (1.41)	0.5 (1.52)	0.7 (1.37)	0.4 (1.36)

14. Primary Outcome

Title	Part 1: Change From Baseline in Clinical Chemistry Parameter: Protein
Description	Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
24 hours, n=6,6,6,6,6,6,6,6,16	-0.3 (3.39)	2.5 (0.84)	-5.2 (3.76)	-1.0 (3.16)	-1.2 (1.72)	0.7 (1.21)	0.3 (2.73)	2.3 (2.25)	-0.8 (2.37)
48 hours, n=6,6,6,6,6,6,6,5,16	0.7 (5.16)	0.0 (1.26)	-4.0 (4.05)	-2.3 (2.42)	0.3 (1.51)	2.2 (1.33)	-0.3 (3.88)	1.8 (2.28)	0.2 (3.31)
96 hours, n=6,6,6,6,6,6,6,6,15	1.2 (3.60)	1.5 (3.39)	-2.0 (4.73)	1.0 (4.10)	-1.7 (5.20)	0.8 (1.94)	-0.3 (2.94)	0.8 (3.60)	1.3 (3.75)
FU (Day 15),n=6,6,6,6,6,6,6,6,16	-0.5 (3.62)	0.7 (2.25)	-1.3 (6.31)	0.2 (3.66)	-2.7 (3.20)	1.7 (2.42)	-1.7 (3.98)	1.7 (1.86)	1.5 (3.85)

15. Primary Outcome

Title	Part 1: Number of Participants With Abnormal Urinalysis
Description	Urine samples were collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Time Frame	Up to Day 15

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN

16. Primary Outcome

Title	Part 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Description	SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
SBP, 1 hour n=6,6,6,6,6,6,6,6,16	2.5 (11.67)	3.2 (4.45)	6.3 (6.22)	4.7 (6.77)	6.2 (7.63)	2.2 (11.07)	5.8 (10.57)	3.5 (4.93)	8.1 (7.25)
SBP, 2 hours n=6,6,6,6,6,6,6,6,16	-0.7 (7.84)	2.2 (4.17)	8.8 (3.06)	10.7 (6.62)	0.5 (7.50)	5.5 (8.46)	5.7 (14.02)	6.2 (6.11)	4.4 (8.05)
SBP, 4.5 hours, n=6,6,6,6,6,6,6,6,16	1.8 (7.22)	5.3 (5.20)	8.8 (5.60)	5.3 (6.12)	6.7 (7.42)	10.8 (9.81)	8.7 (11.04)	4.0 (6.84)	7.4 (11.04)
SBP, 6 hours n=6,6,6,6,6,6,6,6,16	4.7 (5.75)	4.7 (6.41)	3.7 (4.63)	9.5 (7.06)	2.8 (7.73)	4.0 (10.47)	5.8 (12.81)	6.5 (6.09)	8.3 (10.97)
SBP, 12 hours n=6,6,6,6,6,6,6,6,16	3.8 (6.24)	8.7 (6.77)	10.2 (5.04)	8.2 (6.62)	2.5 (8.29)	3.3 (7.23)	2.5 (17.62)	6.3 (3.39)	7.6 (7.90)
SBP, 24 hours n=6,6,6,6,6,6,6,6,16	-1.5 (5.54)	3.2 (2.79)	9.0 (6.32)	3.3 (7.58)	-0.3 (4.46)	2.7 (5.72)	5.8 (8.30)	0.8 (7.57)	5.1 (10.68)
SBP, 48 hours n=6,6,6,6,6,6,6,6,16	-4.3 (6.59)	1.3 (5.35)	2.5 (8.22)	0.3 (9.79)	2.0 (11.45)	-0.5 (7.50)	2.5 (6.98)	2.2 (9.24)	1.0 (8.68)
SBP,72 hours n=6,6,6,6,6,6,6,6,16	-2.0 (5.66)	2.0 (7.24)	-0.8 (5.49)	2.2 (8.52)	-3.0 (6.57)	1.0 (6.00)	2.5 (11.93)	3.0 (12.02)	2.4 (6.13)
SBP, 96 hours n=6,6,6,6,6,6,6,6,15	1.8 (5.42)	1.3 (5.35)	6.0 (11.40)	5.3 (12.71)	3.0 (5.80)	6.3 (7.53)	2.5 (14.34)	0.7 (6.19)	4.5 (9.02)
SBP, FU(Day 15), n=6,6,6,6,6,6,6,6,16	6.7 (9.18)	1.0 (7.69)	11.5 (7.92)	6.8 (7.22)	4.5 (10.21)	4.5 (6.02)	11.5 (3.33)	7.8 (4.22)	7.3 (10.20)
DBP, 1 hour n=6,6,6,6,6,6,6,6,16	-3.2 (8.84)	-3.7 (2.07)	0.8 (6.18)	-1.2 (5.53)	-0.3 (4.32)	-2.0 (4.56)	1.3 (9.87)	0.5 (2.88)	0.3 (8.62)
DBP, 2 hours, n=6,6,6,6,6,6,6,6,16	-7.5 (8.96)	-1.3 (3.27)	1.0 (4.24)	-1.3 (6.83)	-2.7 (3.08)	-3.3 (3.93)	1.0 (10.45)	0.5 (2.35)	0.5 (8.42)
DBP, 4.5 hours, n=6,6,6,6,6,6,6,6,16	-4.8 (6.91)	2.3 (6.44)	6.7 (6.77)	1.7 (6.83)	2.2 (3.06)	1.5 (4.55)	2.2 (6.31)	6.3 (8.16)	6.8 (10.10)
DBP, 6 hours, n=6,6,6,6,6,6,6,6,16	-3.5 (4.42)	-3.7 (4.93)	0.2 (5.71)	2.0 (3.74)	-2.2 (5.15)	-2.0 (6.48)	1.8 (9.15)	3.2 (7.78)	2.4 (9.76)
DBP, 12 hours, n=6,6,6,6,6,6,6,6,16	0.8 (8.23)	0.3 (2.58)	4.2 (3.76)	4.3 (9.09)	1.0 (5.10)	1.0 (6.10)	1.5 (12.61)	5.3 (3.83)	4.8 (7.64)
DBP, 24 hours, n=6,6,6,6,6,6,6,6,16	-0.3 (3.01)	-0.5 (3.78)	4.7 (5.35)	2.8 (7.44)	0.0 (4.00)	0.8 (5.56)	6.2 (8.04)	3.3 (4.63)	3.7 (9.16)
DBP, 48 hours, n=6,6,6,6,6,6,6,6,16	-3.0 (6.29)	-1.7 (6.56)	3.0 (5.29)	-2.5 (7.56)	3.7 (5.65)	-1.3 (5.43)	1.7 (8.71)	1.0 (4.73)	4.3 (8.90)
DBP,72 hours, n=6,6,6,6,6,6,6,6,16	-3.2 (6.08)	0.0 (6.00)	1.7 (7.17)	1.0 (6.84)	-0.5 (5.09)	1.7 (2.73)	2.3 (8.71)	4.7 (6.56)	4.3 (8.02)
DBP, 96 hours, n=6,6,6,6,6,6,6,6,15	-2.1 (6.59)	1.0 (3.10)	5.0 (6.69)	2.5 (8.02)	2.7 (3.78)	2.3 (6.06)	1.5 (12.63)	-0.2 (5.42)	4.0 (7.39)
DBP, FU(Day 15), n=6,6,6,6,6,6,6,6,16	0.7 (12.56)	-4.5 (5.50)	6.8 (4.88)	1.7 (7.37)	2.5 (6.19)	3.7 (5.20)	7.3 (3.83)	7.3 (5.35)	7.1 (9.92)

17. Primary Outcome

Title	Part 1: Change From Baseline in Vital Signs: Pulse Rate
Description	Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
1 hour n=6,6,6,6,6,6,6,6,16	13.3 (6.71)	5.2 (2.48)	14.5 (4.04)	13.7 (5.05)	11.3 (4.80)	7.5 (3.67)	9.0 (3.85)	7.0 (2.97)	9.6 (6.97)
2 hours, n=6,6,6,6,6,6,6,6,16	7.3 (4.89)	3.2 (4.96)	6.8 (4.75)	10.7 (9.09)	12.8 (6.05)	6.0 (3.22)	7.0 (5.80)	3.7 (9.65)	8.2 (3.99)
4.5 hours, n=6,6,6,6,6,6,6,6,16	6.5 (6.72)	2.0 (7.56)	3.7 (1.97)	5.8 (4.40)	8.2 (11.97)	5.5 (3.94)	4.2 (8.08)	6.2 (6.85)	6.4 (5.94)
6 hours,n=6,6,6,6,6,6,6,6,16	16.8 (7.41)	7.7 (5.85)	9.7 (3.98)	11.3 (6.02)	11.2 (6.65)	7.7 (3.88)	8.3 (4.72)	8.0 (3.16)	10.4 (6.59)
12 hours, n=6,6,6,6,6,6,6,6,16	10.2 (4.40)	5.7 (7.55)	11.8 (6.85)	9.0 (5.83)	11.0 (4.90)	6.5 (8.96)	8.0 (11.26)	6.0 (7.51)	7.3 (5.61)
24 hours, n=6,6,6,6,6,6,6,6,16	5.2 (4.58)	3.3 (4.37)	2.3 (6.56)	4.5 (9.48)	6.7 (10.15)	2.5 (5.68)	5.8 (10.38)	1.0 (4.86)	0.2 (3.89)
48 hours, n=6,6,6,6,6,6,6,6,16	0.8 (5.67)	3.5 (7.31)	3.2 (4.58)	4.5 (6.89)	4.8 (6.46)	-2.3 (6.83)	10.8 (15.89)	1.5 (6.35)	1.5 (3.88)
72 hours, n=6,6,6,6,6,6,6,6,16	2.0 (8.58)	3.8 (5.00)	2.8 (4.31)	6.8 (4.49)	2.0 (3.29)	-0.3 (6.19)	4.5 (6.28)	-0.2 (7.14)	1.4 (5.40)
96 hours, n=6,6,6,6,6,6,6,6,15	12.5 (12.93)	4.8 (4.83)	4.8 (5.15)	9.2 (6.88)	5.7 (4.37)	4.0 (2.45)	2.8 (4.54)	8.0 (4.47)	2.5 (4.29)
FU (Day 15), n=6,6,6,6,6,6,6,6,16	6.2 (4.71)	3.3 (8.07)	3.2 (6.52)	6.3 (10.07)	3.5 (3.99)	-0.7 (11.93)	4.8 (6.97)	6.3 (8.24)	1.3 (5.74)

18. Primary Outcome

Title	Part 1: Change From Baseline in Vital Signs: Temperature
Description	Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
1 hour, n=6,6,6,6,6,6,6,6,16	0.33 (0.186)	0.15 (0.378)	0.03 (0.333)	0.18 (0.376)	0.10 (0.303)	0.00 (0.245)	0.28 (0.256)	0.22 (0.407)	0.19 (0.267)
2 hours, n=6,6,6,6,6,6,6,6,16	0.20 (0.237)	0.00 (0.322)	0.15 (0.378)	0.28 (0.256)	0.02 (0.256)	0.27 (0.250)	0.17 (0.388)	0.52 (0.279)	0.23 (0.322)
4.5 hours, n=6,6,6,6,6,6,6,6,16	0.35 (0.308)	0.23 (0.356)	0.03 (0.350)	0.07 (0.280)	0.12 (0.360)	0.45 (0.321)	0.33 (0.308)	0.42 (0.426)	0.22 (0.299)
6 hours, n=6,6,6,6,6,6,6,6,16	0.45 (0.274)	0.27 (0.234)	0.15 (0.339)	0.42 (0.223)	0.20 (0.210)	0.45 (0.394)	0.38 (0.264)	0.75 (0.217)	0.29 (0.390)
12 hours, n=6,6,6,6,6,6,6,6,16	0.30 (0.219)	0.20 (0.261)	0.17 (0.350)	0.20 (0.283)	0.27 (0.493)	0.18 (0.426)	0.07 (0.175)	0.53 (0.398)	0.12 (0.259)
24 hours, n=6,6,6,6,6,6,6,6,16	-0.13 (0.266)	0.10 (0.210)	0.07 (0.175)	0.05 (0.105)	0.05 (0.596)	0.10 (0.310)	0.17 (0.103)	0.23 (0.427)	0.03 (0.244)
48 hours, n=6,6,6,6,6,6,6,6,16	-0.03 (0.234)	0.10 (0.460)	-0.18 (0.214)	0.07 (0.356)	-0.17 (0.250)	-0.03 (0.463)	0.42 (0.694)	0.27 (0.489)	0.04 (0.301)
72 hours, n=6,6,6,6,6,6,6,6,16	0.10 (0.110)	0.23 (0.427)	0.00 (0.316)	0.18 (0.306)	-0.12 (0.488)	0.17 (0.446)	0.25 (0.217)	0.15 (0.362)	0.03 (0.317)
96 hours, n=6,6,6,6,6,6,6,6,15	0.02 (0.232)	0.10 (0.255)	0.12 (0.160)	-0.18 (0.214)	-0.17 (0.628)	0.22 (0.402)	0.17 (0.216)	0.08 (0.240)	-0.07 (0.313)
FU (Day 15), n=6,6,6,6,6,6,6,6,16	0.05 (0.327)	-0.03 (0.344)	0.12 (0.331)	0.00 (0.518)	0.20 (0.506)	0.13 (0.344)	0.18 (0.293)	0.47 (0.398)	0.11 (0.344)

19. Primary Outcome

Title	Part 1: Change From Baseline in Vital Sign: Respiratory Rate
Description	Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
1 hour, n=6,6,6,6,6,6,6,6,16	1.5 (1.52)	0.8 (2.14)	-0.3 (1.97)	1.0 (0.89)	-1.0 (2.37)	0.3 (1.51)	0.5 (1.38)	0.8 (2.04)	0.1 (2.69)
2 hours, n=6,6,6,6,6,6,6,6,16	1.7 (1.51)	1.3 (3.27)	1.0 (2.19)	0.7 (1.37)	0.5 (1.38)	0.8 (2.14)	-0.5 (3.08)	1.3 (2.25)	0.3 (2.02)
4.5 hours, n=6,6,6,6,6,6,6,6,16	1.8 (1.72)	0.8 (3.31)	1.7 (3.20)	0.8 (1.33)	0.3 (1.21)	0.7 (1.63)	1.0 (1.41)	0.7 (2.16)	1.9 (2.31)
6 hours, n=6,6,6,6,6,6,6,6,16	0.7 (1.97)	0.3 (2.34)	-1.7 (1.86)	2.3 (2.80)	-0.2 (2.04)	0.7 (2.73)	0.5 (1.97)	1.3 (1.75)	1.0 (3.35)
12 hours, n=6,6,6,6,6,6,6,6,16	2.2 (2.14)	2.8 (4.26)	2.2 (4.36)	2.7 (2.34)	-1.7 (2.88)	-0.2 (1.33)	1.3 (2.34)	1.0 (2.53)	2.2 (2.59)
24 hours, n=6,6,6,6,6,6,6,6,16	0.7 (1.51)	-0.3 (1.03)	0.7 (2.80)	0.3 (2.80)	-2.0 (1.67)	1.0 (2.61)	-0.2 (0.98)	1.5 (2.07)	0.9 (2.66)
48 hours, n=6,6,6,6,6,6,6,6,16	0.7 (1.97)	-0.2 (2.32)	0.5 (3.08)	1.2 (2.04)	0.0 (1.26)	1.7 (1.21)	1.7 (1.37)	0.3 (2.25)	-0.3 (3.15)
72 hours, n=6,6,6,6,6,6,6,6,16	0.2 (1.47)	0.0 (2.19)	0.3 (2.58)	0.7 (3.50)	-0.5 (2.35)	-0.3 (1.97)	-1.5 (2.35)	0.5 (4.14)	-0.3 (2.73)
96 hours, n=6,6,6,6,6,6,6,6,15	1.3 (1.97)	0.5 (2.07)	0.0 (2.00)	-1.0 (2.37)	0.2 (4.02)	0.0 (1.26)	-1.0 (2.68)	0.3 (2.58)	0.3 (2.37)
FU (Day 15), n=6,6,6,6,6,6,6,6,15	0.2 (2.71)	-0.8 (2.48)	0.5 (3.27)	0.0 (2.90)	0.5 (2.43)	-1.2 (2.64)	-0.5 (1.87)	1.2 (2.86)	0.3 (2.74)

20. Primary Outcome

Title	Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).
Time Frame	Baseline (Day 1 predose), 1,2,4,6,12,24,48,72,96 hours post dose and Follow up (Day 15)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg	Part 1: Single Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1	Participants received single dose of matching placebo following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6	16
CS, Day 1,1 hour n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, Day 1,2 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, Day 1, 4 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, Day 1, 6 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, Day 1, 12 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, Day 1, 24 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS,Day 1, 48 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, Day 1, 72 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, Day 1, 96 hour n=6,6,6,6,6,6,6,6,15	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
CS, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS, Day 1,1 hour n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS, Day 1,2 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS, Day 1, 4 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS, Day 1, 6 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS,Day 1, 12 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS, Day 1, 24 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS,Day 1, 48 hours n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	1 7.1%	0 0%	0 NaN
NCS, Day 1, 72 hours, n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS, Day 1, 96 hour n=6,6,6,6,6,6,6,6,15	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN
NCS, FU (Day 15), n=6,6,6,6,6,6,6,6,16	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 14.3%	0 0%	1 NaN

21. Primary Outcome

Title	Part 2: Number of Participants AEs and SAEs
Description	An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Results are presented treatment wise.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
AE	4 33.3%	5 62.5%	19 316.7%	6 100%	10 40%
SAE	0 0%	0 0%	0 0%	0 0%	0 0%

22. Primary Outcome

Title	Part 2: Change From Baseline in Abnormal Hematology Findings: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Description	Blood samples were collected at indicated time points to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14 : 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Basophils, Day 2, predose, n=6,6,25,7,14	0.003 (0.0103)	0.000 (0.0110)	-0.004 (0.0111)	0.001 (0.0069)	-0.004 (0.0108)
Basophils, Day 4, predose, n=6,6,25,7,14	-0.002 (0.0117)	0.005 (0.0217)	-0.001 (0.0108)	0.001 (0.0107)	-0.002 (0.0119)
Basophils, Day 6, predose, n=6,6,25,7,14	0.002 (0.0075)	0.003 (0.0151)	0.001 (0.0124)	0.009 (0.0135)	-0.002 (0.0105)
Basophils, Day 8 predose, n=6,6,25,7,14	0.005 (0.0138)	0.012 (0.0214)	0.004 (0.0147)	0.014 (0.0098)	-0.002 (0.0105)
Basophils, Day 10, predose, n=6,6,25,7,14	0.005 (0.0055)	0.013 (0.0163)	0.010 (0.0108)	0.011 (0.0121)	0.001 (0.0123)
Basophils, Day 12, predose, n=6,6,25,7,14	0.002 (0.0075)	0.017 (0.0163)	0.008 (0.0121)	0.010 (0.0082)	-0.001 (0.0100)
Basophils, Day 14, predose, n=6,6,25,6,14	0.003 (0.0052)	0.002 (0.0214)	0.007 (0.0140)	0.017 (0.0082)	-0.003 (0.0114)
Basophils, Day 14, 48 hours, n=6,6,24,6,14	0.002 (0.0075)	0.010 (0.0190)	0.007 (0.0137)	0.005 (0.0138)	-0.001 (0.0103)
Basophils, Day 14, 96 hours, n=6,6,24,6,14	0.002 (0.0075)	0.010 (0.0228)	0.004 (0.0110)	0.007 (0.0121)	-0.004 (0.0165)
Basophils, FU(Day 28), n=6,6,25,7,14	-0.007 (0.0103)	0.003 (0.0137)	-0.003 (0.0124)	-0.001 (0.0069)	-0.006 (0.0150)
Eosinophils, Day 2, predose, n=6,6,25,7,14	0.015 (0.0176)	0.032 (0.0147)	0.006 (0.0728)	0.050 (0.0663)	-0.001 (0.0438)
Eosinophils, Day 4, predose, n=6,6,25,7,14	0.015 (0.0536)	0.013 (0.0455)	0.012 (0.0867)	0.043 (0.0605)	-0.006 (0.0520)
Eosinophils, Day 6, predose, n=6,6,25,7,14	0.043 (0.0665)	0.007 (0.0528)	0.000 (0.0876)	0.034 (0.0832)	0.000 (0.0411)
Eosinophils, Day 8 predose, n=6,6,25,7,14	0.027 (0.0516)	0.030 (0.0529)	-0.005 (0.0838)	0.024 (0.0683)	-0.007 (0.0395)
Eosinophils, Day 10, predose, n=6,6,25,7,14	0.028 (0.0426)	0.053 (0.0539)	0.025 (0.1057)	0.026 (0.0824)	-0.012 (0.0437)
Eosinophils, Day 12, predose, n=6,6,25,7,14	0.008 (0.0768)	0.067 (0.0472)	0.021 (0.1075)	0.033 (0.0862)	-0.012 (0.0519)
Eosinophils, Day 14, predose, n=6,6,25,6,14	0.017 (0.0602)	0.013 (0.0468)	0.019 (0.1192)	0.048 (0.0794)	0.011 (0.0589)
Eosinophils, Day 14, 48 hours, n=6,6,24,6,14	0.003 (0.0468)	0.047 (0.0513)	0.000 (0.1193)	0.048 (0.0893)	0.009 (0.0770)
Eosinophils, Day 14, 96 hours, n=6,6,24,6,14	0.045 (0.0647)	0.043 (0.0437)	0.004 (0.1167)	0.050 (0.0851)	0.001 (0.0584)
Eosinophils, FU (Day 28), n=6,6,25,7,14	-0.055 (0.0373)	0.017 (0.0659)	-0.003 (0.1617)	0.023 (0.0804)	-0.041 (0.0618)
Leukocytes, Day 2, predose, n=6,6,25,7,14	0.203 (0.8721)	0.275 (0.4329)	0.355 (1.6576)	-0.081 (0.4831)	-0.202 (1.2439)
Leukocytes, Day 4, predose, n=6,6,25,7,14	0.170 (0.8864)	0.123 (0.5792)	-0.096 (0.9361)	0.063 (0.9600)	-0.250 (1.3609)
Leukocytes, Day 6, predose, n=6,6,25,7,14	0.158 (1.1274)	0.052 (0.4839)	0.100 (1.3054)	-0.347 (0.6065)	-0.026 (1.3748)
Leukocytes, Day 8 predose, n=6,6,25,7,14	0.043 (0.8500)	0.178 (0.6011)	-0.011 (0.9496)	-0.481 (1.2000)	-0.144 (1.3225)
Leukocytes, Day 10, predose, n=6,6,25,7,14	0.117 (0.8565)	0.515 (0.4821)	0.296 (0.8216)	-0.584 (1.1299)	0.064 (1.5507)
Leukocytes, Day 12, predose, n=6,6,25,7,14	0.538 (1.0626)	0.810 (0.4692)	0.165 (0.8511)	-0.567 (1.2112)	-0.052 (1.4813)
Leukocytes, Day 14, predose, n=6,6,25,6,14	0.200 (0.8402)	-0.053 (0.4230)	0.180 (1.0249)	-0.433 (0.9609)	0.046 (1.3461)
Leukocytes, Day 14, 48 hours, n=6,6,24,6,14	0.028 (0.7348)	0.187 (0.4774)	0.097 (1.0672)	-0.597 (1.2776)	0.104 (1.2821)
Leukocytes, Day 14, 96 hours, n=6,6,24,6,14	0.438 (1.0624)	0.300 (0.4367)	0.336 (1.1083)	-0.248 (1.6414)	0.347 (1.3089)
Leukocytes, FU (Day 28), n=6,6,25,7,14	-1.148 (0.7008)	0.263 (1.6261)	-0.209 (0.8990)	-0.709 (1.2790)	-0.049 (1.1939)
Lymphocytes, Day 2, predose, n=6,6,25,7,14	0.003 (0.4892)	0.092 (0.4111)	0.013 (0.3249)	0.163 (0.3174)	-0.026 (0.4478)
Lymphocytes, Day 4, predose, n=6,6,25,7,14	-0.008 (0.6814)	-0.067 (0.5230)	0.000 (0.3242)	0.194 (0.4500)	-0.003 (0.4739)
Lymphocytes, Day 6, predose, n=6,6,25,7,14	-0.035 (0.7416)	-0.017 (0.5384)	0.147 (0.3174)	0.210 (0.5157)	0.112 (0.3739)
Lymphocytes, Day 8 predose, n=6,6,25,7,14	-0.035 (0.6427)	0.100 (0.5655)	0.140 (0.2862)	0.229 (0.4557)	0.013 (0.4660)
Lymphocytes, Day 10, predose, n=6,6,25,7,14	0.053 (0.7320)	0.185 (0.5404)	0.232 (0.3580)	0.190 (0.5199)	0.085 (0.4055)
Lymphocytes, Day 12, predose, n=6,6,25,7,14	0.177 (0.7096)	0.332 (0.3874)	0.180 (0.4106)	0.231 (0.5225)	0.054 (0.5013)
Lymphocytes, Day 14, predose, n=6,6,25,6,14	-0.078 (0.5286)	-0.055 (0.4773)	0.186 (0.2944)	0.125 (0.4923)	0.061 (0.4643)
Lymphocytes, Day 14, 48 hours, n=6,6,24,6,14	-0.022 (0.5561)	0.135 (0.3746)	0.180 (0.3403)	0.072 (0.4776)	0.044 (0.4554)
Lymphocytes, Day 14, 96 hours, n=6,6,24,6,14	0.060 (0.5114)	0.255 (0.4602)	0.247 (0.3308)	0.193 (0.7185)	0.059 (0.4478)
Lymphocytes, FU (Day 28), n=6,6,25,7,14	-0.512 (0.5189)	-0.280 (0.5637)	-0.144 (0.4368)	-0.237 (0.3583)	-0.184 (0.2858)
Monocytes, Day 2, predose, n=6,6,25,7,14	0.003 (0.1046)	-0.038 (0.0791)	0.011 (0.1690)	-0.026 (0.0948)	-0.042 (0.0982)
Monocytes, Day 4, predose, n=6,6,25,7,14	-0.023 (0.0804)	-0.037 (0.0905)	-0.001 (0.1085)	-0.023 (0.1052)	-0.029 (0.1018)
Monocytes, Day 6, predose, n=6,6,25,7,14	-0.030 (0.1489)	-0.075 (0.0817)	-0.019 (0.1169)	-0.067 (0.0808)	-0.021 (0.1045)
Monocytes, Day 8 predose, n=6,6,25,7,14	0.012 (0.1068)	-0.057 (0.1063)	-0.018 (0.1006)	-0.001 (0.1192)	-0.005 (0.1005)
Monocytes, Day 10, predose, n=6,6,25,7,14	0.003 (0.1204)	0.020 (0.1115)	0.016 (0.0881)	-0.021 (0.1122)	-0.001 (0.1356)
Monocytes, Day 12, predose, n=6,6,25,7,14	0.023 (0.0942)	0.022 (0.1269)	-0.002 (0.0926)	-0.011 (0.1530)	-0.009 (0.1244)
Monocytes, Day 14, predose, n=6,6,25,6,14	0.037 (0.1084)	-0.008 (0.0773)	-0.023 (0.1044)	-0.027 (0.1226)	0.003 (0.1007)
Monocytes, Day 14, 48 hours, n=6,6,24,6,14	-0.005 (0.1093)	-0.040 (0.0947)	-0.019 (0.1158)	-0.050 (0.1352)	0.004 (0.0756)
Monocytes, Day 14, 96 hours, n=6,6,24,6,14	0.035 (0.0961)	-0.030 (0.1077)	0.006 (0.1323)	-0.002 (0.1450)	0.038 (0.1207)
Monocytes, FU (Day 28), n=6,6,25,7,14	-0.083 (0.1037)	-0.030 (0.1188)	-0.036 (0.0937)	0.013 (0.1883)	-0.051 (0.0778)
Neutrophils, Day 2, predose, n=6,6,25,7,14	0.178 (0.5500)	0.190 (0.5981)	0.328 (1.5779)	-0.273 (0.6049)	-0.128 (1.0189)
Neutrophils, Day 4, predose, n=6,6,25,7,14	0.188 (0.3853)	0.207 (0.3747)	-0.107 (0.8863)	-0.153 (1.0017)	-0.209 (1.0416)
Neutrophils, Day 6, predose, n=6,6,25,7,14	0.177 (0.4173)	0.135 (0.3031)	-0.030 (1.1214)	-0.533 (0.6285)	-0.114 (1.1418)
Neutrophils, Day 8 predose, n=6,6,25,7,14	0.038 (0.2525)	0.097 (0.3894)	-0.132 (0.8619)	-0.746 (1.2632)	-0.141 (1.0976)
Neutrophils, Day 10, predose, n=6,6,25,7,14	0.028 (0.1317)	0.240 (0.3099)	0.012 (0.8357)	-0.791 (1.1634)	-0.008 (1.3122)
Neutrophils, Day 12, predose, n=6,6,25,7,14	0.328 (0.3414)	0.373 (0.3690)	-0.042 (0.7593)	-0.831 (1.1224)	-0.083 (1.1305)
Neutrophils, Day 14, predose, n=6,6,25,6,14	0.222 (0.4540)	-0.007 (0.4620)	-0.011 (0.9244)	-0.598 (0.9450)	-0.026 (1.1249)
Neutrophils, Day 14, 48 hours, n=6,6,24,6,14	0.048 (0.3746)	0.035 (0.7028)	-0.072 (0.9007)	-0.673 (1.2453)	0.049 (1.1598)
Neutrophils, Day 14, 96 hours, n=6,6,24,6,14	0.292 (0.5710)	0.017 (0.5775)	0.075 (0.9796)	-0.497 (1.0625)	0.255 (1.1764)
Neutrophils, FU (Day 28), n=6,6,25,7,14	-0.490 (0.3072)	0.555 (1.9413)	-0.024 (0.7404)	-0.509 (1.3465)	0.235 (1.3115)
Platelets, Day 2, predose, n=6,5,25,7,14	-0.7 (18.78)	9.8 (6.94)	5.4 (13.46)	17.9 (18.89)	1.3 (20.45)
Platelets, Day 4, predose, n=6,5,25,7,14	2.5 (12.76)	-11.2 (8.23)	2.5 (16.28)	17.6 (31.86)	-3.6 (21.81)
Platelets, Day 6, predose, n=6,6,25,7,14	11.2 (20.61)	10.3 (14.73)	3.4 (18.67)	17.1 (13.28)	3.3 (25.28)
Platelets, Day 8 predose, n=6,5,25,7,14	0.8 (8.82)	4.4 (13.87)	8.6 (19.14)	16.7 (21.66)	0.4 (31.14)
Platelets, Day 10, predose, n=6,6,25,7,14	3.7 (16.38)	14.7 (11.34)	8.0 (30.98)	14.3 (12.38)	4.8 (31.48)
Platelets, Day 12, predose, n=6,6,25,7,14	4.5 (27.40)	9.8 (19.02)	3.6 (34.68)	6.1 (15.00)	2.9 (28.62)
Platelets, Day 14, predose, n=6,6,25,6,14	5.3 (23.52)	-6.2 (19.30)	8.3 (25.49)	7.8 (19.74)	-2.9 (31.90)
Platelets, Day 14, 48 hours, n=6,6,24,6,14	-3.0 (13.73)	-2.8 (13.70)	1.3 (21.79)	-2.2 (17.99)	-1.1 (34.32)
Platelets, Day 14, 96 hours, n=6,6,24,6,14	-4.3 (9.93)	-3.3 (20.74)	1.0 (23.54)	-17.3 (33.99)	-5.4 (25.19)
Platelets, FU (Day 28), n=6,6,25,7,14	-8.7 (10.75)	-11.8 (20.02)	-3.9 (21.61)	-4.0 (28.3)	-5.3 (39.09)

23. Primary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes
Description	Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 2, predose, n=6,6,25,7,14	0.135 (0.2601)	0.200 (0.1411)	0.128 (0.2539)	0.440 (0.1458)	0.131 (0.2100)
Day 4, predose, n=6,6,25,7,14	0.193 (0.2322)	0.112 (0.1057)	0.086 (0.2099)	0.544 (0.1318)	0.091 (0.1589)
Day 6, predose, n=6,6,25,7,14	0.197 (0.3267)	0.230 (0.0994)	0.088 (0.2160)	0.323 (0.1614)	0.146 (0.1480)
Day 8 predose, n=6,6,25,7,14	0.035 (0.3056)	0.272 (0.1685)	0.088 (0.2352)	0.327 (0.1940)	0.115 (0.1816)
Day 10, predose, n=6,6,25,7,14	0.082 (0.3415)	0.293 (0.2238)	0.179 (0.1861)	0.306 (0.1334)	0.206 (0.1637)
Day 12, predose, n=6,6,25,7,14	0.078 (0.2423)	0.387 (0.1643)	0.139 (0.2004)	0.296 (0.1049)	0.179 (0.1372)
Day 14, predose, n=6,6,25,6,14	0.017 (0.2243)	0.037 (0.1394)	0.031 (0.2429)	0.385 (0.2288)	0.005 (0.1931)
Day 14, 48 hours, n=6,6,24,6,14	-0.002 (0.2416)	0.177 (0.2253)	0.109 (0.2116)	0.323 (0.2219)	0.182 (0.2198)
Day 14, 96 hours, n=6,6,24,6,14	0.042 (0.1597)	0.215 (0.2095)	0.068 (0.2039)	0.327 (0.1159)	0.156 (0.1938)
FU (Day 28),n=6,6,25,7,14	-0.187 (0.1632)	-0.123 (0.1835)	-0.093 (0.2015)	0.050 (0.2484)	-0.081 (0.2517)

24. Primary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes MCV
Description	Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 2, predose, n=6,6,25,7,14	-0.20 (0.559)	-0.63 (0.989)	-0.27 (1.223)	-1.13 (1.280)	-0.16 (1.126)
Day 4, predose, n=6,6,25,7,14	-0.50 (0.777)	-1.05 (1.009)	-0.18 (1.321)	-0.19 (1.227)	0.17 (0.675)
Day 6, predose, n=6,6,25,7,14	-0.25 (0.683)	0.10 (1.368)	-0.02 (1.422)	-1.30 (1.390)	0.62 (1.188)
Day 8 predose, n=6,6,25,7,14	0.03 (0.308)	-0.60 (1.226)	-0.53 (1.390)	-0.67 (1.566)	0.79 (1.299)
Day 10, predose, n=6,6,25,7,14	-0.02 (0.534)	-0.73 (1.025)	-0.70 (1.635)	-0.90 (0.933)	0.21 (1.278)
Day 12, predose, n=6,6,25,7,14	-0.33 (0.838)	-0.55 (1.017)	-0.34 (0.908)	-0.99 (0.747)	0.16 (1.161)
Day 14, predose, n=6,6,25,6,14	-0.73 (0.864)	0.72 (0.995)	-0.86 (1.693)	-1.92 (1.059)	0.26 (1.585)
Day 14, 48 hours, n=6,6,24,6,14	0.52 (0.560)	-0.40 (1.322)	-0.67 (1.209)	-1.30 (0.629)	0.01 (1.210)
Day 14, 96 hours, n=6,6,24,6,14	-0.55 (0.409)	-0.25 (1.122)	-0.53 (1.361)	-0.50 (0.738)	0.14 (1.329)
FU (Day 28), n=6,6,25,7,14	0.00 (0.678)	0.63 (0.459)	-0.65 (1.447)	-1.19 (0.832)	0.61 (1.215)

25. Primary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Description	Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocyte MCH. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 2, predose, n=6,6,25,7,14	-0.10 (0.443)	-0.35 (0.217)	-0.08 (0.578)	-0.46 (0.670)	-0.14 (0.759)
Day 4, predose, n=6,6,25,7,14	-0.32 (0.306)	-0.03 (0.367)	0.06 (0.607)	-0.40 (0.408)	0.09 (0.684)
Day 6, predose, n=6,6,25,7,14	-0.43 (0.413)	-0.78 (0.172)	0.06 (0.788)	-0.30 (0.606)	-0.06 (0.677)
Day 8 predose, n=6,6,25,7,14	-0.23 (0.602)	-0.55 (0.226)	0.08 (0.785)	-0.43 (0.577)	0.21 (0.673)
Day 10, predose, n=6,6,25,7,14	-0.22 (0.571)	-0.67 (0.339)	-0.08 (0.573)	-0.26 (0.544)	0.01 (0.617)
Day 12, predose, n=6,6,25,7,14	0.00 (0.522)	-0.68 (0.248)	0.00 (0.450)	-0.10 (0.742)	-0.06 (0.557)
Day 14, predose, n=6,6,25,6,14	0.00 (0.310)	-0.72 (0.264)	-0.02 (0.724)	-0.57 (0.728)	-0.04 (0.637)
Day 14, 48 hours, n=6,6,24,6,14	0.08 (0.504)	-0.68 (0.293)	-0.12 (0.598)	-0.17 (0.698)	-0.15 (0.557)
Day 14, 96 hours, n=6,6,24,6,14	-0.25 (0.647)	-0.87 (0.216)	-0.20 (0.520)	-0.65 (0.740)	0.00 (0.477)
FU, (Day 28), n=6,6,25,7,14	0.03 (0.427)	-0.60 (0.237)	-0.04 (0.644)	-0.36 (0.412)	0.01 (0.637)

26. Primary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Hematocrit
Description	Blood samples were collected at indicated time points to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 2, predose, n=6,6,25,7,14	0.0102 (0.02300)	0.0140 (0.01425)	0.0096 (0.01995)	0.0314 (0.01122)	0.0108 (0.01712)
Day 4, predose, n=6,6,25,7,14	0.0133 (0.02270)	0.0043 (0.01154)	0.0066 (0.01855)	0.0453 (0.01067)	0.0085 (0.01459)
Day 6, predose, n=6,6,25,7,14	0.0148 (0.03205)	0.0202 (0.01304)	0.0075 (0.01857)	0.0206 (0.01397)	0.0155 (0.01108)
Day 8 predose, n=6,6,25,7,14	0.0025 (0.02788)	0.0203 (0.01250)	0.0049 (0.01827)	0.0241 (0.01378)	0.0137 (0.01431)
Day 10, predose, n=6,6,25,7,14	0.0063 (0.03144)	0.0217 (0.01697)	0.0119 (0.02108)	0.0216 (0.00872)	0.0191 (0.01466)
Day 12, predose, n=6,6,25,7,14	0.0047 (0.02439)	0.0302 (0.01396)	0.0102 (0.01872)	0.0203 (0.00739)	0.0159 (0.01201)
Day 14, predose, n=6,6,25,6,14	-0.0027 (0.02276)	0.0070 (0.01053)	-0.0014 (0.02132)	0.0227 (0.01825)	0.0019 (0.01499)
Day 14, 96 hours, n=6,6,24,6,14	0.0003 (0.01419)	0.0170 (0.01665)	0.0032 (0.01808)	0.0255 (0.01086)	0.0145 (0.01594)
Day 14, 48 hours, n=6,6,24,6,14	0.0018 (0.01969)	0.0133 (0.01375)	0.0060 (0.01664)	0.0212 (0.01734)	0.0157 (0.01601)
FU (Day 28), n=6,6,25,7,14	-0.0158 (0.01587)	-0.0070 (0.01628)	-0.0110 (0.01675)	-0.0013 (0.01739)	-0.0046 (0.02040)

27. Primary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Description	Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 2, predose, n=6,6,25,7,14	0.00093 (0.001204)	-0.00103 (0.001214)	0.00088 (0.001818)	-0.00037 (0.001190)	0.00117 (0.001333)
Day 4, predose, n=6,6,25,7,14	0.00215 (0.001099)	-0.00032 (0.001440)	0.00131 (0.002263)	0.00124 (0.001996)	0.00157 (0.001778)
Day 6, predose, n=6,6,25,7,14	0.00232 (0.000999)	0.00138 (0.001118)	0.00125 (0.002761)	0.00106 (0.002192)	0.00208 (0.001785)
Day 8 predose, n=6,6,25,7,14	0.00173 (0.001143)	0.00213 (0.000894)	0.00154 (0.002999)	0.00031 (0.001780)	0.00243 (0.002265)
Day 10, predose, n=6,6,25,7,14	0.00203 (0.000804)	0.00255 (0.001450)	0.00153 (0.002881)	-0.00023 (0.001186)	0.00154 (0.002233)
Day 12, predose, n=6,6,25,7,14	0.00220 (0.001075)	0.00313 (0.001468)	0.00205 (0.002889)	0.00007 (0.001643)	0.00161 (0.002094)
Day 14, predose, n=6,6,25,6,14	0.00287 (0.001810)	0.00318 (0.000842)	0.00212 (0.002924)	-0.00015 (0.001621)	0.00171 (0.002176)
Day 14, 48 hours, n=6,6,24,6,14	0.00270 (0.001788)	0.00295 (0.001524)	0.00205 (0.003168)	0.00063 (0.001429)	0.00184 (0.003189)
Day 14, 96 hours, n=6,6,24,6,14	0.00222 (0.001766)	0.00163 (0.001780)	0.00195 (0.003251)	0.00013 (0.001680)	0.00111 (0.002838)
FU, (Day 28), n=6,6,25,7,14	0.00177 (0.001581)	0.00212 (0.002369)	0.00095 (0.003073)	-0.00084 (0.003085)	0.00104 (0.002853)

28. Primary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Hb
Description	Blood samples were collected at indicated time points to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 2, predose, n=6,6,25,7,14	3.3 (6.28)	4.3 (4.13)	3.4 (7.18)	10.6 (3.31)	3.4 (5.73)
Day 4, predose, n=6,6,25,7,14	3.8 (5.49)	3.2 (2.48)	2.8 (6.28)	13.9 (3.02)	3.1 (4.71)
Day 6, predose, n=6,6,25,7,14	3.5 (8.57)	2.8 (3.19)	3.0 (5.91)	7.7 (3.77)	3.9 (3.87)
Day 8 predose, n=6,6,25,7,14	-0.3 (6.95)	5.3 (5.89)	3.1 (5.93)	7.3 (4.31)	4.2 (5.91)
Day 10, predose, n=6,6,25,7,14	1.2 (8.45)	5.5 (6.22)	4.9 (6.56)	7.7 (3.50)	6.3 (5.80)
Day 12, predose, n=6,6,25,7,14	2.3 (6.62)	8.0 (5.83)	4.1 (5.70)	8.1 (3.08)	4.9 (4.10)
Day 14, predose, n=6,6,25,6,14	0.3 (5.20)	-2.5 (4.23)	0.9 (7.16)	8.3 (3.33)	0.2 (6.15)
Day 14, 48 hours, n=6,6,24,6,14	0.2 (4.92)	1.8 (7.39)	2.8 (6.37)	8.8 (4.58)	4.5 (6.42)
Day 14, 96 hours, n=6,6,24,6,14	-0.2 (3.13)	2.2 (5.98)	1.1 (6.52)	6.5 (2.88)	4.7 (5.09)
FU (Day 28), n=6,6,25,7,14	-5.3 (4.18)	-6.5 (5.82)	-2.9 (5.51)	-0.3 (7.54)	-2.6 (7.42)

29. Primary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameter: ALT, AST,ALP
Description	Blood samples were collected to analyze the chemistry parameter: ALT, AST,ALP. Day -2was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
ALT, Day 2, predose, n=6,6,25,7,14	-1.2 (5.08)	1.0 (4.56)	0.5 (3.43)	1.7 (2.63)	-0.4 (3.71)
ALT, Day 4, predose, n=6,6,25,7,14	0.0 (5.44)	-1.3 (6.35)	1.4 (4.66)	3.4 (5.32)	0.3 (4.01)
ALT, Day 6, predose, n=6,6,25,7,14	3.2 (6.55)	-0.2 (7.86)	0.9 (4.95)	0.3 (4.07)	0.9 (7.45)
ALT, Day 8 predose, n=6,6,25,7,14	3.0 (7.62)	-6.4 (9.66)	1.8 (6.22)	1.7 (4.68)	-0.4 (7.51)
ALT, Day 10, predose, n=6,6,25,7,14	2.2 (8.04)	0.8 (11.75)	3.5 (6.85)	0.7 (4.89)	0.4 (11.55)
ALT, Day 12, predose, n=6,6,25,7,14	4.8 (10.85)	1.8 (13.76)	1.8 (6.08)	0.1 (4.49)	-0.4 (14.70)
ALT, Day 14, predose, n=5,5,25,6,14	1.4 (9.26)	-2.6 (12.97)	2.6 (6.37)	-1.0 (4.10)	-1.2 (13.45)
ALT, Day 14, 48 hours, n=6,6,24,6,14	5.8 (15.54)	1.7 (13.69)	3.7 (6.19)	-0.3 (3.50)	1.0 (13.94)
ALT, Day 14, 96 hours, n=6,6,24,6,14	6.0 (10.35)	-0.3 (13.34)	3.9 (6.98)	1.8 (6.85)	1.1 (15.54)
ALT, FU (Day 28), n=6,6,25,7,14	2.5 (5.09)	7.0 (20.39)	4.6 (9.22)	-1.3 (3.30)	0.3 (8.41)
ALP, Day 2, predose, n=6,6,25,7,14	-0.7 (1.37)	-3.7 (4.97)	-0.9 (4.66)	-0.1 (3.67)	-2.3 (5.74)
ALP, Day 4, predose, n=6,6,25,7,14	3.7 (3.67)	-7.2 (5.23)	0.3 (5.01)	1.6 (6.75)	-2.1 (4.31)
ALP, Day 6, predose, n=6,6,25,7,14	3.3 (7.28)	-5.2 (4.62)	0.3 (5.41)	0.9 (5.52)	-0.6 (4.88)
ALP, Day 8 predose, n=6,5,25,7,14	1.0 (4.52)	-4.4 (4.51)	-0.1 (5.33)	-0.4 (7.41)	-1.4 (5.96)
ALP, Day 10, predose, n=6,6,25,7,14	0.8 (4.92)	-6.2 (3.19)	-0.3 (5.53)	-1.0 (8.85)	-1.2 (5.94)
ALP, Day 12, predose, n=6,6,25,7,14	-1.2 (3.92)	-5.7 (3.39)	0.2 (5.80)	-0.1 (11.44)	-1.4 (6.12)
ALP, Day 14, predose, n=5,5,25,6,14	-3.6 (7.13)	-8.8 (6.10)	-2.2 (4.87)	0.8 (3.19)	-4.2 (6.17)
ALP, Day 14, 48 hours, n=6,6,24,6,14	-1.3 (4.93)	-6.0 (4.73)	-1.6 (5.06)	1.2 (5.53)	-1.5 (6.02)
ALP, Day 14, 96 hours, n=6,6,24,6,14	2.7 (5.13)	-6.8 (6.01)	-1.8 (5.67)	1.2 (3.31)	-1.3 (6.09)
ALP, FU (Day 28), n=6,6,25,7,14	1.5 (5.75)	-6.2 (5.91)	-2.4 (5.41)	-2.4 (8.36)	-1.9 (7.29)
AST, Day 2, predose, n=5,6,24,7,14	-1.4 (3.58)	-1.2 (2.79)	-1.5 (3.51)	-1.3 (4.89)	-2.5 (3.01)
AST, Day 4, predose, n=5,6,25,7,14	0.6 (2.88)	-3.0 (3.10)	-1.4 (4.22)	-2.4 (4.24)	-1.5 (4.29)
AST, Day 6, predose, n=5,6,25,7,14	0.0 (4.18)	-1.3 (3.88)	-1.7 (3.79)	-3.6 (2.94)	-1.9 (5.40)
AST, Day 8 predose, n=5,5,25,7,14	0.6 (4.34)	-6.4 (4.04)	-0.8 (4.64)	-3.1 (4.06)	-1.1 (6.28)
AST, Day 10, predose, n=5,6,25,7,14	0.0 (3.24)	-2.8 (3.60)	-1.6 (4.24)	-3.6 (3.15)	-1.5 (7.62)
AST, Day 12, predose, n=5,6,25,7,14	0.2 (4.32)	-3.3 (5.09)	-2.0 (4.63)	-4.1 (4.38)	-1.6 (7.53)
AST, Day 14, predose, n=4,5,23,5,12	2.8 (3.30)	-5.6 (6.02)	-2.0 (3.42)	-1.6 (5.68)	-2.8 (7.38)
AST, Day 14, 48 hours, n=5,6,24,6,14	0.8 (4.44)	-3.0 (4.69)	-1.8 (3.95)	-3.5 (2.88)	-2.4 (7.67)
AST, Day 14, 96 hours, n=5,6,24,6,14	2.4 (4.22)	-2.8 (4.45)	-2.0 (3.93)	-2.2 (6.43)	-1.2 (9.22)
AST, FU (Day 28), n=6,6,25,7,14	2.0 (6.67)	2.5 (5.89)	2.8 (5.75)	0.6 (6.55)	0.7 (4.70)

30. Primary Outcome

Title	Part 1: Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Magnesium, Phosphate, Potassium, Sodium, Urea
Description	Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Bicarbonate, Day 2, predose, n=6,6,25,7,14	0.7 (2.80)	-1.3 (2.07)	0.2 (2.31)	1.1 (1.57)	0.4 (1.95)
Bicarbonate, Day 4, predose, n=6,6,25,7,14	1.8 (1.72)	-3.3 (1.97)	1.0 (2.23)	3.1 (3.08)	2.1 (2.09)
Bicarbonate, Day 6, predose, n=6,6,25,7,14	0.2 (2.40)	-4.5 (1.22)	1.0 (2.17)	0.4 (1.81)	1.8 (1.72)
Bicarbonate, Day 8 predose, n=6,6,25,7,14	-0.7 (1.86)	-1.5 (1.87)	1.0 (1.63)	1.3 (1.70)	1.6 (1.91)
Bicarbonate, Day 10, predose, n=6,6,25,7,14	-0.5 (2.81)	-0.2 (1.72)	2.4 (3.29)	2.0 (1.63)	2.4 (2.24)
Bicarbonate, Day 12, predose, n=6,6,25,7,14	-1.8 (1.60)	-0.5 (1.64)	1.3 (2.17)	3.4 (2.82)	1.6 (1.65)
Bicarbonate, Day 14, predose, n=6,6,25,6,12	-1.2 (0.98)	-1.2 (1.72)	0.1 (1.93)	1.5 (1.05)	1.0 (1.62)
Bicarbonate, Day 14, 48 hours, n=6,6,24,6,14	0.2 (1.47)	0.8 (0.98)	2.2 (2.30)	2.5 (3.56)	3.0 (2.11)
Bicarbonate, Day 14, 96 hours, n=6,6,24,6,14	-1.2 (1.72)	1.0 (1.67)	1.7 (1.55)	4.3 (2.16)	2.3 (2.05)
Bicarbonate, FU (Day 28), n=6,6,25,7,14	0.3 (2.94)	-1.0 (0.63)	0.3 (2.50)	2.3 (2.56)	0.8 (1.72)
Calcium, Day 2, predose, n=6,6,25,7,14	-0.005 (0.0497)	0.012 (0.0354)	0.003 (0.0701)	0.104 (0.0627)	0.003 (0.0722)
Calcium, Day 4, predose, n=6,6,25,7,14	0.022 (0.0791)	0.010 (0.0385)	0.013 (0.0580)	0.117 (0.0574)	0.030 (0.0479)
Calcium, Day 6, predose, n=6,6,25,7,14	0.028 (0.1063)	0.003 (0.0505)	-0.020 (0.0607)	0.083 (0.0512)	0.011 (0.0578)
Calcium, Day 8 predose, n=6,6,25,7,14	0.005 (0.0528)	0.003 (0.0378)	0.006 (0.0575)	0.074 (0.0387)	0.028 (0.0641)
Calcium, Day 10, predose, n=6,6,25,7,14	0.000 (0.0890)	0.017 (0.0408)	0.014 (0.0699)	0.079 (0.0763)	0.024 (0.0628)
Calcium, Day 12, predose, n=6,6,25,7,14	-0.063 (0.0619)	-0.010 (0.0551)	0.024 (0.0667)	0.066 (0.0608)	0.025 (0.0617)
Calcium, Day 14, predose, n=6,6,25,6,12	-0.063 (0.0779)	-0.034 (0.0404)	-0.015 (0.0843)	0.028 (0.0512)	0.008 (0.0715)
Calcium, Day 14, 48 hours, n=6,6,24,6,14	-0.017 (0.0592)	0.012 (0.0462)	0.035 (0.0566)	0.072 (0.0806)	0.033 (0.0770)
Calcium, Day 14, 96 hours, n=6,6,24,6,14	0.005 (0.0459)	0.027 (0.0472)	0.037 (0.0526)	0.078 (0.1042)	0.046 (0.0580)
Calcium, FU(Day 28), n=6,6,25,7,14	-0.042 (0.0471)	0.003 (0.0550)	-0.018 (0.0572)	0.039 (0.0891)	0.019 (0.0827)
Chloride, Day 2, predose, n=6,6,25,7,14	0.7 (1.03)	2.0 (2.10)	0.4 (1.45)	-0.1 (1.57)	1.1 (1.98)
Chloride, Day 4, predose, n=6,6,25,7,14	0.7 (1.63)	2.3 (1.63)	0.1 (1.72)	0.0 (2.45)	0.9 (1.90)
Chloride, Day 6, predose, n=6,6,25,7,14	-0.2 (1.17)	0.7 (1.21)	0.2 (2.01)	0.4 (1.40)	0.4 (2.10)
Chloride, Day 8 predose, n=6,6,25,7,14	0.5 (1.38)	1.8 (1.33)	-0.2 (1.67)	1.3 (1.70)	0.6 (2.14)
Chloride, Day 10, predose, n=6,6,25,7,14	2.0 (1.41)	1.7 (1.03)	0.0 (1.99)	0.7 (2.43)	0.7 (1.77)
Chloride, Day 12, predose, n=6,6,25,7,14	0.3 (1.75)	2.0 (1.26)	0.8 (1.80)	0.7 (2.29)	1.3 (2.23)
Chloride, Day 14, predose, n=6,6,25,6,12	1.8 (2.14)	2.2 (1.17)	0.9 (2.12)	0.2 (1.47)	1.0 (2.11)
Chloride, Day 14, 48 hours, n=6,6,24,6,14	3.2 (1.72)	1.0 (1.41)	1.0 (1.76)	1.0 (2.53)	1.1 (2.37)
Chloride, Day 14, 96 hours, n=6,6,24,6,14	1.0 (0.00)	2.8 (1.33)	0.6 (1.71)	-0.5 (1.87)	0.5 (2.21)
Chloride, FU(Day 28), n=6,6,25,7,14	1.3 (1.21)	0.5 (1.38)	0.4 (1.55)	0.3 (2.43)	0.8 (1.89)
Magnesium, Day 2, predose, n=6,6,25,7,14	0.055 (0.0596)	-0.012 (0.0436)	-0.004 (0.0486)	0.016 (0.0624)	-0.006 (0.0422)
Magnesium, Day 4, predose, n=6,6,25,7,14	0.063 (0.0472)	-0.027 (0.0520)	0.005 (0.0415)	0.027 (0.0577)	0.007 (0.0347)
Magnesium, Day 6, predose, n=6,6,25,7,14	0.053 (0.0388)	-0.027 (0.0589)	0.019 (0.0476)	0.017 (0.0399)	0.008 (0.0556)
Magnesium, Day 8 predose, n=6,6,25,7,14	0.075 (0.0532)	0.000 (0.0420)	0.002 (0.0426)	0.019 (0.0438)	0.004 (0.0420)
Magnesium, Day 10, predose, n=6,6,25,7,14	0.047 (0.0543)	-0.003 (0.0361)	0.018 (0.0472)	0.017 (0.0390)	0.000 (0.0566)
Magnesium, Day 12, predose, n=6,6,25,7,14	0.038 (0.0585)	0.013 (0.0505)	0.014 (0.0401)	0.007 (0.0446)	0.004 (0.0390)
Magnesium, Day 14, predose, n=5,6,25,6,14	0.030 (0.0495)	-0.013 (0.0653)	0.019 (0.0473)	-0.002 (0.0343)	-0.001 (0.0551)
Magnesium, Day 14, 48 hours, n=6,6,24,6,14	0.040 (0.0555)	-0.022 (0.0445)	0.011 (0.0355)	0.020 (0.0603)	-0.001 (0.0363)
Magnesium, Day 14, 96 hours, n=6,6,24,6,14	0.025 (0.0485)	-0.007 (0.0423)	0.011 (0.0360)	0.022 (0.0331)	-0.002 (0.0662)
Magnesium, FU (Day 28), n=6,6,25,7,14	0.037 (0.0509)	-0.027 (0.0589)	0.001 (0.0387)	-0.003 (0.0415)	-0.009 (0.0469)
Phosphate, Day 2, predose, n=6,6,25,7,14	0.068 (0.1636)	0.062 (0.0760)	-0.024 (0.1248)	0.086 (0.1585)	0.035 (0.2069)
Phosphate, Day 4, predose, n=6,6,25,7,14	0.057 (0.1091)	0.017 (0.1237)	-0.003 (0.1382)	0.057 (0.1045)	0.036 (0.1835)
Phosphate, Day 6, predose, n=6,6,25,7,14	0.100 (0.1324)	0.038 (0.1080)	-0.014 (0.1375)	0.164 (0.1018)	0.060 (0.2119)
Phosphate, Day 8 predose, n=6,6,25,7,14	0.150 (0.1145)	0.075 (0.1140)	0.021 (0.1285)	0.121 (0.1644)	0.074 (0.2112)
Phosphate, Day 10, predose, n=6,6,25,7,14	0.150 (0.1848)	0.118 (0.0937)	0.061 (0.1372)	0.140 (0.1344)	0.129 (0.1626)
Phosphate, Day 12, predose, n=6,6,25,7,14	0.155 (0.1428)	0.090 (0.0827)	0.085 (0.1704)	0.193 (0.1329)	0.139 (0.2000)
Phosphate, Day 14, predose, n=5,6,25,6,14	0.212 (0.1587)	0.087 (0.1388)	0.043 (0.1363)	0.170 (0.1030)	0.101 (0.2161)
Phosphate, Day 14, 48 hours, n=6,6,24,6,14	0.208 (0.1382)	0.063 (0.1516)	0.093 (0.1517)	0.052 (0.1446)	0.082 (0.1873)
Phosphate, Day 14, 96 hours, n=6,6,24,6,14	0.178 (0.1869)	0.140 (0.1255)	0.089 (0.1510)	0.085 (0.1536)	0.119 (0.2051)
Phosphate, FU (Day 28), n=6,6,25,7,14	-0.013 (0.1363)	-0.020 (0.1418)	-0.047 (0.1837)	0.010 (0.1795)	0.010 (0.1741)
Potassium, Day 2, predose, n=6,6,25,7,14	0.10 (0.390)	-0.10 (0.190)	0.12 (0.340)	0.41 (0.662)	0.14 (0.203)
Potassium, Day 4, predose, n=6,6,25,7,14	0.28 (0.279)	-0.07 (0.216)	0.17 (0.369)	0.20 (0.383)	0.19 (0.141)
Potassium, Day 6, predose, n=6,6,25,7,14	0.30 (0.529)	0.12 (0.264)	0.11 (0.396)	0.21 (0.285)	0.06 (0.234)
Potassium, Day 8 predose, n=6,5,25,7,14	0.23 (0.216)	-0.06 (0.152)	0.04 (0.364)	0.20 (0.374)	0.17 (0.307)
Potassium, Day 10, predose, n=6,6,25,7,14	0.32 (0.519)	-0.08 (0.194)	0.06 (0.406)	0.21 (0.358)	0.09 (0.138)
Potassium, Day 12, predose, n=6,6,25,7,14	0.38 (0.431)	-0.13 (0.280)	0.08 (0.384)	0.17 (0.399)	0.22 (0.176)
Potassium, Day 14, predose, n=5,5,24,6,13	-0.12 (0.277)	-0.20 (0.300)	-0.06 (0.388)	-0.05 (0.327)	0.19 (0.348)
Potassium, Day 14, 48 hours, n=6,6,24,6,14	0.27 (0.509)	-0.18 (0.204)	0.07 (0.338)	-0.08 (0.331)	0.04 (0.214)
Potassium, Day 14, 96 hours, n=6,6,24,6,14	0.07 (0.333)	-0.13 (0.137)	0.00 (0.393)	0.08 (0.172)	0.13 (0.261)
Potassium, FU (Day 28), n=6,6,25,7,14	0.05 (0.383)	-0.08 (0.160)	-0.06 (0.347)	-0.13 (0.335)	0.21 (0.530)
Sodium, Day 2, predose, n=6,6,25,7,14	0.2 (1.47)	1.2 (1.47)	-0.5 (1.48)	-1.1 (1.86)	0.1 (2.11)
Sodium, Day 4, predose, n=6,6,25,7,14	1.5 (1.87)	1.5 (1.38)	-0.3 (1.17)	0.9 (1.77)	0.8 (1.93)
Sodium, Day 6, predose, n=6,6,25,7,14	-0.3 (1.21)	1.2 (1.17)	-0.7 (1.14)	-0.1 (1.07)	0.5 (1.70)
Sodium, Day 8 predose, n=6,6,25,7,14	0.5 (1.38)	1.8 (0.75)	-1.0 (1.15)	0.4 (1.40)	0.7 (2.16)
Sodium, Day 10, predose, n=6,6,25,7,14	1.5 (1.22)	2.8 (0.98)	0.3 (2.10)	1.0 (1.63)	0.9 (2.07)
Sodium, Day 12, predose, n=6,6,25,7,14	1.2 (0.98)	1.7 (1.03)	0.2 (1.53)	0.9 (1.57)	1.2 (1.89)
Sodium, Day 14, predose, n=6,6,25,6,14	0.5 (1.52)	2.2 (1.17)	-1.1 (1.83)	-0.5 (0.55)	0.1 (2.34)
Sodium, Day 14, 48 hours, n=6,6,24,6,14	3.3 (1.75)	1.0 (0.89)	0.4 (1.35)	0.5 (0.84)	1.3 (2.27)
Sodium, Day 14, 96 hours, n=6,6,24,6,14	1.5 (1.52)	2.3 (0.82)	0.6 (1.59)	0.3 (1.03)	1.1 (2.59)
Sodium, FU(Day 28), n=6,6,25,7,14	1.8 (2.48)	0.8 (1.72)	-0.1 (1.58)	0.0 (1.73)	0.9 (2.32)
Urea, Day 2, predose, n=6,6,25,7,14	-0.583100 (1.7190989)	-0.383180 (0.8994549)	-0.279888 (1.3039577)	0.242760 (0.8615469)	-0.221340 (1.0565530)
Urea, Day 4, predose, n=6,6,25,7,14	-0.982940 (2.0645229)	-0.616420 (0.8994549)	-0.415834 (1.2169831)	-0.157080 (0.7761282)	-0.535500 (1.2302718)
Urea, Day 6, predose, n=6,6,25,7,14	-0.533120 (1.6805969)	-0.566440 (1.0685283)	-0.439824 (1.3090563)	-0.414120 (0.8948673)	-0.606900 (1.0361954)
Urea, Day 8 predose, n=6,6,25,7,14	-0.716380 (1.4324888)	-0.982940 (1.2427511)	-0.287885 (1.1923207)	-0.257040 (0.7543661)	-0.249900 (1.2544880)
Urea, Day 10, predose, n=6,6,25,7,14	-0.866320 (1.6805969)	-0.066640 (0.8843306)	-0.491803 (1.1108310)	-0.842520 (0.7064873)	-0.207060 (1.4392234)
Urea, Day 12, predose, n=6,6,25,7,14	-1.032920 (1.7088970)	-0.466480 (1.1821793)	-0.139944 (1.1809813)	-1.013880 (0.9698843)	-0.399840 (1.2423284)
Urea, Day 14, predose, n=6,6,25,6,14	-1.049580 (1.9204291)	-1.166200 (1.6051804)	-0.399840 (1.2290067)	-0.882980 (0.9192335)	-0.271320 (1.2493792)
Urea, Day 14, 48 hours, n=6,6,24,6,14	-0.916300 (1.5165176)	-0.533120 (1.2237107)	-0.703885 (1.1463627)	-0.949620 (1.1991034)	-0.521220 (1.4681527)
Urea, Day 14, 96 hours, n=6,6,24,6,14	-0.949620 (1.5674926)	-0.483140 (0.9278887)	-0.749700 (1.1904312)	-0.499800 (0.8387115)	-0.556920 (1.1341178)
Urea, FU (Day 28), n=6,6,25,7,14	-0.882980 (1.2603155)	-1.166200 (0.9580876)	-0.411835 (1.0341231)	-0.571200 (0.6208106)	-0.778260 (0.9818953)

31. Primary Outcome

Title	Part 2: Change From Baseline in Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides
Description	Blood samples were collected at indicated time points to analyze the chemistry parameter: cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), Day 8 (pre dose), Day 14 (48 hours) post dose and Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Cholesterol, Day 8, (predose) n=5,6,25,7,13	0.08 (0.192)	0.07 (0.631)	0.16 (0.466)	0.36 (0.369)	0.38 (0.440)
Cholesterol, Day 14 (48 hours), n= 6,6,24,6,14	-0.05 (0.373)	0.23 (0.589)	0.23 (0.531)	0.40 (0.696)	0.38 (0.647)
Cholesterol, FU (Day 28), n= 6,6,25,7,14	-0.28 (0.147)	0.15 (0.619)	-0.04 (0.461)	-0.29 (0.955)	-0.04 (0.434)
HDL Cholesterol, Day 8, (predose) n=5,6,25,7,14	-0.03 (0.121)	0.00 (0.167)	-0.14 (0.235)	-0.13 (0.150)	-0.14 (0.203)
HDL Cholesterol, Day 14 (48 hours), n= 6,6,24,6,14	-0.08 (0.075)	-0.10 (0.179)	-0.18 (0.129)	-0.08 (0.194)	-0.20 (0.260)
HDL Cholesterol, FU (Day 28), n= 6,6,25,7,14	0.02 (0.041)	0.00 (0.179)	-0.12 (0.277)	0.01 (0.372)	-0.14 (0.195)
LDL Cholesterol, Day 8, (predose) n=5,6,25,7,13	0.08 (0.217)	0.03 (0.463)	0.27 (0.407)	0.49 (0.453)	0.42 (0.420)
LDL Cholesterol, Day 14 (48 hours), n= 6,6,24,6,14	-0.03 (0.234)	0.27 (0.388)	0.33 (0.442)	0.33 (0.615)	0.47 (0.517)
LDL Cholesterol, FU (Day 28),n= 6,6,25,7,14	-0.23 (0.216)	0.12 (0.556)	0.12 (0.456)	-0.33 (0.565)	0.06 (0.455)
Triglycerides, Day 8, (predose) n=5,6,25,7,13	0.12 (0.492)	0.07 (0.137)	0.08 (0.314)	-0.04 (0.424)	0.22 (0.215)
Triglycerides, Day 14 (48 hours), n= 6,6,24,6,14	0.20 (0.502)	0.15 (0.266)	0.18 (0.400)	0.28 (0.479)	0.26 (0.285)
Triglycerides, FU (Day 28), n= 6,6,25,7,14	-0.12 (0.471)	0.07 (0.356)	-0.06 (0.349)	0.06 (0.538)	0.14 (0.665)

32. Primary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameter: Glucose
Description	Blood samples were collected at indicated time points to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), Day 8 (predose), Day 14 (48 hours) post dose and Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 8, (predose) n=5,6,25,7,13	0.02 (0.550)	0.20 (0.237)	-0.10 (0.278)	-0.09 (0.398)	-0.12 (0.394)
Day 14 (48 hours), n= 6,6,24,6,14	0.15 (0.532)	0.03 (0.350)	-0.23 (0.275)	0.00 (0.329)	-0.21 (0.405)
FU (Day 28), n= 6,6,25,7,14	0.05 (0.824)	0.15 (0.389)	-0.12 (0.375)	0.20 (0.507)	-0.02 (0.458)

33. Primary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Description	Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Bilirubin, Day 2, predose, n=6,6,25,7,14	-1.3 (1.97)	-0.8 (2.14)	-0.7 (4.03)	-2.6 (2.94)	-0.9 (4.01)
Bilirubin, Day 4, predose, n=6,6,25,7,14	-1.5 (2.59)	0.2 (0.98)	-0.7 (3.53)	0.3 (1.50)	0.3 (3.50)
Bilirubin, Day 6, predose, n=6,6,25,7,14	-0.8 (1.72)	-2.2 (1.72)	-1.0 (3.67)	-1.1 (3.63)	-0.7 (3.58)
Bilirubin, Day 8 predose, n=6,6,25,7,14	-1.7 (2.07)	-0.5 (1.38)	-0.9 (3.73)	-1.3 (3.64)	-0.1 (3.65)
Bilirubin, Day 10, predose, n=6,6,25,7,14	-1.8 (2.64)	-0.2 (2.04)	0.0 (3.52)	-0.6 (4.20)	-0.1 (3.41)
Bilirubin, Day 12, predose, n=6,6,25,7,14	-1.8 (1.83)	0.2 (2.48)	-1.3 (3.31)	-1.4 (3.69)	-1.1 (3.17)
Bilirubin, Day 14, predose, n=6,6,25,6,14	-0.3 (1.37)	-0.3 (1.86)	-1.0 (3.65)	-1.8 (3.54)	-0.4 (3.75)
Bilirubin, Day 14, 48 hours, n=6,6,24,6,14	-1.7 (2.07)	1.2 (2.64)	0.1 (3.71)	-0.8 (3.60)	0.0 (3.35)
Bilirubin, Day 14, 96 hours, n=6,6,24,6,14	-1.2 (1.17)	1.0 (1.79)	-0.4 (4.71)	-1.0 (3.74)	0.2 (4.02)
Bilirubin, FU (Day 28), n=6,6,25,7,14	1.2 (2.04)	1.8 (2.40)	2.3 (7.28)	0.6 (4.35)	-0.1 (3.90)
Creatinine, Day 2, predose, n=6,6,25,7,14	0.7 (2.50)	8.2 (3.87)	-3.0 (5.30)	6.1 (8.30)	0.4 (3.23)
Creatinine, Day 4, predose, n=6,6,25,7,14	4.7 (4.72)	1.8 (3.43)	1.9 (6.05)	3.1 (3.24)	1.4 (8.90)
Creatinine, Day 6, predose, n=6,6,25,7,14	3.3 (5.72)	3.3 (4.41)	-2.2 (6.13)	5.6 (7.23)	0.5 (7.47)
Creatinine, Day 8 predose, n=6,6,25,7,14	2.7 (7.74)	13.8 (4.67)	2.6 (6.31)	6.9 (6.52)	3.6 (9.71)
Creatinine, Day 10, predose, n=6,6,25,7,14	5.8 (8.66)	7.5 (5.39)	0.8 (6.16)	6.4 (3.46)	4.7 (5.80)
Creatinine, Day 12, predose, n=6,6,25,7,14	4.5 (7.29)	6.8 (5.74)	2.0 (8.62)	3.0 (3.96)	3.6 (7.44)
Creatinine, Day 14, predose, n=6,6,25,6,14	-2.3 (3.83)	1.7 (3.83)	1.2 (6.31)	4.3 (5.05)	3.6 (8.31)
Creatinine, Day 14, 48 hours, n=6,6,24,6,14	4.2 (6.88)	7.8 (5.46)	1.5 (7.08)	8.5 (6.83)	4.0 (7.92)
Creatinine, Day 14, 96 hours, n=6,6,24,6,14	6.0 (5.10)	15.3 (6.53)	5.5 (8.81)	10.2 (5.56)	8.8 (6.22)
Creatinine, FU (Day 28), n=6,6,25,7,14	-0.7 (8.91)	4.5 (4.89)	-0.3 (7.66)	3.6 (3.55)	1.7 (5.17)
Direct Bilirubin, Day 2, predose, n=6,6,25,7,14	-0.6 (0.55)	0.0 (1.00)	-0.4 (1.18)	-1.5 (1.73)	-0.5 (1.31)
Direct Bilirubin, Day 4, predose, n=6,6,25,7,14	-0.8 (0.45)	-0.3 (0.82)	-0.4 (1.03)	-0.2 (0.41)	0.0 (0.95)
Direct Bilirubin, Day 6, predose, n=6,6,25,7,14	-0.4 (0.55)	-1.0 (0.82)	-0.4 (1.20)	-0.5 (1.22)	-0.3 (1.36)
Direct Bilirubin, Day 8 predose, n=6,6,25,7,14	-0.4 (0.89)	0.2 (1.10)	-0.3 (1.19)	-0.3 (1.03)	-0.3 (1.37)
Direct Bilirubin, Day 10, predose, n=6,6,25,7,14	-0.4 (0.89)	0.0 (1.26)	0.0 (1.13)	-0.6 (1.52)	-0.3 (1.14)
Direct Bilirubin, Day 12, predose, n=6,6,25,7,14	-0.4 (0.55)	-0.4 (1.14)	-0.5 (0.99)	-0.6 (1.52)	-0.4 (1.24)
Direct Bilirubin, Day 14, predose, n=6,6,25,6,14	0.0 (0.82)	0.0 (0.82)	-0.4 (1.26)	-2.5 (0.71)	-0.4 (1.43)
Direct Bilirubin, Day 14, 48 hours, n=6,6,24,6,14	-0.8 (0.45)	-0.2 (0.98)	-0.2 (1.14)	-0.2 (1.30)	-0.3 (1.30)
Direct Bilirubin, Day 14, 96 hours, n=6,6,24,6,14	-0.4 (0.55)	-0.2 (0.84)	-0.2 (1.40)	-0.6 (0.89)	-0.3 (1.48)
Direct bilirubin, FU (Day 28), n=6,6,25,7,14	0.8 (0.84)	0.3 (1.21)	0.7 (2.17)	0.4 (1.52)	0.2 (1.54)

34. Primary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameter: Protein
Description	Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 2, predose, n=6,6,25,7,14	-0.5 (2.35)	-1.0 (2.19)	0.2 (3.34)	1.7 (2.14)	-0.9 (3.32)
Day 4, predose, n=6,6,25,7,14	1.5 (3.02)	0.0 (2.37)	-0.3 (2.78)	5.9 (3.53)	-0.6 (2.82)
Day 6, predose, n=6,6,25,7,14	0.7 (5.61)	-1.3 (1.75)	-0.1 (2.53)	2.1 (2.48)	0.0 (2.86)
Day 8 predose, n=6,6,25,7,14	-1.0 (3.03)	-0.8 (2.48)	-0.5 (2.69)	1.4 (2.15)	0.1 (2.56)
Day 10, predose, n=6,6,25,7,14	-0.5 (4.04)	0.7 (1.97)	-0.6 (3.12)	1.7 (1.98)	0.0 (4.08)
Day 12, predose, n=6,6,25,7,14	-2.7 (3.08)	-1.0 (2.45)	-0.3 (2.72)	2.9 (2.12)	-0.3 (3.36)
Day 14, predose, n=6,6,25,6,14	-2.5 (4.32)	-3.5 (1.87)	-2.0 (4.14)	0.2 (1.94)	-1.8 (3.85)
Day 14, 48 hours, n=6,6,24,6,14	-2.2 (3.31)	-1.7 (2.50)	-1.8 (3.57)	2.0 (2.00)	-0.2 (3.79)
Day 14, 96 hours, n=6,6,24,6,14	0.0 (2.53)	-0.8 (2.64)	-1.1 (3.90)	2.7 (2.42)	0.6 (3.90)
FU (Day 28), n=6,6,25,7,14	-1.0 (2.28)	-1.2 (1.94)	-0.5 (3.43)	0.4 (3.26)	0.4 (4.05)

35. Primary Outcome

Title	Part 2: Number of Participants With Abnormal Urinalysis
Description	Urine samples were collected analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

36. Primary Outcome

Title	Part 2: Change From Baseline in Vital Signs: SBP and DBP
Description	SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12,and 14 (pre dose and 72 hours) and Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
SBP, Day 1, predose, n=6,6,25,7,14	0.5 (4.76)	1.2 (9.87)	-0.5 (4.68)	2.9 (5.76)	-1.1 (8.48)
SBP, Day 2, predose, n=6,6,25,7,14	0.5 (2.88)	1.0 (10.30)	0.6 (6.47)	2.6 (3.40)	-2.6 (7.84)
SBP, Day 4, predose, n=6,6,25,7,14	-0.3 (5.79)	-0.5 (9.20)	-2.2 (6.33)	3.0 (5.42)	-3.3 (12.67)
SBP, Day 6, predose, n=6,6,25,7,14	-2.7 (5.09)	1.2 (9.87)	0.0 (5.72)	3.0 (7.48)	-1.2 (12.94)
SBP, Day 8, predose, n=6,6,25,7,14	-2.5 (3.73)	3.3 (9.85)	-1.4 (6.19)	4.3 (5.65)	-1.4 (11.80)
SBP, Day 10, predose, n=6,6,25,7,14	-2.8 (3.06)	0.8 (9.37)	-1.9 (6.66)	3.7 (4.11)	-5.2 (12.77)
SBP, Day 12, predose, n=6,6,25,7,14	-2.8 (2.64)	0.8 (10.15)	-2.0 (5.70)	3.3 (5.71)	-4.6 (11.88)
SBP, Day 14, predose, n=6,6,25,7,14	-0.8 (3.97)	0.3 (14.00)	-1.3 (7.31)	3.8 (5.56)	-4.1 (12.33)
SBP, Day 14, 72 hours, n=6,6,25,7,14	1.3 (3.33)	0.2 (10.98)	-2.3 (6.21)	0.2 (6.85)	-2.0 (11.07)
SBP, follow up, n=6,6,25,7,14	-3.0 (8.56)	1.3 (1.75)	0.8 (6.43)	4.1 (7.60)	1.2 (7.03)
DBP, Day 1, predose, n=6,6,25,7,14	-2.7 (5.65)	-0.4 (2.76)	-0.9 (5.78)	2.3 (5.41)	-0.8 (5.73)
DBP, Day 2, predose, n=6,6,25,7,14	-1.0 (3.03)	-0.3 (5.20)	0.9 (6.93)	2.2 (4.28)	0.8 (4.76)
DBP, Day 4, predose, n=6,6,25,7,14	-2.7 (5.85)	-0.3 (5.68)	-1.6 (7.18)	3.1 (3.80)	-1.3 (4.94)
DBP, Day 6, predose, n=6,6,25,7,14	-4.7 (7.17)	2.0 (2.19)	0.2 (5.21)	1.9 (4.06)	-1.6 (4.62)
DBP, Day 8, predose, n=6,6,25,7,14	-2.5 (7.89)	0.5 (3.73)	-1.3 (6.52)	0.1 (4.63)	0.3 (4.70)
DBP, Day 10, predose, n=6,6,25,7,14	-3.2 (6.27)	0.8 (4.71)	-1.2 (5.79)	3.3 (4.96)	-2.1 (7.13)
DBP, Day 12, n=6,6,25,7,14	0.7 (1.86)	0.5 (4.85)	-1.9 (6.16)	0.9 (5.01)	-2.3 (7.45)
DBP, Day 14, predose, n=6,6,24,6,14	0.2 (3.13)	-0.8 (2.56)	-1.0 (6.93)	0.8 (3.76)	-1.9 (7.07)
DBP, Day 14, 72 hours n=6,6,24,6,14	-0.3 (2.88)	-1.7 (2.42)	-2.0 (6.03)	-1.2 (4.67)	-1.6 (4.50)
DBP, FU (Day 28), n=6,6,25,7,14	-3.0 (8.56)	1.3 (1.75)	0.8 (6.43)	7 (4.1)	1.2 (7.03)

37. Primary Outcome

Title	Part 2: Change From Baseline in Vital Sign: Pulse Rate
Description	Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame	Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 1, predose, n=6,6,25,7,14	-0.3 (4.27)	0.6 (1.86)	1.6 (4.98)	-3.4 (3.31)	5.3 (5.61)
Day 2, predose, n=6,6,25,7,14	0.3 (4.18)	0.5 (4.93)	2.5 (7.22)	2.1 (5.79)	3.1 (5.66)
Day 4, predose, n=6,6,25,7,14	1.5 (3.27)	1.5 (5.96)	0.2 (6.17)	2.7 (7.63)	4.1 (6.34)
Day 6, predose, n=6,6,25,7,14	3.8 (3.60)	2.5 (5.47)	0.8 (6.55)	3.4 (4.43)	3.2 (7.16)
Day 8, predose, n=6,6,25,7,14	-0.5 (3.94)	1.3 (4.89)	1.4 (8.02)	2.7 (6.70)	2.1 (5.34)
Day 10, predose, n=6,6,25,7,14	0.5 (3.94)	3.3 (5.79)	1.0 (7.21)	0.4 (5.62)	1.8 (6.93)
Day 12, predose, n=6,6,25,7,14	3.5 (4.51)	2.5 (7.87)	-0.1 (8.02)	3.1 (10.64)	2.5 (8.12)
Day 14, predose, n=6,6,25,6,14	3.5 (3.62)	-0.2 (5.12)	-0.2 (7.40)	1.5 (3.83)	0.3 (4.61)
Day 14, 72 hours, n=6,6,25,6,14	7.0 (7.62)	1.8 (4.40)	2.9 (6.91)	4.2 (4.31)	5.0 (6.82)
FU (Day 28), n=6,6,25,7,14	6.3 (6.62)	-1.3 (10.63)	0.8 (9.36)	9.6 (7.96)	6.3 (7.33)

38. Primary Outcome

Title	Part 2: Change From Baseline in Vital Sign: Temperature
Description	Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 1, predose, n=6,6,25,7,14	0.38 (0.313)	0.08 (0.222)	0.11 (0.414)	0.11 (0.308)	0.09 (0.276)
Day 2, predose, n=6,6,25,7,14	0.25 (0.281)	0.18 (0.331)	-0.04 (0.507)	-0.11 (0.279)	0.14 (0.367)
Day 4, predose, n=6,6,25,7,14	0.44 (0.512)	0.28 (0.271)	0.04 (0.425)	0.11 (0.204)	0.14 (0.374)
Day 6, predose, n=6,6,25,7,14	0.33 (0.489)	0.25 (0.226)	-0.04 (0.342)	-0.11 (0.491)	0.14 (0.405)
Day 8, predose, n=6,6,25,7,14	0.05 (0.373)	0.20 (0.322)	0.05 (0.255)	-0.09 (0.372)	-0.02 (0.379)
Day 10, predose, n=6,6,25,7,14	0.30 (0.498)	0.10 (0.593)	-0.01 (0.355)	-0.10 (0.289)	0.09 (0.455)
Day 12, predose, n=6,6,25,7,14	0.23 (0.489)	0.23 (0.314)	-0.02 (0.415)	0.03 (0.320)	0.06 (0.393)
Day 14, predose, n=6,6,25,6,14	0.30 (0.290)	0.13 (0.258)	0.05 (0.309)	0.05 (0.266)	-0.02 (0.395)
Day 14, 72 hours, n=6,6,25,6,14	0.30 (0.310)	0.15 (0.302)	0.06 (0.330)	0.22 (0.256)	0.06 (0.363)
FU (Day 28), n=6,6,25,7,14	0.42 (0.264)	0.37 (0.441)	0.04 (0.586)	0.23 (0.364)	0.21 (0.317)

39. Primary Outcome

Title	Part 2: Change From Baseline in Vital Sign: Respiratory Rate
Description	Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Time Frame	Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12 and 14 (pre dose and 72 hours) and Follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
Day 1, predose, n=6,6,25,7,14	-1.0 (2.37)	2.2 (3.49)	0.2 (2.15)	0.1 (2.27)	0.8 (2.22)
Day 2, predose, n=6,6,25,7,14	-0.5 (2.88)	2.3 (1.21)	0.4 (2.00)	1.6 (1.72)	0.5 (1.95)
Day 4, predose, n=6,6,25,7,14	-0.5 (2.17)	2.2 (1.94)	-0.2 (1.50)	0.6 (2.44)	0.2 (1.53)
Day 6, predose, n=6,6,25,7,14	0.7 (2.25)	0.2 (1.47)	0.1 (1.73)	0.0 (1.91)	-0.4 (1.65)
Day 8, predose, n=6,6,25,7,14	-1.2 (3.06)	1.7 (1.03)	0.0 (2.37)	0.6 (1.90)	0.5 (1.91)
Day 10, predose, n=6,6,25,7,14	-0.3 (3.20)	1.5 (2.35)	0.9 (1.69)	0.6 (0.98)	0.5 (1.74)
Day 12, predose, n=6,6,25,7,14	-0.7 (2.25)	2.3 (2.80)	0.4 (1.96)	-0.1 (1.35)	0.4 (2.62)
Day 14, predose, n=6,6,25,6,14	-0.8 (2.14)	2.7 (1.51)	0.6 (1.98)	-0.2 (2.23)	0.4 (2.24)
Day 14, 72 hours, n=6,6,25,6,14	-1.0 (1.41)	2.7 (1.63)	0.5 (1.56)	-0.5 (1.97)	-0.4 (1.98)
FU (Day 28), n=6,6,25,7,14	-0.5 (2.95)	0.8 (1.72)	1.1 (2.38)	0.1 (0.69)	0.6 (2.10)

40. Primary Outcome

Title	Part 2: Number of Participants With Abnormal ECG Findings
Description	12-lead ECG were obtained at given time points. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).Results are presented treatment wise.
Time Frame	Day 1 (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5, 5.5, 6, 8, 12, 24 hours); Pre-dose on Days 3, 4, 6, 8, 10, 12; Day 14: Pre-dose, 1, 2, 4.5, 5, 6, 12, 24, 48, 72 and 96 hours post-dose and follow up (Day 28)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg	Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days	Participants received repeated dose of matching placebo once daily up to 14 days
Measure Participants	6	6	25	7	14
CS, Day 1, 0.5 hours, n=4,0,0,0,2	0 0%	0 0%
CS, Day 1,1 hour, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS, Day 1, 1.5 hours, n=4,0,0,0,1	0 0%	0 0%
CS,Day 1, 2hours, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 1, 2.5 hours, n=4,0,0,0,1	0 0%	0 0%
CS, Day 1, 3 hours n=4,0,0,0,1	0 0%	0 0%
CS,Day 1, 3.5 hours, n=4,0,0,0,1	0 0%	0 0%
CS, Day 1, 4.5 hours, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS, Day 1, 5hours, n=4,0,0,0,1	0 0%	0 0%
CS, Day 1,5.5 hours, n=4,0,0,0,1	0 0%	0 0%
CS,Day 1, 6hours, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 1, 8 hours, n=4,0,0,0,1	0 0%	0 0%
CS, Day 1, 12 hours, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS, Day 1, 24 hours, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 3, Predose, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 4, Predose, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 6, Predose, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 8, Predose, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 10, Predose, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 12, Predose, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, Predose, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS, Day 14, 1hour, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 2 hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 4.5hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 5hours, n=0,0,0,0,1	0 0%
CS,Day 14, 6 hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 12 hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 24 hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 48 hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 72 hours, n=6,6,24, 6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS,Day 14, 96 hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
CS, FU (Day 28), n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
NCS, Day 1,0.5 hours, n=4,0,0,0,2	1 8.3%	0 0%
NCS, Day 1,1 hour, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	1 4%
NCS, Day 1, 1.5 hours, n=4,0,0,0,1	1 8.3%	0 0%
NCS,Day 1, 2hours, n=6,6,25,7,14	0 0%	0 0%	2 33.3%	0 0%	0 0%
NCS,Day 1, 2.5 hours, n=4,0,0,0,1	0 0%	0 0%
NCS Day 1, 3 hours n=4,0,0,0,1	0 0%	0 0%	0 0%	0 0%	0 0%
NCS,Day 1, 3.5 hours, n=4,0,0,0,1	0 0%	0 0%
NCS, Day 1, 4.5 hours, n=6,6,25,7,14	0 0%	0 0%	1 16.7%	1 16.7%	0 0%
NCS, Day 1, 5hours n=4,0,0,0,1	0 0%	0 0%
NCS, Day 1,5.5 hours, n=4,0,0,0,1	0 0%	0 0%	0 0%	0 0%	0 0%
NCS,Day 1, 6hours, n=6,6,25,7,14	0 0%	0 0%	2 33.3%	0 0%	0 0%
NCS,Day 1, 8 hours, n=4,0,0,0,1	0 0%	0 0%
NCS, Day 1, 12 hours, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	0 0%
NCS,Day 3, Predose, n=6,6,25,7,14	0 0%	1 12.5%	1 16.7%	0 0%	0 0%
NCS,Day 4, Predose, n=6,6,25,7,14	0 0%	0 0%	1 16.7%	1 16.7%	0 0%
NCS,Day 6, Predose, n=6,6,25,7,14	0 0%	0 0%	2 33.3%	0 0%	1 4%
NCS,Day 8, Predose, n=6,6,25,7,14	1 8.3%	0 0%	1 16.7%	0 0%	0 0%
NCS,Day 10, Predose, n=6,6,25,7,14	0 0%	0 0%	0 0%	0 0%	1 4%
NCS,Day 12, Predose, n=6,6,25,7,14	0 0%	0 0%	1 16.7%	0 0%	1 4%
NCS,Day 14, Predose, n=6,6,24,6,14	1 8.3%	0 0%	1 16.7%	0 0%	0 0%
NCS, Day 14, 1hour, n=6,6,24,6,14	1 8.3%	0 0%	0 0%	0 0%	1 4%
NCS,Day 14, 2 hours, n=6,6,24,6,14	1 8.3%	0 0%	0 0%	0 0%	1 4%
NCS,Day 14, 4.5 hours, n=6,6,24,6,14	0 0%	0 0%	0 0%	0 0%	0 0%
NCS,Day 14, 5hours, n=0,0,0,0,1	0 0%
NCS, Day 14, 6 hours, n=6,6,24,6,14	0 0%	0 0%	1 16.7%	0 0%	1 4%
NCS,Day 14, 12 hours, n=6,6,24,6,14	0 0%	0 0%	2 33.3%	0 0%	0 0%
NCS,Day 14, 24hours, n=6,6,24,6,14	1 8.3%	0 0%	1 16.7%	0 0%	0 0%
NCS,Day 14, 48 hours, n=6,6,24,6,14	1 8.3%	0 0%	3 50%	0 0%	1 4%
NCS,Day 14, 72 hours, n=6,6,24,6,14	1 8.3%	0 0%	1 16.7%	0 0%	1 4%
NCS,Day 14, 96 hours, n=6,6,24,6,14	0 0%	0 0%	1 16.7%	0 0%	2 8%
NCS, FU (Day 28), n=6,6,24,6,14	0 0%	1 12.5%	2 33.3%	0 0%	0 0%

41. Secondary Outcome

Title	Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hour (AUC[0-24]) of GSK3640254
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,24 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	4	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [Hour*microgram per milliliter]	0.056	0.171	0.576	1.546	4.177	7.334	21.666	20.743

42. Secondary Outcome

Title	Part 1: AUC From Zero to Time of Last Sample Taken (AUC[0-Tlast]) of GSK3640254
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [Hour*microgram per milliliter]	0.020	0.184	1.082	2.816	8.060	14.068	40.238	37.626

43. Secondary Outcome

Title	Part 1: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3640254
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	3	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [Hour*microgram per milliliter]	0.057	0.329	1.227	2.992	8.539	14.952	42.989	39.692

44. Secondary Outcome

Title	Part 1: Apparent Terminal Phase Half-life (T1/2) of GSK3640254
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Most of the concentrations were below limit of quantification (BLQ) at this dose group this value and/ or %AUC extrapolated was >20% for all participants so this value should be used with caution. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	3	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [Hour]	7.886	20.486	25.332	21.221	22.838	22.620	23.737	20.761

45. Secondary Outcome

Title	Part 1: Apparent Oral Clearance (CL/F) of GSK3640254
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	3	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [Liters/hour]	17.685	9.119	8.152	10.027	11.711	13.376	9.305	17.636

46. Secondary Outcome

Title	Part 1: Maximum Observed Concentration (Cmax), Concentration of GSK3640254 at 24 Hours (C24) and Last Quantifiable Concentration (Clast) of GSK3640254
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6
Cmax	0.005	0.014	0.047	0.130	0.372	0.579	1.881	1.724
C24	0.001	0.005	0.017	0.043	0.126	0.245	0.610	0.579
Clast	0.004	0.005	0.004	0.005	0.014	0.024	0.072	0.054

47. Secondary Outcome

Title	Part 1: Time of Occurrence of Cmax (Tmax), Lag Time (Tlag), and Time to Reach Clast (Tlast) of GSK3640254
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6
Tmax	3.500	4.500	3.500	4.000	3.750	3.000	3.250	3.250
Tlag	2.000	1.250	0.750	0.500	0.750	0.500	0.500	0.500
Tlast	6.017	24.017	72.008	96.000	96.000	95.667	95.667	95.542

48. Secondary Outcome

Title	Part 2: AUC(0-24) of GSK3640254: Day 1
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 and 24 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Geometric Mean (Geometric Coefficient of Variation) [Hour*micrograms per milliliter]	2.855 (29.621)	6.801 (22.970)	8.257 (49.782)	13.456 (23.743)

49. Secondary Outcome

Title	Part 2: Cmax, C24 of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Cmax	0.215 (24.412)	0.536 (22.959)	0.614 (44.354)	1.044 (29.225)
C24	0.082 (33.583)	0.207 (22.856)	0.238 (58.452)	0.417 (39.681)

50. Secondary Outcome

Title	Part 2: Tmax, Tlag of GSK3640254 on Day 1
Description	Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Time Frame	Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Tmax	3.750	4.250	4.000	4.000
Tlag	0.508	0.500	0.500	0.500

51. Secondary Outcome

Title	Part 2: Tmax GSK3640254 on Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Median (Full Range) [Hour]	3.775	4.000	3.750	4.250

52. Secondary Outcome

Title	Part 2: Cmax of GSK3640254 on Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter]	0.414 (31.556)	1.182 (10.264)	1.402 (30.839)	2.156 (20.360)

53. Secondary Outcome

Title	Part 2: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [hour* micrograms per milliliter]	6.282 (34.010)	17.506 (13.794)	21.501 (34.205)	31.954 (35.380)

54. Secondary Outcome

Title	Part 2: Plasma Trough Concentration (Ctau) of GSK3640254: Day 14
Description	Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The PK parameter name for Part 2 (Day 14) trough concentration was changed using Phoenix WinNonlin 8 from Ct to Ctrough. Day 15 Ctrough values were used for dose proportionality and time to steady-state assessments.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliter]	0.186 (35.128)	0.558 (21.407)	0.630 (37.814)	0.980 (41.815)

55. Secondary Outcome

Title	Part 2: T1/2 of GSK3640254: Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [Hour]	24.847 (5.087)	28.358 (19.199)	22.125 (14.515)	22.350 (12.641)

56. Secondary Outcome

Title	Part 2: CL/F of GSK3640254: Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour]	7.959 (34.010)	5.712 (13.794)	9.302 (34.205)	10.014 (35.380)

57. Secondary Outcome

Title	Part 1: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [hour*micrograms per mililiter]	0.057	0.329	1.1227	2.992	8.539	14.952	42.989	39.692

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg, Part 1: GSK3640254 100 mg, Part 1: GSK3640254 200 mg, Part 1: GSK3640254 400 mg, Part 1: GSK3640254 700 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power model
	Estimated Value	0.9476
	Confidence Interval	(2-Sided) 90%; 0.8982 to 0.9971
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (AUC0-inf) from all active doses in Part 1

58. Secondary Outcome

Title	Part 1: Dose Proportionality (AUC0-24) Following Single Dose of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [hour*micrograms per mililiter]	0.056	0.171	0.576	1.546	4.177	7.334	21.666	20.743

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg, Part 1: GSK3640254 100 mg, Part 1: GSK3640254 200 mg, Part 1: GSK3640254 400 mg, Part 1: GSK3640254 700 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power model
	Estimated Value	0.9280
	Confidence Interval	(2-Sided) 90%; 0.8877 to 0.9683
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (AUC0-24) from all active doses in Part 1

59. Secondary Outcome

Title	Part 1: Dose Proportionality for Cmax Following Single Dose of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the single dose phase of the study Part 1.

Arm/Group Title	Part 1: GSK3640254 1 mg	Part 1: GSK3640254 3 mg	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 30mg	Part 1: GSK3640254 100 mg	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 400 mg	Part 1: GSK3640254 700 mg
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1	Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1
Measure Participants	6	6	6	6	6	6	6	6
Geometric Mean (95% Confidence Interval) [Micrograms per mililiter]	0.005	0.014	0.047	0.130	0.372	0.579	1.881	1.724

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg, Part 1: GSK3640254 100 mg, Part 1: GSK3640254 200 mg, Part 1: GSK3640254 400 mg, Part 1: GSK3640254 700 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power Model
	Estimated Value	0.9352
	Confidence Interval	(2-Sided) 90%; 0.8970 to 0.9734
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (Cmax) from all active doses in Part 1

60. Secondary Outcome

Title	Part 2: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3640254 on Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [hour*microgram per milliliter]	6.282 (34.010)	17.506 (13.794)	21.501 (34.205)	31.954 (35.380)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power model
	Estimated Value	0.7968
	Confidence Interval	(2-Sided) 90%; 0.6424 to 0.9512
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (AUC0-tau) from all active doses in Part 1

61. Secondary Outcome

Title	Part 2: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3640254 on Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter]	0.205 (33.414)	0.593 (16.359)	0.615 (74.191)	1.255 (37.220)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power model
	Estimated Value	0.7890
	Confidence Interval	(2-Sided) 90%; 0.6149 to 0.9631
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (Ctrough) from all active doses in Part 2

62. Secondary Outcome

Title	Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 on Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	24	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.414 (31.556)	1.182 (10.264)	1.402 (30.839)	2.156 (20.360)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power model
	Estimated Value	0.7955
	Confidence Interval	(2-Sided) 90%; 0.6562 to 0.9349
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (Cmax) from all active doses in Part 2

63. Secondary Outcome

Title	Part 2: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) From Day 1 to Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Number (90% Confidence Interval) [Ratio of AUC(0-tau)]	2.2005	2.5739	2.6167	2.3634

64. Secondary Outcome

Title	Part 2: Accumulation Ratio of Cmax (R [CMAX]) From Day 1 to Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Number (90% Confidence Interval) [Ratio of Cmax]	1.9276	2.2069	2.2994	2.0650

65. Secondary Outcome

Title	Part 2: Accumulation Ratio of C(Tau) (R[CTAU]) From Day 2 to Day 15
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 15 and Day 2, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 15 dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Number (90% Confidence Interval) [Ratio of Ctau]	2.1408	2.5847	2.5335	2.1666

66. Secondary Outcome

Title	Part 2: Pre-dose Concentration of GSK3640254 on Day 2 to Day 14
Description	Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. results are presented treatment wise.
Time Frame	Pre-dose on Days 2,3,4,6,8,10,12 and 14

Outcome Measure Data

Analysis Population Description

PK Population. The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Day 2 Predose	90.20 (25.312)	221.55 (55.722)	283.37 (137.243)	476.58 (197.909)
Day 3 Predose	155.93 (41.869)	449.82 (68.287)	517.96 (239.825)	753.02 (174.186)
Day 4 Predose	196.25 (55.807)	524.87 (120.723)	667.45 (295.479)	926.40 (235.884)
Day 6 Predose	214.64 (75.891)	550.48 (125.873)	701.98 (349.091)	969.06 (225.600)
Day 8 Predose	230.50 (77.819)	595.26 (151.167)	712.79 (342.941)	936.45 (278.866)
Day 10 Predose	218.97 (74.858)	604.52 (137.121)	802.81 (272.000)	1051.91 (375.261)
Day 12 predose	221.10 (75.744)	628.86 (114.448)	726.13 (300.263)	1182.80 (354.948)
Day 14 predose	214.16 (66.980)	599.45 (97.262)	706.76 (299.450)	1324.29 (470.703)

67. Secondary Outcome

Title	Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 at Day 1
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.215 (24.412)	0.536 (22.959)	0.614 (44.354)	1.044 (29.225)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power model
	Estimated Value	0.7370
	Confidence Interval	(2-Sided) 90%; 0.5649 to 0.9091
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (Cmax) from all active doses in Part 2

68. Secondary Outcome

Title	Part 2: Dose Proportionality (AUC0-24) Following Repeated Dose of GSK3640254 at Day 1
Description	Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Time Frame	Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose

Outcome Measure Data

Analysis Population Description

PK Population, The PK Population include all participants who undergo plasma PK sampling and have evaluable PK parameters estimated during the repeat dose phase of the study Part 2. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 2: GSK3640254 50 mg	Part 2: GSK3640254 100 mg	Part 2: GSK3640254 200 mg + Expansion	Part 2: GSK3640254 320 mg
Arm/Group Description	Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days	Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days
Measure Participants	6	6	25	7
Geometric Mean (Geometric Coefficient of Variation) [hour*micrograms per mililiter]	2.855 (29.621)	6.801 (22.970)	8.257 (49.782)	13.456 (23.743)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 1 mg, Part 1: GSK3640254 3 mg, Part 1: GSK3640254 10 mg, Part 1: GSK3640254 30mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Power model
	Estimated Value	0.7397
	Confidence Interval	(2-Sided) 90%; 0.5576 to 0.9218
	Parameter Dispersion	Type: Value:
	Estimation Comments	The statistical model (power model) is based on the PK parameters (AUC0-24) from all active doses in Part 2

Adverse Events

Time Frame	On-treatment and post-treatment non-serious adverse events and serious adverse events were collected up to Day 15 for Part 1 and Day 28 for Part 2 of the study.
Adverse Event Reporting Description	Safety Population was used to collect the adverse events
Arm/Group Title	Part 1:GSK3640254 1 mg		Part 1:GSK3640254 3 mg		Part 1:GSK3640254 10 mg		Part 1:GSK3640254 30 mg		Part 1:GSK3640254 100 mg		Part 1:GSK3640254 200 mg		Part 1:GSK3640254 400 mg		Part 1:GSK3640254 700 mg		Part 1: Single Dose Placebo		Part 2: Repeated Dose GSK3640254 50 mg		Part 2: Repeated Dose GSK3640254 100 mg		Part 2: Repeated Dose GSK3640254 200mg +Expansion		Part 2: Repeated Dose GSK3640254 320 mg		Part 2: Repeated Dose Placebo
Arm/Group Description	Participants received single dose of GSK3640254 1 mg following a moderate fat meal on Day 1		Participants received single dose of GSK3640254 3 mg following a moderate fat meal on Day 1		Participants received single dose of GSK3640254 10 mg following a moderate fat meal on Day 1		Participants received single dose of GSK3640254 30 mg following a moderate fat meal on Day 1		Participants received single dose of GSK3640254 100 mg following a moderate fat meal on Day 1		Participants received single dose of GSK3640254 200 mg following a moderate fat meal on Day 1		Participants received single dose of GSK3640254 400 mg following a moderate fat meal on Day 1		Participants received single dose of GSK3640254 700 mg following a moderate fat meal on Day 1		Participants received single dose of matching placebo following a moderate fat meal on Day 1		Participants received repeated dose of GSK3640254 50 mg once daily up to 14 days		Participants received repeated dose of GSK3640254 100 mg once daily up to 14 days		Participants received repeated dose of GSK3640254 200 mg once daily up to 14 days		Participants received repeated dose of GSK3640254 320 mg once daily up to 14 days		Participants received repeated dose of matching placebo once daily up to 14 days
All Cause Mortality
	Part 1:GSK3640254 1 mg		Part 1:GSK3640254 3 mg		Part 1:GSK3640254 10 mg		Part 1:GSK3640254 30 mg		Part 1:GSK3640254 100 mg		Part 1:GSK3640254 200 mg		Part 1:GSK3640254 400 mg		Part 1:GSK3640254 700 mg		Part 1: Single Dose Placebo		Part 2: Repeated Dose GSK3640254 50 mg		Part 2: Repeated Dose GSK3640254 100 mg		Part 2: Repeated Dose GSK3640254 200mg +Expansion		Part 2: Repeated Dose GSK3640254 320 mg		Part 2: Repeated Dose Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/16 (0%)		0/6 (0%)		0/6 (0%)		0/25 (0%)		0/7 (0%)		0/14 (0%)
Serious Adverse Events
	Part 1:GSK3640254 1 mg		Part 1:GSK3640254 3 mg		Part 1:GSK3640254 10 mg		Part 1:GSK3640254 30 mg		Part 1:GSK3640254 100 mg		Part 1:GSK3640254 200 mg		Part 1:GSK3640254 400 mg		Part 1:GSK3640254 700 mg		Part 1: Single Dose Placebo		Part 2: Repeated Dose GSK3640254 50 mg		Part 2: Repeated Dose GSK3640254 100 mg		Part 2: Repeated Dose GSK3640254 200mg +Expansion		Part 2: Repeated Dose GSK3640254 320 mg		Part 2: Repeated Dose Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/16 (0%)		0/6 (0%)		0/6 (0%)		0/25 (0%)		0/7 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Part 1:GSK3640254 1 mg		Part 1:GSK3640254 3 mg		Part 1:GSK3640254 10 mg		Part 1:GSK3640254 30 mg		Part 1:GSK3640254 100 mg		Part 1:GSK3640254 200 mg		Part 1:GSK3640254 400 mg		Part 1:GSK3640254 700 mg		Part 1: Single Dose Placebo		Part 2: Repeated Dose GSK3640254 50 mg		Part 2: Repeated Dose GSK3640254 100 mg		Part 2: Repeated Dose GSK3640254 200mg +Expansion		Part 2: Repeated Dose GSK3640254 320 mg		Part 2: Repeated Dose Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		2/6 (33.3%)		4/6 (66.7%)		3/6 (50%)		3/6 (50%)		4/6 (66.7%)		4/6 (66.7%)		1/6 (16.7%)		7/16 (43.8%)		4/6 (66.7%)		5/6 (83.3%)		19/25 (76%)		6/7 (85.7%)		10/14 (71.4%)
Congenital, familial and genetic disorders
Bicuspid aortic valve	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	0/14 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	2/6 (33.3%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/16 (6.3%)	1	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	0/14 (0%)	0
Vomiting	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Abdominal pain	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/25 (4%)	1	0/7 (0%)	0	0/14 (0%)	0
Faeces discoloured	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/16 (6.3%)	1	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Faeces pale	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Faeces soft	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Abdominal distension	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/25 (4%)	1	0/7 (0%)	0	1/14 (7.1%)	1
Constipation	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/25 (8%)	2	0/7 (0%)	0	0/14 (0%)	0
Nausea	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/25 (4%)	1	1/7 (14.3%)	1	0/14 (0%)	0
Aphthous ulcer	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Glossodynia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Lip dry	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Lip ulceration	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Mouth ulceration	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
General disorders
Catheter site pain	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	1/14 (7.1%)	1
Chest pain	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Vessel puncture site bruise	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/16 (6.3%)	1	0/6 (0%)	0	0/6 (0%)	0	1/25 (4%)	1	0/7 (0%)	0	1/14 (7.1%)	1
Fatigue	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	2/6 (33.3%)	2	1/6 (16.7%)	1	1/25 (4%)	1	0/7 (0%)	0	2/14 (14.3%)	2
Catheter site bruise	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/25 (4%)	1	0/7 (0%)	0	1/14 (7.1%)	1
Feeling cold	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Mass	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Infections and infestations
Nasopharyngitis	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Viral infection	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Oral herpes	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Upper respiratory tract infection	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Abscess	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Folliculitis	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Hordeolum	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	3/25 (12%)	3	0/7 (0%)	0	1/14 (7.1%)	1
Face injury	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/16 (6.3%)	1	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Limb injury	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Skin abrasion	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Arthropod bite	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	2/7 (28.6%)	2	0/14 (0%)	0
Investigations
Transaminases increased	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	1/16 (6.3%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Back pain	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	2/25 (8%)	2	0/7 (0%)	0	2/14 (14.3%)	2
Musculoskeletal stiffness	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/25 (4%)	1	0/7 (0%)	0	0/14 (0%)	0
Muscle twitching	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Myalgia	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Nervous system disorders
Headache	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	2/6 (33.3%)	2	1/6 (16.7%)	2	2/6 (33.3%)	2	0/6 (0%)	0	1/16 (6.3%)	1	3/6 (50%)	3	1/6 (16.7%)	1	3/25 (12%)	5	2/7 (28.6%)	2	6/14 (42.9%)	6
Dizziness	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/16 (0%)	0	1/6 (16.7%)	1	2/6 (33.3%)	2	2/25 (8%)	2	1/7 (14.3%)	1	1/14 (7.1%)	1
Migraine	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Paraesthesia	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	0/14 (0%)	0
Lethargy	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/25 (4%)	1	1/7 (14.3%)	1	1/14 (7.1%)	1
Disturbance in attention	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/25 (4%)	1	0/7 (0%)	0	1/14 (7.1%)	1
Somnolence	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	0/14 (0%)	0
Psychiatric disorders
Nightmare	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/16 (6.3%)	1	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Depression	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Insomnia	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	0/14 (0%)	0
Agitation	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/25 (4%)	1	0/7 (0%)	0	0/14 (0%)	0
Abnormal dreams	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/25 (8%)	2	0/7 (0%)	0	0/14 (0%)	0
Depressed mood	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Nasal obstruction	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/16 (12.5%)	2	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Cough	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Haemoptysis	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Oropharyngeal pain	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/25 (4%)	1	1/7 (14.3%)	1	0/14 (0%)	0
Epistaxis	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	0/14 (0%)	0
Hiccups	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/16 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	7/25 (28%)	7	0/7 (0%)	0	0/14 (0%)	0
Dry skin	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	1/14 (7.1%)	1
Rash	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/25 (4%)	1	0/7 (0%)	0	1/14 (7.1%)	1
Blister	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	0/7 (0%)	0	1/14 (7.1%)	1
Eczema nummular	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/16 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/25 (0%)	0	1/7 (14.3%)	1	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.